Journal articles on the topic 'Alzheimer's disease. Nutrition. Nutrition disorders in old age'

Alzheimer's disease (AD) is the most common form of dementia among elderly. It is a progressive, neurodegenerative disorder of the brain which leads to the deterioration of cognitive, behavioral and impaired daily functioning and causes the gradual loss of independence. A significant portion of risk for dementia in old age is associated with lifestyle. Three important protective factors are diet, which should be rich in antioxidants, exercise and good cardiovascular health. It is believed that Mediterranean diet has a protective effect from dementia. This diet, rich in fruit and vegetables, legumes, olive oil, whole wheat bread, fish and seafood, with reduced consumption of red meat is also protective from cardiovascular diseases and promotes a healthy long life. There were some studies on the etiology of AD which noted an important role of vitamin B6, B12 and folic acid. All of them are involved in the metabolism of homocysteine, which is regarded as an independent risk factor for the development of AD, atherosclerosis and thrombosis. We also know that supplementation of vitamins C and E in the diet can be protective from AD. On the other hand we know that obesity and undernutrition can increase the risk of development of AD. As we can observe the aging of population we should remember that nutrition constitutes an interesting approach for the prevention of age‑related brain disorders.

The current high life expectancy is overshadowed by neurodegenerative illnesses that lead to dementia and dependence. Alzheimer's disease (AD) is the most common of these conditions, and is considered to be a proteinopathy, with amyloid-β42 as a key factor, leading via a cascade of events to neurodegeneration. Major factors involved are oxidative stress, perturbed Ca homeostasis and impaired energy metabolism. Protection against oxidative stress by micronutrients (including secondary bioactive substances) has been shown in transgenic Alzheimer model systems to delay AD. Epidemiological evidence is less conclusive, but the vast majority of the evidence supports a protective effect on cognitive functions in old age and AD. Thus, a diet rich in fruits and vegetables but also containing meat and fish is the most suitable to provide adequate micronutrients. The strong link between cardiovascular risk and AD may be explained by common pathogenetic mechanisms mediated, for example, by homocysteine and thus dependant on B-vitamins (folate and vitamins B12 and B6). However, micronutrients may also be harmful. The high affinity of amyloid for metals (Fe, Al and Zn) favours the generation of reactive oxygen species and triggers an inflammatory response. Micronutrients in a balanced diet have a long-lasting, albeit low, protective impact on brain aging, hence prevention should be life long.

Cognitive disorders are increasing in prevalence. Nutritional or metabolic stressors during early life, and female sex, are predisposing conditions towards the development of cognitive diseases, including Alzheimer’s disease. Though there is evidence that breastfeeding may play a beneficial role in children’s neurocognitive development, the literature remains controversial. In this study we aimed at assessing the association between exclusive breastfeeding and children’s cognitive development from six months to five years of age, addressing sex differences. In 80 mother-child pairs from the Pisa birth cohort (PISAC), we measured cognitive development in groups of children of 6, 12, 18, 24, 36, and 60 months by Griffiths Mental Development Scales, parents’ intelligence quotient (IQ) by Raven’s progressive matrices, and maternal and infants’ anthropometric parameters. We found that exclusive breastfeeding was associated with higher hearing-language development in five years old girls, independent of maternal IQ, age and BMI (body mass index). Exclusive breastfeeding in the first three months of life seemed sufficient to establish this positive relationship. In conclusion, our data indicate that exclusive breastfeeding is a positive predictor of cognitive development in preschool-age girls, paving the way for the implementation of sex-specific cognitive disease risk detection and prevention strategies from early life. Further studies are warranted to explore causality and longer term effects.

The peripheral hearing alterations and central auditory processing disorder (CAPD) associated with age-related hearing loss (ARHL), may impact cognitive disorders in older age. In older age, ARHL is also a significant marker for frailty, another age-related multidimensional clinical condition with a nonspecific state of vulnerability, reduced multisystem physiological reserve, and decreased resistance to different stressors (i.e. sensorial impairments, psychosocial stress, diseases, injuries). The multidimensional nature of frailty required an approach based on different pathogeneses because this clinical condition may include sensorial, physical, social, nutritional, cognitive, and psychological phenotypes. In the present narrative review, the cumulative epidemiological evidence coming from several longitudinal population-based studies, suggested convincing links between peripheral ARHL and incident cognitive decline and dementia. Moreover, a few longitudinal case-control and population-based studies also suggested that age-related CAPD in ARHL, may be central in determining an increased risk of incident cognitive decline, dementia, and Alzheimer’s disease (AD). Cumulative meta-analytic evidence confirmed cross-sectional and longitudinal association of both peripheral ARHL and age-related CAPD with different domains of cognitive functions, mild cognitive impairment, and dementia, while the association with dementia subtypes such as AD and vascular dementia remained unclear. However, ARHL may represent a modifiable condition and a possible target for secondary prevention of cognitive impairment in older age, social isolation, late-life depression, and frailty. Further research is required to determine whether broader hearing rehabilitative interventions including coordinated counseling and environmental accommodations could delay or halt cognitive and global decline in the oldest old with both ARHL and dementia.

Lown-3 polyunsaturated fatty acid (PUFA) status may be associated with neuro-degenerative disorders, in particular Alzheimer's disease, which has been associated with poor dietary fish orn-3 PUFA intake, and low docosahexaenoic acid (DHA) status. The present case–control study used an established biomarker ofn-3 PUFA intake (serum cholesteryl ester-fatty acid composition) to determinen-3 PUFA status in patients with Alzheimer's disease, who were free-living in the community. All cases fulfilled the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Detailed neuropsychological testing and neuroimaging established the diagnosis in all cases. The subjects (119 females and twenty-nine males) aged 76·5 (SD 6·6) YEARS HAD A CLINICAL DEMENTIA RATING (CDR) OF 1 (sd 0·62) and a mini mental state examination (MMSE) score of 19·5 (sd 4·8). The control subjects (thirty-six females and nine males) aged 70 (sd 6·0) years were not cognitively impaired (defined as MMSE score <24): they had a mean MMSE score of 28·9 (sd 1·1). Serum cholesteryl ester-eicosapentaenoic acid and DHA levels were significantly lower (P<0·05 andP<0·001 respectively) in all MMSE score quartiles of patients with Alzheimer's disease compared with control values. Serum cholesteryl ester-DHA levels were progressively reduced with severity of clinical dementia. DHA levels did not differ in patients with Alzheimer's disease across age quartiles: all were consistently lower than in control subjects. Step-wise multiple regression analysis showed that cholesteryl ester-DHA and total saturated fatty acid levels were the important determinants of MMSE score and CDR. It remains to be determined whether low DHA status in Alzheimer's disease is a casual factor in the pathogenesis and progression of Alzheimer's disease.

Canine and feline cognitive dysfunction syndrome is a common neurodegenerative disorder of old age and a natural model of human Alzheimer’s disease. With the unavoidable expanding life expectancy, an increasing number of small animals will be affected. Although there is no cure, early detection and intervention are vitally important to delay cognitive decline. Knowledge of cellular and molecular mechanisms underlying disease onset and progression is an equally decisive factor for developing effective approaches. Uncontrolled neuroinflammation, orchestrated in the central nervous system mainly by astrocytes, microglia, and resident mast cells, is currently acknowledged as a hallmark of neurodegeneration. This has prompted scientists to find a way to rebalance the altered crosstalk between these cells. In this context, great emphasis has been given to the role played by the expanded endocannabinoid system, i.e., endocannabinoidome, because of its prominent role in physiological and pathological neuroinflammation. Within the endocannabinoidome, great attention has been paid to palmitoylethanolamide due to its safe and pro-homeostatic effects. The availability of new ultramicronized formulations highly improved the oral bioavailability of palmitoylethanolamide, paving the way to its dietary use. Ultramicronized palmitoylethanolamide has been repeatedly tested in animal models of age-related neurodegeneration with promising results. Data accumulated so far suggest that supplementation with ultramicronized palmitoylethanolamide helps to accomplish successful brain aging.

The history of vitamin A goes back over one hundred years, but our realization of its importance for the brain and cognition is much more recent. The brain is more efficient than other target tissues at converting vitamin A to retinoic acid (RA), which activates retinoic acid receptors (RARs). RARs regulate transcription, but their function in the cytoplasm to control nongenomic actions is also crucial. Controlled synthesis of RA is essential for regulating synaptic plasticity in regions of the brain involved in learning and memory, such as the hippocampus. Vitamin A deficiency results in a deterioration of these functions, and failure of RA signaling is perhaps associated with normal cognitive decline with age as well as with Alzheimer's disease. Further, several psychiatric and developmental disorders that disrupt cognition are also linked with vitamin A and point to their possible treatment with vitamin A or RA.

Vitamin B12 deficiency damages nerve cells and aggravates nervous system disorders even in the absence of evidence of anaemia. Prevalence of B12 deficiency increases with age especially over 65 and is frequently associated with Alzheimer's disease. Recent American surveys record a higher prevalence of B12 deficiency and of undiagnosed and untreated pernicious anaemia in the elderly than reported earlier. B12 deficiency is also reported to be a risk factor for heart disease, stroke and accelerated ageing.

Malnutrition in older adults has been recognised as a challenging health concern associated with not only increased mortality and morbidity, but also with physical decline, which has wide ranging acute implications for activities of daily living and quality of life in general. Malnutrition is common and may also contribute to the development of the geriatric syndromes in older adults. Malnutrition in the old is reflected by either involuntary weight loss or low body mass index, but hidden deficiencies such as micronutrient deficiencies are more difficult to assess and therefore frequently overlooked in the community-dwelling old. In developed countries, the most cited cause of malnutrition is disease, as both acute and chronic disorders have the potential to result in or aggravate malnutrition. Therefore, as higher age is one risk factor for developing disease, older adults have the highest risk of being at nutritional risk or becoming malnourished. However, the aetiology of malnutrition is complex and multifactorial, and the development of malnutrition in the old is most likely also facilitated by ageing processes. This comprehensive narrative review summarizes current evidence on the prevalence and determinants of malnutrition in old adults spanning from age-related changes to disease-associated risk factors, and outlines remaining challenges in the understanding, identification as well as treatment of malnutrition, which in some cases may include targeted supplementation of macro- and/or micronutrients, when diet alone is not sufficient to meet age-specific requirements.

Managing infants, children and adolescents, ranging from premature infants to 18-year-old adolescents, on parenteral nutrition (PN) is a challenge. The ability of children to withstand starvation is limited and, unlike adults, children require nutrition for growth. PN in children is often required secondary to a congenital bowel problem rather than because of an acquired condition. Conditions requiring PN include motility disorders, congenital disorders of the intestinal epithelium and short-bowel syndrome (SBS). Intestinal failure may be temporary and children with SBS may be weaned from PN. However, other children require permanent PN. There are no comprehensive guidelines for the nutritional requirements of children and adolescents requiring PN. Practice in individual centres is based on clinical experience rather than clinical trials. Requirements are assessed on an individual basis according to age, nutritional status and clinical condition. These requirements need regular review to ensure that they remain appropriate for the changing age and weight of the child. Assessments of intakes use different methods, e.g. reference tables and predictive equations. Complications of PN include infection, accidental damage to, or removal of, the line and cholestatic liver disease. Home parenteral nutrition (HPN) is associated with fewer line infections and allows continuation of nutritional support in a more normal environment, encouraging normal development and participation in family activities. However, having a child at home on HPN is associated with physical and psychological stresses. A feeling of depression, loneliness and social isolation is common amongst children and their families. Home-care services are essential to supporting children at home and should be tailored to, and sensitive to, the individual needs of each family.

Fructose malabsorption is regarded as one of the most common types of sugar intolerance. However, the correlation between gastrointestinal symptoms and positive results in fructose hydrogen breath tests (HBTs) remains unclear. The aim of this study was to assess the clinical importance of positive fructose HBT by correlating the HBT results with clinical features in children with various gastrointestinal symptoms. Clinical features and fructose HBT results were obtained from 323 consecutive children (2–18 years old, mean 10.7 ± 4.3 years) that were referred to the Tertiary Paediatric Gastroenterology Centre and diagnosed as having functional gastrointestinal disorders. A total of 114 out of 323 children (35.3%) had positive HBT results, of which 61 patients were females (53.5%) and 53 were males (46.5%). Children with positive HBT were significantly younger than children with negative HBT (9.0 vs. 11.6 years old; p < 0.001). The most frequent symptom among children with fructose malabsorption was recurrent abdominal pain (89.5%). Other important symptoms were diarrhoea, nausea, vomiting, and flatulence. However, no correlation between positive fructose HBT results and any of the reported symptoms or general clinical features was found. In conclusion, positive fructose HBT in children with functional gastrointestinal disorders can be attributed to their younger age but not to some peculiar clinical feature of the disease.

Type 1 diabetes mellitus (T1DM) is a chronic disease that can affect the physical and mental health of children and adolescents, often leading to anxiety disorders with chronic activation of the hypothalamic axis (HPA). Moreover, a great proportion of adolescents with T1DM also demonstrate anorexia nervosa (AN), due to the increased preoccupation with food and the need to have an acceptable body image. Herein is described the first case study of an adolescent patient diagnosed with T1DM, anxiety disorder (AD), and AN. A 14-year-old girl with T1DM since the age of 12 years presented weight loss at age 13 years and 3 months and low body mass index (BMI), which did not improve despite dietary recommendations and adequate disease control. Additionally, she presented menstrual disorders at the age of 12 years and 11 months (menstrual age 12 years and 1 month). A psychological evaluation of the teenager was conducted using a semi-structured interview that assessed perceived stress, health status, quality of life, and depression. AD and AN were diagnosed and the patient initiated an intervention focusing on psychological health and nutrition and which incorporated physiotherapeutic relaxation sessions and breathing exercises. After 3 months of treatment, the patient’s BMI was increased, and a normal menstrual cycle was apparent. These results have since remained consistent. Stress leads to the appearance of AN and menstrual disorders. Therefore, physiotherapeutic programs could reduce stress and effectively ameliorate AN and AD.

Obesity and ageing are current issues of global concern. Adaptive homeostasis is compromised in the elderly, who are more likely to suffer age-related health issues, such as obesity, metabolic syndrome, and cardiovascular disease. The current worldwide prevalence of obesity and higher life expectancy call for new strategies for treating metabolic disorders. Grape-seed proanthocyanidin extract (GSPE) is reported to be effective in ameliorating these pathologies, especially in young animal models. In this study, we aimed to test the effectiveness of GSPE in modulating obesity-related pathologies in aged rats fed an obesogenic diet. To do so, 21-month-old rats were fed a high-fat/high-sucrose diet (cafeteria diet) for 11 weeks. Two time points for GSPE administration (500 mg/kg body weight), i.e., a 10-day preventive GSPE treatment prior to cafeteria diet intervention and a simultaneous GSPE treatment with the cafeteria diet, were assayed. Body weight, metabolic parameters, liver steatosis, and systemic inflammation were analysed. GSPE administered simultaneously with the cafeteria diet was effective in reducing body weight, total adiposity, and liver steatosis. However, the preventive treatment was effective in reducing only mesenteric adiposity in these obese, aged rats. Our results confirm that the simultaneous administration of GSPE improves metabolic disruptions caused by the cafeteria diet also in aged rats.

Osteoporosis is a bone disease that results in weakening of bones and breakage of bones in severe cases. It means porous bone. It is most commonly seen in elderly people of both the sexes. In the early stages of bone loss, there are no symptoms. But once the bone gets weakened symptoms such as back pain, stooped posture, loss of height over time and easy breakage of bones can be seen. Age, sex, family history, sex hormones, thyroid problems are the risk factors of osteoporosis. Dietary factors such as low calcium intake and eating disorders are also the risk factor in osteoporosis. Sedentary lifestyle, excessive alcohol consumption and tobacco use can increase the risk of osteoporosis: good nutrition and regular exercise help to keep our bones healthy throughout our life. A self-administered questionnaire containing about 15 questions were prepared and circulated through online survey Google forms link. About 100 middle-aged and old-aged male and female people responded to the survey. The responses were collected, tabulated and statistically analyzed using SPSS software. 54% of the total population was male. 53% of the participants have responded that they have back pain. 38% of people responded that their parents or siblings suffer from osteoporosis. Osteoporosis is more common among elderly people and in postmenopausal women. Also, not only women but men also suffer from osteoporosis. A proper healthy diet and weight-bearing exercises can prevent osteoporosis. Prevention from fractures is the primary goal in osteoporosis.

e20044 Background: Recent advancements in the treatment of plasma cell disorders (PCD) have led to a revolution in treatment options. Despite improved outcomes, patients have unmet symptom management needs. Integrative medicine (IM) is a method for addressing symptoms in cancer, but its use and efficacy is poorly defined in PCD patients. This analysis describes the utilization of IM among myeloma patients and explores associations with symptom burden. Methods: For 3 months, a 70-question online survey was hosted on HealthTree.org, an online resource for myeloma patients and researchers created by the HealthTree Foundation. The survey included questions about demographics, PCD type, disease stage, complementary practice use, PHQ-2 score (depression screen), and quality of life (sum of 6 interference items; possible score range 0-6). Mean outcome values were compared between IM users and non-users using two-sample t-tests. Proportions of supplement users and IM users were compared between patients currently on myeloma-specific treatment and patients not currently on treatment using chi-square tests. Results: Of 195 total respondents, 17 were excluded for not completing the survey section on IM practices. Median age range was 60-69 years old, 61% were female, 91% were non-Hispanic white, and 57% were overweight or obese. Plasma cell subtypes were active myeloma (81%), smoldering myeloma (12%), MGUS (3%), amyloidosis (2%), and plasmacytoma (1%), and 72% of patients were currently on cancer-specific treatment. On a scale of 1-10 (1=very uncomfortable; 10=very comfortable), patients reported a mean score of 3.7 when discussing IM therapies with their oncologist. The top 10 IM modalities reported were aerobic exercise (83%), nutrition (67%), natural products (60%), strength exercise (52%), support groups (48%), breathing exercises (44%), meditation (42%), yoga (40%), mindfulness-based stress reduction (38%), and massage (38%). Those who participated in meditation had significantly higher PHQ-2 scores (worse depression) than non-participants (1.1 vs. 0.8; p=0.05). Users of support groups (3.4 vs. 2.7; p=0.04), medicinal marijuana (4.0 vs. 2.9; p=0.03), or vitamin C (3.6 vs. 2.7; p=0.01) reported higher mean interference (worse quality of life) than non-users. Compared to patients currently on cancer treatment for PCD, untreated patients were significantly more likely to use curcumin (58% vs. 41%; p=0.04) or green tea (44% vs. 17%; p<0.001), were less likely to use medicinal marijuana (6% vs. 18%; p=0.05), and reported significantly lower fatigue (p=0.02). Conclusions: This international survey-based analysis reveals that most patients participated in IM modalities, though felt uncomfortable discussing them with their oncologist. It is unclear if the use of some IM modalities were due to symptom burden or lead to higher symptom burden. This study provides a foundation in the understanding of IM use in PCD, but more research is needed to evaluate its efficacy.

Background. Except for smoking and certain occupational exposures, the etiology of bladder cancer is largely unknown. Several case reports have described familial aggregation of transitional cell carcinoma of the bladder. Although the majority of patients with bladder cancer do not have family history of transitional cell carcinoma of the urinary tract, the study of familial transitional cell carcinoma may lead to the knowledge on the pathogenesis of this disease. The purpose of this study was to describe three cases of urinary bladder cancer in a single three-member family, i.e. in two generations (mother and son) and a family member related by marriage (the patient?s wife). Case report. Three cases of urinary bladder cancer occurred in a three-member family within the interval of 5 years. The following common characteristics were detected in our patients: old age (over 60), working as farmers for more than 50 years, negative personal medical history on relevant health disorders, place of birth - village, place of residence - village, the same water supply, similar nutrition, positive family history on urinary bladder cancer or other malignant tumors, the first sign of illness was macroscopic hematuria in all the patients and the same pathohistological type of cancer - carcinoma papillare transitiocellulare. Conclusion. The stated common characteristics in our cases indicate, above all, the impact of exposure to external surrounding factors on the occurrence of urinary bladder cancer.

Abstract Background Chronic intestinal pseudo-obstruction (CIPO) is a rare condition that is not commonly associated with Crohn’s disease (CD). We performed a cohort study aiming at identifying clinical, immunological and genetic features as well as response to conventional CD treatments of patients co-affected with CIPO and CD. Methods We conducted an observational retrospective cohort study in two tertiary CIPO and IBD centers. Patients with parenteral nutrition-dependent CIPO and features of CD including large intestinal or perianal ulcers, strictures, abscesses and fistula with pathology findings compatible with CD, were included. We used flow-cytometry and targeted-next generation sequencing to identify immune defects and monogenic causes in 129 predefined genes responsible for monogenic enteropathies Results Eight unrelated patients were studied. 5 had a myogenic phenotype and 3 had a neurogenic form with histological exam for all patients. CD involved small bowel in all cases whereas one patient had ileocolonic involvement. Two patients had perianal complex fistula. Seven patients had a stricturing form and 1 had an inflammatory-only behavior. No patient had a penetrating form. All patients were diagnosed with CIPO prior to CD. Median age at CIPO diagnosis was 11.5 years old (IQR 0,31.5) while it was 22.5 (IQR 19,29) at CD diagnosis. At CD diagnosis, mean fecal calprotectin level was 551 ug/g (range 390 - 1200) and citrulline averaged 23.6 umol/l (range 15–35 umol/l). Histopathological analyses of intestinal specimens revealed ulcerations for half of the patients, increase in intraepithelial lymphocytes in 3, granuloma and cryptitis in 1 patient. Abnormalities in peripheral lymphocytes’ subsets were found in 2 patients. 5 patients were ultimately diagnosed with monogenic forms of enteropathy: 2 in ACTG2, with an autosomal dominant inheritance, 1 with a STAT1gain of function, (GOF) and two with recessive inheritance: TYMP. All patients received steroids with clinical response in 2. 6 patients received antiTNF, with only one sustained remission. Two patients received vedolizumab and 2 were treated with ustekinumab. Except for antiTNF in 1 patient, common CD treatments did not lead to any improvement. Of note, antiJAK therapy in a patient with STAT1GOF failed to induce remission. Conclusion Herein is described the first cohort of extensively genetically and immunologically explored patients co-affected with CIPO and CD. Immune defects were common and monogenic forms were found with a high prevalence. Rates of response to biologic treatment were very low. Identification of monogenic cause through immunological and genetic explorations is warranted in patient with CIPO-CD association as it could lead to targeted therapy and genetic counseling.

Abstract Hydroxycarbamide (HU) is a myelosuppressive drug marketed since 1968 for the treatment of hematological cancer, and authorized since 2007 in Europe as orphan medicinal product for the prevention of recurrent vaso-occlusive crises including acute chest syndrome in adults and children older than 2 years with sickle cell disease (SCD). ESCORT-HU (European Sickle Cell Disease Cohort – Hydroxyurea) is a multicenter prospective non interventional study implemented in Europe to collect more information about the safety profile of HU and morbi-mortality in SCD patients treated with HU. The study responds to EMA (European Medicines Agency) request and has been approved by the Ethical of Necker Enfants Malades Hospital (Paris, France).The ongoing study involves the largest number so far of patients with SCD treated with HU. Primary endpoints of ESCORT HU are to determine frequency of adverse events, and possible consequent changes of HU treatment. Secondary endpoints are to evaluate morbi-mortality of the disease although in the absence of control group. From June 2008 to June 2014, 483 patients (255 females; 228 males) were enrolled from 3 European countries, Greece (24%), Germany (19%), and France (56%). 67% patients were adults, median aged 37.35 yrs (17-83.5) and 33% were children, median aged 11.06 yrs (2.6-16.9). genotypes were HbS/HbS in 71.4% cases, and compound heterozygotous HbS/β-thalassemia in 22.8 % (Table 1). 137 (28.4%) patients experienced 421 events (Table 2). 132 (32.2%) of these events may be attributed to HU. The safety profile is roughly similar in children and adults. As expected the most frequent side effects were firstly blood disorders (n=86 events, 42.4%) such as neutropenia or thrombocytopenia. In all cases, these cytopenias were rapidly resolved with the transitory stop of HU. 71 events related to skin and subcutaneous tissue disorders were observed, mostly cutaneous dryness, skin reactions, alopecia and nails or skin pigmentation; 4 patients had a leg ulcer (34.8%). Most of these events are ongoing or stabilized despit the decrease of HU. No secondary cancer has been reported until now. Even if HU is an old drug with a relatively well-known safety profile, some uncertainties remain in terms of long-term safety as well as tolerance in the youngest people. The main interest of ESCORT HU is to offer the possibility of safety surveillance of hydroxycarbamide in European sickle cell patients. Table 1 Demographic data Adults Children < 17 years old Total Number of patients 322 (67%) 161 (33%) 483 Females/Males 183/139 72/89 255/228 Median age (yrs) (range) 37.35 (17-83.5) 11.06 (2.6-16.9) 28.58 Genotype SS 206 (64%) 139 (86.3%) 345 (71.4%) SC 1 (0.3%) 3 (1.86%) 4 (0.8%) Sβ0 51 (15.8%) 11 (6.8%) 62 (12.8%) Sβ+ 46 (14.2%) 2 (1.2%) 48 (9.9%) Other 18 (5.5%) 6 (3.7%) 24 (4.9%) Treatment with HU before enrollment in ESCORT HU No of pts 232 83 315 (65%) Median duration (range) of HU treatment before ESCORT HU 8.2 yrs (0.5 ans-24 yrs) 3. 1 yrs ( 71 days – 8.9 yrs) 6.85 (71 days-24 years)] HU ESCORT Daily mean dose (mg/kg/d) 16.11 ± 4.79 19.63 ± 4.69 17.32 ± 4.94 Abstract 564. Table 2 The most frequent events of hydroxycarbamide in the two populations of SCD patients ADULTS CHILDREN No ofGerman(%) No of adults No ofEpisodes(%) No of children Total(% /411) Events Related to HU treatment (Siklos®)(%**) Blood and lymphatic system disorders (%) 32 (17.7) 22 54 (31.03) 28 86 (20.9) 56 (65.1) Skin and subcutaneous tissue disorders (%) 42 (23.2) 28 29 (16.7) 19 71 (17.3) 46 (64.8) Nervous system disorders Headache (24), Dizziness/vertigo (14), 32 (17.7) 23 12(6.9) 10 44 (10.7) 11 (25) Gastrointestinal disorders Nausea (14), diarrhea (8), other (14) 20 (11) 17 23 (13.2) 16 43 (10.4) 7 (16.3) Metabolic and nutrition disorders: vit D deficiency (17), weight gain (5) 13 (7) 11 18 (18.3) 18 36 (8.75) 4 (11.1) Fever 11 (6) 10 12(6.9) 7 23 (5.6) 1 (4.3) Cardiac disorders (hypertension, bradycardia, chest pain, cardiomegaly) 4 4 2 2 6 1 (16.6) General disorders : fatigue 5 5 0 0 5 0 Hepatobiliary disorders 2 2 0 0 2 0 Neoplasms benign, malignant and unspecified (incl. cysts and polyps) Harmatoma, benign vulvar sebaceous cyst 2 2 0 0 2 0 Renal & urinary disorders 2 2 0 0 2 0 Reproductive system and breast disorders 3 3 0 0 3 0 Other 13 13 21 14 34 6 (17.1%) 181 80 /181(24.8%) 174 57 / 174(35.4%) 411 132/411 (32.2%) ** compared to the total number of “system organ class” events Disclosures No relevant conflicts of interest to declare.

Abstract 100 cases of aged non-hematological anemia patients hospitalized in our hospital since July 1, 2000, were analyzed for study on anemia etiology. The mean age was 72.08+/−10.86 (60–90) years (60~ 42; 70~ 39; 80~ 18; 90~ 3) at hospitalization. The etiology of anemia with known showed as followed: Malignant tumor 34: included digestive system malignant tumor 27 (gastric cancer 7, rectal carcinoma 7, colon cancer 6, liver cancer 3, cholangiocarcinoma 2, pencreatic duct cancer 2), lung cancer 3, urinary tract cancer 2, bone sarcoma 2. Iron deficiency anemia 47: digestive tract ulcer 16, hemorrhoid 14. The total number of iron deficiency anemia includes digestive tumors with bleeding. Single nutrition deficiency anemia, macrocytic anemia, i.e. vitamin B12 and/or folic acid deficiency (non-malignant, Non-iron deficiency anemia) 8. Inherited Anemia 10: Thalassemia 6, Glucose-6-phosphate dehydrogenase (G6PD) deficiency 4. Chronic diseases 23: Bone fracture 19, Stroke 18, infection 12, Diabetes 10, Kidney function failure 8, Gynecological bleeding 4. The etiology of anemia is unknown 29: it included some chronic diseases with anemia. Discussion: Incidence of malignant tumor is very high. The incidence of malignancy was 34% in the series of aged anemia. The chance of gene mutation increased as patients’ age getting older. When to diagnose aged anemia, we should better to consider that the primary disease is tumor maybe, and look for tumor carefully. Mechanism of anemia in patients with tumor Gastrointestinal tumor with chronic bleeding that can result in anemia. But, there is serious anemia without bleeding in our series. There were some different chronic diseases in 34 cases of tumor. Researchers have discovered that structural and metabolic disorders were detected in mature erythrocytes in patients with and without anemia in stomach cancer. Anemia development pathways were dependent on enhanced hemolysis of circulating erythrocytes and influx of immature cells from the bone marrow. Complication of etiology in aged anemia Etiological diseases of aged anemia is different and complicate. The major of aged anemia has two or more primary diseases. The primary presenting of gastrointestinal tumor maybe is iron deficiency anemia. The tumor with anemia can result from nutritional deficiency at advance. For example, there were vitamin B12 or/and folic acid 8 cases in our aged series. Some anemia patients in our series complicated cardiac disease, stroke, and bone fracture. 2 cases of G6PD deficiency had primarily diagnosed when they suffered from infection at very old age, 70 years or more in these aged anemia. There are 100 million G6PD in whole world, the incidence is very high especially in Africa and South China. Diagnosis should make as soon as possible. Many advanced tumors were incurable. About 20 per cent of patients with carcinoma of the colon or rectum present with metastatic disease. Surgeons are frequently asked to consider resection or other operative procedures in these patients for palliation. But, average survival was 11.2 months for operative patients versus 6.5 months for nonoperative patients (P < 0.05). So we should better discover tumor anemia and differentiate from other benign anemia in the aged anemia as soon as possible for curable section. To pay attention to treat of etiological diseases is very important for aged anemia patients.

Acute intestinal infections, including intestinal amebiasis, remain a pressing public health problem. Amebiasis still represents an important and partially solved problem to health care. In the Astrakhan region, intestinal amebiasis is being continuously recorded. We analyzed the clinical picture of acute intestinal amebiasis in 150 adult patients dominated by female patients comprising 60.7%, aged 18 to 79 years old, and treated within 2010–2016 at the Regional Infectious Clinical Hospital. All patients were mostly of young and middle age (up to 50 years) — 108 patients. More than 50% of patients were admitted to the hospital within the first three days of the disease. However, in 35 cases (23.3%), late hospitalization was carried out (5 days after the onset). Proper diagnosis was made to 44 patients (29.3%), most commonly diagnosing preliminarily with acute gastroenteritis and acute dysentery. All cases of intestinal amebiasis were confirmed by detecting in the feces of patients with a vegetative form of entamoeba histolytica. The disease was featured with sporadic course, being mostly recorded during the summer-autumn period (78.0%). In 142 patients (94.7%), the moderate severity was observed. Cardiovascular disorders were mainly found in severe amebiasis as well as patients comorbid with cardiovascular diseases. A coprological method was used to confirm the diagnosis. Microscopic examination of feces was carried out immediately after defecation (warm type). A combination therapy was applied to patients with intestinal amebiasis. A great attention was paid to patient nutrition: high-protein sparing diet, grated food. Patients with ulcerative colitis received individualized diet (restricted carbohydrates, exclusion of milk and fiber). Etiotropic therapy was carried out with using 5-nitroimidazole preparations: metronidazole (Trichopol, Flagin, Tiberal), MacGioror, Tinidazole (Phasycin) combined with tetracycline. The treatment included group B vitamin cocktail, methyluracil (suppository), enzymes (creon, mezim, pancreatin), enterosorbents (smecta, polyphepan, enterosgel), antispasmodics (no-spa, drotaverin). Patients were administered with therapeutic microenemas containing furacilin solution, rosehip oil, and sea buckthorn oil. Infusion therapy consisting of polyionic solutions was applied by assessing blood electrolyte level. Fresh frozen plasma and albumin were transfused upon decline of serum protein and albumin level. Packed erythrocytes Erythrocyte mass and hemostatic drugs were injected in case of severe intestinal amebiasis if indicated: dicynone, cryoprecipitate, and calcium preparations. Finally, anemia cases were treated as well. In all cases, the disease outcome was favorable, without any mortality. Complications were noted in the form of intestinal bleeding observed in 6 patients (4.0%), wherein amebiasis proceeded together with ulcerative colitis. Acute intestinal amebiasis is currently featured with typical clinical picture that proceeds with less severe symptoms. Intestinal bleeding was observed in patients with intestinal amoebiasis in combination with ulcerative colitis. Chronization of intestinal amebiasis occurs in single cases (3.9%).

Abstract Background: DNA hypomethylating agent, decitabine, has become the current standard therapy for patients with higher-risk myelodysplastic syndromes (MDS). Decitabine was launched in China in August 2009 without clinical trials. According to some retrospective studies, the efficacy and safety are similar to those reported in other countries, but there is still a lack of large-scale prospective clinical trials. So we start a prospective clinical trial in China to compare the effect and safety of decitabine in MDS, which was registered at clinicaltrials.gov (NCT02013102). Design: Adults with intermediate or high risk MDS by the International Prognostic Scoring System (IPSS≥0.5) were randomized to receive either decitabine 20 mg/m2 IV daily for 5 days (arm Ⅰ) or decitabine 12 mg/m2 IV daily for 8 days (arm Ⅱ) every four weeks. Patients continued to receive study drug for 4 cycles until death, disease progression, intercurrent illness preventing further administration of treatment, unacceptable adverse event or decision by the patient to withdraw from the study. And supportive care were permitted. The primary end point was overall response rate (ORR, CR+mCR+PR) by International Working Group (IWG 2006) criteria, secondary end points included CR, mCR, PR, HI, safety, et al. Results: We enrolled a total of 198 patients between 8/2013 and 12/2017, among which 7 patients didn't take decitabine, and 191 were included in the analysis. 94 in arm Ⅰ recieved decitabine and 97 in arm Ⅱ. 32.8% of patients withdrew from the study for a variety of reasons, including progression and death (5.1%), personal decision (13.6%), adverse events (6.6%), and other causes (7.6%). The median age of patients in arm Ⅰ was 54.88 years old and 54.82 years old in arm II. The median follow-up was 106 days for patients in both arms. The patients received a mean 2.5 cycles of decitabine therapy for arm Ⅰ and 2.0 cycles for arm Ⅱ. The overall response rate was 39.3% in total, and 41.5% and 38.1% (p=0.6598) for patients in arm Ⅰ and arm Ⅱ, respectively. And CR was 18.1% and 14.4% (p= 0.5584) , PR was 6.4% and 3.1% (p=0.3257) , mCR was 17.0% and 20.6% (p=0.5814) , HI was 3.2% and 1.0% (p=0.3633) , for patients in armⅠand armⅡ, respectively (Table 1). Among all patients, 38.7% were intermediate-1 risk, 40.3% were intermediate-2 risk, 20.4% were high risk. Analysis of response by MDS patient subtypes is shown in Table 2. Those who were higher risk experienced higher ORR and CR, while the difference is not significant between two arms (p>0.05). As expected, cytopenias were the most frequent complications (76.4%). Grade 3-4 neutropenia, thrombocytopenia and anemia considered to be at least possibly related to the study drug occurred at rates of 23.0%, 34.6%, and 34.6% of patients, respectively. Nonhematologic adverse events were also common including abnormal metabolism and nutrition (23.40% vs 18.56%), abnormal gastrointestinal function (29.79% vs 41.24%), cardiac disorders (11.70% vs 14.43%), infection and infectious diseases (32.98% vs 36.08%), abnormal skin and subcutaneous tissue and so on, which were no significant differences between two ams. During the study there were 17 SAE, only 7 cases were possibly related to drug therapy, such as pulmonary infection, Sepsis, myelosuppression, intracranial hemorrhage, hepatic failure, and arrhythmia. Conclusions: The use of 5-day and 8-day schedule decitabine is safe and effective in patients with intermediate and high risk MDS, among which there was no significant differences. Disclosures No relevant conflicts of interest to declare.

Abstract Background As a newly proposed diagnosis, data on the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rare. We aimed to assess the prevalence and risk factors of MAFLD using new definition in the contemporary South China population. Methods In this population based, cross sectional study, a total of 5377 participants aged 30–79 years old were recruited from the South China between 2018 and 2019. MAFLD was diagnosed in subjects who have both hepatic steatosis and metabolic disorders according to the newly international expert consensus. The total prevalence of MAFLD and prevalence by sex and age was estimated. Demographic characteristics, history of disease, and lifestyle were recorded by participants on a questionnaire. Abdominal ultrasonography was performed and evaluated by experienced sonographers. Multivariable logistic regression was used to calculate the odds ratios (ORs) of MAFLD. Results Overall prevalence of MAFLD was 29.2% (95% confidence interval [CI] 28.0% to 30.5%). Prevalence was higher in women (31.7%) than in men (25.5%; p < 0.001 for sex difference) and in subjects aged 50 years or older (30.7%) than in those aged 30–49 years (19.8%; p < 0.001 for age difference). In participants diagnosed with MAFLD, the prevalence of overweight/obesity was up to 90.5%, type 2 diabetes (T2DM) and metabolic dysregulation were 25.0% and 62.2%, respectively. Risk factors for MAFLD included overweight/obesity (OR = 4.67; 95% CI, 3.76–5.83), T2DM (OR = 2.41, 95% CI, 1.68–3.47), hypertriglyceridemia (OR = 2.42, 95% CI, 2.03–2.87), high school education (OR = 1.50, 95% CI, 1.23–1.82), high income (OR = 1.22, 95% CI, 1.05–1.42). A lower risk of MAFLD was associated with high physical activity equivalent (OR = 0.71, 95% CI, 0.60–0.85). A U-shaped association of frequency of soups and ORs of MAFLD was found, the adjusted ORs (95% CI) of lower and higher frequency of soups were 1.58 (1.32–1.89) and 1.36 (1.13–1.63), respectively. Conclusions Our results showed a high prevalence of MAFLD in the general adult population in South China. Obesity has the greatest impact on MAFLD, physical activity and moderate consumption of soups might be the potential protective factors of MAFLD.

Reproductive performance of quail hens (Coturnixcoturnix japonica) at sexual maturity was evaluated following two feeding restriction programs (100%, 90% and 80% of ad libitum) and energy metabolism (EM) of ration: 2900 Kcal/kg and 2800 Kcal/kg) between 2 weeks and 5 weeks of age with five replicates of 10 chicks per replicate. Body weight and feed conversion were measured weekly during feed restriction. After experimental feeding treatment, age at first egg, BW, egg weight, development of reproductive organ on sexual maturity were evaluated of one hen’s quail per treatment. The results of the experiment indicated that the restricted feeding until 80% of ad libitum was consequently (p less than 0.01) delayed sexual maturity and influence the development of the reproductive organ. However, it did not show significant influence on the body weight of the first-laid egg and initial egg production. Restricted feeding at 90% of ad libitum and EM ration 2900 Kcal/kg showed the best results for quail feed management during growthNutrition is a basic human need and a prerequisite to a healthy life. Since it is bonded with food, it is essential to advocate nutrition in terms of food. A proper diet is important from the very early stages (gestation period) of life for proper growth and development. Neuronutrition portrays how food affects the brain and its function. Brain is where the performances begin and end. It monitors and controls all the energy metabolism of the body and it never stops working. Neuronutrition is the nutrition needed to achieve healthy brain and good neurocognitive function. Dietary manipulations are a viable strategy for enhancing cognitive abilities and protecting the brain from damage. No single food is key to good brain health but rather a combination of food. Neurological disorders such as Alzheimer's disease, mental fatigue, and memory problems are prevalent across the world, and this opens the door to provide tailormade products which cater to consumer's desire for better neuronutrition.

Abstract Purpose of review The fastest-growing group of elderly individuals is the “oldest-old,” usually defined as those age 85 years and above. These individuals account for much of the rapid increase in cases of dementing illness throughout the world but remain underrepresented in the body of literature on this topic. The aim of this review is first to outline the unique contributing factors and complications that must be considered by clinicians in evaluating an oldest-old individual with cognitive complaints. Secondly, the evidence for management of these cognitive concerns is reviewed. Recent findings In addition to well-established associations between impaired cognition and physical disability, falls, and frailty, there is now evidence that exercise performed decades earlier confers a cognitive benefit in the oldest-old. Moreover, though aggressive blood pressure control is critical earlier in life for prevention of strokes, renal disease, and other comorbidities, hypertension started after age 80 is in fact associated with a decreased risk of clinical dementia, carrying significant implications for the medical management of oldest-old individuals. The oldest-old are more likely to reside in care facilities, where social isolation might be exacerbated by a consistently lower rate of internet-connected device use. The COVID-19 pandemic has not only highlighted the increased mortality rate among the oldest-old but has also brought the increased social isolation in this group to the forte. Summary Differing from the “younger-old” in a number of respects, the oldest-old is a unique population not just in their vulnerability to cognitive disorders but also in the diagnostic challenges they can pose. The oldest-old are more likely to be afflicted by sensory deficits, physical disability, poor nutrition, frailty, and depression, which must be accounted for in the assessment of cognitive complaints as they may confound or complicate the presentation. Social isolation and institutionalization are also associated with impaired cognition, perhaps as sequelae, precipitants, or both. Ante-mortem diagnostic tools remain particularly limited among the oldest-old, especially given the likelihood of these individuals to have multiple co-occurring types of neuropathology, and the presence of neuropathology in those who remain cognitively intact. In addition to the symptomatic treatments indicated for patients of all ages with dementia, management of cognitive impairment in the oldest-old may be further optimized by use of assistive devices, augmentation of dietary protein, and liberalization of medication regimens for risk factors such as hypertension.

Abstract Objectives Brain aging causes gradual protein accumulation pathology as clearance systems depreciate, leading to synaptic compromise, cognitive decline, and contributing as the primary risk factor of dementia. Removal of old and damaged proteins becomes less efficient with age, Poor nutrition is thought to influence cognitive aging and a growing number of studies point to natural products and a healthy diet as avenues for promoting brain health. The aim of this study was to screen a group of plant extracts for the ability to amplify the brain's autophagy-lysosomal protein clearance pathway and to determine if such amplification reduces synaptic decline in a brain slice model of protein accumulation stress. Methods Using slice cultures of rat hippocampus, a brain region vulnerable to Alzheimer's disease and aging, plant extracts (1–500 μg/ml) were applied daily for 3 days, followed by assessment for changes in synaptic markers and components of theautophagy-lysosomal pathway as compared to vehicle-treated samples. The extract-infused hippocampal slice cultures were also treated with the lysosomal inhibitor chloroquine (CQN) and tested for protection against protein accumulation stress-induced synaptic compromise. Results American ginseng (P. quinquefolius) and bacopa (B. monnieri) extracts markedly enhanced the lysosomal protease cathepsin B (CatB). They both produced a nearly 4-fold increase in the 30-kDa active form of CatB (CatB-30), whereas only brain tissue treated with American ginseng exhibited a correlation between CatB levels and improved measures of the synaptic protein GluR1. Small increases in CatB-30 were produced by extracts from Panax ginseng and wild blueberry (V. myrtillus). Also a primary outcome, American ginseng-treated slices were less prone to synaptic decline due to CQN-mediated protein accumulation stress. Conclusions Plant extracts differentially enrich CatB in hippocampal tissue in a manner that positively influences synaptic integrity. Enhancing the autophagy-lysosomal pathway protected brain synapses in a model of age-related deficiency in protein clearance activity, suggesting a need for additional studies to test for benefits in aged animals with cognitive impairment. Funding Sources USANA Health Sciences (BAB); National Institutes of Health RISE grant.

Dyslipidemias and leukocytosis are associated with cardiovascular disease and immune disorders. Mechanistic studies have shown lipoprotein metabolism to play a significant role in the regulation of atherosclerosis development and leukocyte activation, whereas lipid-lowering treatments have been shown to exert beneficial anti-inflammatory and immunomodulatory effects in clinical trials. However, the relationship between clinical markers of lipid metabolism and immune function has not been extensively evaluated at the population level. Thus, we analyzed data from National Health and Nutrition Examination Surveys 1999-2004 to determine whether blood lipids could be used to predict clinical leukocyte counts, and whether there was a relationship between blood lipids, statin use, and prevalence of antinuclear antibodies (ANA) – the most common form of autoantibodies. After adjusting for age, serum cotinine, BMI, waist circumference, race/ethnicity, statin use, and survey cycle, we observed a strong positive linear trend between serum triglycerides vs. blood lymphocyte and basophil counts (cells/μL) in men and women (> 20 years old; n= 5,647), whereas a positive trend between monocytes vs. triglycerides and lymphocytes vs. total cholesterol and LDL-cholesterol was only detected in women. In multiple regression models, a 10% increase in total cholesterol, LDL-cholesterol, and triglycerides was associated with a predicted 1.6%, 0.6%, and 1.4% increase in blood lymphocyte counts in women, respectively, whereas no relationship was observed in men. In a population subsample (n = 1,526), we further found that women were more likely to be positive for ANA as compared to men (women: 17.4% vs. men: 11.7%); however, we did not observe significant associations between the odds of being ANA positive and serum levels of total cholesterol, LDL-cholesterol, or HDL-cholesterol in either men or women. Interestingly, we found that women who take statins have significantly lower odds of being ANA positive (OR 0.25; 95% CI 0.09-0.76), whereas no significant associations between statin use and ANA prevalence was observed in men. Together, these findings suggest blood lipids and statin usage may be better predictors of clinical markers of immune function in women.

The purpose of this article was to convey information about polycystic ovary syndrome (PCOS), to reveal the information about the diagnosis of this syndrome and methods of treatment under various circumstances and reproductive plans. PCOS is now being diagnosed very often. However, frequently this is performed only on the basis of ultrasound diagnostics of the pelvic organs, which is not entirely correct. The picture of multi-follicular ovaries is just one of the symptoms of this syndrome, which may also indicate the presence of other disorders in the body. This is the main reason why the wrong treatment is prescribed. After all, the wrong diagnosis is the key to the wrong treatment. It is important to understand that even with true PCOS, the most important thing is a woman's reproductive plans. When a woman has reproductive plans, COC therapy is out of the question. The realities of today are such that everyone needs to understand at least a little bit about the anatomy and physiology of their own body. This helps a lot to avoid misdiagnosis and, as a result, incorrect treatment, and also speeds up the search for the true cause of the problem. If misdiagnosed, the underlying problem is ignored, which can serve as a trigger for its aggravation and, as a result, its symptoms. That is why everyone in our time needs to understand everything about it. So, for example, few people understand such things as: what is the menstrual cycle, how it should take place, what is its normal duration, what is the rate of discharge and in what periods of the menstrual cycle, is the pain normal at one time or another, and so on. Very often doctors of the old school prescribe, for example, COCs. Most importantly, this is often unnecessary. Also, in our society, after completing the COC course, the concept of "cancellation effect" was formed, which is not true. Evidence-based medicine believes that eggs have several stages of growth and development, and only one of them is regulated by hormones. The rest of the stages proceed continuously and without stopping, and no exogenous or endogenous hormones can stop this. That is, the eggs always die regardless of whether you take COCs or not - this is an axiom. No method is able to prolong the childbearing age, since the ovarian reserve ends, it stops. The only thing that can save eggs is cryo-freezing. This method can be a solution for those who want to have their own children, but at the moment, for one reason or another, fertilization does not occur. Yes, not all diseases can be cured, but even with those that are incurable, you need to learn to live and adapt, remove their manifestations and, if possible, reduce discomfort. Even in the absence of complete recovery from a particular disease, it is necessary to understand that there are methods of physical therapy, diet and conventional drug therapy that can partially improve the condition. Recently, diet therapy has been actively discussed, namely the presence of a complete, balanced and rational diet for all, without exception. In recent decades, fractional nutrition has shown its effectiveness. A balanced fractional nutrition allows you to provide the body with a sufficient amount of energy, to normalize the intestines, to ensure the normal functioning of the hormonal and nervous systems, etc. What is PCOS and the main health problems in women associated with this syndrome? Can true PCOS be completely cured? The correct and complete diagnosis of PCOS and the main nuances of its "treatment" are offered.

Abstract. The purpose of this article was to convey information about polycystic ovary syndrome (PCOS), to reveal the information about the diagnosis of this syndrome and methods of treatment under various circumstances and reproductive plans. PCOS is now being diagnosed very often. However, frequently this is performed only on the basis of ultrasound diagnostics of the pelvic organs, which is not entirely correct. The picture of multi-follicular ovaries is just one of the symptoms of this syndrome, which may also indicate the presence of other disorders in the body. This is the main reason why the wrong treatment is prescribed. After all, the wrong diagnosis is the key to the wrong treatment. It is important to understand that even with true PCOS, the most important thing is a woman's reproductive plans. When a woman has reproductive plans, COC therapy is out of the question. The realities of today are such that everyone needs to understand at least a little bit about the anatomy and physiology of their own body. This helps a lot to avoid misdiagnosis and, as a result, incorrect treatment, and also speeds up the search for the true cause of the problem. If misdiagnosed, the underlying problem is ignored, which can serve as a trigger for its aggravation and, as a result, its symptoms. That is why everyone in our time needs to understand everything about it. So, for example, few people understand such things as: what is the menstrual cycle, how it should take place, what is its normal duration, what is the rate of discharge and in what periods of the menstrual cycle, is the pain normal at one time or another, and so on. Very often doctors of the old school prescribe, for example, COCs. Most importantly, this is often unnecessary. Also, in our society, after completing the COC course, the concept of "cancellation effect" was formed, which is not true. Evidence-based medicine believes that eggs have several stages of growth and development, and only one of them is regulated by hormones. The rest of the stages proceed continuously and without stopping, and no exogenous or endogenous hormones can stop this. That is, the eggs always die regardless of whether you take COCs or not - this is an axiom. No method is able to prolong the childbearing age, since the ovarian reserve ends, it stops. The only thing that can save eggs is cryo-freezing. This method can be a solution for those who want to have their own children, but at the moment, for one reason or another, fertilization does not occur. Yes, not all diseases can be cured, but even with those that are incurable, you need to learn to live and adapt, remove their manifestations and, if possible, reduce discomfort. Even in the absence of complete recovery from a particular disease, it is necessary to understand that there are methods of physical therapy, diet and conventional drug therapy that can partially improve the condition. Recently, diet therapy has been actively discussed, namely the presence of a complete, balanced and rational diet for all, without exception. In recent decades, fractional nutrition has shown its effectiveness. A balanced fractional nutrition allows you to provide the body with a sufficient amount of energy, to normalize the intestines, to ensure the normal functioning of the hormonal and nervous systems, etc. What is PCOS and the main health problems in women associated with this syndrome? Can true PCOS be completely cured? The correct and complete diagnosis of PCOS and the main nuances of its "treatment" are offered.

Background: The cornea is a component of the animal’s eye that is transparent in appearance because of the arrangement of collagen fibrils and the absence of vascularization and pigmentation. Corneal degeneration can result in a lesion known as corneal arcus, which presents as loss of transparency. It is characterized by a dense white opacity with defined borders. This lesion can be caused by lipid keratopathy, occurring as cholesterol and triglyceride deposits in the corneal stroma. In this case, analysis of the serum lipid profile and evaluation of thyroid and pancreas function are recommended. This study aimed to report on a case of occurrence of corneal arcus in a canine.Case: A 6-year-old dog, of no defined breed, weighing 13.250 kg was attended at the Veterinary Hospital of the Universidade Federal de Alagoas with a 5-day history of constipation. Under ultrasound, fecaloma was observed; however, the finding that drew attention was the presence of an eye alteration presenting as bilateral opacity in the form of a vertical arc in the corneal regions, with whitish crystalline appearance. The lesion did not exhibit roughness or vascularization and had well-defined borders. The animal showed no discomfort or visual acuity changes. The tutor reported that the marks had already been on the animal’s eye when it was adopted four years age, and that it showed a slow progressive growth. Given that there were no clinical signs of metabolic or hormonal diseases that could be a primary cause for the formation of the corneal lesion, lipid or calcium deposition in the corneal stroma was suspected, possibly due to diet or idiopathic cause. Blood samples were collected for a blood count and to determine triglyceride, calcium, and cholesterol levels. Based on the test results (all within the normal range), history, and a physical examination (with no evidence of metabolic and/or endocrine diseases), a diagnosis of corneal arcus was made. Excessive lipids in the diet was suggested as the cause of lesions, given that the dog’s diet had consisted of rice with a beef broth tablet, once a day, which over the years may have contributed to both the formation of the corneal lesions and to the enteric disorder (fecaloma). Dietary correction was indicated for both disorders, consisting of commercial dog food of adequate nutritional value. Keratectomy was not indicated for the corneal lesions, as they did not appear to be compromising the field of vision. Instead, we opted for follow-up to monitor the growth of lesions.Discussion: As no clinical evidence of metabolic or hormonal disease was verified, the primary cause for the formation of the corneal lesions was assumed to be lipid or calcium deposits in the corneal stroma, due to diet or even idiopathic cause. The dog was fed boiled rice and industrialized meat broth tablet, providing inadequate nutrition for the past four years or so, possibly leading to hyperlipidemia and/or hypercalcemia, with consequent deposition in the cornea, causing the arc lesion. Triglyceride, cholesterol, and calcium levels were measured, and were within normal range, probably because the blood collection was performed after the control of the post-enterotomy diet. Therefore, it was not possible to correlate the corneal changes with hyperlipidemia or hypercalcemia. The animal did not present with impaired vision as the lesions were located in the peripheral regions of the cornea, bilaterally. Therefore, it was decided to not to perform keratectomy.

A 22-year-old man presented with a 3-week history of increased thirst, polydipsia, and polyuria. He described consuming large volumes of water and waking up multiple times throughout the night to drink and urinate. He also endorsed symptoms of fatigue and frequent headaches. Prior to this, he had been well. There was no history of diuretic use, lithium use, or renal disease. There was no prior head trauma, cranial irradiation, or intracranial pathology. He denied consumption of nutritional or protein supplements. Clinical exam revealed a well appearing young man with normal heart rate and blood pressure. Visual fields and general neurologic exam were grossly normal.Baselines investigations revealed serum sodium ranging from 141–142 mmol/L (reference range 133–145 mmol/L), creatinine 92 umol/L (50–120 umol/L), random glucose 5.4 mmol/L (3.3–11.0 mmol/L), potassium 4.0 (3.3–5.1 mmol/L) and ionized calcium 1.25 mmol/L (1.15–1.35 mmol/L). A 24-hour urine collection was arranged, and returned a urine volume of 5.6L (normal less than 3 litres/24 hours). Further investigations revealed a serum sodium of 142 mmol/L, serum osmolality 306 mmol/kg (280–300 mmol/kg), and urine osmolality of 102 mmol/kg (50–1200 mmol/kg). AM cortisol was 372 nmol/L (200–690 nmol/L).These results demonstrated inability to concentrate the urine, despite the physiologic stimulus of hyperosmolarity. Based on this, a presumptive diagnosis of diabetes insipidus was made. The patient was instructed to drink as much as he needed to satiate his thirst, and to avoid fluid restriction. The patient was started on DDAVP intranasal spray, which provided immediate relief from his symptoms. Magnetic resonance imaging of the brain revealed an unremarkable pituitary gland with abnormal thickening of the pituitary stalk and loss of the posterior pituitary bright spot. This confirmed the diagnosis of central diabetes insipidus, presumed secondary to infiltrative disease affecting the pituitary stalk.IntroductionPolyuria is defined as inappropriately high urine output relative to effective arterial blood volume and serum sodium. In adults, polyuria can be objectively quantified as urine output in excess of 3–3.5 L per day with a low urine osmolality (<300 mmol/kg).2Daily urine output is dependent on 2 major factors. The first is the amount of daily solute excretion, and the second is the urine concentrating capability of the nephron.3 Disturbances in either of these factors can occur by many different mechanisms, and can lead to a diuresis. This diuresis can be driven either by solute (solute diuresis), water (water diuresis) or a combination of these processes.4 A diagnostic algorithm for polyuria is outlined in Figure 1.Figure 1. Diagnostic Approach to Polyuria Solute DiuresisDaily solute intake varies between individuals, but typically averages about 10 mmol/kg or 500–800 mmol/day.2,3 Solute diuresis is the result of a higher solute load that exceeds the usual solute excretion. 4 Higher solute loads can be a consequence of either increased solute intake or increased solute generation through metabolism. High solute intake can occur from intravenous fluids, enteral or parental nutrition, and any other sources of exogenous protein, glucose, bicarbonate, or sugar alcohols.2,4 Metabolic processes leading to increased solute generation include hyperglycemia and azotemia. 2,4 Increased solute excretion drives urine output in a linear fashion.3 Furthermore, solute diuresis impairs the ability of the kidney to concentrate urine. Typically, in a pure solute diuresis, urine concentration is between 300 and 500 mmol/kg.2,4 The specific cause of solute diuresis can be further delineated with estimation of the urine electrolyte solute over 24 hours: 2(urine [Na]+urine [K]) ×24 hours.4 Values greater than 600 mmol/day suggest electrolytes are the solutes driving the diuresis, while values less than 600 mmol/day imply that the diuresis is due to a non-electrolyte solute, typically glucose or urea.Water DiuresisWater diuresis can occur due to excessive amounts of free water consumption (primary polydipsia) or impaired secretion or response to ADH (diabetes insipidus). In both cases, urine osmolality should be less than 100 mmol/kg.2 Primary polydipsia is characterized by excessive water consumption. This can be a result of compulsive water drinking (often observed in psychiatric disorders) or a defect in the thirst centre of the hypothalamus due to an infiltrative disease process.5,6The osmotic threshold for ADH release occurs at 280–290 mmol/kg. Failure to maximally concentrate the urine (1000–1200 mmol/kg in healthy kidneys) when serum osmolality rises above the osmotic threshold suggest diabetes insipidus.3 Diabetes insipidus (DI) can result from either insufficient ADH secretion from the posterior pituitary (central DI) or ADH resistance (nephrogenic DI).1Central DI can be caused by both congenital and acquired conditions known to affect the hypothalamic-neurohypophyseal system7,8 (Table 1). Polyuria occurs when 80% or more of the ADH secreting neurons are damaged 7. Metastatic disease has a predilection for the posterior pituitary, as its blood supply is derived from the systemic circulation, in contrast to the anterior pituitary which is supplied by the hypophyseal portal system.9 Rapid onset of polydipsia and polyuria in a patient older than 50 years of age should therefore raise immediate suspicion for metastatic disease.9 Treatment of adrenal insufficiency may “unmask” or exacerbate central DI, as normalization of blood pressure following glucocorticoid replacement inhibits ADH release.10 In the pregnant state, ADH degradation is increased due to placental production of vasopressinase. Any mechanism of hepatic dysfunction that occurs in pregnancy (pre-eclampsia, HELLP, acute fatty liver) will augment this normal physiology by reducing vasopressinase clearance, and can subsequently lead to transient DI 11In nephrogenic DI, ADH is present but the kidneys are unable to respond appropriately.8 In normal physiology, ADH acts to concentrate the urine via activation of the vasopressin V2 receptor, which leads to insertion of aquaporin-2 water channels in the collecting duct. 3,12 Nephrogenic DI can be primary (genetic) or secondary (acquired). Primary nephrogenic DI occurs as a result of genetic mutations affecting either the vasopressin 2 receptor or aquaporin-2 water channels; typically, such conditions present in infancy.12 Secondary nephrogenic DI can occur by a variety of mechanisms; the most common is chronic lithium administration. Lithium enters the principal cell in the collecting duct via epithelial sodium channels, and is thought to impair urinary concentrating ability via reduction in the number of principal cells and interference in signalling pathways involved in aquaporin. 12,13 Hypercalcemia, hypokalemia, obstructive uropathy, and pregnancy can lead to transient nephrogenic DI. 12,13 Hypercalcemia can lead to nephrogenic DI by causing a renal concentrating defect when calcium levels are persistently above 2.75 mmol/ L.14 Increased hydrostatic pressure from obstructive uropathy may lead to suppression of aquaporin-2 expression, resulting in transient nephrogenic DI.12 Nephrogenic DI can be caused by various renal diseases due to impairment of renal concentrating mechanisms, even before glomerular filtration rate is impaired. Polycystic kidney disease causes anatomic disruption of the medullary architecture. Polyuria in sickle cell disease results from a similar mechanism, as sickling in the vasa recta interferes with the countercurrent exchange mechanisms 16. Infiltrative renal disease including amyloid and Sjogren’s syndrome impair renal tubular function due to amyloid deposition and lymphocytic infiltration.17,18Mixed Water-Solute DiuresisIn some cases, polyuria can be caused by a combination of both mechanisms. The linear relationship between solute excretion and urine output described above is strongly influenced by ADH. In the setting of a solute diuresis, absence or deficiency of ADH can augment the degree of polyuria quite dramatically.14,19 Clinical examples of mixed diuresis include concurrent loading of both water and solute, chronic renal failure or infiltrative renal disease, relief of prolonged urinary obstruction, and partial DI.2,4 Typically in such scenarios, urine osmolality ranges from 100–300 mmol/kg.2 Conclusion Polyuria has a broad range of causes and can be a diagnostic challenge for clinicians. Understanding the pathophysiology that underpins the different mechanisms of polyuria is essential to appropriate workup, diagnosis, and treatment of this condition. If this is a complaint, the first step is to quantitate the 24-hour urine volume. We recommend referral to endocrinology when there is evidence of hypothalamic or pituitary disease, when a water deprivation test is required, or in cases where the diagnosis is unclear. DisclosureFunding sources: None.Conflicts of interest: None. 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