Aseptic meningoencephalitis mimicking transient ischaemic attacks

Purpose: To highlight meningoencephalitis as a transient ischaemic attack (TIA) mimic and suggest clinical clues for differential diagnosis. Methods: This was an observational study of consecutively admitted patients over a 9.75-year period presenting as TIAs at a stroke unit. Results: A total of 790 patients with TIAs and seven with TIA-like symptoms but a final diagnosis of viral meningoencephalitis were recognised. The most frequent presentations of meningoencephalitis patients were acute sensory hemisyndrome (6) and cognitive deficits (5). Signs of meningeal irritation were minor or absent on presentation. Predominantly lymphocytic pleocytosis, hyperproteinorachia and a normal cerebrospinal fluid (CSF)/serum glucose index (in 5 out of 6 documented patients) were present. Meningeal thickening on a brain magnetic resonance imaging (MRI) scan was the only abnormal imaging finding. Six patients received initial vascular treatment; one thrombolysed. Finally, six patients were treated with antivirals and/or antibiotics. Although neither bacterial nor viral agents were identified on extensive testing, viral meningoencephalitis was the best explanation for all clinical and laboratory findings. Conclusions: Aseptic meningoencephalitis should be part of the differential diagnosis in patients presenting as TIA. The threshold for a lumbar puncture in such patients should be set individually and take into account the presence of mild meningeal symptoms, age and other risk factors for vascular disease, the results of brain imaging and the basic diagnostic work-up for a stroke sourc

Determination of maturation and spawning season of Otolithes ruber (Croaker Fish) in Khuzestan coastal water, Iran

In this study, the stage of gonadal development, type and season of spawning of Otolithes ruber in the North West of Persian Gulf were identified. O.ruber maturation and spawning were studied by macroscopic, microscopic, and histologic observation of gonads which obtained from October 1996 to September 1997 in Khouzestan coasts. In the histologic sections of gonad tissue, stages I to VII of gonadal development were distinguished. Post Spawning follicules were observed only in stages VI and VII (in April and May). Atretic ovums were also clearly observed in these stages. Frequency of Ovum diameter distribution in stages II to V is a unimodal which proves that annual maturation of ovums and spawning of this species are simultaneous. The highest level of GSI was observed in March and also higher stages 01' gonadal maturation were observed in March and April. Fast drop in GSI in May and within occurrence of both spawning and spent individuals in only two months of the year shows the relatively short spawning season is spring (April-May). Sexual maturation of females occured after the males and its first length in females was 216 mm

First-in-Man Phase I Trial of the Selective MET Inhibitor Tepotinib in Patients with Advanced Solid Tumors.

PurposeTepotinib is an oral, potent, highly selective MET inhibitor. This first-in-man phase I trial investigated the MTD of tepotinib to determine the recommended phase II dose (RP2D).Patients and methodsPatients received tepotinib orally according to one of three dose escalation regimens (R) on a 21-day cycle: R1, 30-400 mg once daily for 14 days; R2, 30-315 mg once daily 3 times/week; or R3, 300-1,400 mg once daily. After two cycles, treatment could continue in patients with stable disease until disease progression or unacceptable toxicity. The primary endpoint was incidence of dose-limiting toxicity (DLT) and treatment-emergent adverse events (TEAE). Secondary endpoints included safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effects.ResultsOne hundred and forty-nine patients received tepotinib (R1: n = 42; R2: n = 45; R3: n = 62). Although six patients reported DLTs [one patient in R1 (115 mg), three patients in R2 (60, 100, 130 mg), two patients in R3 (1,000, 1,400 mg)], the MTD was not reached at the highest tested dose of 1,400 mg daily. The RP2D of tepotinib was established as 500 mg once daily, supported by translational modeling data as sufficient to achieve ≥95% MET inhibition in ≥90% of patients. Treatment-related TEAEs were mostly grade 1 or 2 fatigue, peripheral edema, decreased appetite, nausea, vomiting, and lipase increase. The best overall response in R3 was partial response in two patients, both with MET overexpression.ConclusionsTepotinib was well tolerated with clinical activity in MET-dysregulated tumors. The RP2D of tepotinib was established as 500 mg once daily. MET abnormalities can drive tumorigenesis. This first-in-man trial demonstrated that the potent, highly selective MET inhibitor tepotinib can reduce or stabilize tumor burden and is well tolerated at doses up to 1,400 mg once daily. An RP2D of 500 mg once daily, as determined from translational modeling and simulation integrating human population pharmacokinetic and pharmacodynamic data in tumor biopsies, is being used in ongoing clinical trials

Comparison of the Percentage of Regulatory T cells and their p-STAT5 Expression in Allergic and Non-Allergic Common Variable Immunodeficiency Patients

Background: Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by an immunologic deficiency in immunoglobulin production. Regulatory T cells (Tregs) play a key role in preventing the development allergic disorders. p-STAT5 is a known factor for the function and survival of Tregs. This study aimed to investigate the number of Tregs and their p-STAT5 expression in allergic and non-allergic CVID patients. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 10 healthy volunteers, 10 allergic patients, and 16 CVID patients (allergic and non-allergic) using Ficoll density centrifugation. The percentage of Tregs in PBMCs was analyzed by flow cytometry. Tregs were also isolated from participants using an immunomagnetic separation method and p-STAT5 expression was evaluated in Tregs using flow cytometry. Results: The results revealed that Treg percentage was significantly lower in the CVID patients than the control groups (healthy and allergic individuals) (p<0.001). There was a significant reduction in Treg percentage in allergic patients compared to healthy subjects (p<0.05). No significant difference in Treg percentage between allergic and non-allergic CVID patients was observed. The expression of p-STAT5 in Tregs was significantly lower in CVID patients than the control groups (p<0.001). In addition, the expression of p-STAT5 in Tregs of allergic patients was significantly decreased compared to healthy subjects (p<0.001). However, the deference of p-STAT5 level was not statistically significant between allergic and non-allergic CVID patients. Conclusion: These findings suggest that p-STAT5 signaling defect and decreased Treg number may not participate in the development of allergy in CVID patients. © 2018, © 2018 Taylor & Francis

Early-versus-Late Endovascular Stroke Treatment: Similar Frequencies of Nonrevascularization and Postprocedural Cerebrovascular Complications in a Large Single-Center Cohort Study.

Endovascular treatment of acute ischemic stroke is now performed more frequently in the late window in radiologically selected patients. However, little is known about whether the frequency and clinical impact of incomplete recanalization and postprocedural cerebrovascular complications differ between early and late windows in the real world. We retrospectively reviewed all patients with acute ischemic stroke receiving endovascular treatment within 24 hours from 2015 to 2019 and included in the Acute STroke Registry and Analysis of Lausanne. We compared rates of incomplete recanalization and postprocedural cerebrovascular complications (parenchymal hematoma, ischemic mass effect, and 24-hour re-occlusion) in the early (&lt;6 hours) versus late window (6-24 hours, including patients with unknown onset) populations and correlated them with the 3-month clinical outcome. Among 701 patients with acute ischemic stroke receiving endovascular treatment, 29.2% had late endovascular treatment. Overall, incomplete recanalization occurred in 56 patients (8%), and 126 patients (18%) had at least 1 postprocedural cerebrovascular complication. The frequency of incomplete recanalization was similar in early and late endovascular treatment (7.5% versus 9.3%, adjusted P =.66), as was the occurrence of any postprocedural cerebrovascular complication (16.9% versus 20.5%, adjusted P = .36). When analyzing single postprocedural cerebrovascular complications, rates of parenchymal hematoma and ischemic mass effect were similar (adjusted P = .71, adjusted P = .79, respectively), but 24-hour re-occlusion seemed somewhat more frequent in late endovascular treatment (4% versus 8.3%, unadjusted P = .02, adjusted P = .40). The adjusted 3-month clinical outcome in patients with incomplete recanalization or postprocedural cerebrovascular complications was comparable between early and late groups (adjusted P = .67, adjusted P = .23, respectively). The frequency of incomplete recanalization and of cerebrovascular complications occurring after endovascular treatment is similar in early and well-selected late patients receiving endovascular treatment. Our results demonstrate the technical success and safety of endovascular treatment in well-selected late patients with acute ischemic stroke

Food insecurity in adults with severe mental illness living in Northern England: A co-produced cross-sectional study

\ua9 2024 The Authors. Nutrition &amp; Dietetics published by John Wiley &amp; Sons Australia, Ltd on behalf of Dietitians Australia.Aim: This study aimed to explore food insecurity prevalence and experiences of adults with severe mental illness living in Northern England. Methods: This mixed-methods cross-sectional study took place between March and October 2022. Participants were adults with self-reported severe mental illness living in Northern England. The survey included demographic, health, and financial questions. Food insecurity was measured using the US Department of Agriculture Adult Food Security measure. Quantitative data were analysed using descriptive statistics and binary logistic regression; and qualitative data using content analysis. Results: In total, 135 participants completed the survey, with a mean age of 44.7 years (SD: 14.1, range: 18–75 years). Participants were predominantly male (53.3%), white (88%) and from Yorkshire (50.4%). The food insecurity prevalence was 50.4% (n = 68). There was statistical significance in food insecurity status by region (p = 0.001); impacts of severe mental illness on activities of daily living (p = 0.02); and the Covid pandemic on food access (p &lt; 0.001). The North West had the highest prevalence of food insecurity (73.3%); followed by the Humber and North East regions (66.7%); and Yorkshire (33.8%). In multivariable binary logistic regression, severe mental illness\u27 impact on daily living was the only predictive variable for food insecurity (odds ratio = 4.618, 95% confidence interval: 1.071–19.924, p = 0.04). Conclusion: The prevalence of food insecurity in this study is higher than is reported in similar studies (41%). Mental health practitioners should routinely assess and monitor food insecurity in people living with severe mental illness. Further research should focus on food insecurity interventions in this population

Expression of OX40 Gene and its Serum Levels in Neuromyelitis Optica Patients

Neuromyelitis optica (NMO), also known as Devic's disease, is an autoimmune disorder of the central nervous system (CNS) in which immune system cells and antibodies primarily attack the optic nerves and the spinal cord. OX40 (CD134) is a tumor necrosis factor (TNF)-receptor family member expressed primarily on activated CD4 + and CD8 + T-cells. In an autoimmune disease, OX40 is typically up-regulated at sites of inflammation, and increases in the number of peripheral CD4 + T-cells expressing OX40. OX40 and its ligand OX40L are key TNF members that augment T-cell expansion, cytokine production, and promote T-cell survival. The aim of this study was to evaluate and compare of OX40 gene expression and its serum levels in patients with NMO and healthy controls. Twenty sex-/age-matched healthy controls (HC) (median age = 32 years, 15 females/5 males) were engaged for the present study. Expression of OX40 at the transcript level and serum protein levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays, respectively. The results indicated OX40 expression in patients was significantly lower than in healthy controls (p = 0.001). However, the serum level of OX40 was not significantly different between groups (p = 0.37). In addition, the results indicated that CD134 expression was not age-related (p = 0.041). Overall, this study suggests to us that OX40 levels are not a suitable marker for diagnosis or treatment of NMO. © 2019 Parya Alidadiani et al., published by De Gruyter

АНАЛИЗ РЕЛАКСАЦИИ ТРЕХУРОВНЕВОЙ СИСТЕМЫ ВНЕ РАМОК ПРИБЛИЖЕНИЯ ВРАЩАЮЩЕЙСЯ ВОЛНЫ

Quasi-stationary states of the V-configuration three-level system in a driving resonant field is considered in the present article. The main goal of the analysis is to define the conditions when the essential impact on spontaneous emission is possible in this system. It is shown that the spontaneous linewidths substantially change if they are calculated outside the framework of the rotating wave approximation.В настоящей работе исследуются квазистационарные энергетические состояния трехуровневой системы в V-конфигурации, находящейся в управляющем резонансном поле. Целью исследования является определение условий, при которых возможно существенное влияние на вероятность спонтанного излучения в такой системе. Показано, что выход за рамки приближения вращающейся волны значительно изменяет спонтанные ширины линий