Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny

The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl₂ in drinking water; group 3 received 350 ppm CoCl₂ in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity.Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.     

Impact of sertraline on weight,waist circumference and glycemic control: A prospective clinical trial on depressive diabetic type 2 patients

Aim

Depression is prevalent in patients with type 2 diabetes. It may have a negative impact on the management of diabetes mellitus and could affect weight. The main aim of the investigation was to evaluate the effect of antidepressant treatment (sertraline) on anthropometric variables and glycemic control in depressed type 2 diabetic patients.

Spontaneous pneumothorax and Recklinghausen's disease: a case report

The Von Recklinghausen disease is a genetic hereditary neurofibromatosis. It causes neurofibroma, axillary and inguinal lentigines, and café-au-lait spots in the skin. It may affect the lung in 5 to 20% of cases, causing neurofibroma, infiltrative and cystic lesions, emphysematous or bubble injury leading to a chronic respiratory failure. The risk of pneumothorax in theses cases seems higher. Few reviews reported the pulmonary manifestations in the Recklinghausen disease and specially the pneumothorax as a complication while the direct relation between this neurofibromatosis and the lung disease is not clearly established yet. We report a case report of spontaneous pneumothorax with slow evolution complicating the course of a patient with Recklinghausen disease.     

Design of a chattering-free integral terminal sliding mode approach for DFIG-based wind energy systems

This article proposes a Fuzzy Second Order Integral Terminal Sliding Mode (FSOITSM) control approach for DFIG-based wind turbines subject to grid faults and parameter variations. Since traditional terminal sliding mode control (SMC) suffers from singularity, a novel integral terminal sliding manifold is proposed to eliminate chattering and improve the wind turbine's performance in the presence of faults and disturbances. A fuzzy system is proposed to auto-tune the controllers' gains and ensures the invariance of the sliding surfaces even under heavy uncertainties, thus further improving the reliability and performance of the proposed controller. The performance of the proposed approach was assessed under various operating conditions. A comparison analysis with a standard SMC approach as well as the state of the art in voltage sag mitigation was also carried over. Reliability, robustness, and power availability under faulty grid conditions are among the main features of the proposed approach. In addition, the proposed approach exhibited chattering free dynamics and enabled the finite time convergence of the sliding manifold and overcame the singularity problem associated with standard TSMC.     

Bone mineral density in healthy Tunisian women

Interpretation of densitometric results requires a comparison with reference bone mineral density (BMD) values of normal age and sex-matched persons. Thus the aim of this study was to determine these values for healthy Tunisian women, to estimate the prevalence of osteoporosis and to compare our findings with other populations. A cross-sectional study of 1378 Tunisian women aged between 20 and 96 years was carried out using DXA (GE-Lunar Prodigy). Subjects with suspected conditions affecting bone metabolism were excluded. Measurements were taken at the lumbar spine and femoral neck. These values were expressed at T-scores, with reference to the mean BMD values of the group aged 20–40 years. The peak bone mass, estimated in this age group was 1.174 + 0.127 g/cm² at the lumbar spine and 1.016 ± 0.118 g/cm² at the femoral site. It was attained respectively within the age of 25 years and 36 years. For both sites, the expected decline in BMD was shown when the successive age groups [40–49 years] and [50–59 years] were compared. Bone loss was rapid during the first 5 years after menopause. Thereafter BMD declined slowly but continually. The prevalence of osteoporosis in the women over 50 years of age, taking account of peak bone mass observed in our cohort, was 23.3% at the spine and 17.3% at the femoral neck with a combined prevalence of 23.4%. These rates attained respectively 30.4%, 11.8% and 32.9% when we considered the Italian values, which demonstrate the variability of osteodensitometric depending to the reference population adopted.     

Hepatotoxicity induced by gibberellic acid in adult rats and their progeny

Gibberellic acid (GA₃), a plant growth regulator, was largely used in agriculture of many countries including Tunisia. However, its potential hazardous effects on human health were relatively unexplored. The purpose of this study was to investigate the effects of GA₃ on hepatic function in female rats and their pups. Animals were given daily 200 ppm GA₃ in drinking water from the 14th day of pregnancy until day 14 after delivery. It was found that GA₃ induced liver damages as evidenced by the elevation of plasma aminotransferases (ALT, AST), lactate dehydrogenase activities, bilirubin and albumin levels. Hepatotoxicity was objectified by the significant increase of malondialdehyde (MDA) level and a decrease of antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione content in liver of suckling pups and their mothers. Impairment of hepatic function corresponded histologically. We have observed blood vessels congestion and leucocytes infiltration, which were more pronounced in hepatocytes of dams than those of suckling pups.Results of this current study suggest that exposure rats to GA₃ induces hepatotoxicity and histopathological changes in liver of female rats and their progeny.