Osborneengland9471

The Berlin Fat Mouse Inbred (BFMI) line is a model for juvenile obesity. Previous studies on crosses between BFMI and C57Bl/6N (B6N) have identified a recessive defect causing juvenile obesity on chromosome 3 (jObes1). Bbs7 was identified as the most likely candidate gene for the observed effect. Comparative sequence analysis showed a 1578 bp deletion in intron 8 of Bbs7 in BFMI mice. A CTCF-element is located inside this deletion. To investigate the functional effect of this deletion, it was introduced into B6N mice using CRISPR/Cas9. Two mice containing the target deletion were obtained (B6N Bbs7emI8∆1 and Bbs7emI8∆2) and were subsequently mated to BFMI and B6N to generate two families suitable for complementation. Inherited alleles were determined and body composition was measured by quantitative magnetic resonance. Evidence for a partial complementation (13.1-15.1%) of the jObes1 allele by the CRISPR/Cas9 modified B6N Bbs7emI8∆1 and Bbs7emI8∆2 alleles was found. Mice carrying the complementation alleles had a 23-27% higher fat-to-lean ratio compared to animals which have a B6N allele (P(Bbs7emI8∆1) = 4.25 × 10-7; P(Bbs7emI8∆2) = 3.17 × 10-5). Consistent with previous findings, the recessive effect of the BFMI allele was also seen for the B6N Bbs7emI8∆1 and Bbs7emI8∆2 alleles. see more However, the effect size of the B6N Bbs7emI8∆1 and Bbs7emI8∆2 alleles was smaller than the BFMI allele, and thus showed only a partial complementation. Findings suggest additional variants near Bbs7 in addition to or interacting with the deletion in intron 8.

Endovascular treatment represents the first-line therapy for cavernous sinus dural arteriovenous fistulas (CS-dAVF); however, different approaches and embolic agents as well as occlusion rates, complications and clinical outcomes are reported among the published series. In this study we performed acomprehensive meta-analysis to investigate clinical and radiological outcomes after endovascular treatment of CS-dAVFs.

PubMed, Ovid Medline, Ovid EMBASE, Scopus, and Web of Science were screened for acomprehensive literature review from 1990 to 2020 regarding series of patients treated for CS-dAVF with endovascular approaches. We performed aproportion meta-analysis estimating the pooled rates of each outcome also including data of patients treated in our center.

Atotal of 22studies reporting 1043 patients and 1066 procedures were included. Chemosis was reported in 559 out of 1043 patients (45.9%), proptosis in 498 (41.5%), and ophthalmoplegia in 344 (23.5%). Atransvenous embolization was preferred in 753 cases (63.2%) and coils were used in 712 out of 1066 procedures (57.8%). Overall, 85% (95% confidence interval, CI 69.5-96.1%) of patients had acomplete resolution of symptoms, while complications occurred in 7.75% (95% CI 3.82-12.7%) with minimal permanent deficits (0.15%). The mortality rate was1 out of 1043 patients (< 0.001).

Atransvenous coiling is the most common endovascular approach for CS-dAVF, achieving ahigh percentage of radiological and clinical resolution and low complication rates. Transvenous approaches show less complications than transarterial ones, and coils appear safer than liquid embolic agents.

A transvenous coiling is the most common endovascular approach for CS-dAVF, achieving a high percentage of radiological and clinical resolution and low complication rates. Transvenous approaches show less complications than transarterial ones, and coils appear safer than liquid embolic agents.

We aimed to evaluate possible positive and negative effects of postoperative use of transanastomotic feeding tube (TAFT) in neonates operated for congenital duodenal obstruction (CDO).

This is a retrospective study reviewing medical records of neonates operated for CDO during 2003-2020 and comparing postoperative feeding outcomes and complications in patients with and without TAFT. Approval from the hospital's data protection officer was obtained.

One hundred patients, 59% girls, were included, and 37% received TAFT. Mean birth weight and gestational age were 2628 (675.1) grams and 36.6 (2.4) weeks, respectively. Furthermore, 45% had no other malformations, and 36% had Down syndrome. Patient demographics were similar for TAFT and not-TAFT patients, except that not-TAFT neonates weighed median 335g less (p = 0.013). The TAFT group got parenteral nutrition 2 days shorter (p < 0.001) and started enteral feeds 1.5days earlier (p < 0.001) than the not-TAFT group. Fewer neonates with TAFT got a central venous catheter [65 vs 89%, (p = 0.008)]. In the TAFT group, 67% were breast fed at discharge compared to 49% in the not-TAFT group (p = 0.096).

Neonates with TAFT had earlier first enteral feed, fewer days with parenteral nutrition and fewer placements of central venous catheters.

Neonates with TAFT had earlier first enteral feed, fewer days with parenteral nutrition and fewer placements of central venous catheters.

Prehospital administration of tranexamic acid (TXA) to injured patients is increasing worldwide. However, optimal TXA dose and need of a second infusion on hospital arrival remain undetermined. We investigated the efficacy and safety of the second in-hospital dose of TXA in injured patients receiving 1g of TXA in the prehospital setting. We hypothesized that a second in-hospital dose of TXA improves survival of trauma patients.

A prospective, double-blind, placebo-controlled randomized, clinical trial included adult trauma patients receiving 1g of TXA in the prehospital settings. Patients were then blindly randomized to Group I (second 1-g TXA) and Group II (placebo) on hospital arrival. The primary outcome was 24-h (early) and 28-day (late) mortality. Secondary outcomes were thromboembolic events, blood transfusions, hospital length of stay (HLOS) and organs failure (MOF).

A total of 220 patients were enrolled, 110 in each group. The TXA and placebo groups had a similar early [OR 1.000 (0.062-16.192); p = 0.47] and late mortality [OR 0.476 (95% CI 0.157-1.442), p = 0.18].The cause of death (n = 15) was traumatic brain injury (TBI) in 12 patients and MOF in 3 patients. The need for blood transfusions in the first 24h, number of transfused blood units, HLOS, thromboembolic events and multiorgan failure were comparable in the TXA and placebo groups. In seriously injured patients (injury severity score > 24), the MTP activation was higher in the placebo group (31.3% vs 11.10%, p = 0.13), whereas pulmonary embolism (6.9% vs 2.9%, p = 0.44) and late mortality (27.6% vs 14.3%, p = 0.17) were higher in the TXA group but did not reach statistical significance.

The second TXA dose did not change the mortality rate, need for blood transfusion, thromboembolic complications, organ failure and HLOS compared to a single prehospital dose and thus its routine administration should be revisited in larger and multicenter studies.

ClinicalTrials.gov Identifier NCT03846973.

ClinicalTrials.gov Identifier NCT03846973.We report on effects of low-dose exposures of accelerated protons delivered at high-dose rate (HDR) or a simulated solar-particle event (SPE) like low-dose rate (LDR) on immediate DNA damage induction and processing, survival and in vitro transformation of low passage NFF28 apparently normal primary human fibroblasts. Cultures were exposed to 50, 100 and 1,000 MeV monoenergetic protons in the Bragg entrance/plateau region and cesium-137 γ rays at 20 Gy/h (HDR) or 1 Gy/h (LDR). DNA double-strand breaks (DSB) and clustered DNA damages (containing oxypurines and abasic sites) were measured using transverse alternating gel electrophoresis (TAFE) and immunocytochemical detection/scoring of colocalized γ-H2AX pS139/53BP1 foci, with their induction being linear energy transfer (LET) dependent and dose-rate sparing observed for the different damage classes. Relative biological effectiveness (RBE) values for cell survival after proton irradiation at both dose-rates ranged from 0.61-0.73. Transformation RBE values were dose-rate dependent, ranging from ∼1.8-3.1 and ∼0.6-1.0 at low doses (≤30 cGy) for HDR and LDR irradiations, respectively. However peak transformation frequencies were significantly higher (1.3-7.3-fold) for higher doses of 0.5-1 Gy delivered at SPE-like LDR. Cell survival and transformation frequencies measured after low-dose 500 MeV/n He-4, 290 MeV/n C-12 and 600 MeV/n Si-28 ion irradiations also showed an inverse dose-rate effect for transformation at SPE-like LDR. This work demonstrates the existence of inverse dose-rate effects for proton and light-ion-induced postirradiation cell survival and in vitro transformation for space mission-relevant doses and dose rates.

Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance.

Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV (granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to May 5th, 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected.

From 565 articles captured, 10 met the predefined criteria, five phase II and five III trials, 4 assessed remission-induction, 3 remission-maintenance, 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% CI [0.74, 1.52]), with no significant difference by subgroup meta-analysis of trials stratified by different studyl practice.Melatonin, a tryptophan-derived molecule, is endogenously generated in animal, plant, fungal and prokaryotic cells. Given its antioxidant properties, is involved in a myriad of signalling functions associated with various aspects of plant growth and development. In higher plants, melatonin interacts with plant regulators such as phytohormones, as well as reactive oxygen and nitrogen species (ROS/RNS) including hydrogen peroxide (H2O2), nitric oxide (NO) and hydrogen sulfide (H2S). It shows great potential as a biotechnological tool to alleviate biotic and abiotic stress, to delay senescence and to conserve the sensory and nutritional quality of postharvest horticultural products which are of considerable economic importance worldwide. This review provides a comprehensive overview of the biochemistry of melatonin, whose endogenous induction and exogenous application can play an important biotechnological role in enhancing the marketability and hence earnings from postharvest horticultural crops.In the treatment of rheumatoid arthritis (RA), Janus kinase inhibitors (jakinibs) represent an emerging class of targeted therapies in addition to biologics. The number of jakinibs has been growing and as of 2020, filgotinib was the latest jakinib to enter the international market for treating RA. Filgotinib has demonstrated preferential inhibition of JAK1-dependent cytokine signaling in in vitro assays. It has been evaluated in the DARWIN (phase 2) and FINCH (phase 3) series of clinical studies for treating patients with moderately-to-severely active RA. Filgotinib received regulatory approval in Japan and Europe in September 2020, while in August 2020 the United States Food and Drug Administration requested additional data from two ongoing clinical studies assessing the potential impact of filgotinib on sperm parameters. This article will review the pharmacological properties, efficacy, and safety of filgotinib as demonstrated in clinical studies. Expert opinion will be provided on jakinibs for RA treatment from the viewpoints of basic research and clinical practice.