H-adaptive finite element analysis of consolidation problems in geomechanics

In this paper, a computational framework based on the h-adaptive finite element strategy is presented for the solution of consolidation problems in geomechanics. The efficiency and performance of alternative error estimation techniques is demonstrated via the analysis of a slope stability problem

Radiological anatomy of distal phalanx of front foot in the pure Iranian Arabian horse

Background: Among the different breeds of horses, Asil horses with a five thousand year history have played an important role in human life. This study was designed as a result of the lack of information about the normal radiographic anatomy of this breed. Materials and methods: Radiography of the distal phalanx and associated soft tissue structures of the front feet of 10 healthy pure Iranian Arabian horses was performed on lateromedial radiographic projection to determine normal radiographic morphometry of this part. There were no problems in their limbs and in their history. Results: Obtained radiograph of each front distal phalanx was used to measure important distances, angles and ratios of the hoof wall. There was no significant difference between left and right digits for any radiographic determination. Conclusions: Measurements of this study differed from those reported in other breeds, so it can be used in the future as reference values for diagnosis of laminitis in front feet of Iranian Arabian horses.

Rodent models of neuroinflammation for Alzheimer\u27s disease

Alzheimer\u27s disease remains incurable, and the failures of current disease-modifying strategies for Alzheimer\u27s disease could be attributed to a lack of in vivo models that recapitulate the underlying etiology of late-onset Alzheimer\u27s disease. The etiology of late-onset Alzheimer\u27s disease is not based on mutations related to amyloid-beta (A beta) or tau production which are currently the basis of in vivo models of Alzheimer\u27s disease. It has recently been suggested that mechanisms like chronic neuroinflammation may occur prior to amyloid-beta and tau pathologies in late-onset Alzheimer\u27s disease. The aim of this study is to analyze the characteristics of rodent models of neuroinflammation in late-onset Alzheimer\u27s disease. Our search criteria were based on characteristics of an idealistic disease model that should recapitulate causes, symptoms, and lesions in a chronological order similar to the actual disease. Therefore, a model based on the inflammation hypothesis of late-onset Alzheimer\u27s disease should include the following features: (i) primary chronic neuroinflammation, (ii) manifestations of memory and cognitive impairment, and (iii) late development of tau and A beta pathologies. The following models fit the pre-defined criteria: lipopolysaccharide-and PolyI:C-induced models of immune challenge; streptozotocin-, okadaic acid-, and colchicine neurotoxin-induced neuroinflammation models, as well as interleukin-1 beta, anti-nerve growth factor and p25 transgenic models. Among these models, streptozotocin, PolyI:C-induced, and p25 neuroinflammation models are compatible with the inflammation hypothesis of Alzheimer\u27s disease

First Detection of Nosema ceranae, a Microsporidian Protozoa of European Honeybees (Apis mellifera) In Iran

Background: Nosemosis of European honey bee (Apis mellifera) is present in bee colonies world­wide. Until recently, Nosema apis had been regarded as the causative agent of the disease, that causes heavy economic losses in apicultures. Nosema ceranae is an emerging microsporidian para­site of European honeybees, A. mellifera, but its distribution is not well known. Previously, nosemosis in honeybees in Iran was attributed exclusively to N. apis.Methods: Six Nosema positive samples (determined from light microscopy of spores) of adult worker bees from one province of Iran (Savadkouh- Mazandaran, northern Iran) were tested to determine Nosema species using previously- developed PCR primers of the 16 S rRNA gene. As it is difficult to distinguish N. ceranae and N. apis morphologically, a PCR assay based on 16 S ribosomal RNA has been used to differentiate N. apis and N. ceranae.Results: Only N. ceranae was found in all samples, indicating that this species present in Iran apiar­ies.Conclusion: This is the first report of N. ceranae in colonies of A. mellifera in Iran. It seems that intensive surveys are needed to determine the distribution and prevalence of N. ceranae in differ­ent regions of Iran

Investigating the Relationship between hs-CRP Serum Level and Insulin Resistance (HOMA IR) Six Weeks after Childbirth in Patients with Gestational Diabetes Mellitus

Background: Some patients with GDM (Gestational Diabetes Mellitus) still experience impaired glucose tolerance after childbirth and will be affected by diabetes mellitus type 2. Objectives: The aim of this study is to investigate the relationship between hs-CRP serum levels with insulin resistance six weeks after childbirth in patients with gestational diabetes mellitus type 2. Methods: In this descriptive cross-sectional study, 110 patients with GDM were evaluated in terms of the insulin resistance index (HOMA), hs-CRP serum, and the oral glucose tolerance test (OGTT) six weeks after childbirth. Their anthropometric indices were measured in the early pregnancy. Spearman’s rank correlation coefficient and linear regression analysis were used to analyze data in SPSS 16. Results: The mean of hs-CRP was 8.72 µg/ml among the patients in this study. It is higher than the normal range. Moreover, 24.5% of the patients were suffering from impaired glucose tolerance, and hs-CRP levels were higher than the normal range in 92.6% of these patients. Furthermore, 41.8% of patients showed insulin resistance, and hs-CRP levels were high among 73.9% of them. After age adjustment, the increase in hs-CRP serum level was significantly correlated with insulin resistance (HOMA) and the one-hour and two-hour OGTTs (p=0.007 and p<0.001, respectively). Conclusion: It appears that age adjustment can help us figure out the relationship between the increase in hs-CRP serum and insulin resistance in pregnant mothers with diabetes six weeks after childbirth

An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy

BACKGROUND AND AIMS: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated disease of the peripheral nerves, with significant unmet treatment needs. Clinical trials in CIDP are challenging; thus, new trial designs are needed. We present design of an open-label phase 2 study (NCT04658472) evaluating efficacy and safety of SAR445088, a monoclonal antibody targeting complement C1s, in CIDP. METHODS: This phase 2, proof-of-concept, multicenter, open-label trial will evaluate the efficacy, and safety of SAR445088 in 90 patients with CIDP across three groups: (1) currently treated with standard-of-care (SOC) therapies, including immunoglobulin or corticosteroids (SOC-Treated); (2) refractory to SOC (SOC-Refractory); and (3) naïve to SOC (SOC-Naïve). Enrolled participants undergo a 24-week treatment period (part A), followed by an optional treatment extension for up to an additional 52 weeks (part B). In part A, the primary endpoint for the SOC-Treated group is the percentage of participants with a relapse after switching from SOC to SAR445088. The primary endpoint for the SOC-Refractory and SOC-Naïve groups is the percentage of participants with a response, compared to baseline. Secondary endpoints include safety, tolerability, immunogenicity, and efficacy of SAR445088 during 12-week overlapping period (SOC-Treated). Part B evaluates long-term safety and durability of efficacy. Data analysis will be performed using Bayesian statistics (predefined efficacy thresholds) and historical data-based placebo assumptions to support program decision-making. INTERPRETATION: This innovative trial design based on patient groups and Bayesian statistics provides an efficient paradigm to evaluate new treatment candidates across the CIDP spectrum and can help accelerate development of new therapies

Metabolic resting-state brain networks in health and disease

The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson\u27s disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood flow PET scans acquired at rest and during task performance. Consistent task-related deactivation of the DMN-like dominant metabolic RSN was observed in healthy subjects and early PD patients; in contrast, the subordinate RSNs were activated during task performance. Network deactivation was reduced in advanced PD; this abnormality was partially corrected by dopaminergic therapy. Time-course comparisons of DMN loss in longitudinal resting metabolic scans from PD and Alzheimer\u27s disease subjects illustrated that significant reductions appeared later for PD, in parallel with the development of cognitive dysfunction. In contrast, in Alzheimer\u27s disease significant reductions in network expression were already present at diagnosis, progressing over time. Metabolic imaging can directly provide useful information regarding the resting organization of the brain in health and disease

Observation of cardiac profile among the adult population of Sreemangal

Background: Cardiovascular diseases are a leading cause of morbidity and mortality worldwide. The prevalence and risk factors of CVDs vary across different populations and regions. This study aimed to observe the cardiac profile among the adult population of Sreemangal, Bangladesh, to identify the prevalence and risk factors of CVDs in this population. Methods: This prospective observational study was conducted over a six-month period at a public health camp in Sreemangal, Bangladesh. A total of 137 adult participants were purposively selected. Data were collected through a structured questionnaire and physical examination, including measurements of blood pressure and laboratory analysis of blood samples. Results: The study found that 44.53% of participants had elevated blood pressure, and 21.90% had stage 1 hypertension. Interestingly, 36.50% of participants were unaware of their hypertension status. Furthermore, 26.28% of participants had a known history of diabetes, but blood glucose level analysis revealed an additional 14.85% of participants were prediabetic, and 6.93% were diabetic based on fasting blood glucose levels. A statistically significant association was found between increasing age and the stage of hypertension (p&lt;0.001), and between fasting and normal blood glucose levels and the stage of hypertension (p&lt;0.005 and p&lt;0.05, respectively). Conclusions: The findings of this study underscore the need for targeted interventions to prevent and manage CVDs in the adult population of Sreemangal, Bangladesh. These interventions should include regular screening for CVD risk factors, health education to increase awareness of these risk factors, and strategies to promote healthy lifestyle behaviors