tbuckley/cabot-search huggingface dataset:
West Nile virus circulation in Emilia-Romagna, Italy: the integrated surveillance system 2009
Authors: P Angelini, M Tamba, A C Finarelli, R Bellini, A Albieri, P Bonilauri, F Cavrini, M Dottori, P Gaibani, E Martini, A Mattivi, A M Pierro, G Rugna, V Sambri, G Squintani, P Macini
Journal: Eurosurveillance (2010)

Following a large West Nile virus (WNV) epidemic in northeastern Italy in 2008, human and animal surveillance activities were implemented in Emilia Romagna. Human surveillance was performed by serology or genome detection on blood and cerebrospinal fluid for all suspected cases suffering from acute meningoencephalitis in the regional territory. Animal surveillance consisted of passive and active surveillance of horses and active surveillance of wild birds and mosquitoes. Between 15 June and 31 October 2009, nine of 78 possible cases of West Nile neuroinvasive disease were confirmed (three fatal). From May to October, 26 cases of neurological West Nile disease were confirmed among 46 horses. The overall incidence of seroconversion among horses in 2009 was 13%. In 2009, 44 of 1,218 wild birds yielded positive PCR results for WNV infection. The planned veterinary and entomological surveillance actions detected WNV activity from the end of July 2009, about 2-3 weeks before the onset of the first human neurological case. Passive surveillance of horses seems to be an early and suitable tool for the detection of WNV activity, but it will be less sensitive in the future, because an intensive programme of horse vaccination started in June 2009.
Mental Health Disparities Among Transgender Youth
Authors: Johanna Olson-Kennedy
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Inhibitory Effect of Adult Bovine Serum on Release of Infectious Epstein-Barr Virus From a Virus-Carrier Cell Line&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: T Sairenji, Y Hinuma
Journal: JNCI Journal of the National Cancer Institute (1975)

When certain bovine sera (BS) were used to culture P3HR-1 cells, the amount of infectious Epstein-Barr virus (EBV) released into the culture fluid was significantly less than that obtained when calf serum (CS) or fetal calf serum (FCS) was used. A direct dose-response relationship was noted between the concentration of BS and the degree of inhibition of virus production. Cell growth was not inhibited nor was virus infectivity neutralized by BS. Similarly, EBV infectivity was not reduced by spent medium containing BS. The inhibition of virus production by BS could be reversed by replacement of the serum supplement with CS. The formation of viral capsid antigen and of infectious virus within the cells was not inhibited by BS, whereas the amount of virus released was significantly decreased in comparison with culture media containing FCS or CS. These findings suggested the presence of a factor(s) in the BS which inhibited the release of EBV from the cell.
Development of stratum corneum chymotrypsin-like protease activity and natural moisturizing factors from birth to 4 weeks of age compared with adults
Authors: J. Chittock, A. Cooke, T. Lavender, K. Brown, A. Wigley, S. Victor, M.J. Cork, S.G. Danby
Journal: British Journal of Dermatology (2016)

Summary Background From birth, the functional properties of the neonatal epidermal barrier mature whereby the stratum corneum (SC) hydrates and the skin surface acidifies. The identification of a thinner infant SC compared with adults suggests underdeveloped mechanisms underlying differentiation and desquamation. Objectives To assess the functional properties of the neonatal SC from birth, in conjunction with the quantification of superficial chymotrypsin-like protease activity [kallikrein-7 (KLK-7)] and filaggrin-derived natural moisturizing factors (NMF). Methods A total of 115 neonates recruited to the Oil in Baby SkincaRE (OBSeRvE) randomized controlled trial underwent a full evaluation of the SC at birth (&amp;lt; 72 h old) and at 4 weeks of age (n = 39, no oil control group) using minimally invasive instrumentation and methodology. A cohort of 20 unrelated adults was recruited for comparison. Results At birth NMF levels correlated with SC hydration (r = 0·50) and skin-surface pH (r = −0·54). From birth to 4 weeks, transepidermal water loss (TEWL), superficial KLK-7 activity and filaggrin-derived NMF significantly elevated. Impaired epidermal barrier function at birth (&amp;gt; 75th percentile TEWL) was accompanied by significantly elevated chymotrypsin-like protease activity and reduced levels of NMF. Conclusions The biophysical, biological and functional properties of the developing neonatal SC are transitional from birth to 4 weeks of age and differ significantly from adults. The presence of impaired barrier function with elevated protease activity and reduced NMF at birth suggests why certain infants are predisposed to epidermal barrier breakdown and the development of atopic dermatitis.
Breg Cells Are Numerically Decreased and Functionally Impaired in Patients With Systemic Sclerosis
Authors: Athanasios Mavropoulos, Theodora Simopoulou, Areti Varna, Christos Liaskos, Christina G. Katsiari, Dimitrios P. Bogdanos, Lazaros I. Sakkas
Journal: Arthritis & Rheumatology (2015)

Breg cells, a regulatory cell subset that produces interleukin-10 (IL-10), play a significant role in suppressing autoimmune responses and preventing autoimmunity. This study was undertaken to examine the number and function of Breg cells in patients with systemic sclerosis (SSc), a disease with many autoantibodies.Forty-five patients with SSc (12 with early SSc, 33 with established disease including 16 with SSc-associated pulmonary fibrosis [PF]), 12 healthy control subjects, and 10 patients with rheumatoid arthritis (RA)-associated PF were studied. The phenotypes of immature/transitional Breg cells (CD19+CD24(high) CD38(high) ) and memory Breg cells (CD19+CD27+CD24(high) ) were evaluated by flow cytometry. The function of Breg cells was assessed by measuring the production of IL-10 after B cell activation. In addition, activation of p38 MAPK and STAT-3 was measured following stimulation of the cells with B cell receptor (BCR) and Toll-like receptor 9 (TLR-9).Percentages of memory Breg cells were decreased in patients with early SSc (mean ± SEM 1.85 ± 0.38%), those with established SSc (1.6 ± 0.88%), those with SSc-associated PF (1.52 ± 0.17%), and those with RA-associated PF (1.58 ± 0.26%), compared to healthy controls (6.3 ± 0.49%; each P < 0.001). Percentages of transitional Breg cells were also decreased. Expression of IL-10 by Breg cells after stimulation with TLR-9 was impaired in patients with SSc, particularly those with SSc-associated PF. Activation of STAT-3 and p38 MAPK was impaired in naive and memory B cells from patients with SSc after stimulation with BCR and TLR-9. Expression of the stimulatory CD19 receptor was increased in B cells and also increased, to a lesser extent, in Breg cells from patients with SSc compared to healthy controls. Percentages of memory B cells were decreased in patients with SSc, particularly in those with SSc-associated PF.This is the first study to demonstrate that Breg cells are phenotypically and functionally impaired in patients with SSc. Furthermore, in SSc, B cells exhibit impaired p38 MAPK and STAT-3 activation upon stimulation with BCR and TLR-9. The findings of decreased numbers of Breg cells along with increased expression of CD19 support the idea of B cell autoaggression acting as an immunopathogenic mediator in SSc.
TSLP Neutralization Inhibits ILC2 Activation Induced By Multiple Pathogenic Clinical Isolates of RSV
Authors: Matthew T. Stier, Shinji Toki, Dawn C. Newcomb, Melissa H. Bloodworth, Tina V. Hartert, Martin L. Moore, R. Stokes Peebles
Journal: Journal of Allergy and Clinical Immunology (2016)
Use of hormonal therapy in men with metastatic prostate cancer
Authors: G. L. Lu-Yao, D. F. Moore, R. S. Dipaola, S.-L. Yao
Journal: Journal of Clinical Oncology (2005)

4559 Background: Although the timing of hormonal treatment is controversial, there is agreement that prostate cancer patients should receive hormonal therapy before dying of cancer. The objectives of this study were to 1) provide population-based cohort estimates of the effect of hormonal therapy use on overall survival in men with metastatic prostate cancer, and 2) provide population-based estimates of hormonal therapy use in men who ultimately died of prostate cancer, a population for which hormonal therapy is clearly indicated. Methods: The Surveillance, Epidemiology and End Results (SEER)-Medicare linked database was used to measure hormonal therapy use in 9,110 men who died of prostate cancer during 1991–2000 whereas the impact of hormonal use on survival was examined in men ≥65 years old diagnosed with metastatic prostate cancer (N=6,098). Hormonal therapy was defined as orchiectomy or use of luteinizing hormone releasing hormone agonist. Logistic regression was used to identify factors associated with hormone use. Kaplan-Meier estimates were used to estimate survival. Results: Approximately one third (36%) of African-American and one quarter (22%) of Caucasian men aged 65 or older did not receive hormonal therapy prior to death caused by prostate cancer. Compared with Caucasians, African-Americans were 57% less likely to receive hormonal therapy (P=0.005). Similar ethnic differences were observed in all subgroups examined (age, cancer stage and grade at diagnosis, income, geographic regions, and comorbidity status). Median overall survival was significantly better for men who received hormonal therapy (26 months) compared with those who did not (10 months), largely due to differences in prostate cancer specific survival. Survival in African-Americans and Caucasians was similar when adjusted for hormonal therapy use. Conclusions: Hormonal therapy is associated with improved disease-specific and overall survival in men with metastatic prostate cancer. However, implementation of this treatment may not be optimal and there are substantial ethnically dependent differences. No significant financial relationships to disclose.
PTH-043 Characterisation of motor nerve responses to electrical field stimulation in human isolated colon
Authors: J Broad, G Boundouki, C H Knowles, G J Sanger
Journal: Gut (2010)

<h3>Introduction</h3> The ability of drugs to affect gastrointestinal (GI) motility may be predicted <i>in vitro</i> by studying how they modify changes in muscle tension evoked by motor nerve activation with electrical field stimulation (EFS). In human tissues, variations in types of response to EFS make the technique difficult unless only one type is studied, ignoring the others.1 This study aimed to characterise the variations so all tissues may be used. <h3>Methods</h3> Human ascending/ transverse colon were obtained at surgery for cancer, following informed consent. After removing the mucosa, 20 strips (∼4 mm wide, 10 mm long) were cut parallel to the circular muscle from each colon. They were suspended between 2 ring electrodes in tissue baths (Kreb9s; 5% CO<sub>2</sub> in O<sub>2</sub>; 37°C; 1 g tension) for isometric recording. EFS was applied (5 Hz, 0.5 ms pulse width, 50 V, 10 s) every 1 min. <h3>Results</h3> Responses to EFS in strips from the same patient were inconsistent but prevented by tetrodotoxin 1 μM (n=24 strips; four patients). During EFS the muscle contracted (54% of 65 strips; seven patients), relaxed (18%) or did not respond (28%). After terminating EFS a large “after-contraction” usually occurred (86%), decaying quickly (duration 13.5±0.7 s, type 1; 59%) or slowly (35.1±1.5 s, type 2; 41%). Atropine 10 μM prevented contraction during EFS (n=6) revealing muscle relaxation, and attenuated type 1 after-contraction (by 59.3±13.4%; n=8); the remaining contraction was abolished by neurokinin (NK) NK<sub>1,2,3</sub> receptor antagonists L732138 1 μM, MDL29913 1 μM+SB235375 0.1 μM. Atropine less effectively reduced type 2 after-contraction (by 25.1±16.9%, n=3) with NK<sub>1,2,3</sub> antagonism further reducing the contraction to 45.3±15.9% of control. NK<sub>1,2,3</sub> antagonists alone decreased type 1 and 2 after-contraction (by 38.4±34.8%, n=3 total). The NO synthase inhibitor L-NAME 0.3 mM prevented relaxation during EFS, revealing an atropine-sensitive contraction, and enhanced type 1 (by 164.0±98.6%, n=5) or attenuated type 2 after-contraction (by 27.4±26.7%, n=8). The 5-HT<sub>4</sub> receptor agonist prucalopride 10 μM increased contraction during EFS (by 90.6±52.5%, n=4) and variably decreased type 1 and 2 after-contraction (by 22.5±22.4 and 38.1±13.0%, respectively; n=2–4). In the presence of L-NAME prucalopride increased contraction during EFS by 30.8 ±30.2%, n=8. <h3>Conclusion</h3> The results suggest interplay between cholinergic, nitrergic and tachykinergic systems, so agents changing GI motility exert both inhibitory and excitatory actions on neurotransmission. Understanding these interactions now allows a more complete characterisation of the mechanisms by which agents affect colonic motility.
Preliminary results of a phase II/III clinical study of the TLR9 agonist MGN1703 in patients with advanced colorectal carcinoma with disease control after first-line therapy: IMPACT study.
Authors: M. Schmidt, H. Schmoll, F. Mayer, J. Riera, G. Hapke, J. Andel, D. Nitsche, R. Ziebermayr, E. Weith, M. Schroff, M. Tschaika, B. Wittig
Journal: Journal of Clinical Oncology (2011)

e14114 Background: This clinical study with MGN1703 was started after a phase I clinical study provided clear evidence that the investigational drug is safe and well tolerated by patients with advanced solid malignancies. MGN1703 acts as an agonist of TLR9 and an immunmodulator. Its antineoplastic activity was already proven in several in vitro and in vivo models. The favorable safety profile was confirmed in a full GLP-program of toxicity studies. The mentioned studies provided impressive evidence that the safety profile of the investigational drug in clinical setting is very good as well. Promising efficacy results were also shown in this study. Methods: This ongoing phase II/III clinical study is conducted in patients with advanced colorectal cancer (CRC) with disease control after first-line therapy. 129 patients have to be recruited and randomized 2:1 to MGN1703 or placebo. Patients are treated twice a week with s.c. administration of 60 mg MGN1703. In the ongoing phase II/III clinical study, efficacy and safety of MGN1703 will be evaluated based on extensive immunological tests, radiological assessment, clinical and laboratory safety evaluations and monitoring of the quality of life. The study treatment will be continued up to occurrence of tumor progression, intolerable toxicity, exclusion criteria, and withdrawal of consent or death. Results: From 15 adverse events reported so far, four were assessed as drug-related by the investigator: mild fever in one patient (at three occasions) and mild arthralgia in another one. Local reactions in terms of mild redness were reported only in single patients and did not cause discomfort and intolerability in these patients. No laboratory or clinical signs of the developing of autoimmunity were reported. Conclusions: The preliminary safety results of this ongoing clinical study in patients with advanced CRC show clearly that treatment with MGN1703 is well tolerated and safe. Reported adverse events assessed as possibly drug-related belong to expected study drug reactions known for immune modulating drugs. These events were not accompanied by any signs of autoimmunity.
Abstract 12122: Absence of Rgs5 Prolongs Cardiac Repolarization and Predisposes to Ventricular Tachyarrhythmia in Mice
Authors: Mu Qin, Teng Wang, He Hu, Yu Liu, Cong X Huang
Journal: Circulation (2012)

Objective  The aim of this study was to elucidate the effects of regulator of G-protein signaling 5 (Rgs5), a negative regulator of G-protein-mediated signaling, on cardiac repolarization and arrhythmia in mice.   Methods and Results  Wild-type (WT) and Rgs5 -/-  mice were subjected to in vivo, in vitro, and cellular electrophysiological experiments. Compared with WT group, Rgs5 -/-  mouse hearts showed significantly prolonged cardiac repolarization, including prolonged QT c  interval (55.3±6.3ms vs 45.4±6.6ms, P 90 ) in left ventricle (60.6±5.5ms vs 54.2±6.1ms, P + currents in ventricular myocytes of Rgs5 -/-  mice revealed lower density of the outward voltage-dependent K +  currents than that in wild-type mice, including I peak , I to,  I kur , andI ss  (P -/-  mouse ventricle (P -/-  during program electrical stimuli (PES) (53.3%, 12/23) and burst pacing (39.1%, 9/23). And the incidence of sustained VAs were also increased in Rgs5 -/-  group (16.7%, 3.23), but none of them in WT mice. Importantly, the facilitated electrically induced VAs were associated with increased transmural dispersion of repolarization (TDR) (Rgs5 -/- : 9.1±2.1, WT: 5.1±1.6, P peak , I to  and I Kur  between the epicardium and endocardium in the Rgs5 [[Unable to Display Character: -]]/-  heart (P   Conclusion  The results strongly indicate that (i) Knockout of Rgs5 induced prolongation of the QT interval and the APD, which were due to the decreased K +  current density and reduced channel expression. (ii) The spatial heterogeneity of K +  current density increased the dispersion of APD and predisposed Rgs5 -/-  mice to electrically induced VAs.
Conditional Deletion of <i>Hsd11b2</i> in the Brain Causes Salt Appetite and Hypertension
Authors: Louise C. Evans, Jessica R. Ivy, Caitlin Wyrwoll, Julie A. McNairn, Robert I. Menzies, Thorbjørn H. Christensen, Emad A.S. Al-Dujaili, Christopher J. Kenyon, John J. Mullins, Jonathan R. Seckl, Megan C. Holmes, Matthew A. Bailey
Journal: Circulation (2016)

Background— The hypertensive syndrome of Apparent Mineralocorticoid Excess is caused by loss-of-function mutations in the gene encoding 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), allowing inappropriate activation of the mineralocorticoid receptor by endogenous glucocorticoid. Hypertension is attributed to sodium retention in the distal nephron, but 11βHSD2 is also expressed in the brain. However, the central contribution to Apparent Mineralocorticoid Excess and other hypertensive states is often overlooked and is unresolved. We therefore used a Cre-Lox strategy to generate 11βHSD2 brain-specific knockout ( Hsd11b2 .BKO) mice, measuring blood pressure and salt appetite in adults. Methods and Results— Basal blood pressure, electrolytes, and circulating corticosteroids were unaffected in Hsd11b2 .BKO mice. When offered saline to drink, Hsd11b2 .BKO mice consumed 3 times more sodium than controls and became hypertensive. Salt appetite was inhibited by spironolactone. Control mice fed the same daily sodium intake remained normotensive, showing the intrinsic salt resistance of the background strain. Dexamethasone suppressed endogenous glucocorticoid and abolished the salt-induced blood pressure differential between genotypes. Salt sensitivity in Hsd11b2 .BKO mice was not caused by impaired renal sodium excretion or volume expansion; pressor responses to phenylephrine were enhanced and baroreflexes impaired in these animals. Conclusions— Reduced 11βHSD2 activity in the brain does not intrinsically cause hypertension, but it promotes a hunger for salt and a transition from salt resistance to salt sensitivity. Our data suggest that 11βHSD2-positive neurons integrate salt appetite and the blood pressure response to dietary sodium through a mineralocorticoid receptor–dependent pathway. Therefore, central mineralocorticoid receptor antagonism could increase compliance to low-sodium regimens and help blood pressure management in cardiovascular disease.
A phase I study of sirolimus (rapamycin) and bevacizumab in patients with advanced malignancies.
Authors: E. E. Cohen, M. Sharma, L. A. Janisch, W. M. Stadler, S. P. Kang, G. F. Fleming, M. J. Ratain
Journal: Journal of Clinical Oncology (2010)

2591 Background: Both mTOR and VEGF inhibitors have shown antitumor efficacy. We performed a single institution, phase I study of sirolimus and bevacizumab, with primary objective to determine the dose-limiting toxicity (DLT) and recommended phase II dose (RPTD) of the combination. Secondary endpoints were tumor response and pharmacokinetics of sirolimus. Methods: Eligible patients had previously treated advanced malignancies and ECOG PS 0 or 1, and were enrolled in three sequential cohorts. In cohort 1, patients received sirolimus 90 mg PO weekly (45 mg on days 1 and 2) and bevacizumab 7.5 mg/kg IV q3weeks. In cohort 2, the bevacizumab dose was escalated to 15 mg/kg IV q3weeks. In cohort 3, patients received sirolimus 4 mg PO daily and bevacizumab 15 mg/kg IV q3weeks. CT scans were performed every 6 weeks (2 cycles). Results: 28 patients enrolled from 5/08 to 10/09. The most common tumor types were colorectal (21%), head/neck (14%), and renal cell (11%). No DLTs were observed in cohorts 1 (4 patients) and 2 (12 patients). For cohort 3, one DLT (grade 3 confusion) was observed in the first three patients. The cohort was expanded to 6 patients, and another DLT (grade 3 fatigue) was observed. At this point, the dose in cohort 3 was designated the RPTD and no further dose escalation was planned. The cohort was further expanded to 12, and an additional two grade 3 toxicities observed (fatigue and liver transaminase elevation). The most common grade 3 toxicities overall were fatigue (14%), hypertension (14%), anorexia (11%), dyspnea (11%), diarrhea (11%), and hypokalemia (11%), and one patient developed grade 4 toxicity (hypoxia). There were no partial responses, but stable disease was observed for up to 30 weeks (tongue cancer). The mean percent change in tumor size at best response was −2.9% (SD = 12.0%), based on 18 patients with evaluable and measurable disease. Conclusions: The combination of sirolimus and bevacizumab is well tolerated, and can be combined at full dose. The availability and cost of sirolimus (<$1000/month) compared with other mTOR inhibitors make this an attractive agent to combine with bevacizumab. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
O117 : Predictors of clinical response: Results from a large, randomized controlled study with tenofovir disoproxil fumarate (TDF) plus peginterferon alfa-2A (PEG) combination for chronic hepatitis B (CHB)
Authors: H.L. Chan, S.H. Ahn, W.L. Chuang, A.J. Hui, F. Tabak, R. Mehta, J. Petersen, C.-M. Lee, X. Ma, F.A. Caruntu, W.Y. Tak, M. Elkhashab, L. Lin, P. Dinh, E.B. Martins, P. Charuworn, J.G. McHutchinson, G.M. Subramanian, S.G. Lim, G.R. Foster, S. Fung, L. Morano, D. Samuel, K. Agarwal, R. Idilman, S. Strasser, M. Buti, G.B. Gaeta, G. Papatheodoridis, R. Flisiak, P. Marcellin
Journal: Journal of Hepatology (2015)