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Hislop, Malcolm, Shane Kelleher, and Susanna Wade Martins. "'Vernacular' or 'Polite'? George Tollet's Farm Buildings at Old Hall Farm, Betley, Newcastle Under Lyme, Staffordshire." Vernacular Architecture 39, no. 1 (December 2008): 50–62. http://dx.doi.org/10.1179/174962908x365037.
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Davies, Glenys, A. Scholl, D. Boschung, H. von Hesberg, and A. Linfert. "Corpus Signorum Imperii Romani. Corpus of Sculpture of the Roman World. Great Britain. Vol. 3. Fasc. 7. Die antiken Skulpturen in Farnborough Hall sowie in Althorp House, Blenheim Palace, Lyme Park und Penrice Castle." Britannia 30 (1999): 416. http://dx.doi.org/10.2307/526711.
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Hündersen, Finja, Stefanie Forst, and Erich Kasten. "Neuropsychiatric and Psychological Symptoms in Patients with Lyme Disease: A Study of 252 Patients." Healthcare 9, no. 6 (June 14, 2021): 733. http://dx.doi.org/10.3390/healthcare9060733.
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This study examined the relationship between neuropsychiatric and psychological symptoms in patients with Lyme borreliosis. We collected data from an experimental group of 252 Lyme disease patients and a control group of 267 healthy individuals. The quality of life and sleep, attention and memory performance were assessed in both groups. Additionally, we investigated depressive symptoms in patients with Lyme disease to examine whether the duration of the disease had an influence on the severity of symptoms shown. Furthermore, various data on the diagnostics and treatment carried out in the patient group were recorded. On average, patients visited almost eight physicians to obtain a diagnosis, and eight years passed between the tick bite and diagnosis (SD ± 7.8); less than half of the sample (46%) received their diagnosis within the first five years after the development of symptoms. It became clear that Lyme disease is often diagnosed very late. It appears that people suffering from Lyme disease have significantly lower quality of life and sleep and show cognitive impairments when it comes to attention and memory. This study shows that 3.1% of Lyme patients were satisfied with their lives and that 37% scored in the lower third of the quality-of-life scale. It was also shown that Lyme patients tend to have depressive symptoms.
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McCarthy, Meghan L., Rebecca Reece, Sara E. Vargas, Jennie Johnson, Jennifer Adelson-Mitty, and Timothy P. Flanigan. "613. Lessons learned from a Rhode Island academic out-patient Lyme and tick-borne disease clinic." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S367. http://dx.doi.org/10.1093/ofid/ofaa439.807.
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Abstract Background Although the prevalence of tick-borne diseases (TBD) continues to increase, there remains significant confusion regarding treatment for Lyme and other TBDs. We conducted a chart review of all new patients that came to an academic center for Lyme and TBDs. We then initiated a quality improvement project for feedback from a small subset of patients with Post-treatment Lyme disease syndrome (PTLDS). Methods Charts of patients visiting the clinic between March and November 2018 were reviewed. Data abstracted from the electronic health record included demographics, laboratory and clinical data. A small subset of patients who reported a history of Lyme and at least 6 months of symptoms after antibiotic treatment were enrolled in a phone survey to evaluate their experience with treatment for PTLDS. Results Symptoms most commonly seen in 218 new patients included fatigue (66.5%), joint pain (58.2%), cognitive difficulty (32.1%), headache (27.9%) and sleep disturbance (27.5%). 87% had already received tick-borne disease directed antibiotic treatment. Over half (60.5%) of patients report having symptoms for more than 6 months. More than half of patients (54.8%) who had more than 6 months of Lyme-related symptoms had positive serological testing. Common themes identified in the 16 phone surveys of patients with PTLDS conducted so far included significant frustration related to the dismissive attitudes from medical professionals (n=9/16), and many sought alternative or complementary therapies (n=11/16). Six patients reported receiving very long-term antibiotic regimens from other Lyme specialists. Many patients expressed satisfaction with the visit and medical advice even in the absence of curative therapy (n=9/16), although a significant number continued to seek care elsewhere (n=6/16). Conclusion More than half of new patients reported symptoms lasting more than 6 months after targeted antibiotic therapy. Further research is needed to develop interventions for the common symptoms of fatigue, joint pain, cognitive difficulty and sleep disturbance. Treatments to improve sleep, diet, and physical activity and decrease inflammation among patients who suffer from PTLDS are needed. Disclosures All Authors: No reported disclosures
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Minoranskaya, N. S., and E. I. Minoranskaya. "Clinical and epidemiologic characteristics of lyme borreliosis and tick-borne encephalitis mixed infections in Krasnoyarsk kray." Kazan medical journal 94, no. 2 (April 15, 2013): 211–15. http://dx.doi.org/10.17816/kmj1591.
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Aim. To reveal clinical features of Lyme borreliosis and tick-borne encephalitis mixed infections in Krasnoyarsk Kray. Methods. The main group consisted of 226 patients with mixed infection of Lyme borreliosis and tick-borne encephalitis (males - 57.1%, females- 42.9%, mean age 43.7±1.0 years), who were examined and compared to the control group of 88 patients with tick-borne encephalitis alone (males - 56.8%, females - 43.2%, mean age 43.9±1.8 years). Results. About 40% of acute Lyme borreliosis cases in Krasnoyarsk Kray are a mixed infection of Lyme borreliosis and tick-borne encephalitis, that is closely related to a large population of Ixodidae infected by both agents. There is no characteristic epidemiologic background in more than a half of all cases. Typical clinical features for mixed infection of Lyme borreliosis and tick-borne encephalitis are severe onset with toxic constant hyperthermia or hyperpyrexia, and joint pain (18.6% of cases). Erythema migrans was present in 22.6% of cases, involvement of central nervous system (35.4%) was mostly often associated with meningitis and meningoencephalitis (29.2%). Bannwarth syndrome (3.1%) is a clinical type of Lyme borreliosis not associated with erythema in mixed infection. Cardiovascular system damage is transient and associated with intoxication. In 57.1% of cases the diagnosis of mixed infection was confirmed at dispensary follow-up 1.5, 3, 6 months after the clinical manifestations of the disease. Conclusion. The most common clinical form of mixed infection is the non-erithemic form of Lyme borreliosis and febrile form of tick-borne encephalitis, late Lyme borreliosis after the suffered mixed infection was registered in 30.1% of cases.
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Marx, Grace E., Amy M. Schwartz, Camay On, and Alison F. Hinckley. "1614. Single-Dose Doxycycline as Lyme Disease Post-Exposure Prophylaxis in a National Commercial Insurance Claims Database―the United States, 2014–2017." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S589. http://dx.doi.org/10.1093/ofid/ofz360.1478.
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Abstract Background Approximately 300,000 cases of Lyme disease occur annually in the UNITED STATES, with children aged 5–9 years disproportionately affected. A single dose of doxycycline administered within 72 hours of a high-risk tick bite is recommended for post-exposure prophylaxis (PEP) to prevent Lyme disease in areas of high incidence. However, it is not known how often or for which patients PEP is used. We aimed to describe recent patterns of single-dose doxycycline medication claims in states with high and low Lyme disease incidence, and the associated patient and prescription characteristics in a large national commercial insurance claims database. Methods Outpatient medication claims in the IBM Watson Health MarketScan Database®, a large nation-wide database of de-identified insurance claims filed between January 1, 2014–December 31, 2017 were reviewed. Claims of single-dose doxycycline were identified and associated patient demographics and medication characteristics were analyzed. Results During 2014–2017, 66,210 medication claims for single-dose doxycycline were filed by 63,112 enrollees; mean annual incidence of receiving at least one single-dose doxycycline prescription was 56 per 100,000 enrollees. Mean patient age was 43 years (IQR 33–56 years); only 8% were for children aged <18 years. About half (46%) were male patients. Most claims (71%) were made by patients residing in the 14 states with high Lyme disease incidence, defined as an average annual incidence of ≥ 10 confirmed Lyme disease cases per 100,000 population. The majority (80%) of medication claims were during the 6 months of peak tick activity (April–July for nymphal ticks and October–November for adult ticks). Conclusion Single-dose doxycycline medication claims are common in states with high Lyme disease incidence and are highest during months of peak tick activity, consistent with the assumption that most single-dose doxycycline is used for Lyme disease PEP. Use of single-dose doxycycline to prevent Lyme disease is infrequent in children, despite being a group at high risk for Lyme disease. Efforts to educate pediatric healthcare providers and parents should be made to increase Lyme disease PEP access for children. Disclosures All authors: No reported disclosures.
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Richter, Dania, and Franz-Rainer Matuschka. "Perpetuation of the Lyme Disease Spirochete Borrelia lusitaniae by Lizards." Applied and Environmental Microbiology 72, no. 7 (July 2006): 4627–32. http://dx.doi.org/10.1128/aem.00285-06.
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ABSTRACT To determine whether the Lyme disease spirochete Borrelia lusitaniae is associated with lizards, we compared the prevalence and genospecies of spirochetes present in rodent- and lizard-associated ticks at a site where this spirochete frequently infects questing ticks. Whereas questing nymphal Ixodes ricinus ticks were infected mainly by Borrelia afzelii, one-half of the infected adult ticks harbored B. lusitaniae at our study site. Lyme disease spirochetes were more prevalent in sand lizards (Lacerta agilis) and common wall lizards (Podarcis muralis) than in small rodents. Although subadult ticks feeding on rodents acquired mainly B. afzelii, subadult ticks feeding on lizards became infected by B. lusitaniae. Genetic analysis confirmed that the spirochetes isolated from ticks feeding on lizards are members of the B. lusitaniae genospecies and resemble type strain PotiB2. At our central European study site, lizards, which were previously considered zooprophylactic for the agent of Lyme disease, appear to perpetuate B. lusitaniae.
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Brinck, Thomas, Klaus Hansen, and Jes Olesen. "Headache Resembling Tension-Type Headache as the Single Manifestation of Lyme Neuroborreliosis." Cephalalgia 13, no. 3 (June 1993): 207–9. http://dx.doi.org/10.1046/j.1468-2982.1993.1303207.x.
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We present two patients with monosymptomatic headache resembling chronic tension-type headache as the first manifestation of Lyme neuroborreliosis. The headache developed over a few days in both cases and lasted for three months in the first case and for two and a half years in the second case before the diagnosis of Lyme neuroborreliosis was made. Neuroimaging and many laboratory investigations did not lead to the diagnosis, which was only established after lumbar puncture. The CSF in both cases showed high protein, lymphocytic pleocytosis and Borrelia burgdorferi-specific intrathecal antibody synthesis. The headache disappeared completely after treatment with penicillin G. In patients suffering from daily headaches which have developed subacutely, Lyme neuroborreliosis should be considered even in the absence of signs of meningeal irritation. A lumbar puncture should be performed more often than is presently customary and the CSF should be examined for pleocytosis as well as Borrelia burgdorferi-specific intrathecal antibody synthesis.
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DRYDEN, M. S., K. SAEED, S. OGBORN, and P. SWALES. "Lyme borreliosis in southern United Kingdom and a case for a new syndrome, chronic arthropod-borne neuropathy." Epidemiology and Infection 143, no. 3 (May 9, 2014): 561–72. http://dx.doi.org/10.1017/s0950268814001071.
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SUMMARYThis series of serologically confirmed Lyme disease is the largest reported in the UK and represents 508 patients who presented to one hospital in the South of England between 1992 and 2012. The mean rate of borreliosis throughout this period was 9·8/100 000 population, much higher than the reported national rate of 1·7/100 000. The actual rate increased each year until 2009 when it levelled off. Patients clinically presented with rash (71%), neurological symptoms (16%, of whom half had VII cranial nerve palsies), arthropathy (8%), pyrexia (5%), cardiac abnormalities (1%) or other manifestations (<1%). Twenty percent of patients had additional non-specific symptoms of fatigue, myalgia, and cognitive changes. Serological diagnosis was with a two-tiered system of ELISA and immunoblot. There was a marked seasonal presentation in the summer months and in the first and sixth decades of life. A third of patients gave a clear history of a tick bite. The median interval between tick bite and clinical symptoms was 15 days [interquartile range (IQR) 9–28 days], with a further interval of 14 days to clinical diagnosis/treatment (IQR 2–31 days). Most cases were acquired locally and only 5% abroad. Patients responded to standard antibiotic therapy and recurrence or persistence was extremely rare. A second group of patients, not included in the clinical case series, were those who believed they had Lyme disease based on a probable tick bite but were seronegative by currently available validated tests and presented with subjective symptoms. This condition is often labelled chronic Lyme disease. These patients have a different disease from Lyme disease and therefore an alternative name, chronic arthropod-borne neuropathy (CAN), and case definition for this condition is proposed. We suggest that this chronic condition needs to be distinguished from Lyme disease, as calling the chronic illness ‘Lyme disease’ causes confusion to patients and physicians. We recommend research initiatives to investigate the aetiology, diagnosis and therapy of CAN.
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Walter, Katharine S., Kim M. Pepin, Colleen T. Webb, Holly D. Gaff, Peter J. Krause, Virginia E. Pitzer, and Maria A. Diuk-Wasser. "Invasion of two tick-borne diseases across New England: harnessing human surveillance data to capture underlying ecological invasion processes." Proceedings of the Royal Society B: Biological Sciences 283, no. 1832 (June 15, 2016): 20160834. http://dx.doi.org/10.1098/rspb.2016.0834.
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Modelling the spatial spread of vector-borne zoonotic pathogens maintained in enzootic transmission cycles remains a major challenge. The best available spatio-temporal data on pathogen spread often take the form of human disease surveillance data. By applying a classic ecological approach—occupancy modelling—to an epidemiological question of disease spread, we used surveillance data to examine the latent ecological invasion of tick-borne pathogens. Over the last half-century, previously undescribed tick-borne pathogens including the agents of Lyme disease and human babesiosis have rapidly spread across the northeast United States. Despite their epidemiological importance, the mechanisms of tick-borne pathogen invasion and drivers underlying the distinct invasion trajectories of the co-vectored pathogens remain unresolved. Our approach allowed us to estimate the unobserved ecological processes underlying pathogen spread while accounting for imperfect detection of human cases. Our model predicts that tick-borne diseases spread in a diffusion-like manner with occasional long-distance dispersal and that babesiosis spread exhibits strong dependence on Lyme disease.
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Parise, Christina M., Nicole E. Breuner, Andrias Hojgaard, Lynn M. Osikowicz, Adam J. Replogle, Rebecca J. Eisen, and Lars Eisen. "Experimental Demonstration of Reservoir Competence of the White-Footed Mouse, Peromyscus leucopus (Rodentia: Cricetidae), for the Lyme Disease Spirochete, Borrelia mayonii (Spirochaetales: Spirochaetaceae)." Journal of Medical Entomology 57, no. 3 (December 10, 2019): 927–32. http://dx.doi.org/10.1093/jme/tjz242.
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Abstract The white-footed mouse, Peromyscus leucopus (Rafinesque), is a reservoir for the Lyme disease spirochete Borrelia burgdorferi sensu stricto in the eastern half of the United States, where the blacklegged tick, Ixodes scapularis Say (Acari: Ixodidae), is the primary vector. In the Midwest, an additional Lyme disease spirochete, Borrelia mayonii, was recorded from naturally infected I. scapularis and P. leucopus. However, an experimental demonstration of reservoir competence was lacking for a natural tick host. We therefore experimentally infected P. leucopus with B. mayonii via I. scapularis nymphal bites and then fed uninfected larvae on the mice to demonstrate spirochete acquisition and passage to resulting nymphs. Of 23 mice fed on by B. mayonii-infected nymphs, 21 (91%) developed active infections. The infection prevalence for nymphs fed as larvae on these infected mice 4 wk post-infection ranged from 56 to 98%, and the overall infection prevalence for 842 nymphs across all 21 P. leucopus was 75% (95% confidence interval, 72–77%). To assess duration of infectivity, 10 of the P. leucopus were reinfested with uninfected larval ticks 12 wk after the mice were infected. The overall infection prevalence for 480 nymphs across all 10 P. leucopus at the 12-wk time point was 26% (95% confidence interval, 23–31%), when compared with 76% (95% confidence interval, 71–79%) for 474 nymphs from the same subset of 10 mice at the 4-wk time point. We conclude that P. leucopus is susceptible to infection with B. mayonii via bite by I. scapularis nymphs and an efficient reservoir for this Lyme disease spirochete.
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Kozlova, T. V., T. I. Khomyakova, V. G. Dedkov, M. V. Safonova, L. S. Karan, Y. E. Grigoryev, V. V. Kozlov, A. A. Lopatin, S. M. Ivanova, and Yu N. Khomyakov. "THE IDENTIFICATION OF «NEW» PATHOGENS FOR FOCAL INFECTIONS IN IXODES TICKS ON THE TERRITORY OF TULA REGION." Epidemiology and Infectious Diseases (Russian Journal) 23, no. 4 (August 15, 2018): 172–77. http://dx.doi.org/10.18821/1560-9529-2018-23-4-172-177.
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The most of ixodes ticks in Tula region belongs to the group of pasture mites. It is generally accepted to estimate the tick’s contamination by the tick-borne encephalitis virus and raoueti inducing Lyme Borellia. The aim of the present work was to educe the aetiologic agents of the set of potentially-enable infections out of ticks Dermacentor reticulatus, Ixodes ricinus and Ixodes сrenulatus collected at the different terrains of Tula Region by PCR method. The results: a considerable number of pathogenic rickettsiae R. raoultii was educes from the ticks D. reticulatus, which including them as the component of mixed infection together with the human monocytic ehrlichiosis agent. R. raoultii was determined in more than a half of the cases in ticks I. ricinus including the mixed infection together with ticks’ borreliosis virus and Kemerovo fever agent. Conclusion. The reasons, induced the quantity changes of the ticks’ distribution at Tula Region terrains, apparently promote the rise in frequency of the ticks contamination with the agents of herd tick-transmissive infection. It demand an infectiologist’s attention rise and dictate the necessity of the above mentioned diseases monitoring as well as Fr. tularensis, the tick-borne encephalitis virus and Lyme disease.
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Kozlova, T. V., T. I. Khomyakova, V. G. Dedkov, M. V. Safonova, L. S. Karan, Y. E. Grigoryev, V. V. Kozlov, A. A. Lopatin, S. M. Ivanova, and Yu N. Khomyakov. "THE IDENTIFICATION OF «NEW» PATHOGENS FOR FOCAL INFECTIONS IN IXODES TICKS ON THE TERRITORY OF TULA REGION." Epidemiology and Infectious Diseases (Russian Journal) 23, no. 4 (August 15, 2018): 172–77. http://dx.doi.org/10.18821/1560-9529-2019-23-4-172-177.
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The most of ixodes ticks in Tula region belongs to the group of pasture mites. It is generally accepted to estimate the tick’s contamination by the tick-borne encephalitis virus and raoueti inducing Lyme Borellia. The aim of the present work was to educe the aetiologic agents of the set of potentially-enable infections out of ticks Dermacentor reticulatus, Ixodes ricinus and Ixodes сrenulatus collected at the different terrains of Tula Region by PCR method. The results: a considerable number of pathogenic rickettsiae R. raoultii was educes from the ticks D. reticulatus, which including them as the component of mixed infection together with the human monocytic ehrlichiosis agent. R. raoultii was determined in more than a half of the cases in ticks I. ricinus including the mixed infection together with ticks’ borreliosis virus and Kemerovo fever agent. Conclusion. The reasons, induced the quantity changes of the ticks’ distribution at Tula Region terrains, apparently promote the rise in frequency of the ticks contamination with the agents of herd tick-transmissive infection. It demand an infectiologist’s attention rise and dictate the necessity of the above mentioned diseases monitoring as well as Fr. tularensis, the tick-borne encephalitis virus and Lyme disease.
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Moss, Robert A. "Willie Keeler: From the Playgrounds of Brooklyn to the Hall of Fame by Lyle Spatz." NINE: A Journal of Baseball History and Culture 24, no. 1-2 (2015): 192–94. http://dx.doi.org/10.1353/nin.2015.0043.
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HANINCOVÁ, K., S. M. SCHÄFER, S. ETTI, H. S. SEWELL, V. TARAGELOVÁ, D. ZIAK, M. LABUDA, and K. KURTENBACH. "Association of Borrelia afzelii with rodents in Europe." Parasitology 126, no. 1 (January 2003): 11–20. http://dx.doi.org/10.1017/s0031182002002548.
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Borrelia burgdorferi sensu lato (s.l.) is maintained in nature by complex zoonotic transmission cycles, involving a large variety of vertebrates as hosts and hard ticks of the genus Ixodes as vectors. Recent studies suggest that the genospecies of B. burgdorferi s.l. and sometimes their subtypes are propagated by different spectra of hosts, mainly birds and rodents. In order to test the concept of host-association, we analysed the relationships between Borrelia genospecies, rodent hosts and I. ricinus ticks in an endemic focus of Lyme borreliosis in western Slovakia. Rodents and questing ticks were collected at a forested lowland locality near Bratislava. Tick infestation levels on rodents were determined, and spirochaete infections in ticks and in ear punch biopsies were analysed by PCR followed by genotyping. Mice were more heavily infested with ticks than bank voles, and a higher proportion of mice was infected with spirochaetes than voles. However, the infectivity of voles was much higher than that of mice. The vast majority of infections detected in the skin and in ticks feeding on the rodents represented B. afzelii. In contrast, more than half of all infections in questing ticks collected in the same region of Slovakia were identified as B. valaisiana and B. garinii. In conclusion, whilst the study reveals that mice and voles play different quantitative roles in the ecology of Lyme borreliosis, it demonstrates that B. afzelii is specifically maintained by European rodents, validating the concept of host-association of B. burgdorferi s.l.
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Costa, Rayssa Ribeiro da, Talita de Oliveira Ferreira, and Maria Auxiliadora Coêlho de Lima. "Training systems, rootstocks and climatic conditions influence quality and antioxidant activity of ‘BRS Cora’ grape." Acta Scientiarum. Agronomy 43 (November 5, 2020): e49054. http://dx.doi.org/10.4025/actasciagron.v43i1.49054.
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Environmental and production factors might affect grapevine physiology. Estimating these effects is essential for planning the harvest and predicting the quality of grapes. The aim of this study was to characterize the quality and antioxidant potential of ‘BRS Cora’ grapes with different training systems and rootstocks in production cycles of the second half of the year under tropical conditions. The experimental design was randomized blocks with sub-subdivided plots over time. Three training systems and two rootstocks were studied in production cycles referring to the second halves of 2017 and 2018. In 2017, the grapes of plants trained with lyre and vertical shoot positioning (VSP) had the highest soluble solids and sugars contents, and in 2018, this response occurred with the overhead trellis system. There was lower variation in titratable acidity between cycles of grapevines trained with VSP and lyre, as well as in those grafted onto ‘IAC 572’. In 2018, lyre with ‘IAC 572’ promoted higher pigment accumulation. Climatic conditions in 2017 provided a higher accumulation of polyphenols and antioxidant activity in grapes of plants trained with lyre with ‘IAC 766’. The efficiency of the training system within each cycle, associated with the effect of the rootstock, resulted in differentiated responses according to climatic conditions.
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Pantelias, Anastasia, John M. Pagel, Nathan Hedin, Yukang Lin, Donald Axworthy, Louis J. Theodore, and Oliver W. Press. "Comparison of Biodistributions and Therapeutic Efficacies of Pretargeted Radioimmunoconjugates Targeting the CD20, CD22, and DR Molecules on Human B Cell Lymphomas." Blood 106, no. 11 (November 16, 2005): 611. http://dx.doi.org/10.1182/blood.v106.11.611.611.
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Abstract Radioimmunotherapy (RIT) using anti-CD20 monoclonal antibodies (Ab) produces response rates of 60–95% in relapsed non-Hodgkin’s lymphoma (NHL) patients; however, tumor-to-normal organ ratios of absorbed radiation are low and many patients relapse. The efficacy of RIT is limited by non-specific delivery of radiation to normal tissues due to the long circulating half-life of radiolabeled antibodies. Pretargeted RIT (PRIT) using streptavidin (SA)-Ab conjugates followed by a clearing agent and radiolabeled biotin can augment the efficacy of RIT and decrease toxicity compared with conventional RIT. Although PRIT using anti-CD20-SA Abs have been studied with promising results, targeting multiple antigens may increase efficacy. Since successful clinical trials have been conducted with directly radiolabeled anti-DR and anti-CD22 Abs, we initiated in vitro and in vivo studies comparing pretargeted anti-CD20 Ab-SA conjugate (1F5/SA) with pretargeted anti-CD22-SA (HD39/SA) and anti-HLA-DR-SA (Lym-1/SA) conjugates in three different human B-lymphoma cell lines, RAMOS (Burkitt), RAJI (Burkitt) and FL-18 (transformed follicular). Using standard flow cytometry techniques all three Ab-SA conjugates bound to ≥ 97% of FL18 cells. Cell binding for 1F5/SA, Lym-1/SA, and HD39/SA was 99%, 99%, and 83% to RAJI cells, respectively, and 99%, 22%, and 85% to RAMOS cells. The blood half-life of each conjugate in vivo was measured by injecting groups of 4 mice i.v. with 0.7nmol (150μg) of 125I labeled Ab-SA conjugate and drawing 10μl of blood at various time points to determine the percent injected dose per gram (% ID/g). The half-lives of 1F5/SA, Lym-1/SA and HD39/SA were 18.38, 14.92 and 16.23 hours, respectively. When 5.8nmol (50μg) of a clearing agent (synthetic biotin-N-acetyl-galactosamine) was given 24 hours post 125I-Ab-SA injection, the % ID/g in blood fell by more than 80% of the initial dose within a half-hour. Blood, tumor and non-specific organ uptake was determined by biodistribution experiments in mice (Balb/c nu/nu) bearing human lymphoma xenografts. Athymic mice with s.c. RAMOS, RAJI, or FL-18 xenografts received 1.4nmol (300μg) of either 1F5/SA, HD39/SA, or Lym-1/SA i.v. followed 24 hours later by 5.8nmol (50μg) clearing agent to remove non-localized conjugate from circulation, and 3 hours later by an 111In labeled DOTA-biotin ligand (1μg). The biodistributions of each conjugate were evaluated by sacrificing mice at 24 and 48 hours after 111In-DOTA-biotin. At 24 hours, the ID/g was 18.2±13.6% in FL18 xenografts for pretargeted Lym-1/SA, 18.2±17.4% ID/g for 1F5/SA and 3.3±0.7% ID/g for HD39/SA. Conversely, at 24 hours pretargeted Lym-1/SA uptake in RAJI tumors was 10.8±2.1% ID/g, and 1F5/SA and HD39/SA RAJI tumor localization was 5.2±1.9% ID/g and 2.2±0.5% ID/g. respectively. 1F5/SA had superior uptake (7.1±3.3% ID/g) in RAMOS xenografts compared with Lym-1/SA (3.5±1.5% ID/g) and HD39/SA (2.7±1.0% ID/g). These data suggest a strong correlation between in vitro cell binding results and in vivo biodistributions for all three Ab-SA conjugates in all three human lymphoma cell lines. Using these agents in combination may result in a synergistic effect that has the potential to increase the efficacy of PRIT over using any one of the agents alone. Biodistribution and therapy studies using the Ab-SA conjugates in combination in tumored mice are on-going.
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Dattwyler, Raymond J., and Benjamin J. Luft. "Overview of the Clinical Manifestations ofBorrelia burgdorferiInfection." Canadian Journal of Infectious Diseases 2, no. 2 (1991): 61–63. http://dx.doi.org/10.1155/1991/902928.
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Lyme disease, caused by the spirocheteBorrelia burgdorferi,has classically been divided into three stages: erythema migrans; neurological or cardiac involvement; and arthritis. Rather than defining a set disease pattern, however, one should, more logically, conceptualize a progressive infection that may be localized or disseminated, acute or chronic. Erythema migrans, the earliest and most easily recognized manifestation ofB burgdorferiinfection, is an expanding annular erythematous skin lesion with a central clearing that develops soon after the bite of an infected ixodes tick. Musculoskeletal manifestations are common, with approximately one-half of untreated individuals developing arthritis. Of these, only 10% have chronic arthritis. Invasion of the central nervous system occurs as the infection disseminates hematogenously, with encephalitis, myelitis and meningopolyneuritis being the most severe results. Acute cardiac involvement is recognized in up to 8% of adult patients, and less often in children. Early antibiotic treatment of the infection is highly effective.
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G.Hahn, Robert. "Clinical pharmacology of infusion fluids." Acta medica Lituanica 19, no. 3 (October 1, 2012): 210–12. http://dx.doi.org/10.6001/actamedica.v19i3.2451.
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Fluids are used for intravenous infusion during practically all surgeries, but several different compositions are available on the market. Crystalloid fluids comprise lactated or acetated Ringer solutions, normal saline, Plasma-Lyte, hypertonic saline, and glucose. They lack allergic properties but are prone to cause peripheral tissue oedema. Their turn over is governed by physiological factors such as dehydration and drug effects. Colloid fluids include hydroxyethyl starch, albumin, dextran, and gelatin. These fluids have various degrees of allergic properties and do not promote peripheral oedema. Their half-life is usually about hours. Factors increasing the turnover rate are poorly known but might include inflammatory states. Current debates include the widespread use of normal saline, which should be replaced by Ringer’s or Plasma-Lyte in most situations, and the kidney damage associated with the use of starch in septic patients. New studies show that hypertonic saline does not improve survival or neurological damage in prehospital care.
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Hu, C. M., S. Leuba-Garcia, M. D. Kramer, A. Aeschlimann, and L. Gern. "Comparison in the immunological properties ofBorrelia burgdorferiisolates fromIxodes ricinusderived from three endemic areas in Switzerland." Epidemiology and Infection 112, no. 3 (June 1994): 533–42. http://dx.doi.org/10.1017/s0950268800051232.
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SUMMARYBorrelia burgdorferiisolates were obtained fromIxodes ricinusfrom three sites in Switzerland. They were examined by SDS-PAGE and immunoblotting. The phenotypes, in respect of three outer surface proteins (Osp), differed between the sites of collection. In site 1, most isolates had an OspA of 31 kDa and an OspB of 34 kDa: in site 2, isolates presenting an OspA of 33 kDa dominated and in site 3, the isolates with an OspA of 32 kDa and an OspB of 35 kDa were most frequent. This distribution differed significantly. About half of the isolates from sites 1 and 3 reacted with anti-OspA monoclonal antibody H5332 compared to 29% from site 2. Site 1 isolates reacted significantly more frequently (81 %) with another anti-OspA monoclonal antibody LA-31 than isolates from site 3 (P< 0·0001). These findings have implications for the epidemiology of Lyme borreliosis, for the further development of serodiagnostic reagents and for the development of a vaccine.
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Kirkley, Scott A., Kelly F. Henrichs, Amy P. Schmidt, Majed A. Refaai, Richard P. Phipps, Sherry L. Spinelli, Debra Masel, et al. "Decreased Hemolysis of Red Cells Washed with Plasma-Lyte As Compared with 0.9% Sodium Chloride." Blood 126, no. 23 (December 3, 2015): 3557. http://dx.doi.org/10.1182/blood.v126.23.3557.3557.
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Abstract Introduction -Washed red blood cell (RBC) and platelet transfusions have been a valuable therapeutic option for patients with repeated or severe allergic or febrile reactions. Recent data from randomized and observational clinical trials demonstrate that washed transfusions reduce inflammatory and immunologic complications, including recurrence of acute leukemia, death after coronary surgery, elevations of IL-6 and C-reactive protein after pediatric cardiac surgery, and transfusion related acute lung injury and transfusion associated cardiac overload. However, washing of RBCs may not be completely benign. Increased hemolysis may occur in vitro. Washing of RBCs stored for longer periods (>28 days) is associated with increased morbidity in pediatric cardiac surgery patients receiving massive transfusions of older RBCs. Current washing techniques and dilution of RBCs for transfusion employ 0.9% normal saline (NS) which is both hypertonic and acidic. We evaluated whether use of a more physiologic solution, Plasma-Lyte, causes less damage to RBCs than use of NS. Methods -We employed RBC units (n=15) collected for, but not suitable for clinical transfusion. Median storage age was 19 days (range 10-39 days). Each donor unit (11 AS-1, 3 AS-3 and 1 CPD-A1) was split in two using aseptic technique, and washed with either a liter of NS or Plasma-Lyte employing a standard clinical protocol on a Terumo 2991. Each half was resuspended in 20 ml of washing solution. Aliquots (12 ml) were removed prior to and immediately after washing, and after 24, 48 and 72 hours of storage at 1-6¡ C. These aliquots were immediately centrifuged (15 min at 4,300 x g) and the supernatant stored at -80¡ C. Hemoglobin and heme in the supernatant were quantitated using QuantiChrom kits. All comparisons were by Wilcoxon matched pairs non-parametric tests. Results -Supernatants immediately after washing had similar mean free hemoglobin (pre = 160 mg/dl ± 80 [SEM]; post = 66 ± 12 for NS and 58 ± 10 for Plasma-Lyte) and heme (pre = 92 µM ± 46; post = 36 ± 8 for NS and 33 ± 7 for Plasma-Lyte ). However, by 24 hours of storage after washing (the current limit for clinical use), supernatant heme and hemoglobin were significantly greater by about 50% in RBCs stored in NS (87 µM ± 22 and 151 mg/dl ± 36) as compared to Plasma-Lyte (59 µM ± 21 and 108 mg/dl ± 36; p = 0.014 and 0.02). These changes accelerated during subsequent storage (see figure for heme levels-differences in hemoglobin were comparable). Prolonged storage after NS washing predisposed to greater hemolysis than did Plasma-Lyte washing. Supernatant heme levels at 72 hours post washing increased from early (10-18 days; n=5) to late (31-39 days; n=5) storage by a mean of 61% in Plasma-Lyte washed RBCs (p=0.26) compared with 200% in NS washed RBCs (p=0.016) Conclusions -RBCs stored for 10-39 days and then washed with Plasma-Lyte experience strikingly less hemolysis. Whether such differences would occur in vivo is not known, and the clinical implications are yet to be determined. Circulating free heme and hemoglobin levels have been associated with thrombosis in animal models, transfused patients and patients with sickle cell disease. NS, as opposed to Plasma-Lyte, has been linked to increased renal injury and mortality in animal models and patients. We speculate that hemolysis may be a contributing cause. Our results indicate that RBC washing with Plasma-Lyte is a superior approach and potentially safer than NS. These findings also suggest the hypothesis for further investigation of whether NS is truly a suitable diluent for RBC transfusion, and whether NS is the safest choice when crystalloid is indicated for volume replacement or apheresis. Plasma-Lyte washing might also facilitate increasing the storage period of washed RBCs. Figure 1. Figure 1. Disclosures Off Label Use: See Dr. Blumberg's disclosure. Blumberg:Biomet: Consultancy; Terumo: Consultancy.
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Nevin, Sonya. "Sappho 44: Creativity and Pedagogy with Ancient Poetry, Pottery, and Modern Animation." Clotho 1, no. 2 (February 8, 2020): 5–15. http://dx.doi.org/10.4312/clotho.1.2.5-15.
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The Panoply Vase Animation Project has created a new animation from the decoration on an ancient Greek hydria. The vase depicts the poet Sappho with a lyre. The animation enables her to move, touch the strings, and play the instrument. It also features the words from Fragment 44 of her poetry and geometric figures acting out the poem. The music accompanying the animation was scored from the original poem and therefore offers the melody that the poem would have been sung to. This article discusses the decision-making process that informed the creation of the animation and suggests ways in which the animation and its vase can be used in the classroom or lecture-hall as a flexible learning resource.
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Yang, Shuying. "Bayesian biostatistics and diagnostic medicine broemeling Lyle D (2007) ISBN 1584887672; 216 pages; £42.99, $83.95 Chapman & Hall/CRC; http://www.crcpress.com/." Pharmaceutical Statistics 10, no. 3 (June 4, 2009): 283. http://dx.doi.org/10.1002/pst.385.
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Zhu, Jian, and Yabin Wu. "COVID-19 Epidemic: Clinical Characteristics of Patients in Pediatric Isolation Ward." Clinical Pediatrics 59, no. 12 (July 9, 2020): 1069–73. http://dx.doi.org/10.1177/0009922820941228.
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In order to accurately admit children with COVID-19 to an isolation ward, our study retrospectively analyzed the clinical characteristics of children in isolation wards during the COVID-19 epidemic. It was found that 55 cases (83.3%) had fever and 48 cases (72.7%) coughed in the isolated area, 31 cases (47%) had a history of exposure, 26 cases (39.4%) had a decrease in lymphocytes (LYM), more than half had an increase in lactate dehydrogenase and creatine kinase isoenzyme, 14 cases (21.2%) had positive SARS-CoV-2 nucleic acid, 58 cases (87.9%) had abnormal chest computed tomography (CT), and 11 cases (16.7%) had sinus arrhythmia. Therefore, for some suspected children with COVID-19, we can make a comprehensive judgment through clinical symptoms, epidemiological history, LYM number, myocardial enzyme spectrum, chest CT, and electrocardiogram; put these children in an isolation ward for treatment; and then transfer them to a general ward for treatment after excluding COVID-19.
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Troyano-Luque, Juan, Ana Padilla-Pérez, Ingrid Martínez-Wallin, Margarita Álvarez de la Rosa, Salvatore Andrea Mastrolia, José Luis Trujillo, and Tirso Pérez-Medina. "Short and Long Term Outcomes Associated with Fetal Cholelithiasis: A Report of Two Cases with Antenatal Diagnosis and Postnatal Follow-Up." Case Reports in Obstetrics and Gynecology 2014 (2014): 1–5. http://dx.doi.org/10.1155/2014/714271.
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The aims of this study were to present and discuss ultrasound findings of prenatal fetal cholelithiasis in two cases with different etiology and evolution. Case 1: a pregnant woman from sub-Saharan Africa, suffering from Lyme disease, was treated with ceftriaxone sodium. Six weeks later, biliary sludge associated with polyhydramnios was detected in the fetus and the fetal growth percentile was 14. Emergency caesarean was performed at 36 weeks of gestation due to fetal distress. Biliary sludge persists in the two-and-a-half-year-old child. Case 2: the fetus of a Caucasian woman with normal pregnancy showed multiple cholelithiasis associated with polyhydramnios at 31 weeks of gestation. At 39 weeks and 4 days, cesarean section was performed due to lack of dilation. The biliary disease resolved spontaneously at seven months of age, with no associated abnormalities. In conclusion, prenatal diagnosis of cholelithiasis is straightforward, but prognosis cannot be defined yet. Serious complications do not arise in 70% of cases, but severe diseases may ensue in 20%. Persistence of cholelithiasis after one year of age results in cholelithiasis in childhood and beyond. Biliary sludge is associated with worse prognosis than cholelithiasis when it appears before 28 weeks of gestation.
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Congdon, Peter. "BAYESIAN METHODS FOR REPEATED MEASURES. Lyle D. Broemeling. Boca Raton: Chapman & Hall/CRC Press, 568 pages, ISBN 978-1-4822-4819-7." Biometrical Journal 60, no. 1 (November 20, 2017): 222. http://dx.doi.org/10.1002/bimj.201700198.
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Christova, I. "Enzyme-Linked Immunosorbent Assay, Immunofluorescent Assay X and Recombinant Immunoblotting in the Serodiagnosis of Early Lyme Borreliosis." International Journal of Immunopathology and Pharmacology 16, no. 3 (September 2003): 261–68. http://dx.doi.org/10.1177/039463200301600312.
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Serum samples from Bulgarian patients with physician-diagnosed erythema migrans (EM) (n=105) were examined using Borrelia burgdorferi ELISA (Boehring, Germany) after previous absorption with Treponema phagedenis. For IgM antibody detection sera were additionally pretreated with anti-IgG serum (RF absorbent). Serum samples of 93 % of persons from healthy control group were IgM negative and all were IgG negative. Out of 105 patients with EM, 49 % were IgM positive and 14 % were borderline. IgG ELISA showed positive results for 17 % and borderline for 6 % of the patients. Positive and borderline serum samples were examined further by immunofluorescent assay (IFA) and immunoblot test with recombinant B. burgdorferi proteins from strain PKo ( B. afzelii) - p100, flagellin, OspA and OspC, and internal flagellin fragments from strains PKo and PBi ( β. garinii) [B. Wilske, V. Fingerle, P. Herzer et al. 1993. Med. Microbiol. Immunol. 182:255]. IFA detected IgM antibodies against B. burgdorferi in 47 % of the positive and in none of the borderline by IgM ELISA serum samples as well as IgG antibodies in 83 % of the positive and in 50% of the borderline by IgG ELISA samples. Presence of specific antibodies was confirmed by immunoblot in 71 % of the IgM ELISA postive and in 67 % of the IgG ELISA positive sera. In addition, anti-β. burgdorferi antibodies were detected in 60 % of the borderline by IgM ELISA serum samples. IgM serum reactivity was directed mainly against OspC antigen and flagellin and IgG antibodies were directed mainly against flagellin and p100. These findings clearly showed advantages of the ELISA test based on previous pretreatment of sera and capable to detect specific antibodies in more than half of patients with early Lyme borreliosis despite the well-known delayed immune response. IFA was less sensitive than ELISA in detection of anti- B. burgdorferi antibodies. An additional examination of ELISA borderline sera by immunoblot revealed more positive results. Serum reactivity to a single OspC antigen seems to be a sufficient criterion for positive IgM immunoblot.
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Ciubuc, Constantin. "Changes in the Trichoptera (Insecta) Communities from Corbii Ciungi Complex of Streams and Springs (Romanian Plain) in the Past Half Century." Travaux du Muséum National d’Histoire Naturelle “Grigore Antipa” 59, no. 1 (June 1, 2016): 31–48. http://dx.doi.org/10.1515/travmu-2016-0011.
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Abstract The paper presents a comparative analysis of the present day caddisfly communities structure with that of their previous structure, recorded about 45 years ago in several ecosystems of plain springs in the Romanian Plain, such as Valea Izvorului (Corbi Ciungi), in Motaş et al. (1962). Several structural parameters such as species richness, species diversity (H’), frequency of occurrence and sex ratio of some populations of adult Trichoptera were considered. 41 taxa belonging to nine families of Trichoptera were presently identified in comparison with only 14 taxa (adults and larvae) recorded in Motaş (op. cit.). Out of the 41 taxa, two are recorded for the first time in the Romanian fauna (Hydropsyche contubernalis ssp. iranica and Limnephilus tauricus). Seven out of the 14 taxa recorded by Motaş (op. cit.) disappeared completely from the studied spring ecosystems (Lype reducta, Halesus digitatus, Lithax obscurus, Notidobia ciliaris, Triaenodes bicolor, Adicella syriaca and A. filicornis). The disappearance of the seven species from the studied ecosystems and the occurrence of many species unrecorded by the previous studies which are not characteristic to mountain waters are a clear indication of the deterioration of the quality of those ecosystems, which led to a new structure of Trichoptera communities.
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Cheng, Lie, Wei-Liang Liu, Hsing-Han Li, Matthew P. Su, Shih-Cheng Wu, Hsin-Wei Chen, Chao-Ying Pan, Jih-Jin Tsai, and Chun-Hong Chen. "Releasing Intracellular NS1 from Mosquito Cells for the Detection of Dengue Virus-Infected Mosquitoes." Viruses 12, no. 10 (September 29, 2020): 1105. http://dx.doi.org/10.3390/v12101105.
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Dengue virus (DENV), the pathogen that causes dengue fever, is mainly transmitted by Aedes aegypti. Surveillance of infected mosquitoes is a major component of integrated mosquito control methods for reducing the risk of vector-born disease outbreaks. However, a specialized rapid test for DENV detection in mosquitoes is not currently available. Utilizing immunoblotting, we found that the secretion of NS1 from both a DENV-infected mosquito cell line and mosquito bodies was below the detection threshold. However, when Triton X-100 was used to lyse infected mosquitoes, intracellular NS1 was released, and could then be effectively detected by the NS1 rapid test. The distribution of DENV NS1 in intrathoracically infected mosquitoes was different from that of orally infected mosquitoes. Next, we performed sensitivity tests by bisecting mosquitoes longitudinally; one half of each mosquito was subjected to the NS1 rapid test while the other half was used for qPCR confirmation. This modified test had a sensitivity of nearly 90% from five days post-infection onwards, while DENV had escaped from the midgut barrier. This adapted test offers a valuable, easy-to-use tool for mosquito surveillance, which is a crucial component of DENV disease control.
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Liang, Fang Ting, Mary B. Jacobs, and Mario T. Philipp. "C-Terminal Invariable Domain of VlsE May Not Serve as Target for Protective Immune Response against Borrelia burgdorferi." Infection and Immunity 69, no. 3 (March 1, 2001): 1337–43. http://dx.doi.org/10.1128/iai.69.3.1337-1343.2001.
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ABSTRACT VlsE, the variable surface antigen of the Lyme disease spirochete,Borrelia burgdorferi, contains two invariable domains, at the amino and carboxyl termini, respectively, which collectively account for approximately one-half of the entire molecule's length and remain unchanged during antigenic variation. It is not known if these two invariable domains are exposed at the surface of either the antigen or the spirochete. If they are exposed at the spirochete's surface, they may elicit a protective immune response against B. burgdorferi and serve as vaccine candidates. In this study, a 51-mer synthetic peptide that reproduced the entire sequence of the C-terminal invariable domain of VlsE was conjugated to the carrier keyhole limpet hemocyanin and used to immunize mice. Generated mouse antibody was able to immunoprecipitate native VlsE extracted from cultured B. burgdorferi B31 spirochetes, indicating that the C-terminal invariable domain was exposed at the antigen's surface. However, this domain was inaccessible to antibody binding at the surface of cultured intact spirochetes, as demonstrated by both an immunofluorescence experiment and an in vitro killing assay. Mouse antibody to the C-terminal invariable domain was not able to confer protection against B. burgdorferi infection, indicating that this domain was unlikely exposed at the spirochete's surface in vivo. We concluded that the C-terminal invariable domain was exposed at the antigen's surface but not at the surface of either cultured or in vivo spirochetes and thus cannot elicit protection against B. burgdorferi infection.
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Embers, Monica E., Nicole R. Hasenkampf, Mary B. Jacobs, and Mario T. Philipp. "Dynamic Longitudinal Antibody Responses during Borrelia burgdorferi Infection and Antibiotic Treatment of Rhesus Macaques." Clinical and Vaccine Immunology 19, no. 8 (June 20, 2012): 1218–26. http://dx.doi.org/10.1128/cvi.00228-12.
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ABSTRACTInfection withBorrelia burgdorferielicits robust yet disparate antibody responses in infected individuals. A longitudinal assessment of antibody responses to multiple diagnostic antigens following experimental infection and treatment has not previously been reported. Our goal was to identify a combination of antigens that could indicate infection at all phases of disease and response to antibiotic treatment. Because the rhesus macaque recapitulates the hallmark signs and disease course of human Lyme disease, we examined the specific antibody responses to multiple antigens ofB. burgdorferifollowing infection of macaques. Five macaques infected with strain B31 and 12 macaques infected with strain JD1 were included in the analysis. Approximately half of these animals were treated with antibiotics at 4 to 6 months postinoculation. Antibody responses to severalB. burgdorferirecombinant antigens, including OspC, DbpA, BBK32, OspA, and OppA-2, were measured at multiple points throughout infection. We have previously shown a decline in the response to the C6 peptide following antibiotic treatment. Responses to OspA and OspC, however, were variable over time among individuals, irrespective of antibiotic treatment. Not every individual responded to BBK32, but anti-DbpA IgG levels were uniformly high and remained elevated for all animals. All responded to OppA-2, with a decline posttreatment that was slow and incomplete. This is the first demonstration ofB. burgdorferiOppA-2 antigenicity in nonhuman primates. The combination of DbpA, OspC, OspA, and OppA-2 with the C6 diagnostic peptide has the potential to detect infection throughout all disease phases.
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Chan, Rita, Peter T. Buckley, Aidan O’Malley, William E. Sause, Francis Alonzo, Ashira Lubkin, Kristina M. Boguslawski, et al. "Identification of biologic agents to neutralize the bicomponent leukocidins of Staphylococcus aureus." Science Translational Medicine 11, no. 475 (January 16, 2019): eaat0882. http://dx.doi.org/10.1126/scitranslmed.aat0882.
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A key aspect underlying the severity of infections caused by Staphylococcus aureus is the abundance of virulence factors that the pathogen uses to thwart critical components of the human immune response. One such mechanism involves the destruction of host immune cells by cytolytic toxins secreted by S. aureus, including five bicomponent leukocidins: PVL, HlgAB, HlgCB, LukED, and LukAB. Purified leukocidins can lyse immune cells ex vivo, and systemic injections of purified LukED or HlgAB can acutely kill mice. Here, we describe the generation and characterization of centyrins that bind S. aureus leukocidins with high affinity and protect primary human immune cells from toxin-mediated cytolysis. Centyrins are small protein scaffolds derived from the fibronectin type III–binding domain of the human protein tenascin-C. Although centyrins are potent in tissue culture assays, their short serum half-lives limit their efficacies in vivo. By extending the serum half-lives of centyrins through their fusion to an albumin-binding consensus domain, we demonstrate the in vivo efficacy of these biologics in a murine intoxication model and in models of both prophylactic and therapeutic treatment of live S. aureus systemic infections. These biologics that target S. aureus virulence factors have potential for treating and preventing serious staphylococcal infections.
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Höghammar, Kerstin, and Warren W. Esty. "On the dating of two early 2nd century coin issues from Kos and the IGCH 1320 hoard." Opuscula. Annual of the Swedish Institutes at Athens and Rome 6 (November 2013): 261–305. http://dx.doi.org/10.30549/opathrom-06-09.
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This paper presents and discusses the dates of two Koan silver issues, drachms with young Herakles/crab and club in incuse, and hemidrachms with Apollo/lyre. A date in the 190s BC is suggested on several grounds. Weights and diameters correspond with those of HI XII and XIII of the 3rd century, suggesting that the issues discussed here followed shortly thereafter. The other Koan silver issues of the 2nd century were minted on a lower weight-standard. The IGCH 1320 hoard contains examples of both issues, and the other Koan issues in it date to the middle and second half of the 3rd century or the 190s/c. 190. Groups of homonyms occur in issues dating to the end of 3rd/early 2nd century. A connection with Kalymnos seems likely for the hemidrachms, and this may suggest a date early in the 190s during the war with king Philip V of Macedonia.
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Krotin, Mirjana, Branislav Milovanovic, Dejana Vukovic, and Dusica Celeketic. "An unusual cause of complete atrioventricular block: A case report." Medical review 59, no. 11-12 (2006): 577–79. http://dx.doi.org/10.2298/mpns0612577k.
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Introduction. Complete atrioventricular block is a serious disorder, since patients may be asymptomatic. However, it is an important risk for sudden cardiac death. Case report. A 48-year old male patient was admitted to the coronary care unit, due to recurring substernal chest pain. It was followed by fatigue, weakness and confusion, it lasted more than half an hour and occurred twice. Loss of consciousness did not occur. The patient had a tick bite two months earlier. Physical examination was unremarkable, except for low heart rate (50/minute) electrocardiogram showed a complete atrioventricular block with narrow QRS complexes and good ventricular function. Elevation of ST segment was observed in the inferior ECG leads, with reciprocal ST depression in precordial leads; it was highly suspicious for acute myocardial infarction, but markers of myocardial necrosis (Troponin, Creatine kinase-MB) were normal. The chest pain recurred without evolutive changes in the electrocardiogram or increase in markers of myocardial necrosis. Tests for Lyme disease were negative, too. The cause of atrioventricular conduction disturbance was found by transthoracic echocardiography. A giant tumor was found in the right atrium and right ventricle. Further examinations excluded its secondary cause and the patient was sent to surgery. The tumor was inoperable and bled excessively. Although permanent pacing was performed, the patient died suddenly after dismisal. Conclusion. We can conclude that a giant primary tumor of the heart can be asymptomatic for a long time causing complete atrioventricular block, and in this case it clinically presented as acute myocardial infarction. Echocardiographic examination was the main diagnostic tool in our case. .
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Azizi, Lamiae. "Lyle D.Broemeling, Chapman & Hall/CRC Biostatistics Series: Boca Raton, London, New York, 2014. No. of Pages: 454. Price: $85.46, 59.99GBP. ISBN: 978-1-4665-6497-8." Statistics in Medicine 34, no. 22 (September 1, 2015): 3079–80. http://dx.doi.org/10.1002/sim.6521.
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Goldstein, Rebecca L., Ana Goyos, Chi-Ming Li, Petra Deegen, Pamela Bogner, Alexander Sternjak, Oliver Thomas, et al. "AMG 701 induces cytotoxicity of multiple myeloma cells and depletes plasma cells in cynomolgus monkeys." Blood Advances 4, no. 17 (September 4, 2020): 4180–94. http://dx.doi.org/10.1182/bloodadvances.2020002565.
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Abstract Multiple myeloma (MM) is a hematologic malignancy that is characterized by the accumulation of abnormal plasma cells (PCs) in the bone marrow (BM). Patient outcome may be improved with BiTE (bispecific T-cell engager) molecules, which redirect T cells to lyse tumor cells. B-cell maturation antigen (BCMA) supports PC survival and is highly expressed on MM cells. A half-life extended anti-BCMA BiTE molecule (AMG 701) induced selective cytotoxicity against BCMA-expressing MM cells (average half-maximal effective concentration, 18.8 ± 14.8 pM), T-cell activation, and cytokine release in vitro. In a subcutaneous mouse xenograft model, at all doses tested, AMG 701 completely inhibited tumor formation (P < .001), as well as inhibited growth of established tumors (P ≤ .001) and extended survival in an orthotopic MM model (P ≤ .01). To evaluate AMG 701 bioactivity in cynomolgus monkeys, a PC surface phenotype and specific genes were defined to enable a quantitative digital droplet polymerase chain reaction assay (sensitivity, 0.1%). Dose-dependent pharmacokinetic and pharmacodynamic behavior was observed, with depletion of PC-specific genes reaching 93% in blood and 85% in BM. Combination with a programmed cell death protein 1 (PD-1)–blocking antibody significantly increased AMG 701 potency in vitro. A model of AMG 701 binding to BCMA and CD3 indicates that the distance between the T-cell and target cell membranes (ie, the immunological synapse) is similar to that of the major histocompatibility complex class I molecule binding to a T-cell receptor and suggests that the synapse would not be disrupted by the half-life extending Fc domain. These data support the clinical development of AMG 701.
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Haider, Rana Zeeshan, Najeed Ahmed Khan, Eloisa Urrechaga, and Tahir Sultan Shamsi. "Mature and Immature/Activated Cells Fractionation: Time for a Paradigm Shift in Differential Leucocyte Count Reporting?" Diagnostics 11, no. 6 (May 21, 2021): 922. http://dx.doi.org/10.3390/diagnostics11060922.
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Leucocytes, especially neutrophils featuring pro- and anti-cancerous characteristics, are involved in nearly every stage of tumorigenesis. Phenotypic and functional differences among mature and immature neutrophil fractions are well reported, and their correlation with tumor progression and therapy has emerging implications in modern oncology practices. Technological advancements enabled modern hematology analyzers to generate extended information (research parameters) during complete blood cell count (CBC) analysis. We hypothesized that neutrophil and lymphocyte fractions-related extended differential leucocytes count (DLC) parameters hold superior diagnostic utility over routine modalities. The present study was carried out over a four-and-a-half-year period wherein extended neutrophil (immature granulocyte [IG] and mature neutrophil [NEUT#&]), and lymphocyte (activated/high fluorescence lymphocyte count [HFLC] and resting lymphocyte [LYMP#&]) parameters were challenged over routine neutrophil [NEUT#] and lymphocyte [LYMP#] items in a study population of 1067 hematological neoplasm patients. Extending the classical statistical approaches, machine-learning-backed data visualization was used to explore trends in the study parameters. As a whole, extended neutrophil and lymphocyte count outperformed and was diagnostically more relevant than routine neutrophil and lymphocyte parameters by showing the least difference from their respective (gold-standard) manual DLC counts. The mature neutrophil count was compared to IG, and resting lymphocyte count was compared to HFLC by calling the function ‘correlation’ as a ‘clustering function’ for heatmap based visualization. The aforementioned study parameters displayed close clustering (rearrangement) for their respective study items by presenting distinct trends of equally valuable weights (deviated values), advocating fractions-based extended DLC reporting. Importantly, using a Bland and Altman analysis analogously to a manual neutrophil count, the mature neutrophil count [NEUT#&] remained unbiased since a routine neutrophil count [NEUT#] was found to be a negatively biased. The extended DLC-parameter-driven fractions-based reporting has superior diagnostic utility over classical routine approaches; this finding can largely minimize labor-intensive manual DLC practices, especially in hematology–oncology departments.
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Hayen, Andrew. "Bayesian biostatistics and diagnostic medicine. Lyle D. Broemeling, Chapman & Hall/CRC, Boca Raton, FL, 2007. No. of pages: xiii+198. Price: $79.95. ISBN13: 97-1-584-88767-6." Statistics in Medicine 27, no. 28 (December 10, 2008): 6035–36. http://dx.doi.org/10.1002/sim.3396.
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Osokin, Mikhail Yu. "Ippolit Bogdanovič, a Court Translator of Catherine II: An Episode from His Biography of “The Lyre” Period (1773)." Russkaia Rech, no. 1 (February 2021): 84–94. http://dx.doi.org/10.31857/s013161170013908-7.
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Bogdanovič’s humble petition of 1773 to the Empress Catherine II, where the poet reminds about his diligent services and askes to help him with clearing his 3000 ruble debt. His translations of poems devoted to Catherine II by Michelangiolo Gianetti and by Jean-François Marmontel (the latter poem was inspired directly by the Imperial Court) gave him the moral right for this request. Bogdanovič shortened Marmontel’s poem by half and edited what was left. The autocracy criticism was transformed into lamentations on the lack of artistic freedom, which, in turn, was mitigated by the translator’s note. Moreover, the text was placed in panegyric context in Bogdanovič’s collection of poems “Lira” (1773) along the line with the translations of eulogistic poems to Catherine The Great by Voltaire and Michelangiolo Gianetti, an Italian doctor who did not seem to have any wish to lecture monarchs. 1000 rubles, which Bogdanovič had received, can be seen as a payment for this job. This collaboration allows us to revise the prevailing outlook on Bogdanovič’s creative evolution as a history of compromises of “latent oppositionist” with a “secret liberty of beliefs” from the circle of the Count Nikita Panin.
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Mattson, C., K. Wikström, C. Sterky, and G. Pohl. "Synergism between Tissue-Type Plasminogen Activator and a Genetically Engineered Variant Lacking the Finger Domain, the Growth Factor Domain and the First Kringle Domain." Thrombosis and Haemostasis 65, no. 03 (1991): 286–90. http://dx.doi.org/10.1055/s-0038-1648136.
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SummaryA modified variant of human tissue-type plasminogen activator (t-PA) lacking the finger domain (F), the growth factor domain (G) and the first kringle domain (K1), has an extended plasma half-life in vivo, compared to that of t-PA. When the variant (denoted K2P) was tested in vitro for its ability to lyse human plasma clots we found that the activity was characterized by a time lag phase and a sigmoidal dose-response curve. However, an attenuation of the lag phase in vitro was observed both when K2P was mixed with t-PA in a w/w ratio of 4 : 1 and when K2P was allowed to lyse a clot that had been pre-exposed to t-PA i.e. submitted to a limited plasmic digestion. Dosis that in vitro caused 50% lysis within 6 h were calculated from individual dose-response curves and were for K2P, t-PA and K2P/t-PA (4 : 1 w/w) 540 ng/ml, 360 ng/ml and 310 ng/ml, respectively. These results indicated a synergistic effect between K2P and t-PA. However, the data from individual dose-response curves showed that the effect of the K2P/t-PA mixture never was better than that of t-PA alone, and the synergistic effect in vitro is therefore considered to be of limited use. The thrombolytic activity in vivo was evaluated in a rabbit jugular vein thrombus model. Despite the lag phase observed in vitro, K2P was approximately 3 times as effective as t-PA in vivo (bolus injection). The thrombolytic effect of K2P was further potentiated when it was administred together with a small amount of t-PA (4 : 1 w/w). This potentiation in vivo was, in contrast to the effect in vitro, a useful synergistic effect as the dose-response curve for the K2P/t-PA mixture was steeper than that of t-PA and K2P alone. Doses that caused 50% lysis within 3 h were for t-PA, K2P and K2P/t-PA 1.28 mg/kg, 0.56 mg/kg and 0.35 mg/kg, respectively.
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Jastrzębowska, Elzbieta. "Wall Paintings in the House of Aion at Nea Paphos." Polish Archaeology in the Mediterranean 27, no. 1 (April 11, 2018): 527–97. http://dx.doi.org/10.5604/01.3001.0013.2015.
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This paper studies a collection of painted plaster fragments excavated between 1984 and 1989 in the northern part of the so-called House of Aion, that is, three small rooms (Nos 3, 13, 14, 15 and 7). The architectural context of these finds and their dating is first recapitulated: the house was constructed in the second half of the 4th century only to be demolished by a strong earthquake at the end of the century or the beginning of the following one. Most of the plaster pieces were small and of little significance in terms of the remaining colors, but a few from Room 7 were sufficiently well preserved to support a reconstruction of parts of five figural images (three muses, Apollo and a mask) and determine their hypothetical position in this room. Parallels, in painting and floor mosaics, range from Ephesos and Kos in the east to Vichen (Luxembourg) in the west. Based on the iIconographic identification, the 4th century AD Muses from Paphos could be recognized as: a standing Thalia holding a mask, a seated Urania and a standing Euterpe with a double flute in her hand, accompanied by Apollo holding a lyre. Together they constituted typical decoration of a Mediterranean Roman house, common from the early Empire through late antiquity.
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Maclean, Allan. "Cognitive processes (2nd edn), Lyle Bourne, Roger Dominowski, Elizabeth Loftus and Alice Healy, Prentice-Hall International, Englewood Cliffs N.J., 1986. No. of pages: 374. Price: £12.95 (Paperback). ISBN 0 13 139841 501." Applied Cognitive Psychology 1, no. 1 (January 1987): 73–74. http://dx.doi.org/10.1002/acp.2350010111.
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Spaan, Andras, Tamara Reyes-Robles, Cédric Badiou, Sylvie Cochet, Kristina Boguslawski, Pauline Yoong, Christopher J. Christopher J. Day, et al. "Staphylococcus Aureus Targets the Duffy Antigen Receptor for Chemokines (DARC) to Lyse Erythrocytes." Blood 126, no. 23 (December 3, 2015): 162. http://dx.doi.org/10.1182/blood.v126.23.162.162.
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Abstract Introduction: Staphylococcus aureus is a major human pathogen. Infections by this bacterium range from minor skin and soft tissue infections, to more invasive and life threating infections like sepsis, osteomyelitis, and pneumonia. In order to successfully infect the mammalian host, S. aureus has to overcome iron scarcity within the host. As such, S. aureus is thought to produce toxins that lyse erythrocytes, releasing hemoglobin, a critical iron source for S. aureus in mammals. The bi-component β-barrel pore-forming leukocidins kill human neutrophils and were mostly considered as virulence factors fighting the host innate immune system. We show here thatHlgAB and LukED are two potent hemolytic leukocidins against human erythrocytes. Furthermore, we describe the identification of the Duffy antigen receptor for chemokines (DARC) as the red blood cell receptor for both LukED and HlgAB leukocidins. Results: We took advantage of erythrocyte samples from different Duffy (Fy) genotyped individuals from the French National Blood Transfusion Institute. We evaluated the receptor expression on the surface of erythrocytes (Figure 1). DARC-negative erythrocytes (phenotype Fya-/b-) were fully resistant to HlgAB and LukED. Compared to individuals expressing normal levels of DARC (phenotypes Fya+/b+, Fya+/b+weak, Fya+/a+, and Fyb+/b+), individuals expressing intermediate (phenotype Fyb+weak/b+weak) or very low levels of DARC (phenotype Fyb-/b+weak) showed intermediate susceptibility to both HlgAB and LukED (Figure 1). These data demonstrate that the hemolytic activity of HlgAB and LukED is dependent on the expression of DARC at the red blood cell surface. To better understand the interaction of HlgAB and LukED with DARC, we screened HEK293T cells transfected with plasmids encoding DARC mutants (Tournamille et al, 2003). We demonstrate that while both HlgAB and LukED bind to DARC with nanomolar affinities, they do so by recognizing different domains of the receptor. To directly evaluate whether LukED and HlgAB can promote bacterial replication as a result of erythrocyte lysis, S. aureus was grown in iron-starved medium supplemented with cell-free extracts of erythrocytes treated with LukED or HlgAB. We observed that HlgAB and LukED were each capable of promoting S. aureus growth in a DARC and hemoglobin scavenging system (IsdBH)-dependent manner. These in vitro studies were supported by a murine bacteremia model. Discussion: By combining human studies of DARC polymorphisms with gain and loss of function experiments and biochemical analyses, we demonstrate that DARC is necessary and sufficient to render host cells susceptible to LukED and HlgAB. By targeting DARC, HlgAB and LukED support S. aureus growth in a hemoglobin-acquisition dependent-manner. Thus, these findings provide the missing link of how S. aureus targets and lyses erythrocytes to release one of the scarcest nutrient within the mammalian host. Human epidemiological studies comparing the severity of S. aureus infection in patients with DARC positive or DARC negative erythrocytes are now required to evaluate the contribution of DARC-mediated hemolysis in human staphylococcal diseases. Given the resistance of DARC negative erythrocytes to the parasites Plasmodium vivax and P. knowlesi, and now to the hemolytic activity of the bacterium S. aureus, our findings suggest the possibility of a positive selection event in response to these important human pathogens. (A) Susceptibility of human erythrocytes to S. aureus β-barrel pore forming toxins. The dashed line indicates 50% hemolysis. n = 6. (B) Levels of DARC and CD55 on erythrocytes of donors with different Fy phenotypes. The dashed line indicates the detection threshold. n = 2-7 ± SEM. (C,E) Susceptibility of human erythrocytes with different Fy phenotypes to HlgAB (C) and LukED (E). The dashed line indicates 50% hemolysis. n = 2-7 ± SEM. (D, F) Correlation of half-maximal effective concentrations (EC50) of HlgAB (D) and LukED (F) with the total number of receptors expressed on the erythrocyte surface. For Fyb+weak/Fyb- donors, LukED EC50 could not be calculated. n = 2-7 ± SEM. Figure 1. Hemolytic activity of HlgAB and LukED depends on DARC. Figure 1. Hemolytic activity of HlgAB and LukED depends on DARC. Disclosures No relevant conflicts of interest to declare.
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Lefferts, Peter M. "Facsimiles of Fourteenth-Century English Polyphony." Royal Musical Association Research Chronicle 21 (1988): 83–95. http://dx.doi.org/10.1080/14723808.1988.10540930.
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With the proliferation of comprehensive commercial microfilming of major music collections, careful consideration needs to be given to the production of hard-cover books of facsimiles that traverse the same ground. Of course, a book is still a convenient way of storing and handling certain kinds of material. In compensation for its bulk it is tangible, accessible and portable, not to mention the fact that it can be annotated. And certain kinds of facsimile volume are obviously still going to be desirable: those reproducing single sources of great importance; those containing the contents of smaller libraries and obscure or less accessible collections; and those that comprise within a single volume an important cross-section of some scattered repertory or corpus of sources. In the light of those considerations, the publication of these two volumes of facsimiles of late-medieval English polyphony is most welcome. They make widely available at reasonable quality and price a vast amount of buried treasure found up to now only in the file drawers of a few specialists. The hoard consists of a large proportion of the surviving English polyphony from the era between the Worcester fragments and the Old Hall manuscript. This is an important and little-known repertory, spanning the entire fourteenth century but dispersed among numerous fragmentary sources. Both volumes will be necessary and welcome additions to public collections as well as to the private libraries of specialists in medieval music. They are also an essential complement to the four-volume edition of this same repertory recently published by Editions de L'Oiseau Lyre in the series Polyphonic Music of the Fourteenth Century, and they will surely prove invaluable for the teaching of surveys and seminars on early English polyphony.
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Perry, Julie, Sébastien Debuisson, and Arnaud Descôtes. "Experimental training systems in Champagne: an overview of agronomical and qualitative parameters." E3S Web of Conferences 50 (2018): 01042. http://dx.doi.org/10.1051/e3sconf/20185001042.
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Vine implantation in Champagne is strictly regulated. Row spacing is limited to 1,50 meter and the canopy height can not exceed 1,40 m. The traditional training system is therefore characterized by narrow spaced vines. From the late eighties, different vine training systems, such as lyres, have been tested in the Champagne area. The aim is to assess their interests in the terroir of Champagne, which is characterised by its cool climate, soil profile and its customs. Whereas the lyre training showed its limits in the Champagne context, some other training systems have been implemented such as half-widely-spaced vines. These devices are characterised by a row spacing of two meters, a consistent cover crop and a canopy up to two meters. The plots are located in various places in the area and are strictly followed each year since 2006 (and 2000 for the first sites). Phenological, agronomical and ripening parameters are controlled and compared to the traditional training system plots. Experimental vinifications are done each year so that sensory analysis can be undertaken to assess the ability of these vines to produce wines with a Champagne typicality. The results of this experimental device show interesting conclusions on the agronomical behaviour of experimental widely-spaced vines in a cool climate region. Spring frost resistance, cover crop management and ripening are some elements which show differences between the reference traditional system (REF) and the widely-spaced vines (VSL).
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Franke, Werner W., Lisa M. Domke, Yvette Dörflinger, and Ralf Zimbelmann. "The cell–cell junctions of mammalian testes. III. Absence of an endothelial cell layer covering the peritubular wall of the seminiferous tubules—an immunocytochemical correction of a 50-year-old error in the literature." Cell and Tissue Research 379, no. 1 (November 12, 2019): 75–92. http://dx.doi.org/10.1007/s00441-019-03116-5.
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Abstract In the molecular biological and ultrastructural studies of the peritubular wall cells encasing the seminiferous tubules of mammalian testes, we found it necessary to characterize the outermost cell layer bordering on the interstitial space in detail. For half a century, the extremely thin cells of this monolayer have in the literature been regarded as part of a lymphatic endothelium, in particular in rodents. However, our double-label immunofluorescence microscopical results have shown that in all six mammalian species examined, including three rodent ones (rat, mouse, guinea pig), this classification is not correct: the very attenuated cells of this monolayer are not of lymphatic endothelial nature as they do not contain established endothelial marker molecules. In particular, they do not contain claudin-5-positive tight junctions, VE-cadherin-positive adherens junctions, “lymph vessel endothelium hyaluronan receptor 1” (LYVE-1), podoplanin, protein myozap and “von Willebrand Factor” (vWF). By contrast and as controls, all these established marker molecules for the lymphatic endothelial cell type are found in the endothelia of the lymph and—partly also—blood vessels located nearby in the interstitial space. Thus, our results provide evidence that the monolayer cells covering the peritubular wall do not contain endothelial marker molecules and hence are not endothelial cells. We discuss possible methodological reasons for the maintenance of this incorrect cell type classification in the literature and emphasize the value of molecular analyses using multiple cell type–specific markers, also with respect to physiology and medical sciences.
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Johnston, Demerise, Jill Kelly, Michel Ledizet, Nathalie Lavoie, and Peter J. Krause. "644. Borrelia miyamotoi and Borrelia burgdorferi Seroprevalence in New England." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S381. http://dx.doi.org/10.1093/ofid/ofaa439.838.
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Abstract Background Diseases vectored by the tick species Ixodes scapularis have increased in incidence over the past 50 years and have been expanding into previously non-endemic areas. The emergence of Borrelia miyamotoi, a recently described spirochetal pathogen, has been less well documented than that of Borrelia burgdorferi, the causative agent of Lyme disease. The objective of this study was to compare the geographic range of human exposure to B. miyamotoi and B. burgdorferi in New England, the pattern of their spatial expansion, and factors that influence their frequency. Methods Serum samples were collected from 11 study sites across New England. Age, gender, race, and residential zip code or county were recorded for each study participant and aggregate data analyzed by study sites, study site zones, and residential county for spatial analysis. Serum samples were tested for B. miyamotoi antibody using a multiplex Luminex assay and for B. burgdorferi antibody using a recently FDA approved two-tiered ELISA (Zeus ELISA Test Systems). Fischer exact tests and map visualizations in ArcGIS Pro 2.4.2 (Copyright ©2019 Esri Inc.) were used to determine spatial distribution of human B. miyamotoi and B. burgdorferi infection in New England. A logistic regression model was used to determine any association in seropositivity with tick-borne infection risk factors. Results B. burgdorferi seroprevalence was greater than that of B. miyamotoi at all but one study site. The average B. burgdorferi seroprevalence at all study sites was not quite double that of B. miyamotoi (mean 2.3% [0.6-6.2%] and mean 4.1% [2.2-7.5%], respectively). No longitudinal or latitudinal gradient was observed for B. miyamotoi or B. burgdorferi seroprevalence by study site zone or county analysis. Men were twice as likely as women to be seropositive for B. miyamotoi and B. burgdorferi. Conclusion Human exposure to B. miyamotoi and B. burgdorferi is highly dispersed throughout New England. B. miyamotoi seroprevalence is about half that of B. burgdorferi in New England. Additional studies are needed to explain the disparity between B. burgdorferi and B. miyamotoi infection and disease. Disclosures All Authors: No reported disclosures
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Hamakiotes, Costas C., and Stanley A. Berger. "Periodic flows through curved tubes: the effect of the frequency parameter." Journal of Fluid Mechanics 210 (January 1990): 353–70. http://dx.doi.org/10.1017/s002211209000132x.
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In a previous paper we reported on the effect of Dean number, κm, on the fully developed region of periodic flows through curved tubes. In this paper we again consider a sinusoldally varying volumetric flow rate in a curved pipe of arbitrary curvature ratio, δ, and investigate the effect of frequency parameter α, and Reynolds number Rem on the flow. Specifically, we report on the flow-field development for the range 7.5 [les ] α [les ] 25, and 50 [les ] Rem [les ] 450. The results, obtained by numerical integration of the full Navier–Stokes equations, reveal a number of characteristics of the flow previously unreported. For low values of Rem the secondary flow consists of a single vortex (Dean-type motion) in the half-cross-section at all times and for all values of α studied. For higher Rem we observe inward ‘centrifuging’ (Lyne-type motion) at the centre. This motion always occurs during the accelerating period of the volumetric flow rate. It appears at lower α for higher Rem and, for the given Rem at which it appears, it occurs at earlier times in the cycle for lower a. A striking feature is observed for α = 15 for the range 315 [les ] Rem [les ] 400: period tripling. The flow field varies periodically with time for the duration of three volumetric-flow-rate cycles then repeats for the subsequent three cycles, and so on. The computed axial pressure gradient also varies periodically with time but with the same period as the volumetric flow rate.
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Island, Michael D., Xiaoling Cui, Betsy Foxman, Carl F. Marrs, Walter E. Stamm, Ann E. Stapleton, and John W. Warren. "Cytotoxicity of Hemolytic, Cytotoxic Necrotizing Factor 1-Positive and -Negative Escherichia coli to Human T24 Bladder Cells." Infection and Immunity 66, no. 7 (July 1, 1998): 3384–89. http://dx.doi.org/10.1128/iai.66.7.3384-3389.1998.
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ABSTRACT Approximately one-half of Escherichia coli isolates from patients with cystitis or pyelonephritis produce the pore-forming cytotoxin hemolysin, a molecule with the capacity to lyse erythrocytes and a range of nucleated cell types. A second toxin, cytotoxic necrotizing factor 1 (CNF1), is found in approximately 70% of hemolytic, but rarely in nonhemolytic, isolates. To evaluate the potential interplay of these two toxins, we used epidemiological and molecular biologic techniques to compare the cytotoxicity of hemolytic, CNF1+, and CNF1− cystitis strains toward human T24 bladder epithelial cells in vitro. A total of 29 isolates from two collections of cystitis-associated E. coli were evaluated by using methylene blue staining of bladder monolayers at 1-h intervals after inoculation with each strain. Most (20 of 29) isolates damaged or destroyed the T24 monolayer (less than 50% remaining) within 4 h after inoculation. As a group, CNF1+ isolates from one collection (11 strains) were less cytotoxic at 4 h than the CNF1− strains in that collection (P = 0.009), but this pattern was not observed among isolates from the second collection (18 strains). To directly evaluate the role of CNF1 in cytotoxicity of hemolytic E. coli without the variables present in multiple clinical isolates, we constructed mutants defective in production of CNF1. Compared to the CNF1+ parental isolates, no change in cytotoxicity was detected in thesecnf1 mutants. Our results indicate that CNF1 does not have a detectable effect on the ability of hemolytic E. coli to damage human bladder cell monolayers in vitro.
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Cerveny, Karen E., Angelo DePaola, Donna H. Duckworth, and Paul A. Gulig. "Phage Therapy of Local and Systemic Disease Caused by Vibrio vulnificus in Iron-Dextran-Treated Mice." Infection and Immunity 70, no. 11 (November 2002): 6251–62. http://dx.doi.org/10.1128/iai.70.11.6251-6262.2002.
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ABSTRACT Vibrio vulnificus is a gram-negative bacterium that contaminates filter-feeding shellfish such as oysters. After ingestion of contaminated oysters, predisposed people may experience highly lethal septicemia. Contamination of wounds with the bacteria can result in devastating necrotizing fasciitis, which can progress to septicemia. The extremely rapid progression of these diseases can render antibiotic treatment ineffective, and death is a frequent outcome. In this study, we examined the potential use of bacteriophages as therapeutic agents against V. vulnificus in an iron-dextran-treated mouse model of V. vulnificus infection. Mice were injected subcutaneously with 10 times the lethal dose of V. vulnificus and injected intravenously, either simultaneously or at various times after infection, with phages. Treatment of mice with phages could prevent death; systemic disease, as measured by CFU per gram of liver and body temperature; and local disease, as measured by CFU per gram of lesion material and histopathologic analysis. Two different phages were effective against three different V. vulnificus strains with various degrees of virulence, while a third phage that required the presence of seawater to lyse bacteria in vitro was ineffective at treating mice. Optimum protection required that the phages be administered within 3 h of bacterial inoculation at doses as high as 108 PFU. One of the protective phages had a half-life in blood of over 2 h. These results demonstrate that bacteriophages have therapeutic potential for both localized and systemic infections caused by V. vulnificus in animals. This model should be useful in answering basic questions regarding phage therapy.