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Autosomal dominant mutations in transcription factor 4 (TCF4) are associated with a rare syndromic form of Autism Spectrum Disorder (ASD) called Pitt-Hopkins Syndrome (PTHS). Here, we report the generation of a collection of induced pluripotent stem cells (iPSCs) from 5 patients diagnosed with PTHS and 5 familial controls. These patient-derived iPSCs contain a variety of mutations within the TCF4 gene, possess a normal karyotype and express all the appropriate pluripotent stem cell markers. These novel patient lines will be a useful resource for the research community to study PTHS and the function of TCF4.Long non-coding RNA predicting cardiac remodeling (lnc LIPCAR) was implicated in several human diseases, while its role in atrial fibrillation (AF) remained poorly understood. Our study aimed to discover the role of LICPAR played in AF. Samples of atrial muscle tissues from patients diagnosed with sinus rhythm (SR) and atrial fibrillation (AF) were collected, and human atrial fibroblasts were isolated and identified under immunofluorescence staining. After Angiotensin II (Ang II, as a activator of TGF-β) stimulation with LICPAR overexpression or knockdown, the viability and proliferation of atrial fibroblasts were respectively determined using cell counting kit-8 (CCK-8) assay and clone formation assay. Relative expressions of LICPAR, fibrosis- and transforming growth factor-β (TGF-β)/Smad2/3-pathway related proteins were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. LICPAR and TGF-β1 were upregulated and were positively correlated in atrial muscle tissues from AF. Atrial fibroblasts were identified as Vimentin positive. Further analysis indicated that Ang II enhanced the levels of LIPCAR, Smad2/3 phosphorylation and α-smooth muscle actin (α-SMA). Also, upregulating LIPCAR further promoted the promotive effects of Ang II on levels of LIPCAR, Collagen I, Collagen II, α-SMA and Smad2/3 phosphorylation, cell viability and proliferation of atrial fibroblasts, whereas silencing LIPCAR resulted in opposite effects. LICPAR regulates atrial fibrosis via modulating TGF-β/Smad pathway, which provided a potential therapeutic method for AF in clinical practice in the future.A unique endometrial immune reaction should occur to promote the human embryo implantation. We postulated that an immune disequilibrium may impact the initial dialogue between the mother and her embryo. In 2012, we set a method of uterine immune profiling for patients with unexplained repeated implantation failures (RIF). The method documents the local Th-1/ Th-2 equilibrium and the recruitment and state of maturation/activation of uNK cells. In function of the disequilibrium observed, personalization of assisted reproductive treatments was suggested. read more As the concept of personalization in function of the uterine immune profile had never been proposed, a large cohort study and a controlled cohort study were first conducted in RIF patients. 80 % of the RIF patients showed a local disequilibrium if compared to fertile controls. The local disequilibrium was identified in 3 categories over-immune activation in 45 %, low- local immune activation in 25 % and mixed profile in 10 %. Personalization of treatments in function of the immune profile allowed to restore a live birth rate by 40 % at the following embryo transfer. RIF patients with endometriosis show some particularities regarding their immune profiles. We also suggested that immunotherapy (corticoids, intralipids) may have targeted indications based on a better understanding of the immune type of disequilibrium documented. Personalization of treatments for RIF patients seems to be essential to promote the subsequent live birth rate. The endometrial immune profiling is an innovative method aiming to detect a local immune disequilibrium and, if present, to test preventively its correction under treatment.Radix aconiti lateralis (Fuzi) is widely used in China as a traditional Chinese medicine for the treatment of asthenia, pain and inflammation. However, its toxic alkaloids often lead to adverse reactions. Currently, most of the toxicity studies on Fuzi are focused on the heart and nervous system, and more comprehensive toxicity studies are needed. In this study, based on the previous reports of Fuzi hepatotoxicity, serum pharmacochemistry and network toxicology were used to screen the potential toxic components of Heishunpian(HSP), a processed product of Fuzi, and to explore the possible mechanism of HSP-induced hepatotoxicity. The results obtained are expressed based on the toxicological evidence chain (TEC). It was found that 22 potential toxic components screened can affect Th17 cell differentiation, Jak-STAT signaling pathway, glutathione metabolism, and other related pathways by regulating AKT1, IL2, F2, GSR, EGFR and other related targets, which induces oxidative stress, metabolic disorders, cell apoptosis, immune response, and excessive release of inflammatory factors, eventually inducing liver damage in rats. This is the first study on HSP-induced hepatotoxicity based on the TEC concept, providing references for further studies on the toxicity mechanism of Fuzi.Tebuconazole (TBZ), an azole pesticide, is one of the most frequently detected fungicides in surface water. Despite its harmful effects, mainly related to endocrine disturbance, the consequences of TBZ exposure in amphibians remain poorly understood. Here, we investigated the adverse and delayed effects of TBZ chronic exposure on a native anuran species, often inhabiting cultivated areas, the Italian tree frog (Hyla intermedia). To disclose the multiple mechanisms of action through which TBZ exerts its toxicity we exposed tadpoles over the whole larval period to two sublethal TBZ concentrations (5 and 50 μg/L), and we evaluated histological alterations in three target organs highly susceptible to xenobiotics liver, kidney, and gonads. We also assessed morphometric and gravimetric parameters snout-vent length (SVL), body mass (BM), liver somatic index (LSI), and gonad-mesonephros complex index (GMCI) and determined sex ratio, gonadal development, and differentiation. Our results show that TBZ induces irreversible effects on multiple target organs in H. intermedia, exerting its harmful effects through several pathological pathways, including a massive inflammatory response. Moreover, TBZ markedly affects sexual differentiation also by inducing the appearance of sexually undetermined individuals and a general delay of germ cell maturation. Given the paucity of data on the effects of TBZ in amphibians, our results will contribute to a better understanding of the environmental risk posed by this fungicide to the most endangered group of vertebrates.Chlorantraniliprole (CAP) is extensively used for rice pest management. Lack of information on the role of standing water and amount and timing of rainfall on CAP dissipation in rice ecosystem could hamper its prospective use. Present study was performed to investigate the effects of different water regimes (saturated, 5 and 10 cm standing water) and simulated rainfall (40 and 100 mm occurred at 4, 8 and 24 h after CAP application) on leaching, surface runoff and dissipation of CAP into components of rice ecosystem. The results showed highest concentration of CAP residues in soil and plant under saturated condition followed by 5 and 10 cm standing water conditions. Whereas, the highest concentration of CAP in leachates was detected under 10 cm standing water (12.19 ng mL-1). The results revealed large amount of leaching (21.99 ng mL-1) and surface runoff (42.25 ng mL-1) losses of CAP when 100 mm rainfall occurred at 4 h after pesticide application. The total quantity of CAP residues in soil and plant was highest when rainfall occurred at 24 h after pesticide application under both the rainfall amounts. Water stagnation and high intensity rainfall occurred shortly after pesticide application will contribute to pesticide loss to non-target sites through surface run-off and leaching. There will be less pesticide available in soil for plant uptake which may not be sufficient to kill the target organisms.We describe a unique case of focal nodular hyperplasia (FNH) in a 6-month-old-girl with elevated alpha-fetoprotein (AFP). Given the patient's age and elevated AFP, a diagnosis of hepatoblastoma was presumed. However, the histopathologic assessment of the lesion was typical for focal nodular hyperplasia. This was further corroborated using hepatobiliary contrast agent to exclude the possibility of a collision or a composite liver tumor.
Sepsis is defined as organ dysfunction due to severe infection. Septic patients face a significant mortality risk. Thus, timely recognition with prompt focus identification and control are essential. This study aims to determine the current role of computed tomography (CT) in the diagnostic workup of septic patients.

We retrospectively identified 357 patients in the emergency department (ED) of a large university center with suspected sepsis in a two-year period. A total of 132 patients underwent CT scanning within 72h of admission. Patients were characterized by clinical and laboratory findings. CT reports were categorized and matched with clinical data.

Of 357 ED patients with suspected sepsis, 37.0% (132/357) underwent CT imaging within 72h. The most commonly identified septic foci in CT were chest 38.6% (49/127), abdomen 22.0% (28/127) and genitourinary tract 20.5% (26/127) in descending order. The focus detection rate was 76.5% per patient with a concurrent number-needed-to-scan of 1.31. Contrast mms less relevant for focus detection than expected, as it did not increase diagnostic confidence.
Chromium picolinate (CrPic) and vitamin D3 are known as two antioxidant micronutrients. Through inducing endothelial dysfunction, oxidants such as homocysteine (Hct) and malondialdehyde (MDA) lead to cardiovascular disease in type 2 diabetes mellitus (T2DM). No published data has directly examined the effects of these two antioxidants on improving the endothelial dysfunction in T2DM throughreducing homocysteine and oxidative stress.

Subjects (n = 92) in this randomized, double blind, placebo-control study were randomly assigned to receive oral placebo (group I), D
(group II 50,000 IU/ week), chromium picolinate (CrPic) (group III 500 μg/day), and both vitamin D
and CrPic (group IV) for four months. Fasting blood samples were drawn at study baseline and following intervention to determine Hct, MDA, total antioxidant capacity (TAC), total thiol groups (SHs), vascular cell adhesion molecule- 1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1).

After intervention, MDA significantly decreased in groups II and IV; TAC significantly increased in group IV, and SHs significantly augmented in group III; Hct was significantly reduced in groups II, III, and IV; and VCAM-1 significantly decreased in groups III and IV and PAI-1 was significantly reduced in groups II, III, and IV.

Our findings suggest that through reducing homocysteine and oxidative stress and improving endothelial dysfunction, chromium and vitamin D
co-supplementation might be predictive and preventive of cardiovascular diseasesassociated with T2DM. IRCT, IRCT20190610043852N1, registered 21 October 2019, https//fa.irct.ir/user/trial/42293/view.
Our findings suggest that through reducing homocysteine and oxidative stress and improving endothelial dysfunction, chromium and vitamin D3 co-supplementation might be predictive and preventive of cardiovascular diseasesassociated with T2DM. IRCT, IRCT20190610043852N1, registered 21 October 2019, https//fa.irct.ir/user/trial/42293/view.
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