Journal articles on the topic 'Lovage root'

Summary A preliminary survey indicated that the root-knot nematode Meloidogyne javanica is widely distributed in the rhizosphere of medicinal plants in Boyer-Ahmad region (Iran). Host suitability of ten species of medicinal plants to M. javanica was examined in a pot experiment under controlled greenhouse conditions: alkakengy (Physalis alkekengi L.), chamomile (Matricaria chamomilla L.), English plantain (Plantago lanceolata L.), fennel (Foeniculum vulgare Mill.), garden anchusa (Anchusa italica Retz.), horehound (Marrubium vulgare L.), lovage (Levisticum officinale L.), sorrel (Rumex acetosella L.), thistle (Echinops adenocaulos Boiss.) and woundwort (Stachys pilifera Benth.). According to the scheme of Canto-Saenz, seven species, namely garden anchusa, fennel, horehound, alkakengy, English plantain, woundwort and sorrel can be considered susceptible hosts with gall index (GI) > 2 and reproduction factor (RF) > 1, and thistle, lovage and chamomile, can be considered as hyper-susceptible with GI > 2 and RF ≤ 1.

Lovage (Levisticum officinale W.D.J. Koch) is an aromatic plant from the Apiaceae (Umbelliferae) family used as a condiment in several regions of Europe and also described to have medicinal properties. While the aerial parts are used as foods, the roots are generally discarded. In the past, lovage roots were used in folk medicine for their diuretic, carminative, and spasmolytic properties. Therefore, the exploitation of this undervalued part of the plant can be a source of valuable bioactive compounds for food and/or pharmaceutical industries. Thus, in this study, extracts of different polarity were prepared and studied regarding their chemical composition and bioactive properties. To the best of our knowledge, the composition in phenolic compounds and the volatile profile of the n-hexane extract are reported for the first time. A total of 24 compounds were identified by GC-MS in the n-hexane extract, evidencing a high relative abundance of phthalides. A total of eight phenolic compounds were identified in lovage root extracts (decoction and hydroethanolic extract), with vanillic acid being the major compound. Regarding antioxidant activity, also reported for the first time, decoction and hydroethanolic extract exhibited a high antioxidant capacity in thiobarbituric acid reactive substances (TBARS) (179 ± 11 μg/mL) and in oxidative hemolysis (OxHLIA) assays (510 ± 6 μg/mL), respectively. n-Hexane extract showed relevant anti-proliferative activity against all tumor cell lines tested (GI50, 48–69 μg/mL), despite inhibiting also the growth of a non-tumoral hepatocyte cell line, however, presenting a significantly higher GI50 value (147 μg/mL). This study revealed that lovage root, an agri-food residue, can be a source of valuable bioactive compounds also presenting biological properties that deserve being explored, which could lead to a circular economy for food and/or the pharmaceutical industry.

The objective: to determine the effectiveness of herbal medicine, which includes yarrow, lovage root and rosemary leaves, hepatoprotector with field artichoke and intestinal dialysis (a mixture of electrolytes, macrogol and activated carbon) to normalize kidney function in patients with active tuberculosis (TB). Materials and methods. During 6 years, 738 patients from 6 till 81 years old with active TB of various localizations, including kidneys, were examined and treated. We evaluated symptoms, anamnesis, clinical, biochemical tests of blood, urine, glomerular filtration rate, bacteriological analysis, polymerase chain reaction for DNA of Mycobacterium tuberculosis, immunological studies, methods of radiological diagnosis (sonography, radiography, multislice computed tomography, magnetic resonance imaging, radioisotope method), endoscopic research methods with targeted aspiration and biopsy to obtain biological material. The participants of the research were divided into two groups: main and control ones. Patients in the main group (n=73) were prescribed herbal medicine, which includes yarrow, lovage root and rosemary leaves, hepatoprotector with field artichoke and intestinal dialysis (a mixture of electrolytes, macrogol and activated carbon). The patients in the control group (n=70) used only herbal medicine, which includes yarrow, lovage root and rosemary leaves and hepatoprotector with artichoke. Variation statistics methods were used to process the obtained data. Results. According to the result of the study, 68 (93.1%) patients out of 73 persons in the main group with active TB, had symptoms of the improvement. In the control group, only 37 (52.8%) patients reported positive results. In 68 patients of the main group, normalization of renal function was achieved: normalization of blood creatinine levels, glomerular filtration rate, reduction of protein, leukocytes, erythrocyturia. Conclusions. The proposed method of treatment of patients with active tuberculosis of different localization, including kidneys, on the background of antimycobacterial therapy is one of the possible treatment options. It is proved that normalization of renal function was determined in 93.1% of patients, which is on 40% higher compared to the control group.

<strong>The objective:&nbsp;</strong>to determine the effectiveness of herbal medicine, which includes yarrow, lovage root and rosemary leaves, hepatoprotector with field artichoke and intestinal dialysis (a mixture of electrolytes, macrogol and activated carbon) to normalize kidney function in patients with active tuberculosis (TB). <strong>Materials and methods.&nbsp;</strong>During 6 years, 738 patients from 6 till 81 years old with active TB of various localizations, including kidneys, were examined and treated. We evaluated symptoms, anamnesis, clinical, biochemical tests of blood, urine, glomerular filtration rate, bacteriological analysis, polymerase chain reaction for DNA of Mycobacterium tuberculosis, immunological studies, methods of radiological diagnosis (sonography, radiography, multislice computed tomography, magnetic resonance imaging, radioisotope method), endoscopic research methods with targeted aspiration and biopsy to obtain biological material. The participants of the research were divided into two groups: main and control ones. Patients in the main group (n=73) were prescribed herbal medicine, which includes yarrow, lovage root and rosemary leaves, hepatoprotector with field artichoke and intestinal dialysis (a mixture of electrolytes, macrogol and activated carbon). The patients in the control group (n=70) used only herbal medicine, which includes yarrow, lovage root and rosemary leaves and hepatoprotector with artichoke. Variation statistics methods were used to process the obtained data. <strong>Results.&nbsp;</strong>According to the result of the study, 68 (93.1%) patients out of 73 persons in the main group with active TB, had symptoms of the improvement. In the control group, only 37 (52.8%) patients reported positive results. In 68 patients of the main group, normalization of renal function was achieved: normalization of blood creatinine levels, glomerular filtration rate, reduction of protein, leukocytes, erythrocyturia. <strong>Conclusions.&nbsp;</strong>The proposed method of treatment of patients with active tuberculosis of different localization, including kidneys, on the background of antimycobacterial therapy is one of the possible treatment options. It is proved that normalization of renal function was determined in 93.1% of patients, which is on 40% higher compared to the control group.

Objective. Initial optimized prescription of Chinese herb medicine for unstable angina (UA).Methods. Based on partially observable Markov decision process model (POMDP), we choose hospitalized patients of 3 syndrome elements, such asqideficiency, blood stasis, and turbid phlegm for the data mining, analysis, and objective evaluation of the diagnosis and treatment of UA at a deep level in order to optimize the prescription of Chinese herb medicine for UA.Results. The recommended treatment options of UA forqideficiency, blood stasis, and phlegm syndrome patients were as follows: Milkvetch Root + Tangshen + Indian Bread + Largehead Atractylodes Rhizome (ADR=0.96630); Danshen Root + Chinese Angelica + Safflower + Red Peony Root + Szechwan Lovage Rhizome Orange Fruit (ADR=0.76); Snakegourd Fruit + Longstamen Onion Bulb + Pinellia Tuber + Dried Tangerine peel + Largehead Atractylodes Rhizome + Platycodon Root (ADR=0.658568).Conclusion. This study initially optimized prescriptions for UA based on POMDP, which can be used as a reference for further development of UA prescription in Chinese herb medicine.

Urinary tract infections (UTIs) are an extremely common pathology among pregnant women and women in labor, the manifestation of which occurs during pregnancy. Physiological changes in a woman’s organism form an optimal background for infection or activation of the aggression of one’s own microbial environments – the microflora that colonizes the periurethral area and mostly belongs to the family of enterobacteria and staphylococci.Clinical manifestations of UTIs during pregnancy are extremely variable and do not always correspond to the usual course of the disease, which necessitates the search for modern approaches to diagnosis and treatment. Also, UTI is one of the leading factors that provoke severe pregnancy complications and can lead to adverse obstetric outcomes.The objective: to evaluate the effectiveness of the modern etiopathogenetic approach to the treatment of UTIs during pregnancy.Materials and methods. In the study, which began in 2022 and is ongoing, 1615 pregnant women at gestational ages 6-37 weeks with clinical manifestations of urinary tract infections (UTIs). This work presents the survey results of 615 pregnant women with UTIs at gestational ages from 20 to 28 weeks, both before and one month after treatment initiation. These women were monitored during their pregnancies in prenatal care clinics of municipal non-commercial enterprises across all regions of Ukraine. At the stage of prescribing treatment the examined women are divided into two groups. The main group included 374 pregnant women with established diagnoses of acute urethritis, acute cystitis, gestational pyelonephritis (GP) and asymptomatic bacteriuria (ABU), who have received antibacterial and uroseptic agents for treatment in accordance with current clinical guidelines in combination with a herbal uroantiseptic containing 120 mg of cranberry berry extract and 36 mg each of extracts of goldenseal, lovage root, rosemary, as well as auxiliary substances. The comparison group included 241 pregnant women with established diagnoses of acute urethritis, acute cystitis, GP and ABU, who were treated exclusively with antibacterial and uroseptic agents for UTIs manifestations.The effectiveness of treatment methods was evaluated on the basis of a developed questionnaire with information on the main symptoms characteristic of diseases of the urinary system, before and one month after the prescribed treatment.Results. On the background of addition to the main antibacterial and uroseptic therapy the herbal uroantiseptic, containing 120 mg of cranberry berry extract and 36 mg each of extracts of yarrow, lovage root, rosemary, as well as auxiliary substances already a month after the start of treatment, the absence of complaints was found in the majority of pregnant women in the main group, related:with frequent urination – 354 (94.6%) (comparison group – 208 (86.3%); p&lt;0.05), the need for urgent urination – 374 (99.1%) (comparison group – 232 (96.3%); p&lt;0.05), the feeling of incomplete emptying of the bladder – 348 (93.3%) (comparison group – 202 (83.9%); p&lt;0.05),with pain: during urination – 369 (98.7%) (comparison group – 231 (95.9%); p&lt;0.05), in the lower abdomen, not associated with urination – 366 (97.9%) (comparison group – 230 (95.9%); p&lt;0.05), in the lower back – 369 (98.7%) (comparison group – 229 (95.1%); p&lt;0.05),with discharge from the urethra not related to urination – 374 (100.0%) (comparison group – 233 (96.7%); p&lt;0.05).Conclusions. On the background of the prescribing of a herbal uroantiseptic containing 120 mg of cranberry extract and 36 mg of extracts of yarrow, lovage root, and rosemary, as well as auxiliary substances, additionally to the main antibacterial and uroseptic therapy in pregnant women of the main group, in a significantly greater number of cases the absence of complaints, which are associated with manifestations of urinary tract infections, was determined.The use of the herbal uroantiseptic, containing 120 mg of cranberry berry extract and 36 mg of extracts of yarrow, lovage root, and rosemary, is safe and creates favorable conditions for the course of pregnancy and further childbirth due to the potentiation of the effects of antibacterial and uroseptic therapy and the effective prevention of recurrences of urinary tract infections.

Abstract The repellency to female Stomoxys calcitrans (L.) (Diptera: Muscidae) of 21 essential oils (EOs) alone or in combination with Calophyllum inophyllum L. (Clusiaceae) nut oil (tamanu oil) was examined using an exposed human hand bioassay. Results were compared with those of commonly used repellent N,N-diethyl-3-methylbenzamide (DEET). In tests with six human male volunteers at a dose of 0.5 mg/cm2, patchouli (protection time [PT], 3.67 h) was the most effective EO but less active than DEET (4.47 h), as judged by the PT to first bite. Very strong repellency also was produced by clove bud, lovage root, and clove leaf EOs (PT, 3.50–3.25 h), whereas strong repellency was obtained from thyme white EO (2.12 h). Thyme red, oregano, and geranium EOs exhibited moderate repellency (PT, 1.24–1.11 h). At 0.25 mg/cm2, protection time of clove bud, clove leaf, and lovage root EOs (PT, ≈1 h) was shorter than that of DEET (2.17 h). An increase in the protection time was produced by binary mixtures (PT, 2.68–2.04 h) of five EOs (clove bud, clove leaf, thyme white, patchouli, and savory) and tamanu oil (0.25:2.0 mg/cm2) compared with that of either the constituted essential oil or tamanu oil alone (PT, 0.56 h). The protection time of these binary mixtures was comparable with that of DEET. With the exception of savory EO, the other EOs, tamanu oil, and binary mixtures did not induce any adverse effects on the human volunteers at 0.5 mg/cm2. Thus, binary mixtures of essential oils and tamanu oil described merit further study as potential repellents for protection from humans and domestic animals from biting and nuisance caused by S. calcitrans.

Background. Asymptomatic bacteriuria in pregnant women can contribute to urological and gestational complications. Antibiotic therapy is recommended in patients with 105 CFU/mL and above in the urine. However, choosing antimicrobial therapy is challenging for those with 103104 CFU/mL.&#x0D; Aim. To assess the effectiveness of Superlymph combined with phytotherapy in pregnant women with asymptomatic bacteriuria.&#x0D; Materials and methods. Pregnant women aged 21 to 38 with asymptomatic bacteriuria (bacterial count of 103104 CFU/mL), comparable in age, reproductive history, and extragenital comorbidities, were divided into three groups. In group 1 (32 subjects), Superlymph and a herbal medicine containing centaury, lovage root, and rosemary leaves were used. In group 2 (33 subjects), only the herbal medicinal product was used. In group 3 (35 subjects), the above drug products were not used. The patients received the herbal medicinal product containing centaury, lovage root, and rosemary leaves 2 tablets TID for 14 days. Superlymph was administered intravaginally (1 suppository [10 units] BID for 10 days). A follow-up urine culture for groups 1 and 2 was taken 23 weeks after the completion of therapy, and for patients of group 3, 23 weeks after the previous culture. A routine general clinical assessment of pregnant women was performed. Statistical analysis was carried out using the Statistica 12.0 software.&#x0D; Results. Patients of the main group that received the peptide-cytokine and herbal medicinal products had the most significant improvement compared with pregnant women of other groups, as shown by complete eradication from the urinary tract of Escherichia coli, improved urinary laboratory tests, cytology, and fewer gestational complications. Premature onset of labor was significantly less common (6-fold) in patients of the main group versus controls, who refused the proposed therapy for asymptomatic (moderate) bacteriuria.&#x0D; Conclusion. The addition of peptide-cytokine agent Superlymph increases the treatment effectiveness in pregnant women with asymptomatic bacteriuria.

Urinary tract infections (UTIs) are an extremely common pathology among pregnant women and women in labor, the manifestation of which occurs during pregnancy. Physiological changes in a woman&rsquo;s organism form an optimal background for infection or activation of the aggression of one&rsquo;s own microbial environments &ndash; the microflora that colonizes the periurethral area and mostly belongs to the family of enterobacteria and staphylococci.Clinical manifestations of UTIs during pregnancy are extremely variable and do not always correspond to the usual course of the disease, which necessitates the search for modern approaches to diagnosis and treatment. Also, UTI is one of the leading factors that provoke severe pregnancy complications and can lead to adverse obstetric outcomes.The objective: to evaluate the effectiveness of the modern etiopathogenetic approach to the treatment of UTIs during pregnancy.Materials and methods. In the study, which began in 2022 and is ongoing, 1615 pregnant women at gestational ages 6-37 weeks with clinical manifestations of urinary tract infections (UTIs). This work presents the survey results of 615 pregnant women with UTIs at gestational ages from 20 to 28 weeks, both before and one month after treatment initiation. These women were monitored during their pregnancies in prenatal care clinics of municipal non-commercial enterprises across all regions of Ukraine.At the stage of prescribing treatment the examined women are divided into two groups. The main group included 374 pregnant women with established diagnoses of acute urethritis, acute cystitis, gestational pyelonephritis (GP) and asymptomatic bacteriuria (ABU), who have received antibacterial and uroseptic agents for treatment in accordance with current clinical guidelines in combination with a herbal uroantiseptic containing 120 mg of cranberry berry extract and 36 mg each of extracts of goldenseal, lovage root, rosemary, as well as auxiliary substances. The comparison group included 241 pregnant women with established diagnoses of acute urethritis, acute cystitis, GP and ABU, who were treated exclusively with antibacterial and uroseptic agents for UTIs manifestations.The effectiveness of treatment methods was evaluated on the basis of a developed questionnaire with information on the main symptoms characteristic of diseases of the urinary system, before and one month after the prescribed treatment.Results. On the background of addition to the main antibacterial and uroseptic therapy the herbal uroantiseptic, containing 120&nbsp;mg of cranberry berry extract and 36 mg each of extracts of yarrow, lovage root, rosemary, as well as auxiliary substances already a month after the start of treatment, the absence of complaints was found in the majority of pregnant women in the main group, related:with frequent urination &ndash; 354&nbsp;(94.6%) (comparison group &ndash; 208&nbsp;(86.3%); p&lt;0.05), the need for urgent urination &ndash; 374&nbsp;(99.1%) (comparison group &ndash; 232&nbsp;(96.3%); p&lt;0.05), the feeling of incomplete emptying of the bladder &ndash; 348&nbsp;(93.3%) (comparison group &ndash; 202&nbsp;(83.9%); p&lt;0.05),with pain: during urination &ndash; 369&nbsp;(98.7%) (comparison group &ndash; 231&nbsp;(95.9%); p&lt;0.05), in the lower abdomen, not associated with urination &ndash; 366&nbsp;(97.9%) (comparison group &ndash; 230&nbsp;(95.9%); p&lt;0.05), in the lower back &ndash; 369&nbsp;(98.7%) (comparison group &ndash; 229&nbsp;(95.1%); p&lt;0.05),with discharge from the urethra not related to urination &ndash; 374&nbsp;(100.0%) (comparison group &ndash; 233&nbsp;(96.7%); p&lt;0.05).Conclusions. On the background of the prescribing of a herbal uroantiseptic containing 120&nbsp;mg of cranberry extract and 36 mg of extracts of yarrow, lovage root, and rosemary, as well as auxiliary substances, additionally to the main antibacterial and uroseptic therapy in pregnant women of the main group, in a significantly greater number of cases the absence of complaints, which are associated with manifestations of urinary tract infections, was determined.The use of the herbal uroantiseptic, containing 120 mg of cranberry berry extract and 36 mg of extracts of yarrow, lovage root, and rosemary, is safe and creates favorable conditions for the course of pregnancy and further childbirth due to the potentiation of the effects of antibacterial and uroseptic therapy and the effective prevention of recurrences of urinary tract infections.

Study objective: to study the effect of a herbal preparation containing a standardised BNO 1040 extract* (based on lovage root, rosemary leaves and aerial parts of centaury) on the extracorporeal shockwave lithotripsy (ESWL) results in patients with urolithiasis (UL).&#x0D; Methodology. 150 patients with UL (aged 18–65 years) treated with ESWL method were divided into 2 equal groups. The main group (n = 75) received standard recommendations and herbal preparation (12 months). The control group (n = 75) received standard recommendations only. The following was evaluated: time and degree of elimination of fragments; the presence of pain and leukocyturia; recurrent stone formation.&#x0D; Results. The elimination of fragments was observed up to 14 days in 94.7 % of patients in the main group versus 76 % of patients in the control group. Renal colic was observed in 6.7 % of patients in the main group versus 10.7 % of patients in the control group; cases of leukocyturia were observed within 14 days in 10.7 % versus 22.7 %, respectively. During the year, a recurrent lithiasis was diagnosed in 6.7% of patients in the main group and in 16 % of patients in the control group.&#x0D; Conclusion. The use of BNO 1040 extract in combination with ESWL: contributes to more rapid and safe elimination of fragments of the calculi and reduces the risk of recurrent stone formation.

Abstract Plants belonging to the Apiaceae family (including Levisticum officinale WDJ Koch) are rich sources of phytochemicals and secondary metabolites, with possible health-promoting and agrochemical potential. The objective of this work was to provide important guidelines for controlling conventional aqueous extraction to obtain Levisticum officinale root extracts with maximised levels of bioactive compounds. The ultimate goal was to optimise the total phenolic compounds, flavonoid content, sugars, and total antioxidant capacity to identify the process conditions necessary to produce highly bioactive extracts that could be used in a wide range of industries. Biomass extraction of lovage root was carried out using water as the extraction solvent. To perform the optimisation of the aqueous extraction, multivariate regression models were used and multi-criteria analysis was performed using Pareto set navigation. Pareto front analysis showed that for the maximum extraction efficiency of bioactive compounds from Levisticum officinale, the optimal extraction process parameters were 0.0714 g·mL−1 as biomass/water ratio and a time of 35.7142 min, at the highest analysed temperature. For the highest analysed value of plant biomass/solvent ratio (0.075 g·mL−1) and maximum process temperature (95ºC), extraction could be carried out for 20 min or in the range 37.1429-38.5714 min. On the other hand, if the extraction time reaches 40 min and the sam-ple/solvent ratio 0.075 g·mL−1, the optimum process temperature is be-tween 75ºC and 95ºC.

Levisticum officinale (lovage) is an aromatic and medicinal plant traditionally used for its antioxidant, anti-inflammatory and antimicrobial properties. The aim of this study was to evaluate the phytochemical composition and antioxidant activity of hydroalcoholic extracts obtained from leaves, roots and the whole plant, as well as to develop hydrogels with pharmaceutical potential. The hydroalcoholic extracts (70% ethanol) were characterized by spectrophotometric and HPLC-DAD methods to determine the total content of phenolic compounds, phenolic acids, flavonoids and condensed tannins. The antioxidant activity was evaluated by DPPH and ABTS methods. The extracts were included in 2% carbopol-based hydrogels and tested for stability and antioxidant efficacy. The hydroalcoholic extract of the leaves showed the highest content of total phenolic compounds (20.84 ± 2.18 mg GAE/g), total flavones (11.39 ± 2.48 mg QE/g) and condensed tannins (1.98 ± 1.55 mg CE/g), and was also the richest in quercetin (3.32 ± 1.25 mg/g), kaempferol (1.84 ± 1.63 mg/g), luteolin (2.12 ± 1.19 mg/g), rutin (4.38 ± 1.84 mg/g) and apigenin (1.91 ± 1.44 mg/g). The root extract had the highest content of phenolic acids, including ferulic acid (3.86 ± 1.37 mg/g), vanillic acid (2.53 ± 1.76 mg/g) and caffeic acid (3.28 ± 1.28 mg/g). The antioxidant activity was highest in the leaves extract, with values of 276.2 ± 3.4 µmol TE/g (ABTS) and 246.4 ± 3.6 µmol TE/g (DPPH). The whole-plant extracts showed intermediate values, offering a balance between flavonoids and phenolic acids. Hydrogels formulated with 5% extracts demonstrated stability and sustained antioxidant activity over time. Leaf extracts, due to their high flavonoid content, are recommended for formulations with antioxidant and photoprotective effects, while root extracts are suitable for anti-inflammatory and antimicrobial applications. Hydrogels obtained based on 2% carbopol represent a promising delivery system for dermato-cosmetic and pharmaceutical applications because they exhibited significant antioxidant action.

Background. With increasing life expectancy in cervical cancer patients, new medical and social problems associated with radiation therapy become apparent. The combination of radiation therapy and chemotherapy is an important therapeutic component in treatment of malignant neoplasms of the genital area in women, but the frequency and severity of side effects has been increasing. Radiation complications occur in 20–50 % of patients. In 5 % of patients, they can represent a severe and potentially life-threatening condition. Prevention of negative effects on the genitourinary system in cervical cancer patients receiving radiation therapy on the pelvis is a matter of importance.Aim. To evaluate the clinical efficacy of a phytotherapeutic preparation Canephron N containing centaury, lovage root, rosemary leaves in the prevention of radiation cystitis during chemoradiotherapy in patients with advanced cervical cancer.Materials and methods. The study included 60 patients with locally advanced cervical cancer receiving radical chemoradiotherapy. The patients were divided into 2 groups: treatment group consisting of patients receiving phytotherapeutic preparation Canephron N for prevention of radiation complications, and control group consisting of patients not receiving symptomatic treatment. The treatment results were evaluated using questionnaires, clinical, laboratory and instrumental studies. The obtained data were compared with the results of treatment of the control group which were not prescribed a medication for prevention of urological complications.Results and conclusion. The use of Canephron N in accompanying therapy had significantly decreased the risk and incidence of radiation cystitis.

Abnormal findings in urinalysis are one of the most common symptoms kidneys and urinary tract diseases. Authors discuss assessment of changes in urinalysis from the position of general pediatrician. The normal values of protein, erythrocytes, leukocytes, cylinders, crystals, glucose in urine are considered, as evidenced by changes in these parameters, as well as changes of urinary color and specific gravity. The algorithm of the pediatrician's tactics after detection of different degrees of proteinuria, erythrocyturia and leukocyturia is presented. It is shown that with a high degree of severity of changes in urine, especially in combination with arterial hypertension, edema, fever, and other clinical symptoms, needs in emergent specialized impatient medical aid. In other cases, outpatient examination and treatment are recommended. The issues of urinary tract infection (UTI), diagnosed by the presence of piuria and bacteriuria, are discussed. Routine method of UTIs treatment is antibiotic therapy, but the existence of uropathogens in the form of biofilms contributes to their drug resistance, which dictates actuality of alternative therapeutic methods search. In cases without anatomical obstacles to urinary flow, including patients with functional disorders of urination, the application of the phytodrug Canephron N, which contains three medicinal plants (centaury herb, lovage root and rosemary leaves), can be effective. The drug is prescribed after antibacterial therapy or simultaneously with it, is effective as an anti-relapse therapy, helps to reduce crystalluria and normalize the passage of urine. In vitro experiments show its ability to inhibit the formation of microbial biofilms. The drug in the form of a solution can be prescribed to children aged 1 year and older.

Aim. The aim of this observational study was to evaluate the effectiveness of a phytotherapic drug (Canephron N) in preventing urinary tract infection (UTI) in high-risk women undergoing urodynamic studies (UDS). Methods. The study protocol was approved by the local institutional ethical committee. Adult women with at least one risk factor for acquiring UTI (defined as: age over 70, elevated postvoid residual urine&gt;100 ml, recurrent UTI, pelvic organ prolapse (POP) ≥II in POP-Q scale, and neurogenic bladder) had received after UDS either a single oral dose of fosfomycin trometamol (FT) (3 grams) or a phytodrug containing centaury herb, lovage root, and rosemary leaves (5 ml taken orally three times daily for one week). All patients included in the study had no pyuria according to urine dipstick (nitrite and/or blood and/or leukocyte esterase) and negative urine culture (CFU &lt; 103/ml) before UDS. Urine samples were also tested 7 days after UDS. Results. Seventy-two high-risk participants completed the study. Seven days after urodynamic studies UTI symptoms, pyuria (nitrite and/or blood and/or leukocyte esterase) and bacteriuria with E. coli occurred in two patients (one (2.8%) in the FT and one (2.7%) in the phytodrug group, respectively). No statistical differences in UTI incidence were found between both treatment groups. We did not observe any additional adverse events in both groups. The major disadvantage of prophylaxis with the phytodrug as compared to FT was the necessity of continuing therapy for 7 days. Conclusion. Prophylaxis of UTI with a phytodrug (Canephron N) may be considered a good alternative to antibiotic prophylaxis use after UDS in high-risk female patients.

Lovage (Levisticum officinale W.D.J. Koch) is a known aromatic apiaceous species that is widely used as a culinary and medicinal plant. Traditionally, more scientific attention has been paid to lovage volatiles, while other groups of compounds have been underutilized. In this study, metabolites of fresh lovage roots were investigated by liquid chromatography–mass spectrometry, and 25 compounds were identified, including coumarins as basic components and minor hydroxycinnamates; most were detected for the first time in the plant. Four major coumarins (including apterin, xanthotoxin, isopimpinellin, and pimpinellin) were successfully separated by a validated HPLC–PDA method, and the fresh roots of seven lovage cultivars as well as the dry roots of commercial lovage were quantified. The coumarin content deviation was 1.7–2.9 mg/g in the fresh roots and 15–24 mg/g in the dry roots. A variation in the coumarin level was found during storage of the fresh lovage roots at chill and room temperatures, while storage of the dried roots at room temperature showed the lowest loss of target compounds. This new information about the metabolites of lovage indicates the prospects of the plant roots as a source of dietary coumarins.

Aim. To assess the frequency of pregnancy complications in women with type 1 diabetes mellitus and without diabetes combined with urinary infection and the effect of various treatment options for urinary infection on the frequency of pregnancy complications in type 1 diabetes.&#x0D; Methods. Pregnant women with urinary tract infection were examined: 110 people with type 1 diabetes (main group) and 133 women without diabetes (comparison group). The diagnosis of urinary infection was confirmed by a double bacteriological culture. Patients of the main group were divided into three subgroups depending on the method of treatment of urinary tract infection: subgroup A received antibiotic therapy and phytopreparation (Centaurium + Lovage root + Rosemary leaves), subgroup Б received antibiotic therapy, subgroup B received phytopreparation. After treatment, the preservation of pregnancy complications such as the threat of miscarriage, proteinuria, intrauterine infection of fetus, anemia, premature birth, which developed on a background of urinary tract infection, was evaluated. The significance of differences in groups was evaluated using the Pearson chi-square tests, and the effectiveness of each type of therapy was evaluated using the McNemar test.&#x0D; Results. The risk of miscarriage, intrauterine infection, anemia, and premature birth was higher in pregnant women of main group with all types of urinary infection, preeclampsia with pyelonephritis, and asymptomatic bacteriuria. Both complex therapy of pyelonephritis (antibiotics with phytopreparation) and monotherapy with antibiotics were effective in eliminating the threat of miscarriage, intrauterine infection and anemia. Adding herbal medicine to antibiotic therapy for pyelonephritis reduced the preterm birth rate compared with antibiotic monotherapy, and other complications did not reveal differences between subgroups. In asymptomatic bacteriuria, complex therapy and monotherapy with antibiotics were effective in eliminating the threat of miscarriage, intrauterine infection and anemia. Monotherapy with a phytopreparation in pregnant women with type 1 diabetes did not lead to the elimination of these complications. Combination therapy asymptomatic bacteriuria was more effective than antibiotic monotherapy in terms of the effect on preterm delivery and equally effective in terms of the threat of miscarriage, intrauterine infection and anemia.&#x0D; Conclusion. Adding phytopreparation to antibiotic therapy for pyelonephritis and asymptomatic bacteriuria in pregnant women with type 1 diabetes mellitus to prevent premature birth seems appropriate; monotherapy of asymptomatic bacteriuria with a phytopreparation is ineffective for eliminating the threat of miscarriage, intrauterine infection, anemia, therefore antibiotics should be prescribed at the beginning of therapy for asymptomatic bacteriuria.

Current trends in scholarship—epitomized in the works of, inter alia, Lewis Ayres, Adrian Pabst, and Rowan Williams—argue for a metaphysics of relationality at the heart of Christian thought that is at its root Platonic. This metaphysic is in turn typified by its commitment to divine simplicity and its corresponding apophatic grammar, which serve as useful points of contact with Plotinus’s own thought. Examination of key texts in Plotinus’s Enneads demonstrates a shared trinitarian grammar when speaking about the first principle. These connections prompt a need to articulate trinitarian dogma as an important step in the history of philosophy, and not just theology, especially for resolving the perennial problem of the one and the many. This “Christian Platonism” has been in a necessary process of recovery and re-articulation, of which the above is put forward as a contribution.

Urinary tract infections (UTIs) are a significant public health problem. Every year the situation becomes more complicated due to the high rate of recurrence and the growth of resistance among the population.Research results show that about 150 million people suffer from bacterial infections of the urinary tract every year, and about 6 million visits to the doctor about UTIs are registered in the US every year, of which more than 2 million are related to cystitis. In Ukraine, UTIs rank first among all urological diseases, more than 170,000 cystitis patients are registered annually for the first time. 20% of girls till 20 years old have at least one episode of acute cystitis, and 25–40% of women experience a recurrent episode within a year after an episode of acute cystitis.Treatment of cystitis depends on the influence of many factors, which include: age, gender, state of the immune system, recurrences, urological pathologies, severity of the disease and the risk of developing multiple drug resistance. For the prevention of the antibiotic resistance development, it is recommended to use combined herbal preparations for long-term prevention of episodes of recurrent cystitis.The objective: to evaluate the effectiveness of the use of the proposed herbal preparation in the complex treatment and prevention of recurrence in patients with acute uncomplicated cystitis and the chronometry of the onset of action of the drug in monotherapy.Materials and methods. The study was included the patients with acute uncomplicated cystitis. The main group involved 40 persons who were prescribed antibacterial therapy in the form of a single use of fosfomycin trometamol 3 g per os or sulfamethoxazole/trimethoprim 400 mg/80 mg 2 tablets twice a day for 5 days in combination with a herbal preparation (a combination of medicinal plant components of centaury herb, lovage root and rosemary leaves) 1 tablet 3 times a day for 3 months. Patients of the comparison group (40 subjects) received only antibacterial therapy.Treatment effectiveness and side effects were evaluated 10 days after its initiation. Determination of the presence and frequency of recurrence of the disease was carried out 3 and 6 months after its onset. At the second stage of the study, the effectiveness of the use of the herbal preparation was evaluated as a prevention of recurrence of cystitis and relief of its first signs.At the appearance of the first signs of recurrence of the disease within 6 months after the end of the primary course, patients of both groups were recommended to immediately start using the herbal preparation, 1 tablet three times a day. To determine the speed of the onset of the pharmaceutical action of the drug, each patient was asked to fill out a questionnaire regarding the chronometry of the reduction or disappearance of symptoms.Results. After completion of treatment, a positive effect was observed in 38 (95.0%) patients of the main group and 37 (92.5%) of the comparison group, leukocyturia stopped in 39 (97.5%) and 38 (95.0%) patients, respectively, dysuria – in 37 (92.5%) and 38 (95.0%), respectively. The effect of the proposed herbal preparation was maximally manifested in reducing the rate of recurrence of cystitis, which has important clinical significance.It is quite clear that for the occurrence of a sporadic episode of acute cystitis, timely and effective antibiotic therapy is self-sufficient and accordingly hides the effect of phytotherapy. Use of the proposed herbal preparation for 3 months provides long-term rehabilitation of the lower urinary tract due to the aquaretic and antimicrobial effect of the herbal preparation and prevents the recurrence of the disease.Conclusions. The use of the proposed herbal preparation as part of combined therapy in patients with acute uncomplicated cystitis demonstrated its effectiveness in 95.0% of patients. The appointment of the proposed drug of plant origin prevents the occurrence of recurrence in 97.5% of patients, which allows us to recommend it for use in order to prevent relapses of the disease.The use of the proposed preparation of herbal origin helps to reduce the feeling of incomplete emptying of the bladder, starting from 62.9±17.0 min and the disappearance of pollakiuria – by 179.7±23.0 min, which allows to make quick assess of phytotherapy effectiveness and, if necessary to strengthen it in time.

Urinary tract infections (UTIs) are a significant public health problem. Every year the situation becomes more complicated due to the high rate of recurrence and the growth of resistance among the population.Research results show that about 150 million people suffer from bacterial infections of the urinary tract every year, and about 6 million visits to the doctor about UTIs are registered in the US every year, of which more than 2 million are related to cystitis. In Ukraine, UTIs rank first among all urological diseases, more than 170,000 cystitis patients are registered annually for the first time. 20% of girls till 20 years old have at least one episode of acute cystitis, and 25&ndash;40% of women experience a recurrent episode within a year after an episode of acute cystitis.Treatment of cystitis depends on the influence of many factors, which include: age, gender, state of the immune system, recurrences, urological pathologies, severity of the disease and the risk of developing multiple drug resistance. For the prevention of the antibiotic resistance development, it is recommended to use combined herbal preparations for long-term prevention of episodes of recurrent cystitis.The objective: to evaluate the effectiveness of the use of the proposed herbal preparation in the complex treatment and prevention of recurrence in patients with acute uncomplicated cystitis and the chronometry of the onset of action of the drug in monotherapy.Materials and methods. The study was included the patients with acute uncomplicated cystitis. The main group involved 40 persons who were prescribed antibacterial therapy in the form of a single use of fosfomycin trometamol 3 g per os or sulfamethoxazole/trimethoprim 400 mg/80 mg 2 tablets twice a day for 5 days in combination with a herbal preparation (a combination of medicinal plant components of centaury herb, lovage root and rosemary leaves) 1 tablet 3 times a day for 3 months. Patients of the comparison group (40 subjects) received only antibacterial therapy.Treatment effectiveness and side effects were evaluated 10 days after its initiation. Determination of the presence and frequency of recurrence of the disease was carried out 3 and 6 months after its onset. At the second stage of the study, the effectiveness of the use of the herbal preparation was evaluated as a prevention of recurrence of cystitis and relief of its first signs.At the appearance of the first signs of recurrence of the disease within 6 months after the end of the primary course, patients of both groups were recommended to immediately start using the herbal preparation, 1 tablet three times a day. To determine the speed of the onset of the pharmaceutical action of the drug, each patient was asked to fill out a questionnaire regarding the chronometry of the reduction or disappearance of symptoms.Results. After completion of treatment, a positive effect was observed in 38&nbsp;(95.0%) patients of the main group and 37&nbsp;(92.5%) of the comparison group, leukocyturia stopped in 39&nbsp;(97.5%) and 38&nbsp;(95.0%) patients, respectively, dysuria &ndash; in 37&nbsp;(92.5%) and 38&nbsp;(95.0%), respectively. The effect of the proposed herbal preparation was maximally manifested in reducing the rate of recurrence of cystitis, which has important clinical significance.It is quite clear that for the occurrence of a sporadic episode of acute cystitis, timely and effective antibiotic therapy is self-sufficient and accordingly hides the effect of phytotherapy. Use of the proposed herbal preparation for 3 months provides long-term rehabilitation of the lower urinary tract due to the aquaretic and antimicrobial effect of the herbal preparation and prevents the recurrence of the disease.Conclusions. The use of the proposed herbal preparation as part of combined therapy in patients with acute uncomplicated cystitis demonstrated its effectiveness in 95.0% of patients. The appointment of the proposed drug of plant origin prevents the occurrence of recurrence in 97.5% of patients, which allows us to recommend it for use in order to prevent relapses of the disease.The use of the proposed preparation of herbal origin helps to reduce the feeling of incomplete emptying of the bladder, starting from 62.9&plusmn;17.0 min and the disappearance of pollakiuria &ndash; by 179.7&plusmn;23.0 min, which allows to make quick assess of phytotherapy effectiveness and, if necessary to strengthen it in time.

It is difficult to speak calmly and quietly about what one loves passionately, and next to my wife and my children I love the Catholic church more than any other thing. The passion for it has perdured all the years, and grows stronger the longer I live in it even though it must be said that my years with it have been far from easy. I do not love the church because I examined it and found it lovable; I loved it long before I could have examined it, and no examination has lessened my love for it. I cannot go back far enough in time or dig deeply enough in my psychic archaeology to find the root of that love. I think the root is the grace of God, yet I do have memories of important places and persons.

<strong><em>Abstract</em></strong> The purpose of this study was to find out the effect of the program on the treatment of the case of a student in the second grade of Khadija Bint Khuwailad School. I noticed his condition while I was observing observations and applied my class. When I asked him about his teacher, she told me that the student suffers from slow reading. , bad hand script , reflecting letters, weak in spelling words, weak in reading, slow speech, delayed in response and writes from left to right, quiet, friendly, lovable by students but he has no social relationships, unsure of himself and hesitant,&nbsp; he was transferred to the resources room in Khadija School to diagnose his condition according&nbsp; to the request from his second-grade teacher to identify the student&#39;s problem, to identify language skills and linguistic weakness, and to develop a remedial program to help him improve his academic performance, strengthen his self-confidence, and improve his social relationship with his colleagues, With the educational program offered to the student and the use of alternatives appropriate to the level of difficulty that he suffered from in addition to all aspects of the student, psychological, social, educational, cognitive and linguistic, there has been a clear improvement and markedly to the situation and became almost at the level of class

To find out effects of adding ginger roots powder and vitamin E and mutual synergy between them on productive performance and some carcass features of Awassi lambs. An experimement was conducted at animal farm designated for raising sheep of the Department of Animal Production/College of Agriculture and Forestry, University of Mosul. Twenty-four of Awassi lambs (males) were selected homogeneously with average of initial weight (27.250- 27.525 kg) and close in age (5.5-6 months) at the beginning of experiment. The fattening diet was prepared as a peleted ration free of feed additives (control diet).While ginger roots powder was added at a rate of 20 gm/kg dry matter to the second ration and vitamin E was added at a rate of 200 mg/kg to the third diet's components.As for fourth treatment a mixture of 20 gm of ginger roots powder and 200 mg of vitamin E was added to concentrate pelleted. The lovable concentrated diets of Awassi lambs were provided with uniform protein level (15.59%) and metabolize energy level (2750 Kcal) during fattening period (90 day). The current study found that lambs treated with the experimental treatments had significantly higher rates of final weight, daily gains, and total weight than lambs treated with the control treatments. The rates of final weight were 45.475, 48.167, 49.410, 51.512 kg, daily weight gain was 199, 232, 244, 268 gm/day and total weight gain was 17.983, 20.917, 21.978, 24,205 kg/head for four treatments respectively. In terms of carcass features, the results demonstrated a highly significant improvement (P≤0.01) on an averages of hot and cold carcasses weights was in favor of lambs treated with ginger, vitamin E, and a synergistic treatment between them as compared to lambs given with a control treatment. The averages of hot carcass weights were 20.983, 24.545, 25,711, 27.580 kg, and cold carcass weights were 20.515, 24.177, 25.325, 26,994 kg for four treatments respectively.While the current study found a substantial superiority (P≤0.05) on rates of ocular muscle area and significant decrease on fat under skin thickness which was comparison to the control group.

Family life is a love nest, a love castle, a castle of love that separates men and women without alienation and brings them closer, even making them feel like each other over time, transforming them from being “you-me” to literally “us”. Family life is a soul partnership that is measured a hundred times, carries not only emotions but also the basis of reason and logic, and aims for eternal happiness as well as living together for a lifetime. Family life is one of the greatest blessings God has given to people. For this reason, Imam Zeynalabdin (peace be upon him) says: “May or female, each of you should thank Allah for the existence of each other”. Let each of you know that you are a blessing from God to each other. Everyone has the right to marry and start a family. No sane person gets married to get divorced later. The success of a marriage is measured by reminding one of the heavenly life. Failure is living hell. Let's note one thing, the fate of unsuccessful families should not frighten the younger generation and deter them from getting married. Everyone, each family has their own destiny and share of happiness. Couples getting married to start a family make life more enjoyable. But what is the family itself? A family is not just two people living under one roof. Living together, sitting next to each other, sitting at the same table, going shopping together, etc. Issues are not yet about being a family. Being a family means that the parties open up to each other spiritually, share their heart world, share their most intimate feelings, and build their partnership on compassion and love. Keywords: Family, Islamic values, Imam Zeynalabdin, married

Every individual has a distinct personality, and this uniqueness shapes how they express and interpret love. Understanding these differences, both within oneself and in significant relationships, one can recognize the root causes of conflicts, and foster deeper connections, and more profound relationships. Hence, this study aims to explore the love language of male senior citizens. Using a research design that utilizes interactive phenomenological analysis, the purpose of this study is to understand how senior citizens express and receive love through love languages. This study included fifteen male senior residents of Bulacan District IV (Obando, Marilao, and City of Meycauayan). The participants also accomplished a semi-structured interview guide that included the experiences, challenges, and coping strategies of male seniors. The study's findings revealed that male seniors experience difficulty expressing and receiving their love languages. The participants stated that they were frustrated, distressed, sad, and regretful because they were having difficulties in expressing and receiving their preferred love language from their partner. The difference in love language is one of the reasons why there is difficulty in expressing and accepting that preferred love language with their partner. Despite negative emotions, they show respect, handle disagreements with patience, and understand the importance of clear communication and conflict handling for successful relationships.

This paper is deliberated to highlight the bond of love shared by different characters in Khaled Hosseini&rsquo;s <em>The Kite Runner.</em> Love, friendship and father-son relationship remain fulcrum as discussed, the themes by Khaled Hosseini in his work. The author through his work <em>The Kite Runner</em> tried to explain the meaning of love by showing a bond between half brothers Amir and Hassan with their father and other characters. <em>The Kite Runner </em>is the story how beautiful Afghanistan was before Taliban affected Afghans, how Hazaras, lower caste muslims lived peacefully with Pastuns, high class muslims and how Afghanistan was destroyed by Taliban and how it affected the lives of Afghans, specially of Hazaras. Hosseini&rsquo;s story is about the two characters Hassan was Hazara and Amir was Pashtun who were half-brothers and their lives were totally changed after Kite flying competition that was held every year, one got the peaceful life other was sodomised and roof over his head was also snatched. . It mainly had the male characters which made it different from the platonic, cosmic or romantic love which urged the researcher to find out the warmth shared by the characters in the novel. The researcher explored the novel in depth to accentuate the endearment shown by the characters amidst tough times. This paper analyzed several types of love shown by different characters in the novel <em>The Kite Runner.</em> &nbsp; .

<strong>Abstract: </strong>The purpose of this study was to find out the effect of the program on the treatment of the case of a student in the second grade of Khadija Bint Khuwailad School. I noticed his condition while I was observing observations and applied my class. When I asked him about his teacher, she told me that the student suffers from slow reading. , bad hand script , reflecting letters, weak in spelling words, weak in reading, slow speech, delayed in response and writes from left to right, quiet, friendly, lovable by students but he has no social relationships, unsure of himself and hesitant,&nbsp; he was transferred to the resources room in Khadija School to diagnose his condition according&nbsp; to the request from his second-grade teacher to identify the student's problem, to identify language skills and linguistic weakness, and to develop a remedial program to help him improve his academic performance, strengthen his self-confidence, and improve his social relationship with his colleagues, With the educational program offered to the student and the use of alternatives appropriate to the level of difficulty that he suffered from in addition to all aspects of the student, psychological, social, educational, cognitive and linguistic, there has been a clear improvement and markedly to the situation and became almost at the level of class <strong>Keywords: Treatment program, &nbsp;&nbsp;Language disorders.</strong> <strong>&nbsp;</strong> <strong>تأثير برنامج علاجي في خفض الاضطرابات اللغوية لدى طالب في الصف الثاني الابتدائي</strong> <strong>&nbsp;</strong> <strong>الملخص:</strong> هدفت هذه الدراسة لمعرفة تأثير برنامج معالجة لحالة طالب في الصف الثاني من مدرسة خديجة بنت خويلد , تمت ملاحظتي لحالته أثناء حضوري لعمل مشاهدات وتطبيق صفي عملي, ولدى استفساري عنه من قبل معلمته أخبرتني أن الطالب يعاني من القراءة البطيئة ,ولا يميز الحروف عن بعضها بشكل جيد، خطه سيء ويعكس الحروف، ضعيف في تهجئة الكلمات، وضعيف في القراءة، بطيء الكلام يتأخر في الاستجابة يكتب من اليسار إلى اليمين، هادئ، ودود، محبوب من قبل الطلاب إلا أنه لا توجد لديه علاقات اجتماعية، غير واثق من نفسه ومتردد، وقد تم تحويله إلى غرفة المصادر/ مدرسة خديجة لتشخيص حالته بناءاً على طلب معلمة الصف الثاني لتحديد مشكلة الطالب ولتشخيص المهارات اللغوية والضعف اللغوي لديه ولوضع برنامج علاجي لمساعدته في تحسين أداءه، وتحصيله الأكاديمي، وتقوية ثقته بنفسه وتعزيزها، ولتحسين علاقته الاجتماعية بزملائه. ومع ما قدم من برنامج علاجي تربوي للطالب صاحب الحالة واستخدام البدائل المناسبة لمستوى الصعوبة التي يعاني منها ومراعاة جميع جوانب الطالب النفسية والاجتماعية والتربوية والإدراكية واللغوية، فقد طرأ تحسن واضح وبشكل ملحوظ لصاحب الحالة وأصبح تقريباً في مستوى صفه. <strong>الكلمات المفتاحية:</strong> <strong>برنامج علاجي</strong><strong>، </strong><strong>&nbsp;الاضطرابات اللغوية</strong><strong>.</strong>

Abstract Background. Drug resistance and central nervous system (CNS) metastasis often hampers response to precision therapy for RET-rearranged solid tumors. Vepafestinib (Vepa) is a clinical-stage, potent and selective RET tyrosine-kinase inhibitor (TKI) with proven activity against on-target resistance mutations that arise post first-generation RET TKI. Here, we utilized an array of structural and pharmacokinetic methods to determine blood-brain barrier (BBB) permeability of vepa compared with other RET TKIs. Furthermore, we correlate BBB penetrability of RET inhibitors with in vivo efficacy in preclinical models of RET-rearranged intracranial solid tumors. Methods. RET inhibitors were generated by rational chemical design to identify agents which penetrate BBB more effectively than currently approved RET TKIs, and with reduced efflux transporter susceptibility. Transcellular transport assays were conducted in LLC-PK1 and MDCK II cells expressing P-gp and BCRP, respectively. Brain penetrability was assessed by total (Kp) and unbound (Kp,uu) brain:plasma concentration ratios in male Balb/c mice and microdialysis studies in freely-moving male Wistar rats. Models of CNS metastasis were generated by implanting cells labelled with luciferase into the cerebellum of mice. Studies were conducted in comparison with selpercatinib (Selp), pralsetinib (Pral) and TPX-0046. Results. Assessment of Kp and Kp,uu parameters of analogs revealed an excellent structure-activity relationship where modification at the 6-position of the pyrrolopyrimidine core resulted in improved BBB penetrability. The analog with the most favorable physiochemical and biological properties was Vepa. Vepa showed poor susceptibility to P-gp and BCRP-mediated efflux and better CNS penetrability (Kp,uu: 1.3) and retention than Sel, Pral and TPX-0046. The ratio of the observed concentrations of Vepa in microdialysates from the prefrontal cortex, cerebrospinal fluid (CSF) and plasma free fraction was approximately 1:1:1; these ratios were maintained from 2h to 6.5h after Vepaadministration (up to 8h for CSF). Importantly, Vepa was more effective than Selp at causing regression of intracranial xenograft tumors of RET fusion-driven malignancies (lung adenocarcinoma and sarcoma), thus extending survival of tumor-bearing animals. Common first-generation RET TKI resistance mutations at the solvent front (G810A/C/S/R), gatekeeper (V804L/M), hinge (Y806C) and roof (L730Q/R) regions remained sensitive to Vepa. Vepa was more selective than Selp, Pral and TPX-0046, inhibiting only RET when profiled against a panel of 256 kinases. In contrast, Selp, Pral and TPX-0045 also inhibited VEGFR2, and 4, 11 and 39 additional kinases, respectively. Conclusions. Vepafestinib is a structurally distinct and specific RET inhibitor, with superior brain penetration and retention kinetics. It is more effective than selpercatinib in controlling CNS disease. Vepafestinib is currently undergoing phase 1 and 2 clinical trial for patients with advanced solid tumors with RET alterations (margaRET, NCT04683250). Citation Format: Igor Odintsov, Kentaro Wakayama, Tom Zhang, Satoru Iguchi, Masanori Kato, Allan JW Lui, Inna Khodos, Morana Vojnic, Claudio Giuliano, Annalisa Bonifacio, Monika A Davare, Elisa de Stanchina, Emanuela Lovati, Marc Ladanyi, Isao Miyazaki, Romel Somwar. Preclinical evaluation of the blood-brain barrier permeability and intracranial efficacy of the next-generation RET inhibitor Vepafestinib [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B157.

This paper investigated human&ndash;robot interaction as a research field that aims to enrich the user experience and the consumer market. Starting with the functionalist approach to the field based on narrow technologism perspectives, the paper pointed out that it is necessary to adopt a method that goes beyond the limited technology orientation. Drawng insights from Aristotle"s theory of friendship on social ontology, Winner"s theory of interaction with computers and robots, and social exchange theory, it proposed critical interdisciplinarity as the best approach to artificial intelligence, computer science, cognitivism and engineering. It argued that the major challenge of the field is to be truly open-ended, innovative and capable of breaking new frontiers. From this light, it suggested priority should be given to new issues such as the sociality between robots and humans, the question of social acceptance, intimacy with robots, relationships and perception of benefits, the interface of humans and technology and the role of the enactive in cognitive science. In addition, the researcher should take into consideration the problematic of co-habitation, the morality and rights of/ rights over robots, discussions about perceptions of and physical responses to intimacy with robots, the fear of &bdquo;Deleuzian bodies" and the need for coordination.

The most distinctive feature that distinguishes human being from other living creatures is his/her deep and broad love ability. However, as in all abilities, the ability of love can be disabled with ifrat and tafrit. (exaggeration/understate&not;ment). The Islamic tradition, which teach the measure under the guidance of the Qur&rsquo;an and the Sunnah for almost every human behavior and reaction, also made ifrat/tafrit warnings to keep ability of &ldquo;love&rdquo; in &ldquo;mediocre&rdquo;. One of the attempts to present these warnings in a tidy manner belongs to Ibn al-Jawzī, who was a name of the source of pride of the Ḥanbalī school in the sixth century (d. 597/1201) Ibn al-Jawzī took lessons from many scholars of Ḥanbalī school who were active in Baghdad. Contrary to the transmitting and anti-kalām tendency of the Ḥanbalī school, some of the scholars who took the lessons tended to rational interpretations and kalām. Ibn al-Jawzī must also have been influenced by this fact that he has not approached the phe-nomenon of love only with the harsh prohibitive attitude of the Ḥanbalī school. He tried to make deep examination by gooing to the background of the feeling from time to time and tried to make deep analyzes and analysed the root causes to deal with the problem. As a matter of fact, it is known that moral degeneration was common in the Islamic society during the Abbasid period. Apparently, the &ldquo;love&rdquo; also got its share from this degeneration and the measureless love that will end with worldly-destructive currents has gnawed the Muslim body. Ibn al-Jawzī tried to cope with one of the bleeding wounds of the society. In his work Dham al-Hawā, the purpose of the work was clearly stated by the author himself. Someone came to Ibn al-Jawzī and stated that he suffered from love and that he could not get rid off this pain. The patheticness of the person seeking a cure for his troubles pro-voked his patronage with the words of Ibn al-Jawzī, so the author wrote a selection of advice that would sprinkle the hearts of both that person and those who lived the same spirit. In his work, Ibn al-Jawzī, talked about the worldly and destructive consequences of the person&rsquo;s compliance with the &ldquo;hawa&rdquo;, which means whim that does not think about the fate. By drawing attention to these facts, he aimed to strengthen reason and will and to enable the Muslim person to perform individual and social duties more efficiently. While doing this, he often conveyed the verses and hadiths without interpretation with the effect of the sectarian view based on narration and surrender, and also bene-fited from the influence of literature by using the poetry, which was the diwan of the Arabs, very effectively. Although the author seems to be approaching the phenomenon of &ldquo;love&rdquo; as a whole negatively, it is remarkable that the quotations he made from the ghazal poems and the idea he shared that love without overdo has maturing effect on individual. The work is composed of fifty chapters and chapters, each of which has no specific standard in itself. Although the author seems to be approaching the phenomenon of &ldquo;love&rdquo; as a whole, it is remarkable that the quotations made from the ghazal poems share the idea that they have maturing aspects of the transcendent, provided that they do not overdo it. The work is composed of fifty chapters and each of chapters has no specific standard in itself. The author, after the headlines, rarely made comments on the subject at the begin-ning. According to Ibn al-Jawzī, the feeling called &ldquo;hawa&rdquo; sets its eyes on flavors that are mostly urgent. In fact, even if these ready-made tastes are mashed with pain and cause loss of great tastes, what is called &ldquo;hawa&rdquo; will not give up on follow these ready-made tastes. Mind, on the contrary, will know the necessity to abandon a delicacies that is followed by pain. As the child&#39;s reason ability has not yet developed, it tends to things that can harm it. However, adults will prevent him because they know this state of the child. Likewise, because the animals are deprived of reasoning ability, they are running after ready-made delicacies and even perished by being trapped. So, the reason must prevail, and it is necessary to restrain the tendencies of the hawa by thinking about the fate. According to Ibn al-Jawzī, the reasons for some of them falling in love are the result of their repetitive and continuing glances. In fact, even insistent glances at a person who is not very suitable for him/her as a character may cause love to flare up. It is possible that not only glances, but also togetherness for a long time (muhālata) will lead to an unexpected love. The repetitive glances ultimately tranforming to fell in love likened to a garden. If a person plants a sapling and takes care of it, the sapling will develop further. Otherwise, it is not a remote possibility that if a sprout not watered and neglected turns into a tree. Many other evaluations of love such as this are discussed in the study. On the other hand, some critics are made about form and content. For example, the work was criticized in the context of the case of khashw, which means unnecessary repetitions. As it can be seen, Dham al-Hawā is prone to &ldquo;khashw&rdquo; with a considerable number of &ldquo;more than necessary repetitions&rdquo; passages. From another point of view, it is seen that the work enters into issues that are not directly related to the purpose of the work. For example; in the work, legal practices regarding the punishment of homosexuality are mentioned. Considering all aspects of the work, from the title of the work to the literary and morality of the content, it can be said that the evaluations regarding the punishment of the homosexuality are an &ldquo;exceeding purpose&rdquo; in the integrity of the work. In the study, criticisms were made from other aspects of the work. As a result; there are many works for Ibn al-Jawzī which were translated into Turkish. However, Dham al-Hawā has not yet been brought into the Turkish literature. In my opinion, there is a lot of information and admirable persuasive approaches that the young people will benefit from this work. However, according to the conclusion of this study, our recommendation is that the work includes long narratives, more repetitions and extraordinary details that will not present much to today&#39;s reader. I am of the opinion that It would be better than not to translate them, and it will be useful to pay attention to these points in a possible translation in order to benefit from the work more effectively.

Objective: To analyze syndrome differentiation and medication rules for leucorrhoea in ancient books of traditional Chinese medicine (TCM) based on the Chinese Medical Code using the latent structure model. Methods: The formulations for leucorrhoea were searched in the Chinese Medical Code (software), based on which an Excel sheet was created to conduct frequency analysis and construct a matrix of high-frequency medications. The high-frequency medications for leucorrhoea were then analyzed using the Latent 5.0 software and a latent structure model. With SPSS Modeler and Latent 5.0 as the main analysis methods, Chinese medications with a frequency greater than 1.00% were investigated using the latent structure model and association rules, and the medication rules in treating leucorrhoea with TCM were dissected based on the data of frequency. Results: For 373 kinds of Chinese medicines retrieved from 236 TCM prescriptions, the total medication frequency was 2522. Chinese Angelica (Angelicae Sinensis Radix), White Peony Root (Paeoniae Radix Alba), Indian Buead Tuckahoe (Poria), Common Oyster Shell (Ostreae Concha), and Largehead Atractylodes Rhizome (Atractylodis Macrocephalae Rhizoma) were high-frequency medicines for leucorrhoea. Tonic, heat-clearing and qi-regulating medicines had a high frequency of usage. According to a formula-based analysis of the evidence, the main syndromes of leucorrhoea included liver qi affecting the spleen pattern, damp heat accumulation pattern, liver qi stagnation pattern, liver-stomach disharmony pattern, yin deficiency of the liver and kidney pattern, and spleen deficiency with dampness pattern, which are generally in line with the etiology and pathogenesis of leucorrhoea, namely pathogenic dampness as the detrimental factor together with spleen-kidney dysfunction. However, in ancient books, emphasis was laid out on the regulation of the liver. This study determined 31 association rules for treating leucorrhoea, where the primary compatible medicines contained Chinese Angelica (Angelicae Sinensis Radix)-Nutgrass Galingale Rhizome (Cyperus rotundus), Chinese Angelica (Angelicae Sinensis Radix)-Szechwan Lovage Rhizome (Ligusticum chuanxiong Hort.), White Peony Root (Paeoniae Radix Alba)-Szechwan Lovage Rhizome (Ligusticum chuanxiong Hort.), White Peony Root (Paeoniae Radix Alba)-Adhesive Rehmannia Root Tuber (Rehmanniae Radix) and Tangerine Peel (Citri Reticulatae Pericarpium)-Ternate Pinellia (Rhizoma Pinelliae). Conclusion: The medication rules targeting leucorrhoea in the Chinese Medical Code was mainly represented by regulation of qi and blood, as well as the three internal organs—the kidney, spleen, and liver.

Abstract Study objective To study the effect of a herbal preparation containing a standardised BNO 1040 extract* (based on lovage root, rosemary leaves and aerial parts of centaury) on the extracorporeal shockwave lithotripsy (ESWL) results in patients with urolithiasis (UL). Methodology 150 patients with UL (aged 18–65 years) treated with ESWL method were divided into 2 equal groups. The main group (n = 75) received standard recommendations and herbal preparation (12 months). The control group (n = 75) received standard recommendations only. The following was evaluated: time and degree of elimination of fragments; the presence of pain and leukocyturia; recurrent stone formation. Results The elimination of fragments was observed up to 14 days in 94.7% of patients in the main group versus 76% of patients in the control group. Renal colic was observed in 6.7% of patients in the main group versus 10.7% of patients in the control group; cases of leukocyturia were observed within 14 days in 10.7% versus 22.7%, respectively. During the year, a recurrent lithiasis was diagnosed in 6.7% of patients in the main group and in 16% of patients in the control group. Conclusion The use of BNO 1040 extract in combination with ESWL: contributes to more rapid and safe elimination of fragments of the calculi and reduces the risk of recurrent stone formation. Trial registration DRKS ID 00021200. Registered retrospectively in German Clinical Trial Register 27.03.2020. https://www.drks.de/

Abstract Background: Severe gestational hypertriglyceridemia is a dangerous and life threatening illness. Management can be difficult due to the limited data on safety of medical therapy during pregnancy. We present a case of severe gestational hypertriglyceridemia. Case Presentation: A 29 year old woman, G4P2012 at 23w3d, with a past medical history of gestational diabetes, nontoxic thyroid nodule, and hypertriglyceridemia presented to the emergency room for abdominal pain and nausea. She has no known family history of lipid disorders. Her last pregnancy was complicated by acute pancreatitis due to hypertriglyceridemia. Between pregnancies, her triglyceride level was &amp;gt;900 mg/dL and gemfibrozil therapy was advised, however reported nonadherence. In current pregnancy and after counseling, she was prescribed omega-3 acid ethyl esters (Lovaza) 2 grams twice a day and referred to maternal fetal medicine. Triglyceride level on admission was 3640 mg/dL, and she admitted to poor adherence to Lovaza. Liver function tests were within normal limits. She was started on an insulin drip, as well omega-3 fatty acids 4g daily. However, the triglyceride level remained elevated despite 72 hours on the insulin drip and it was subsequently discontinued. Plasmapheresis was discussed but deferred given no evidence of pancreatitis. Gemfibrozil 600mg twice a day was added to the omega-3 fatty acids which were titrated up to 2g three times a day. On her day of discharge, her triglyceride level was 2200 mg/dL and abdominal pain had resolved. She was maintained on gemfibrozil and Omega-3 fatty acids, with plans to increase them by 1g per week to reach a goal of 10g per day with a goal triglyceride level &amp;lt;1000mg/dL. Pre-gestational diabetes was tightly controlled with insulin. She was also seen by the nutritionist for counseling of a low fat diet and was followed very closely as an outpatient. Although the omega-3 fatty acids were titrated to 8g per day, the triglyceride level remained ~2000mg/dL. She remained asymptomatic and delivered a healthy baby boy weighing 3446 grams at 36 weeks 4 days, with no complications. She continues follow up with endocrinology with triglycerides 6 months later being 1618 mg/dl. Conclusion: We present a patient with severe gestational hypertriglyceridemia with a known history of pancreatitis. Due to the rarity of this condition, there is limited data on the safety of treatments for hypertriglyceridemia in pregnant women. This case demonstrates the use of gemfibrizol is appropriate when the hypertriglyceridemia threatens the health of the mother and baby. Further studies are needed to establish efficacy and safety of the use of these treatments in pregnant patients.

The Snow in Casablanca, 2005, is a novel which magnificently presents the life of Kica Kolbe&rsquo;s heroine - Dina Asprova in Macedonia in the 1990&rsquo;s. Dina is an Aegean woman who lives in many capital cities in Europe in search of her true identity and then comes back to Macedonia and continues her quest for her roots, identity and the sense of belonging. This novel is a typical form of Macedonian Women&rsquo;s Writing &ndash; Ĕcriture Feminine. Dina Asprova is a writer who suffers from anxiety of writing as a result of her loss of identity, which she manages to recover and to become a good writer. This prose work deals with the important questions of the restitution of the homeland, the cultural, the personal and the national identity of the Aegean people, the exile and the self-exile, the importance of one&rsquo;s roots, religion and love. Dina undergoes through a personal transitional period and Kolbe magnificently shows Dina&rsquo;s struggle to get out of the margins, her wish to re-connect to her roots, her quest to find her own identity and her transition from a woman who does not know where she belong, to a woman who finds her true identity and roots.

After reading British, Indian, American &amp; some Commonwealth literature, I found huge works scattered here and there in various books which sometimes confuses the readers/ competitors in the examination hall due to the inherent similarities in these entitled works. To avoid this type of common confusion, I planned to search and arrange the important works first , their similarity wise and their frequency wise and then I compiled an exhaustive list of these selected works to facilitate the learners to make clear cut distinction among the various titles of the literary works. My research paper is based on the principles of effective teaching- learning and effective memorization. My research paper is also entertaining since it enhances the concept of -Learning is Fun. This is my attempt in the pedagogy of teaching-learning of English Literature. I hope my collection will help the students as well as teachers who can frame confusing Multiple Choice Questions (M.C.Q) to refine their learning and also to check the depth of students&rsquo; learning. This research paper will be more useful to those who have read at least once The History of English Literature. It will make the readers to realize similar titles of the different literary works as dissimilar and vice-versa. I have divided my research paper in two parts, as Part-I &amp; Part-II. This paper is the continuance of my previous research paper &amp; there are around 850 literary works included in it which readers often confused and these works are not the last but the least

After reading British, Indian, American &amp; some Commonwealth literature, I found huge works scattered here and there in various books which sometimes confuses the readers/ competitors in the examination hall due to the inherent similarities in these entitled works. To avoid this type of common confusion, I planned to search and arrange the important works first , their similarity wise and their frequency wise and then I compiled an exhaustive list of these selected works to facilitate the learners to make clear cut distinction among the various titles of the literary works. My research paper is based on the principles of effective teaching- learning and effective memorization. My research paper is also entertaining since it enhances the concept of -Learning is Fun. This is my attempt in the pedagogy of teaching-learning of English Literature. I hope my collection will help the students as well as teachers who can frame confusing Multiple Choice Questions (M.C.Q) to refine their learning and also to check the depth of students&rsquo; learning. This research paper will be more useful to those who have read at least once The History of English Literature. It will make the readers to realize similar titles of the different literary works as dissimilar and vice-versa. I have divided my research paper in two parts, as Part-I &amp; Part-II. This paper is the continuance of my previous research paper &amp; there are around 850 literary works included in it which readers often confused and these works are not the last but the lea

February 15, 1999 THE DIGITAL EXAM digital was such a sanitary hi-tech word until my urologist snuck up from behind and gave me the bird shocked and taken back I try to ignore the painful experience by pondering the conundrum of homosexuality there had to be more to it than that "You can get dressed now" was the good doctor’s way of saying "Pull up your pants, Dude, and I’ll see you back in my office." but his casual demeanor seemed to exude foreboding "There is a stiffness in the gland demanding further examination. I’d like to schedule a blood test, ultrasound and biopsy." the doctor’s lips kept moving but I couldn’t hear him through the sheet of white fear that guillotined between us CANCER! The big C! Me? I spent the rest of that day up to my genitals in the grave I was digging. Hamlet gazing full into the face of the skull "Alas poor Yorick, I knew him well, Horatio. Before scalpel took gland. Back when he sang in a bass baritone." desperate for encouragement I turn to the illustrated brochure the informative flyer detailing the upcoming procedure where in the ultrasound and biopsy probe resembled the head of a black water moccasin baring its fang "Dang!" says I jumping back relief came 36 hours later something about the PSA blood test the prostate specific-antigen results leading the doctor to now suspect infection prescribing an antibiotic of course five weeks from now the FOLLOW-UP APPOINTMENT! and as the date approaches tension will build like in those Mel Gibson Lethal Weapon films when you know there’s a snake in the grass and Danny Glover isn’t there to cover your ass *** April 2, 1999 As it turns out, at the follow-up appointment, things had worsened so the biopsy and bone scan were re-scheduled and it was discovered that I do have incurable metastatic advanced prostate cancer. Of course the doctor is most optimistic about all the new and miraculous treatments available. But before I go into that, I want you to know that I find myself experiencing a strange and wonderful kind of peace. Hell, I’ve lived 70 years already — done exactly what I wanted to do with my life. All worthwhile dreams have come true. Made my living since 1968 as a "Performance Poet" — Billie Barbara and I have been together for 47 years — growing closer with each passing day. We have four great kids, five neat and nifty grandchildren. All things considered, I’ve been truly blessed and whether my departure date is next year or 15 years from now I’m determined not to wreck my life by doing a lousy job with my death. LIKE HAROLD / LIKE HOWARD like Harold I don’t want to blow my death I don’t want to see a lifetime of pluck and courage rubbed out by five weeks of whiny fractious behavior granted Harold’s was a scary way to go from diagnosis to last breath the cancer moving fast but five weeks of bitching and moaning was more than enough to erase every trace of a man I have wanted to emulate his wife sending word that even she can’t remember what he was like before his undignified departure no — I don’t want to go like Harold like Howard let me come swimming up out of the deepening coma face serene as if seen through undisturbed water breaking the surface to eagerly take the hand of bedside well wishers unexpected behavior I must admit as Howard has always been a world class hypochondriac second only to me the two of us able to sit for hours discussing the subtle shade of a mole turning each other on with long drawn out organ recitals in the end one would have thought such a legendary self centered soul would cower and fold up completely like Harold but no — when my time comes let me go sweetly like Howard *** April 7, 1999 The treatment was decided upon. Next Monday, the good Doctor is going to pit my apricots. From here on the Sultan can rest easy when Masten hangs with his harem. Prognosis good. No more testosterone - no more growth. Now, don’t get me wrong, I’m not looking forward to giving up the family jewels. I must say that over the years they’ve done me proud and to be totally honest I don’t think Billie Barbara will be all that disappointed either. I’m told that Viagra will help in this area., However, I’m also told that the drug is very expensive. Something like twelve bucks a pop. But hell, Billie Barbara and I can afford twenty four dollars a year.. Some thoughts the morning of— Yesterday I did a program for the Unitarian Society of Livermore. About 60 people. I had a bet with the fellow who introduced me, that at least 7 out of the 60 would come up after the reading (which would include my recent prostate musings) and share a personal war story about prostate cancer. I was right. Exactly 7 approached with an encouraging tale about themselves, a husband, a brother, a son. I was told to prepare myself for hot flashes and water retention. To which Billie Barbara said "Join the club!" I ended the presentation with one of those inspirational poetic moments. A hot flash, if you will. "It just occurred to me," I said, " I’m going to get rich selling a bumper sticker I just thought of — REAL MEN DON’T NEED BALLS A couple of days after the event The Community Hospital of the Monterey Peninsula is referred to as CHOMP, and the afternoon of April 12th I must say this august institution certainly lived up to it’s name. The waiting room in the Out Patient Wing is an event unto itself. Patients huddled together with friends and family, everyone speaking in hushed voices. The doomed keeping a wary eye on the ominous swinging doors, where a big tough looking nurse appeared from time to time shouting: NEXT! Actually the woman was quite sweet and mild mannered, enunciating each patient’s name in a calm friendly manner. But waiting to have done to me what was going to be done to me - the chilling word "NEXT!" is what I heard and "Out Patient Wing" certainly seemed a misnomer to me. Wasn’t the "Out-Patient Wing" where you went to have splinters removed? Of course I knew better, because in the pre-op interview the young interviewer, upon reading "Bilateral Orchiectomy" winced visibly, exclaiming under her breath "Bummer!" I recently came across this haiku — bilateral orchiectomy the sound a patient makes when he learns what it is Our daughter April lives in New York and couldn’t join the Waiting Room rooting section so as her stand in she sent her best friend Molly Williams. Now, Molly works as a veterinarian in a local animal shelter and a when I told her my operation was supposed to take no more than half an hour, she laughed: "Heck Ric, I’ll do it in five minutes and not even use gloves." NEXT! My turn to be led through those swinging doors, pitifully looking back over my shoulder. Wife, family and friends, bravely giving me the thumbs up. Things blur and run together after that. I do remember telling the nurse who was prepping me that I was afraid of being put to sleep. "Not to worry" she said, I’d have a chance to express these fears to the anesthetist before the operation would begin. And as promised the man did drop by to assure me that I would get a little something to ease my anxiety before he put me under. When the moment finally arrived, he said that I might feel a slight prick as he gave me the relaxant. Of course, that is the last thing I remember - the prick! Obviously, I‘d been suckered in by the mask man’s modus operandi. On the other side of this I surface to begin the waiting. WAITING for the catheter to be removed — for the incision to heal — WAITING to see if the pain subsides and I can loose the cane — WAITING to learn if my PSA will respond to treatment. Waiting—waiting—waiting—and I’ve never been a cheerful waiter. *** May 7, 1999 The doctor tells me I must keep taking Casodex— one a day at eleven dollars a cap - for the rest of my life. And no more doctor freebees. No wonder the listed side effect of this pricey medication is depression. But the recent funk I’ve fallen into is much deeper than dollars and cents. In the past I’ve had my share of operations and illnesses and always during the recuperation I could look forward to being my old self again. But not this time .... Not this time. Funny bumper stickers can only hold reality at bay for a short while. And anyway Billie had me remove the homemade REAL MEN DON’T NEED BALLS bumper sticker from the back of our car — She didn’t like the dirty looks she got while driving around town alone. *** Eight months later BILATERAL ORCHECTOMY never could look up words in the dictionary in a high school assignment writing an autobiography I described my self as a unique person scribbled in the margin the teachers correction fairly chortled "unique" not "eunuch" how could he have known that one day I would actually become a misspelling backed against the wall by advanced prostate cancer I chose the operation over the enormous ongoing expense of chemical castration "No big deal." I thought at the time what’s the difference they both add up to the same thing but in the movies these days during the hot gratuitous sex scene I yawn…bored... wishing they’d quit dicking around and get on with the plot and on TV the buxom cuties that titillate around the products certainly arn’t selling me anything I realize now that although it would probably kill them the guys who went chemical still have an option I don’t philosophically I’m the same person but biologically I ‘m like the picture puzzle our family traditionally puts together over the holidays the French impressionist rendition of a flower shop interior in all it’s bright colorful confusion this season I didn’t work the puzzle quite as enthusiastically... and for good reason this year I know pieces are missing where the orchids used to be "So?" says I to myself "You’re still here to smell the roses." *** January 13, 2000 Real bad news! At the third routine follow-up appointment. My urologist informs me that my PSA has started rising again. The orchectomy and Casodex are no longer keeping the cancer in remission. In the vernacular, I have become "hormone refractory" and there was nothing more he, as a urologist could do for me. An appointment with a local oncologist was arranged and another bone scan scheduled. The "T" word having finally been said the ostrich pulled his head from the sand and began looking around. Knowing what I know now, I’m still annoyed at my urologist for not telling me when I was first diagnosed to either join a support group and radically change my diet or find another urologist. I immediately did both - becoming vegan and finding help on-line as well as at the local Prostate Cancer Support Group. This during the endless eighteen day wait before the oncologist could fit me in. *** IRON SOCKS time now for a bit of reverse prejudice I once purchased some stockings called "Iron Socks" guaranteed to last for five years they lasted ten! but when I went back for another pair the clerk had never heard of them as a cancer survivor… so far in an over populated world I consider the multi-billion dollar medical and pharmaceutical industries realizing that there is absolutely no incentive to come up with a permanent cure *** From here on, I’ll let the poems document the part of the journey that brings us up to the present. A place where I can say — spiritually speaking, that the best thing that ever happened to me is metastatic hormone refractory advanced prostate cancer. *** SUPPORT GROUPS included in this close fraternity... in this room full of brotherly love I wonder where I’ve been for the last 11 months no — that’s not quite right… I know where I’ve been I’ve been in denial after the shock of diagnosis the rude indignity of castration the quick fix of a Casodex why would I want to hang out with a bunch of old duffers dying of prostate cancer? ignoring the fact that everybody dies we all know it but few of us believe it those who do, however rack up more precious moments than the entire citizenry of the fools paradise not to mention studies showing that those who do choose to join a support group on average live years longer than the stiff upper lip recluse and while I’m on the subject I wonder where I’d be without the internet and the dear supportive spirits met there in cyber-space a place where aid care and concern are not determined by age, gender, race, physical appearance, economic situation or geological location and this from a die-hard like me who not ten years ago held the computer in great disdain convinced that poetry should be composed on the back of envelopes with a blunt pencil while riding on trains thank god I’m past these hang-ups because without a support system I doubt if this recent malignant flare-up could have been withstood how terrifying… the thought of being at my writing desk alone… disconnected typing out memos to myself on my dead father’s ancient Underwood *** PC SPES in the sea that is me the hormone blockade fails my urologist handing me over to a young oncologist who recently began practicing locally having retired from the stainless steel and white enamel of the high tech Stanford medical machine in the examination room numbly thumbing through a magazine I wait expecting to be treated like a link of sausage another appointment ground out in a fifteen minute interval what I got was an 18th century throw back a hands-on horse and buggy physician with seemingly all the time in the world it was decided that for the next three weeks (between blood tests) all treatment would cease to determine how my PSA was behaving this done, at the next appointment the next step would be decided upon and after more than an hour of genial give and take with every question answered all options covered it was I who stood up first to go for me a most unique experience in the annals of the modern medicine show however condemned to three weeks in limbo knowing the cancer was growing had me going online reaching out into cyberspace to see what I could find and what I found was PC SPES a botanical herbal alternative medicine well documented and researched but not approved by the FDA aware that the treatment was not one my doctor had mentioned (I have since learned that to do so would make him legally vulnerable) I decided to give it a try on my own sending off for a ten day supply taking the first dose as close after the second blood test as I could two days later back in the doctors office I confess expecting a slap on the wrist instead I receive a bouquet for holding off until after the second PSA then taking the PC SPES container from my hand and like a Native American medicine man he holds it high over his head shaking it "Okay then, this approach gets the first ride!" at the receptionist desk scheduling my next appointment I thought about how difficult it must be out here on the frontier practicing medicine with your hands tied *** PREJUDICE "It's a jungle out there!" Dr. J. George Taylor was fond of saying "And all chiropractors are quacks! Manipulating pocket pickers!" the old physician exposing his daughter to a prejudice so infectious I suspect it became part of her DNA and she a wannabe doctor herself infects me her son with the notion that if it wasn’t performed or prescribed by a licensed M.D. it had to be Medicine Show hoopla or snake oil elixir certainly today’s countless array of practitioners and patent remedies has both of them spinning in their grave but Ma you and Grandpa never heard the words hormone-refractory even the great white hunters of our prestigious cancer clinics don't know how to stop the tiger that is stalking me and so with a PSA rising again to 11.9 I get my oncologist to let me try PC SPES a Chinese herbal formula yes, the desperate do become gullible me, reading and re-reading the promotional material dutifully dosing myself between blood tests and this against the smirk of disapproval mother and grandfather wagging their heads in unison: "It won’t work." "It won’t work." having condemned myself beforehand the moment of truth finally arrives I pace the floor nervously the doctor appears at the door "How does it feel to be a man with a PSA falling to 4.8?" it seems that for the time being at least the tiger is content to play a waiting game which is simply great! Mother tell Grandpa I just may escape our families bigotry before it’s too late *** HELPLINE HARRY "Hi, how are you?" these days I'm never sure how to field routine grounders like this am I simply being greeted? or does the greeter actually want a list of grisly medical details my wife says it's easy she just waits to see if the "How is he?" is followed by a hushed "I mean… really?" for the former a simple "Fine, and how are you?" will do for the latter the news isn't great indications are that the miracle herbal treatment is beginning to fail my oncologist offering up a confusing array of clinical trials and treatments that flirt seductively but speak in a foreign language I don't fully understand so Harry, once again I call on you a savvy old tanker who has maneuvered his battle scared machine through years of malignant mine fields and metastatic mortar attacks true five star Generals know much about winning wars and such but the Command Post is usually so far removed from the front lines I suspect they haven't a clue as to what the dog-faces are going through down here in the trenches it's the seasoned campaigners who have my ear the tough tenacious lovable old survivors like you *** "POOR DEVIL!" in my early twenties I went along with Dylan Thomas boasting that I wanted to go out not gently but raging shaking my fist staring death down however this daring statement was somewhat revised when in my forties I realized that death does the staring I do the down so I began hoping it would happen to me like it happened to the sentry in all those John Wayne Fort Apache movies found dead in the morning face down — an arrow in the back "Poor devil." the Sergeant always said "Never knew what hit him." at the time I liked that... the end taking me completely by surprise the bravado left in the hands of a hard drinking Welshman still wet behind the ears older and wiser now over seventy and with a terminal disease the only thing right about what the Sergeant said was the "Poor devil" part "Poor devil" never used an opening to tell loved ones he loved them never seized the opportunity to give praise for the sun rise or drink in a sunset moment after moment passing him by while he marched through life staring straight ahead believing in tomorrow "Poor devil!" how much fuller richer and pleasing life becomes when you are lucky enough to see the arrow coming *** END LINE (Dedicated to Jim Fulks.) I’ve always been a yin / yang - life / death - up / down clear / blur - front / back kind of guy my own peculiar duality being philosopher slash hypochondriac win win characteristics when you’ve been diagnosed with advanced prostate cancer finally the hypochondriac has something more than windmills to tilt with the philosopher arming himself with exactly the proper petard an anonymous statement found in an e-mail message beneath the signature of a cancer survivor’s name a perfect end line wily and wise quote: I ask God: "How much time do I have before I die?" "Enough to make a difference." God replies *** STRUM lived experience taught them most of what they know so MD's treating men diagnosed with androgen-independent advanced prostate cancer tend to put us on death row and taking the past into account this negativity is understandable… these good hearted doctors watching us come and go honestly doing what they can like kindly prison guards attempting to make the life we have left as pleasant as possible to be otherwise a physician would have to be a bit delusional evangelical even… to work so diligently for and believe so completely in the last minute reprieve for those of us confined on cell block PC doing time with an executioner stalking it is exhilarating to find an oncologist willing to fly in the face of history refusing to call the likes of me "Dead man walking." *** BAG OF WOE there are always moments when I can almost hear the reader asking: "How can you use that as grist for your poetry mill? How can you dwell on such private property, at least without masking the details?" well... for the feedback of course the war stories that my stories prompt you to tell but perhaps the question can best be answered by the ‘bag of woe’ parable the "Once Upon a Time" tale about the troubled village of Contrary its harried citizens and the magical mystical miracle worker who showed up one dreary day saying: I am aware of your torment and woe and I am here to lighten your load! he then instructed the beleaguered citizens to go home and rummage through their harried lives bag up your troubles he said both large and small stuff them all in a sack and drag them down to the town square and stack them around on the wall and when everyone was back and every bag was there the magical mystical miracle worker said: "It’s true, just as I promised. You won’t have to take your sack of troubles home leave it behind when you go however, you will have to take along somebody’s bag of woe so the citizens of Contrary all went to find their own bag and shouldering the load discovered that it was magically and mystically much easier to carry --- End ---

This essay combines life writing with meditations on the significance of walking as integral to the ritual practice of pilgrimage, where the individual improves her soul or health through the act of walking to a shrine containing healing relics of a saint. Braiding together insights from medieval literature, contemporary ecocriticism, and memory studies, I reflect on my own pilgrimage practice as it impacts the land itself. Canterbury, England serves as the central shrine for four pilgrimages over decades: 1966, 1994, 1997, and 2003.The act of memory was not invented in the Anthropocene. Rather, the nonhuman world has taught humans how to remember. From ice-core samples retaining the history of Europe’s weather to rocks embedded with fossilized extinct species, nonhuman actors literally petrifying or freezing the past—from geologic sites to frozen water—become exposed through the process of anthropocentric discovery and human interference. The very act of human uncovery and analysis threatens to eliminate the nonhuman actor which has hospitably shared its own experience. How can humans script nonhuman memory?As for the history of memory studies itself, a new phase is arguably beginning, shifting from “the transnational, transcultural, or global to the planetary; from recorded to deep history; from the human to the nonhuman” (Craps et al. 3). Memory studies for the Anthropocene can “focus on the terrestrialized significance of (the historicized) forms of remembrance but also on the positioning of who is remembering and, ultimately, which ‘Anthropocene’ is remembered” (Craps et al. 5). In this era of the “self-conscious Anthropocene” (Craps et al. 6), narrative itself can focus on “the place of nonhuman beings in human stories of origins, identity, and futures point to a possible opening for the methods of memory studies” (Craps et al. 8). The nonhuman on the paths of this essay range from the dirt on the path to the rock used to build the sacred shrine, the ultimate goal. How they intersect with human actors reveals how the “human subject is no longer the one forming the world, but does indeed constitute itself through its relation to and dependence on the object world” (Marcussen 14, qtd. in Rodriguez 378). Incorporating “nonhuman species as objects, if not subjects, of memory [...] memory critics could begin by extending their objects to include the memory of nonhuman species,” linking both humans and nonhumans in “an expanded multispecies frame of remembrance” (Craps et al. 9). My narrative—from diaries recording sacred journey to a novel structured by pilgrimage—propels motion, but also secures in memory events from the past, including memories of those nonhuman beings I interact with.Childhood PilgrimageThe little girl with brown curls sat crying softly, whimpering, by the side of the road in lush grass. The mother with her soft brown bangs and an underflip to her hair told the story of a little girl, sitting by the side of the road in lush grass.The story book girl had forgotten her Black Watch plaid raincoat at the picnic spot where she had lunched with her parents and two older brothers. Ponchos spread out, the family had eaten their fresh yeasty rolls, hard cheese, apples, and macaroons. The tin clink of the canteen hit their teeth as they gulped metallic water, still icy cold from the taps of the ancient inn that morning. The father cut slices of Edam with his Swiss army knife, parsing them out to each child to make his or her own little sandwich. The father then lay back for his daily nap, while the boys played chess. The portable wooden chess set had inlaid squares, each piece no taller than a fingernail paring. The girl read a Junior Puffin book, while the mother silently perused Agatha Christie. The boy who lost at chess had to play his younger sister, a fitting punishment for the less able player. She cheerfully played with either brother. Once the father awakened, they packed up their gear into their rucksacks, and continued the pilgrimage to Canterbury.Only the little Black Watch plaid raincoat was left behind.The real mother told the real girl that the story book family continued to walk, forgetting the raincoat until it began to rain. The men pulled on their ponchos and the mother her raincoat, when the little girl discovered her raincoat missing. The story book men walked two miles back while the story book mother and girl sat under the dripping canopy of leaves provided by a welcoming tree.And there, the real mother continued, the storybook girl cried and whimpered, until a magic taxi cab in which the father and boys sat suddenly appeared out of the mist to drive the little girl and her mother to their hotel.The real girl’s eyes shone. “Did that actually happen?” she asked, perking up in expectation.“Oh, yes,” said the real mother, kissing her on the brow. The girl’s tears dried. Only the plops of rain made her face moist. The little girl, now filled with hope, cuddled with her mother as they huddled together.Without warning, out of the mist, drove up a real magic taxi cab in which the real men sat. For magic taxi cabs really exist, even in the tangible world—especially in England. At the very least, in the England of little Susie’s imagination.Narrative and PilgrimageMy mother’s tale suggests how this story echoes in yet another pilgrimage story, maintaining a long tradition of pilgrimage stories embedded within frame tales as far back as the Middle Ages.The Christian pilgrim’s walk parallels Christ’s own pilgrimage to Emmaus. The blisters we suffer echo faintly the lash Christ endured. The social relations of the pilgrim are “diachronic” (Alworth 98), linking figures (Christ) from the past to the now (us, or, during the Middle Ages, William Langland’s Piers Plowman or Chaucer’s band who set out from Southwark). We embody the frame of the vera icon, the true image, thus “conjur[ing] a site of simultaneity or a plane of immanence where the actors of the past [...] meet those of the future” (Alworth 99). Our quotidian walk frames the true essence or meaning of our ambulatory travail.In 1966, my parents took my two older brothers and me on the Pilgrims’ Way—not the route from London to Canterbury that Chaucer’s pilgrims would have taken starting south of London in Southwark, rather the ancient trek from Winchester to Canterbury, famously chronicled in The Old Road by Hilaire Belloc. The route follows along the south side of the Downs, where the muddy path was dried by what sun there was. My parents first undertook the walk in the early 1950s. Slides from that pilgrimage depict my mother, voluptuous in her cashmere twinset and tweed skirt, as my father crosses a stile. My parents, inspired by Chaucer’s Canterbury Tales, decided to walk along the traditional Pilgrims’ Way to Canterbury. Story intersects with material traversal over earth on dirt-laden paths.By the time we children came along, the memories of that earlier pilgrimage resonated with my parents, inspiring them to take us on the same journey. We all carried our own rucksacks and walked five or six miles a day. Concerning our pilgrimage when I was seven, my mother wrote in her diary:As good pilgrims should, we’ve been telling tales along the way. Yesterday Jimmy told the whole (detailed) story of That Darn Cat, a Disney movie. Today I told about Stevenson’s Travels with a Donkey, which first inspired me to think of walking trips and everyone noted the resemblance between Stevenson’s lovable, but balky, donkey and our sweet Sue. (We hadn’t planned to tell tales, but they just happened along the way.)I don’t know how sweet I was; perhaps I was “balky” because the road was so hard. Landscape certainly shaped my experience.As I wrote about the pilgrimage in my diary then, “We went to another Hotel and walked. We went and had lunch at the Boggly [booglie] place. We went to a nother hotel called The Swan with fether Quits [quilts]. We went to the Queens head. We went to the Gest house. We went to aother Hotle called Srping wells and my tooth came out. We saw some taekeys [turkeys].” The repetition suggests how pilgrimage combines various aspects of life, from the emotional to the physical, the quotidian (walking and especially resting—in hotels with quilts) with the extraordinary (newly sprung tooth or the appearance of turkeys). “[W]ayfaring abilities depend on an emotional connection to the environment” (Easterlin 261), whether that environment is modified by humans or even manmade, inhabited by human or nonhuman actors. How can one model an “ecological relationship between humans and nonhumans” in narrative (Rodriguez 368)? Rodriguez proposes a “model of reading as encounter [...] encountering fictional story worlds as potential models” (Rodriguez 368), just as my mother did with the Magic Taxi Cab story.Taxis proliferate in my childhood pilgrimage. My mother writes in 1966 in her diary of journeying along the Pilgrims’ Way to St. Martha’s on the Hill. “Susie was moaning and groaning under her pack and at one desperate uphill moment gasped out, ‘Let’s take a taxi!’ – our highborn lady as we call her. But we finally made it.” “Martha’s”, as I later learned, is a corruption of “Martyrs”, a natural linguistic decay that developed over the medieval period. Just as the vernacular textures pilgrimage poems in the fourteeth century, the common tongue in all its glorious variety seeps into even the quotidian modern pilgrim’s journey.Part of the delight of pilgrimage lies in the characters one meets and the languages they speak. In 1994, the only time my husband and I cheated on a strictly ambulatory sacred journey occurred when we opted to ride a bus for ten miles where walking would have been dangerous. When I ask the bus driver if a stop were ours, he replied, “I'll give you a shout, love.” As though in a P. G. Wodehouse novel, when our stop finally came, he cried out, “Cheerio, love” to me and “Cheerio, mate” to Jim.Language changes. Which is a good thing. If it didn’t, it would be dead, like those martyrs of old. Like Latin itself. Disentangling pilgrimage from language proves impossible. The healthy ecopoetics of languages meshes with the sustainable vibrancy of the land we traverse.“Nettles of remorse…”: Derek Walcott, The Bounty Once my father had to carry me past a particularly tough patch of nettles. As my mother tells it, we “went through orchards and along narrow woodland path with face-high nettles. Susie put a scarf over her face and I wore a poncho though it was sunny and we survived almost unscathed.” Certain moments get preserved by the camera. At age seven in a field outside of Wye, I am captured in my father’s slides surrounded by grain. At age thirty-five, I am captured in film by my husband in the same spot, in the identical pose, though now quite a bit taller than the grain. Three years later, as a mother, I in turn snap him with a backpack containing baby Sarah, grumpily gazing off over the fields.When I was seven, we took off from Detling. My mother writes, “set off along old Pilgrims’ Way. Road is paved now, but much the same as fifteen years ago. Saw sheep, lambs, and enjoyed lovely scenery. Sudden shower sent us all to a lunch spot under trees near Thurnham Court, where we huddled under ponchos and ate happily, watching the weather move across the valley. When the sun came to us, we continued on our way which was lovely, past sheep, etc., but all on hard paved road, alas. Susie was a good little walker, but moaned from time to time.”I seem to whimper and groan a lot on pilgrimage. One thing is clear: the physical aspects of walking for days affected my phenomenological response to our pilgrimage which we’d undertaken both as historical ritual, touristic nature hike, and what Wendell Berry calls a “secular pilgrimage” (402), where the walker seeks “the world of the Creation” (403) in a “return to the wilderness in order to be restored” (416). The materiality of my experience was key to how I perceived this journey as a spiritual, somatic, and emotional event. The link between pilgrimage and memory, between pilgrimage poetics and memorial methods, occupies my thoughts on pilgrimage. As Nancy Easterlin’s work on “cognitive ecocriticism” (“Cognitive” 257) contends, environmental knowledge is intimately tied in with memory (“Cognitive” 260). She writes: “The advantage of extensive environmental knowledge most surely precipitates the evolution of memory, necessary to sustain vast knowledge” (“Cognitive” 260). Even today I can recall snatches of moments from that trip when I was a child, including the telling of tales.Landscape not only changes the writer, but writing transforms the landscape and our interaction with it. As Valerie Allen suggests, “If the subject acts upon the environment, so does the environment upon the subject” (“When Things Break” 82). Indeed, we can understand the “road as a strategic point of interaction between human and environment” (Allen and Evans 26; see also Oram)—even, or especially, when that interaction causes pain and inflames blisters. My relationship with moleskin on my blasted and blistered toes made me intimately conscious of my body with every step taken on the pilgrimage route.As an adult, my boots on the way from Winchester to Canterbury pinched and squeezed, packed dirt acting upon them and, in turn, my feet. After taking the train home and upon arrival in London, we walked through Bloomsbury to our flat on Russell Square, passing by what I saw as a new, less religious, but no less beckoning shrine: The London Foot Hospital at Fitzroy Square.Now, sadly, it is closed. Where do pilgrims go for sole—and soul—care?Slow Walking as WayfindingAll pilgrimages come to an end, just as, in 1966, my mother writes of our our arrival at last in Canterbury:On into Canterbury past nice grassy cricket field, where we sat and ate chocolate bars while we watched white-flannelled cricketers at play. Past town gates to our Queen’s Head Inn, where we have the smallest, slantingest room in the world. Everything is askew and we’re planning to use our extra pillows to brace our feet so we won’t slide out of bed. Children have nice big room with 3 beds and are busy playing store with pounds and shillings [that’s very hard mathematics!]. After dinner, walked over to cathedral, where evensong was just ending. Walked back to hotel and into bed where we are now.Up to early breakfast, dashed to cathedral and looked up, up, up. After our sins were forgiven, we picked up our rucksacks and headed into London by train.This experience in 1966 varies slightly from the one in 1994. Jim and I walk through a long walkway of tall, slim trees arching over us, a green, lush and silent cloister, finally gaining our first view of Canterbury with me in a similar photo to one taken almost thirty years before. We make our way into the city through the West Gate, first passing by St. Dunstan’s Church where Henry II had put on penitential garb and later Sir Thomas More’s head was buried. Canterbury is like Coney Island in the Middle Ages and still is: men with dreadlocks and slinky didjeridoos, fire tossers, mobs of people, tourists. We go to Mercery Lane as all good pilgrims should and under the gate festooned with the green statue of Christ, arriving just in time for evensong.Imagining a medieval woman arriving here and listening to the service, I pray to God my gratefulness for us having arrived safely. I can understand the fifteenth-century pilgrim, Margery Kempe, screaming emotionally—maybe her feet hurt like mine. I’m on the verge of tears during the ceremony: so glad to be here safe, finally got here, my favorite service, my beloved husband. After the service, we pass on through the Quire to the spot where St. Thomas’s relic sanctuary was. People stare at a lit candle commemorating it. Tears well up in my eyes.I suppose some things have changed since the Middle Ages. One Friday in Canterbury with my children in 2003 has some parallels with earlier iterations. Seven-year-old Sarah and I go to evensong at the Cathedral. I tell her she has to be absolutely quiet or the Archbishop will chop off her head.She still has her head.Though the road has been paved, the view has remained virtually unaltered. Some aspects seem eternal—sheep, lambs, and stiles dotting the landscape. The grinding down of the pilgrimage path, reflecting the “slowness of flat ontology” (Yates 207), occurs over vast expanses of time. Similarly, Easterlin reflects on human and more than human vitalism: “Although an understanding of humans as wayfinders suggests a complex and dynamic interest on the part of humans in the environment, the surround itself is complex and dynamic and is frequently in a state of change as the individual or group moves through it” (Easterlin “Cognitive” 261). An image of my mother in the 1970s by a shady tree along the Pilgrims’ Way in England shows that the path is lower by 6 inches than the neighboring verge (Bright 4). We don’t see dirt evolving, because its changes occur so slowly. Only big time allows us to see transformative change.Memorial PilgrimageOddly, the erasure of self through duplication with a precursor occurred for me while reading W.G. Sebald’s pilgrimage novel, The Rings of Saturn. I had experienced my own pilgrimage to many of these same locations he immortalizes. I, too, had gone to Somerleyton Hall with my elderly mother, husband, and two children. My memories, sacred shrines pooling in familial history, are infused with synchronic reflection, medieval to contemporary—my parents’ periodic sojourns in Suffolk for years, leading me to love the very landscape Sebald treks across; sadness at my parents’ decline; hope in my children’s coming to add on to their memory palimpsest a layer devoted to this land, to this history, to this family.Then, the oddest coincidence from my reading pilgrimage. After visiting Dunwich Heath, Sebald comes to his friend, Michael, whose wife Anne relays a story about a local man hired as a pallbearer by the local undertaker in Westleton. This man, whose memory was famously bad, nevertheless reveled in the few lines allotted him in an outdoor performance of King Lear. After her relating this story, Sebald asks for a taxi (Sebald 188-9).This might all seem unremarkable to the average reader. Yet, “human wayfinders are richly aware of and responsive to environment, meaning both physical places and living beings, often at a level below consciousness” (Easterlin “Cognitive” 265). For me, with a connection to this area, I startled with recollection emerging from my subconscience. The pallbearer’s name in Sebald’s story was Mr Squirrel, the very same name of the taxi driver my parents—and we—had driven with many times. The same Mr Squirrel? How many Mr Squirrels can there be in this small part of Suffolk? Surely it must be the same family, related in a genetic encoding of memory. I run to my archives. And there, in my mother’s address book—itself a palimpsest of time with names and addressed scored through; pasted-in cards, names, and numbers; and looseleaf memoranda—there, on the first page under “S”, “Mr. Squirrel” in my mother’s unmistakable scribble. She also had inscribed his phone number and the village Saxmundum, seven miles from Westleton. His name had been crossed out. Had he died? Retired? I don’t know. Yet quick look online tells me Squirrell’s Taxis still exists, as it does in my memory.Making KinAfter accompanying a class on a bucolic section of England’s Pilgrims’ Way, seven miles from Wye to Charing, we ended up at a pub drinking a pint, with which all good pilgrimages should conclude. There, students asked me why I became a medievalist who studies pilgrimage. Only after the publication of my first book on women pilgrims did I realize that the origin of my scholarly, long fascination with pilgrimage, blossoming into my professional career, began when I was seven years old along the way to Canterbury. The seeds of that pilgrimage when I was so young bore fruit and flowers decades later.One story illustrates Michel Serres’s point that we should not aim to appropriate the world, but merely act as temporary tenants (Serres 72-3). On pilgrimage in 1966 as a child, I had a penchant for ant spiders. That was not the only insect who took my heart. My mother shares how “Susie found a beetle up on the hill today and put him in the cheese box. Jimmy put holes in the top for him. She named him Alexander Beetle and really became very fond of him. After supper, we set him free in the garden here, with appropriate ceremony and a few over-dramatic tears of farewell.” He clearly made a great impression on me. I yearn for him today, that beetle in the cheese box. Though I tried to smuggle nature as contraband, I ultimately had to set him free.Passing through cities, landscape, forests, over seas and on roads, wandering by fields and vegetable patches, under a sky lit both by sun and moon, the pilgrim—even when in a group of fellow pilgrims—in her lonesome exercise endeavors to realize Serres’ ideal of the tenant inhabitant of earth. Nevertheless, we, as physical pilgrims, inevitably leave our traces through photos immortalizing the journey, trash left by the wayside, even excretions discretely deposited behind a convenient bush. Or a beetle who can tell the story of his adventure—or terror—at being ensconced for a time in a cheese box.On one notorious day of painful feet, my husband and I arrived in Otford, only to find the pub was still closed. Finally, it became time for dinner. We sat outside, me with feet ensconced in shoes blessedly inert and unmoving, as the server brought out our salads. The salad cream, white and viscous, was presented in an elegantly curved silver dish. Then Jim began to pick at the salad cream with his fork. Patiently, tenderly, he endeavored to assist a little bug who had gotten trapped in the gooey sauce. Every attempt seemed doomed to failure. The tiny creature kept falling back into the gloppy substance. Undaunted, Jim compassionately ministered to our companion. Finally, the little insect flew off, free to continue its own pilgrimage, which had intersected with ours in a tiny moment of affinity. Such moments of “making kin” work, according to Donna Haraway, as “life-saving strateg[ies] for the Anthropocene” (Oppermann 3, qtd. in Haraway 160).How can narrative avoid the anthropocentric centre of writing, which is inevitable given the human generator of such a piece? While words are a human invention, nonhuman entities vitally enact memory. The very Downs we walked along were created in the Cretaceous period at least seventy million years ago. The petrol propelling the magic taxi cab was distilled from organic bodies dating back millions of years. Jurassic limestone from the Bathonian Age almost two hundred million years ago constitutes the Caen stone quarried for building Canterbury Cathedral, while its Purbeck marble from Dorset dates from the Cretaceous period. Walking on pilgrimage propels me through a past millions—billions—of eons into the past, dwarfing my speck of existence. Yet, “if we wish to cross the darkness which separates us from [the past] we must lay down a little plank of words and step delicately over it” (Barfield 23). Elias Amidon asks us to consider how “the ground we dig into and walk upon is sacred. It is sacred because it makes us neighbors to each other, whether we like it or not. Tell this story” (Amidon 42). And, so, I have.We are winding down. Time has passed since that first pilgrimage of mine at seven years old. Yet now, here, I still put on my red plaid wollen jumper and jacket, crisp white button-up shirt, grey knee socks, and stout red walking shoes. Slinging on my rucksack, I take my mother’s hand.I’m ready to take my first step.We continue our pilgrimage, together.ReferencesAllen, Valerie. “When Things Break: Mending Rroads, Being Social.” Roadworks: Medieval Britain, Medieval Roads. Eds. Valerie Allen and Ruth Evans. Manchester: Manchester UP, 2016.———, and Ruth Evans. Introduction. Roadworks: Medieval Britain, Medieval Roads. Eds. Valerie Allen and Ruth Evans. Manchester: Manchester UP, 2016.Alworth, David J. Site Reading: Fiction, Art, Social Form. Princeton: Princeton UP, 2016.Amidon, Elias. “Digging In.” Dirt: A Love Story. Ed. Barbara Richardson. Lebanon, NH: ForeEdge, 2015.Barfield, Owen. History in English Words. Grand Rapids: William B. 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Baltimore: Johns Hopkins UP, 2010. 257-274.Haraway, Donna. “Anthropocene, Capitalocene, Plantationocene, Chthulucene: Making Kin.” Environmental Humanities 6 (2015): 159-65.James, Erin, and Eric Morel. “Ecocriticism and Narrative Theory: An Introduction.” English Studies 99.4 (2018): 355-365.Marcussen, Marlene. Reading for Space: An Encounter between Narratology and New Materialism in the Works of Virgina Woolf and Georges Perec. PhD diss. University of Southern Denmark, 2016.Oppermann, Serpil. “Introducing Migrant Ecologies in an (Un)Bordered World.” ISLE 24.2 (2017): 243–256.Oram, Richard. “Trackless, Impenetrable, and Underdeveloped? Roads, Colonization and Environmental Transformation in the Anglo-Scottish Border Zone, c. 1100 to c. 1300.” Roadworks: Medieval Britain, Medieval Roads. Eds. Valerie Allen and Ruth Evans. 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Introduction It is very common for children’s films to adapt, rework, or otherwise re-imagine existing cultural material. Such re-imaginings are potential candidates for fidelity criticism: a mode of analysis whereby an adaptation is judged according to its degree of faithfulness to the source text. Indeed, it is interesting that while fidelity criticism is now considered outdated and problematic by adaptation theorists (see Stam; Leitch; and Whelehan) the issue of fidelity has tended to linger in the discussions that form around material adapted for children. In particular, it is often assumed that the re-imagining of cultural material for children will involve a process of “dumbing down” that strips the original text of its complexity so that it is more easily consumed by young audiences (see Semenza; Kellogg; Hastings; and Napolitano). This is especially the case when children’s films draw from texts—or genres—that are specifically associated with an adult readership. This paper explores such an interplay between children’s and adult’s culture with reference to the re-imagining of the horror genre in children’s animated film. Recent years have seen an inrush of animated films that play with horror tropes, conventions, and characters. These include Frankenweenie (2012), ParaNorman (2012), Hotel Transylvania (2012), Igor (2008), Monsters Inc. (2001), Monster House (2006), and Monsters vs Aliens (2009). Often diminishingly referred to as “kiddie horror” or “goth lite”, this re-imagining of the horror genre is connected to broader shifts in children’s culture, literature, and media. Anna Jackson, Karen Coats, and Roderick McGillis, for instance, have written about the mainstreaming of the Gothic in children’s literature after centuries of “suppression” (2); a glance at the titles in a children’s book store, they tell us, may suggest that “fear or the pretence of fear has become a dominant mode of enjoyment in literature for young people” (1). At the same time, as Lisa Hopkins has pointed out, media products with dark, supernatural, or Gothic elements are increasingly being marketed to children, either directly or through product tie-ins such as toys or branded food items (116-17). The re-imagining of horror for children demands our attention for a number of reasons. First, it raises questions about the commercialisation and repackaging of material that has traditionally been considered “high culture”, particularly when the films in question are seen to pilfer from sites of the literary Gothic such as Mary Shelley’s Frankenstein (1818) or Bram Stoker’s Dracula (1897). The classic horror films of the 1930s such as James Whale’s Frankenstein (1931) also have their own canonical status within the genre, and are objects of reverence for horror fans and film scholars alike. Moreover, aficionados of the genre have been known to object vehemently to any perceived simplification or dumbing down of horror conventions in order to address a non-horror audience. As Lisa Bode has demonstrated, such objections were articulated in many reviews of the film Twilight, in which the repackaging and simplifying of vampire mythology was seen to pander to a female, teenage or “tween” audience (710-11). Second, the re-imagining of horror for children raises questions about whether the genre is an appropriate source of pleasure and entertainment for young audiences. Horror has traditionally been understood as problematic and damaging even for adult viewers: Mark Jancovich, for instance, writes of the long-standing assumption that horror “is moronic, sick and worrying; that any person who derives pleasure from the genre is moronic, sick and potentially dangerous” and that both the genre and its fans are “deviant” (18). Consequently, discussions about the relationship between children and horror have tended to emphasise regulation, restriction, censorship, effect, and “the dangers of imitative violence” (Buckingham 95). As Paul Wells observes, there is a “consistent concern […] that horror films are harmful to children, but clearly these films are not made for children, and the responsibility for who views them lies with adult authority figures who determine how and when horror films are seen” (24). Previous academic work on the child as horror viewer has tended to focus on children as consumers of horror material designed for adults. Joanne Cantor’s extensive work in this area has indicated that fright reactions to horror media are commonly reported and can be long-lived (Cantor; and Cantor and Oliver). Elsewhere, the work of Sarah Smith (45-76) and David Buckingham (95-138) has indicated that children, like adults, can gain certain pleasures from the genre; it has also indicated that children can be quite media savvy when viewing horror, and can operate effectively as self-censors. However, little work has yet been conducted on whether (and how) the horror genre might be transformed for child viewers. With this in mind, I explore here the re-imagining of horror in two children’s animated films: Frankenweenie and ParaNorman. I will consider the way horror tropes, narratives, conventions, and characters have been reshaped in each film with a child’s perspective in mind. This, I argue, does not make them simplified texts or unsuitable objects of pleasure for adults; instead, the films demonstrate that the act of re-imagining horror for children calls into question long-held assumptions about pleasure, taste, and the boundaries between “adult” and “child”. Frankenweenie and ParaNorman: Rewriting the Myth of Childhood Innocence Frankenweenie is a stop-motion animation written by John August and directed by Tim Burton, based on a live-action short film made by Burton in 1984. As its name suggests, Frankenweenie re-imagines Shelley’s Frankenstein by transforming the relationship between creator and monster into that between child and pet. Burton’s Victor Frankenstein is a young boy living in a small American town, a creative loner who enjoys making monster movies. When his beloved dog Sparky is killed in a car accident, young Victor—like his predecessor in Shelley’s novel—is driven by the awfulness of this encounter with death to discover the “mysteries of creation” (Shelley 38): he digs up Sparky’s body, drags the corpse back to the family home, and reanimates him in the attic. This coming-to-life sequence is both a re-imagining of the famous animation scene in Whale’s film Frankenstein and a tender expression of the love between a boy and his dog. The re-imagined creation scene therefore becomes a site of negotiation between adult and child audiences: adult viewers familiar with Whale’s adaptation and its sense of electric spectacle are invited to rethink this scene from a child’s perspective, while child viewers are given access to a key moment from the horror canon. While this blurring of the lines between child and adult is a common theme in Burton’s work—many of his films exist in a liminal space where a certain childlike sensibility mingles with a more adult-centric dark humour—Frankenweenie is unique in that it actively re-imagines as “childlike” a film and/or work of literature that was previously populated by adult characters and associated with adult audiences. ParaNorman is the second major film from the animation studio Laika Entertainment. Following in the footsteps of the earlier Laika film Coraline (2009)—and paving the way for the studio’s 2014 release, Boxtrolls—ParaNorman features stop-motion animation, twisted storylines, and the exploration of dark themes and spaces by child characters. The film tells the story of Norman, an eleven year old boy who can see and communicate with the dead. This gift marks him as an outcast in the small town of Blithe Hollow, which has built its identity on the historic trial and hanging of an “evil” child witch. Norman must grapple with the town’s troubled past and calm the spirit of the vengeful witch; along the way, he and an odd assortment of children battle zombies and townsfolk alike, the latter appearing more monstrous than the former as the film progresses. Although ParaNorman does not position itself as an adaptation of a specific horror text, as does Frankenweenie, it shares with Burton’s film a playful intertextuality whereby references are constantly made to iconic films in the horror genre (including Halloween [1978], Friday the 13th [1980], and Day of the Dead [1985]). Both films were released in 2012 to critical acclaim. Interestingly, though, film critics seemed to disagree over who these texts were actually “for.” Some reviewers described the films as children’s texts, and warned that adults would likely find them “tame and compromised” (Scott), “toothless” (McCarthy) or “sentimental” (Bradshaw). These comments carry connotations of simplification: the suggestion is that the conventions and tropes of the horror genre have been weakened (or even contaminated) by the association with child audiences, and that consequently adults cannot (or should not) take pleasure in the films. Other reviewers of ParaNorman and Frankenweenie suggested that adults were more likely to enjoy the films than children (O’Connell; Berardinelli; and Wolgamott). Often, this suggestion came together with a warning about scary or dark content: the films were deemed to be too frightening for young children, and this exclusion of the child audience allowed the reviewer to acknowledge his or her own enjoyment of and investment in the film (and the potential enjoyment of other adult viewers). Lou Lumenick, for instance, peppers his review of ParaNorman with language that indicates his own pleasure (“probably the year’s most visually dazzling movie so far”; the climax is “too good to spoil”; the humour is “deliciously twisted”), while warning that children as old as eight should not be taken to see the film. Similarly, Christy Lemire warns that certain elements of Frankenweenie are scary and that “this is not really a movie for little kids”; she goes on to add that this scariness “is precisely what makes ‘Frankenweenie’ such a consistent wonder to watch for the rest of us” (emphasis added). In both these cases a line is drawn between child and adult viewers, and arguably it is the film’s straying into the illicit area of horror from the confines of a children’s text that renders it an object of pleasure for the adult viewer. The thrill of being scared is also interpreted here as a specifically adult pleasure. This need on the part of critics to establish boundaries between child and adult viewerships is interesting given that the films themselves strive to incorporate children (as characters and as viewers) into the horror space. In particular, both films work hard to dismantle the myths of childhood innocence—and associated ideas about pleasure and taste—that have previously seen children excluded from the culture of the horror film. Both the young protagonists, for instance, are depicted as media-literate consumers or makers of horror material. Victor is initially seen exhibiting one of his home-made monster movies to his bemused parents, and we first encounter Norman watching a zombie film with his (dead) grandmother; clearly a consummate horror viewer, Norman decodes the film for Grandma, explaining that the zombie is eating the woman’s head because, “that’s what they do.” In this way, the myth of childhood innocence is rewritten: the child’s mature engagement with the horror genre gives him agency, which is linked to his active position in the narrative (both Norman and Victor literally save their towns from destruction); the parents, meanwhile, are reduced to babbling stereotypes who worry that their sons will “turn out weird” (Frankenweenie) or wonder why they “can’t be like other kids” (ParaNorman). The films also rewrite the myth of childhood innocence by depicting Victor and Norman as children with dark, difficult lives. Importantly, each boy has encountered death and, for each, his parents have failed to effectively guide him through the experience. In Frankenweenie Victor is grief-stricken when Sparky dies, yet his parents can offer little more than platitudes to quell the pain of loss. “When you lose someone you love they never really leave you,” Victor’s mother intones, “they just move into a special place in your heart,” to which Victor replies “I don’t want him in my heart—I want him here with me!” The death of Norman’s grandmother is similarly dismissed by his mother in ParaNorman. “I know you and Grandma were very close,” she says, “but we all have to move on. Grandma’s in a better place now.” Norman objects: “No she’s not, she’s in the living room!” In both scenes, the literal-minded but intelligent child seems to understand death, loss, and grief while the parents are unable to speak about these “mature” concepts in a meaningful way. The films are also reminders that a child’s first experience of death can come very young, and often occurs via the loss of an elderly relative or a beloved pet. Death, Play, and the Monster In both films, therefore, the audience is invited to think about death. Consequently, there is a sense in each film that while the violent and sexual content of most horror texts has been stripped away, the dark centre of the horror genre remains. As Paul Wells reminds us, horror “is predominantly concerned with the fear of death, the multiple ways in which it can occur, and the untimely nature of its occurrence” (10). Certainly, the horror texts which Frankenweenie and ParaNorman re-imagine are specifically concerned with death and mortality. The various adaptations of Frankenstein that are referenced in Frankenweenie and the zombie films to which ParaNorman pays homage all deploy “the monster” as a figure who defies easy categorisation as living or dead. The othering of this figure in the traditional horror narrative allows him/her/it to both subvert and confirm cultural ideas about life, death, and human status: for monsters, as Elaine Graham notes, have long been deployed in popular culture as figures who “mark the fault-lines” and also “signal the fragility” of boundary structures, including the boundary between human and not human, and that between life and death (12). Frankenweenie’s Sparky, as an iteration of the Frankenstein monster, clearly fits this description: he is neither living nor dead, and his monstrosity emerges not from any act of violence or from physical deformity (he remains, throughout the film, a cute and lovable dog, albeit with bolts fixed to his neck) but from his boundary-crossing status. However, while most versions of the Frankenstein monster are deliberately positioned to confront ideas about the human/machine boundary and to perform notions of the posthuman, such concerns are sidelined in Frankenweenie. Instead, the emphasis is on concerns that are likely to resonate with children: Sparky is a reminder of the human preoccupation with death, loss, and the question of why (or whether, or when) we should abide by the laws of nature. Arguably, this indicates a re-imagining of the Frankenstein tale not only for child audiences but from a child’s perspective. In ParaNorman, similarly, the zombie–often read as an articulation of adult anxieties about war, apocalypse, terrorism, and the deterioration of social order (Platts 551-55)—is re-used and re-imagined in a childlike way. From a child’s perspective, the zombie may represent the horrific truth of mortality and/or the troublesome desire to live forever that emerges once this truth has been confronted. More specifically, the notion of dealing meaningfully with the past and of honouring rather than silencing the dead is a strong thematic undercurrent in ParaNorman, and in this sense the zombies are important figures who dramatise the connections between past and present. While this past/present connection is explored on many levels in ParaNorman—including the level of a town grappling with its dark history—it is Norman and his grandmother who take centre stage: the boundary-crossing figure of the zombie is re-realised here in terms of a negotiation with a presence that is now absent (the elderly relative who has died but is still remembered). Indeed, the zombies in this film are an implicit rebuke to Norman’s mother and her command that Norman “move on” after his grandmother’s death. The dead are still present, this film playfully reminds us, and therefore “moving on” is an overly simplistic and somewhat disrespectful response (especially when imposed on children by adult authority figures.) If the horror narrative is built around the notion that “normality is threatened by the Monster”, as Robin Wood has famously suggested, ParaNorman and Frankenweenie re-imagine this narrative of subversion from a child’s perspective (31). Both films open up a space within which the child is permitted to negotiate with the destabilising figure of the monster; the normality that is “threatened” here is the adult notion of the finality of death and, relatedly, the assumption that death is not a suitable subject for children to think or talk about. Breaking down such understandings, Frankenweenie and ParaNorman strive not so much to play with death (a phrase that implies a certain callousness, a problematic disregard for human life) but to explore death through the darkness of play. This is beautifully imaged in a scene from ParaNorman in which Norman and his friend Neil play with the ghost of Neil’s recently deceased dog. “We’re going to play with a dead dog in the garden,” Neil enthusiastically announces to his brother, “and we’re not even going to have to dig him up first!” Somewhat similarly, film critic Richard Corliss notes in his review of Frankenweenie that the film’s “message to the young” is that “children should play with dead things.” Through this intersection between “death” and “play”, both films propose a particularly child-like (although not necessarily child-ish) way of negotiating horror’s dark territory. Conclusion Animated film has always been an ambiguous space in terms of age, pleasure, and viewership. As film critic Margaret Pomeranz has observed, “there is this perception that if it’s an animated film then you can take the little littlies” (Pomeranz and Stratton). Animation itself is often a signifier of safety, fun, nostalgia, and childishness; it is a means of addressing families and young audiences. Yet at the same time, the fantastic and transformative aspects of animation can be powerful tools for telling stories that are dark, surprising, or somehow subversive. It is therefore interesting that the trend towards re-imagining horror for children that this paper has identified is unfolding within the animated space. It is beyond the scope of this paper to fully consider what animation as a medium brings to this re-imagining process. However, it is worth noting that the distinctive stop-motion style used in both films works to position them as alternatives to Disney products (for although Frankenweenie was released under the Disney banner, it is visually distinct from most of Disney’s animated ventures). The majority of Disney films are adaptations or re-imaginings of some sort, yet these re-imaginings look to fairytales or children’s literature for their source material. In contrast, as this paper has demonstrated, Frankenweenie and ParaNorman open up a space for boundary play: they give children access to tropes, narratives, and characters that are specifically associated with adult viewers, and they invite adults to see these tropes, narratives, and characters from a child’s perspective. Ultimately, it is difficult to determine the success of this re-imagining process: what, indeed, does a successful re-imagining of horror for children look like, and who might be permitted to take pleasure from it? 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