T Helper Cells Fate Mapping by Co-stimulatory Molecules and its Functions in Allograft Rejection and Tolerance

T cell differentiation is dictated by a combination of T cell receptor (TCR) interaction with an antigen-bound major histocompatibility complex (MHC), and co-stimulatory molecules signal. The co-stimulatory signal can be positive or negative, and amplifying or diminishing the initial signal. However, the secondary co-stimulatory signal is not obligatory and its necessity is dictated, in part, by the stage of T cell development. In the field of transplantation, directing the T cell differentiation process can lead to therapeutic possibilities that promote allograft tolerance, and hinder unfavorable alloimmune responses. Therefore, understanding the details of T cell differentiation process, including the influence of co-stimulatory signals, is of paramount importance. It is important to note there is functional overlap between co-stimulatory molecules. It has been observed that some co-stimulatory signals have different effects on different T cell subsets. Hence, blockade of a co-stimulatory signal pathway, as part of a therapeutic regimen in transplantation, may have far reaching effects beyond the initial therapeutic intent and inhibit co-stimulatory signals necessary for desirable regulatory responses. In this review, co-stimulatory molecules involved in the differentiation of naïve T cells into T helper 1 (Th1), T helper 2 (Th2), T helper 17 (Th17), inducible regulatory T cells (iTregs), and T helper 9 (Th9) cells and their overlap are discussed

Exertional abdominal pain as a symptom of secondary pulmonary hypertension in mitral stenosis

We report a rare presentation of mitral stenosis (MS). MS is a common valvular disease, the first manifestation of which is usually easy fatigability and exertional dyspnea. As the disease progresses in severity, other signs and symptoms appear, such as orthopnea, hemoptysis, and peripheral edema. This is the first report of a case of mitral stenosis presenting with exertional abdominal pain as the first manifestation. This case report describes the clinical characteristics of a 55-year-old woman with mitral stenosis and severe pulmonary hypertension, whose first symptom was exertional abdominal pain.Key words: Abdominal pain, mitral stenosis, pulmonary hypertensio

Association between sleep duration and diabetes mellitus: Isfahan Healthy Heart Program

Background: Recent studies revealed an association between sleep disturbance and metabolic disorders, such as obesity and metabolic syndrome. An aim of this study was to assess the relation between sleep duration and diabetes mellitus in a representative sample of the Iranian population.Materials and Methods: Participants were 12514 individuals, (6123 men  and 6391 women) studied in the baseline survey of a community based program entitled Isfahan healthy heart program (IHHP). Sleep time was obtained by validated questionnaire. Diabetes mellitus was defined as fasting glucose over 126 mg/dl or 2 hour post prandial glucose at glucose tolerance test over 200 mg/dl, or if the patient was on diabetic medication. The relation between the sleep time and diabetes was examined using categorical logistic regression with adjustment for sex, body mass index and waist circumference.Results: Compared with those, sleeping 7.8 hours per night, the  individuals with sleeping time of 5 hours or less and aged <60 years had an increased odd ratio for diabetes and an impaired glucose tolerance. (OR = 1.37 and 95% CI = 1.13,1.67).Conclusion: Sleep duration of 5 hours or less in individuals under age 60 years is associated with an increased prevalence of diabetes mellitus and an impaired glucose tolerance test. This finding should be confirmed in longitudinal studies.Key words: Diabetes mellitus, glucose tolerance, slee

Various methods of simulating wave kinematics on the structural members of 100-year responses

The main force acting on an offshore structure is usually due to wind-generated random waves. According to the Morison equation, the wave force on a cylindrical member of an offshore structure depends on wave kinematics at the centre of the element. It is therefore essential to accurately estimate the magnitude of wave-induced water particle kinematics at all points in a random wave field. Linear random wave theory (LRWT) is the most-frequently used theory to simulate water particle kinematics at different nodes of an offshore structure. Several empirical techniques have been suggested to provide a more realistic representation of the near-surface wave kinematics. The empirical techniques popular in the offshore industry include Wheeler stretching and vertical stretching. Most recently, two new effective methods (effective node elevation and the effective water depth) have been recently introduced. The problem is that these modified methods differ from one another in their predictions. Hence, the aim of this study is to investigate the effects of predicting the 100-year responses from various methods of simulating wave kinematics accounting for the current effect. In this paper, four versions of the wave kinematics procedure have been tested by comparing the short-term probability distributions of extreme responses. For all current cases, the highest vertical ratios for zero, positive and negative current cases are 1.414, 1.175 and 1.831, respectively. It is observed that even for positive-current cases, the difference between Wheeler and vertical stretching predictions is quite high and cannot be neglected. Thus, further investigation is necessary to resolve this problem and the outcomes in providing useful design information for the oil and gas industry

Prolonged, Low-Dose Anti-Thymocyte Globulin, Combined with CTLA4-Ig, Promotes Engraftment in a Stringent Transplant Model

Background: Despite significant nephrotoxicity, calcineurin inhibitors (CNIs) remain the cornerstone of immunosuppression in solid organ transplantation. We, along with others, have reported tolerogenic properties of anti-thymocyte globulin (ATG, Thymoglobulin®), evinced by its ability both to spare Tregs from depletion in vivo and, when administered at low, non-depleting doses, to expand Tregs ex vivo. Clinical trials investigating B7/CD28 blockade (LEA29Y, Belatacept) in kidney transplant recipients have proven that the replacement of toxic CNI use is feasible in selected populations. Methods: Rabbit polyclonal anti-murine thymocyte globulin (mATG) was administered as induction and/or prolonged, low-dose therapy, in combination with CTLA4-Ig, in a stringent, fully MHC-mismatched murine skin transplant model to assess graft survival and mechanisms of action. Results: Prolonged, low-dose mATG, combined with CTLA4-Ig, effectively promotes engraftment in a stringent transplant model. Our data demonstrate that mATG achieves graft acceptance primarily by promoting Tregs, while CTLA4-Ig enhances mATG function by limiting activation of the effector T cell pool in the early stages of treatment, and by inhibiting production of anti-rabbit antibodies in the maintenance phase, thereby promoting regulation of alloreactivity. Conclusion: These data provide the rationale for development of novel, CNI-free clinical protocols in human transplant recipients

Comparison of efficacy and safety of two available natural surfactants in Iran, Curosurf and Survanta in treatment of neonatal respiratory distress syndrome: A randomized clinical trial

Introduction The benefit of surfactant prescription for respiratory distress syndrome (RDS) has been approved. Curosurf and Survanta are two commonly used natural surfactants in Iran. Previous studies did not report priority for one of these two drugs. The present study aimed to compare the effectiveness and safety of Curosurf and Survanta in treatment of RDS. Methods In this randomized clinical trial, neonates were born with RDS diagnosis in two governmental and referral hospitals of Tehran (the capital of Iran) in 2014 were randomly selected. Neonates were randomly assigned into two groups receiving 100 mg/kg Curosurf or Survanta as soon as possible after randomization. Complications, mortality and needing the second dose were compared between the two groups. Results A total 112 patients with the mean gestational age of 32.59 ± 3.39 weeks were evaluated (56 patients in each group). There were no significant differences regarding birth weight, gestational age, delivery method, and parity between the two groups (P > 0.05). The complications were occurred in 18 neonates (32.1) of Curosurf group and 20 neonates (35.7) of Survanta group (RR = 0.922, 95 CI = 0.617-1.379). There were no significant differences regarding complications, mortality, and needing nasal CPAP and endotracheal tube between the two groups. In the neonates with gestational age of 29-32 weeks the IVH and NEC incidence were significantly more in Curosurf group compared to Survanta group (27.8 vs 0 and 22.3 vs 0, P 32 birth weeks subgroup) and NCPAP (in 29-32 birth weeks subgroup) (p = 0.008). Further evaluations with longer follow-up duration are needed for comparing these two surfactants. © 2016 Published by Elsevier Inc

Cooling dynamics of carbon cluster anions

A series of ion storage experiments on small carbon cluster anions was conducted to understand size-dependent cooling processes. The laser-induced delayed electron detachment time profile show clear even/odd alternation due to the presence of the electronic cooling. The time evolution of the internal energy distribution was simulated for Cn- (n=4 to 7) with a common procedure taking vibrational and electronic cooling into account

Offshore structural reliability assessment by probabilistic procedures—a review

Offshore installations must be built to resist fatigue as well as extreme forces caused by severe environmental conditions. The structural reliability analysis is the popular practise to assess a variety of natural waves determined by the long‐term probability distribution of wave heights and corresponding periods on the site. In truth, however, these structures are subjected to arbitrary wave‐induced forces in the open ocean. Hence, it is much more reasonable to account for the changed loading characteristics by determining the probabilistic characteristics of the random loads and outcomes responses. The key challenges are uncertainties and the non‐linearity of Morison’s drag element, which results in non‐Gaussian loading and response distributions. This study would analyze advances achieved to date in a comprehensive probabilistic review of offshore fixed jacket-type platforms

The association between sleeping time and metabolic syndrome features among older adults living in Mediterranean region. The MEDIS study.

Background: Metabolic Syndrome (MetS) as a combination of features has been known to significantly increase Cardiovascular Disease (CVD) risk, whilst MetS presence is linked to lifestyle parameters including physical activity and dietary habits; recently, the potential impact of sleeping habits has also become an issue under consideration. The aim of this study was to investigate the role of sleep quantity in several MetS components. Methods: Design:Cross-sectional observational study. Setting: 26 Mediterranean islands and the rural Mani region (Peloponnesus) of Greece. Participants: during 2005-2017, 3130 older (aged 65-100 years) Mediterranean residents were voluntarily enrolled. Measurements: Dietary habits (including MedDietScore assessment), physical activity status, socio-demographic characteristics, lifestyle parameters (sleeping and smoking habits) and clinical profile aspects including Metabolic Syndrome (MetS) components (i.e., waist circumference, systolic and diastolic blood pressure, fasting glucose, triglycerides, LDL and HDL-cholesterol) were derived through standard procedures. Results: The number of daily hours of sleep was independently associated with greater waist circumference (b coefficient per 1 hour=0.91, 95% Confidence Interval (CI); 0.34, 1.49), higher LDL-cholesterol levels (b per 1 hour=3.84, 95%CI; 0.63, 7.05) and lower diastolic blood pressure levels (b per 1 hour=-0.98, 95%CI; - 1.57, -0.39) after adjusting for participants’ age, gender, body mass index, daily walking time, level of adherence to Mediterranean diet and smoking status. No association was revealed between hours of sleep per day and fasting glucose, triglycerides, HDL-cholesterol and systolic blood pressure. Conclusions: Increased hours of sleep is an indicator of metabolic disorders among elderly inviduals, and further research is needed to identify the paths through which sleep quantity is linked to MetS features in different age-groups