Bariatric Surgery as a Molecular Modulator: The Role of FSHR Polymorphisms in Enhancing eNOS Expression and Reproductive Hormone Dynamics in Women with Severe Obesity.

Background/objectives: Severe obesity (BMI > 40 kg/m) has a severe influence on vascular health and reproduction. This study looks at how bariatric surgery affects endothelial nitric oxide synthase (eNOS) expression and reproductive hormone regulation across different follicle-stimulating hormone receptor (FSHR) polymorphism groups in women with extreme obesity.

Methods: Twenty-nine women with extreme obesity had bariatric surgery.

Nitrate-Nitrite-Nitric Oxide Pathway, Oxidative Stress, and Fertility Outcomes in Morbidly Obese Women Following Bariatric Surgery: A Systematic Review.

Obesity reduces nitric oxide (NO) production due to endothelial nitric oxide synthase (eNOS) dysfunction, resulting in oxidative stress, mitochondrial dysfunction, and chronic inflammation. These factors have a negative impact on reproductive health, including oocyte quality, endometrial receptivity, and embryo implantation. When oxidative stress affects eNOS function, the nitrate-nitrite-nitric oxide (NO-NO-NO) pathway provides an alternate route for NO production.

Near-infrared cholangiography with intragallbladder indocyanine green injection in minimally invasive cholecystectomy.

Laparoscopic cholecystectomy (LC) remains one of the most commonly performed procedures in adult and paediatric populations. Despite the advances made in intraoperative biliary anatomy recognition, iatrogenic bile duct injuries during LC represent a fatal complication and consist an economic burden for healthcare systems. A series of methods have been proposed to prevent bile duct injury, among them the use of indocyanine green (ICG) fluorescence.

EURO-NMD registry: federated FAIR infrastructure, innovative technologies and concepts of a patient-centred registry for rare neuromuscular disorders.

Background: The EURO-NMD Registry collects data from all neuromuscular patients seen at EURO-NMD's expert centres. In-kind contributions from three patient organisations have ensured that the registry is patient-centred, meaningful, and impactful. The consenting process covers other uses, such as research, cohort finding and trial readiness.

Biliary Anatomy Visualization and Surgeon Satisfaction Using Standard Cholangiography versus Indocyanine Green Fluorescent Cholangiography during Elective Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

: Intraoperative biliary anatomy recognition is crucial for safety during laparoscopic cholecystectomy, since iatrogenic bile duct injuries represent a fatal complication, occurring in up to 0.9% of patients. Indocyanine green fluorescence cholangiography (ICG-FC) is a safe and cost-effective procedure for achieving a critical view of safety and recognizing early biliary injuries.

Rehabilitation via HOMe-Based gaming exercise for the Upper limb post Stroke (RHOMBUS): a qualitative analysis of participants' experience.

Objective: To report participants' experiences of trial processes and use of the Neurofenix platform for home-based rehabilitation following stroke. The platform, consisting of the NeuroBall device and Neurofenix app, is a non-immersive virtual reality tool to facilitate upper limb rehabilitation following stroke. The platform has recently been evaluated and demonstrated to be safe and effective through a non-randomised feasibility trial (RHOMBUS).

Sediment recontamination potential and biological impacts of hydrophobic organics from stormwater in a mixed-use watershed.

This study focused on understanding the influence of stormwater on sediment recontamination and biota bioaccumulation. Stormwater and sediment sampling was conducted at Paleta Creek San Diego, CA, a mixed-use urban watershed. Stormwater samples were size fractioned into clay, silt, sand, and filtered fractions to better understand the association of PAHs and PCBs with different particle sizes.

Eupatilin Improves Cilia Defects in Human CEP290 Ciliopathy Models.

The photoreceptor outer segment is a highly specialized primary cilium that is essential for phototransduction and vision. Biallelic pathogenic variants in the cilia-associated gene cause non-syndromic Leber congenital amaurosis 10 (LCA10) and syndromic diseases, where the retina is also affected. While RNA antisense oligonucleotides and gene editing are potential treatment options for the common deep intronic variant c.

CRISPR-Cas9 correction of a nonsense mutation in rescues lebercilin expression and localization in human retinal organoids.

Mutations in the lebercilin-encoding gene cause one of the most severe forms of Leber congenital amaurosis, an early-onset retinal disease that results in severe visual impairment. Here, we report on the generation of a patient-specific cellular model to study -associated retinal disease. CRISPR-Cas9 technology was used to correct a homozygous nonsense variant in (c.

Eupatilin improves cilia defects in human CEP290 ciliopathy models.

The photoreceptor outer segment is a highly specialized primary cilium essential for phototransduction and vision. Biallelic pathogenic variants in the cilia-associated gene cause non-syndromic Leber congenital amaurosis 10 (LCA10) and syndromic diseases, where the retina is also affected. While RNA antisense oligonucleotides and gene editing are potential treatment options for the common deep intronic variant c.

Environmental Impacts of Hurricane Harvey on the Neches-Brakes Bayou River System in Beaumont, Texas.

Hurricane Harvey caused unprecedented floods across large regions of Southeast Texas resulting in several infrastructural issues. One of the notable failures was of a drinking water source pump in Beaumont, Texas, that necessitated the emergency use of a temporary pump intake station in the Neches River system. This study examines the environmental consequences of Harvey-induced flooding in the Neches River system by focusing on sensitive locations, including a Superfund site (International Creosoting, IC) and adjacent to the temporary pump intake.

Rehabilitation using virtual gaming for Hospital and hOMe-Based training for the Upper limb post Stroke (RHOMBUS II): protocol of a feasibility randomised controlled trial.

Introduction: Upper limb (UL) rehabilitation is most effective early after stroke, with higher doses leading to improved outcomes. For the stroke survivor, the repetition may be monotonous. For clinicians, providing a clinically meaningful level of input can be challenging.

Safety, feasibility, acceptability and preliminary effects of the Neurofenix platform for Rehabilitation via HOMe Based gaming exercise for the Upper-limb post Stroke (RHOMBUS): results of a feasibility intervention study.

Objectives: To investigate the safety, feasibility and acceptability of the Neurofenix platform for home-based rehabilitation of the upper limb (UL).

Design: A non-randomised intervention design with a parallel process evaluation.

Setting: Participants' homes, South-East England.

The association of T786C and G894T polymorphisms of eNOS gene with diabetic retinopathy in Greece.

Purpose: To investigate whether eNOS T786C (rs2070744) and G894T (rs1799983) gene polymorphisms are associated with diabetic retinopathy in Greek diabetic patients.

Materials: 271 patients with type-2 diabetes mellitus participated in our study; 130 suffered from diabetic retinopathy and 141 not. All the patients underwent a complete ophthalmological examination, while clinical and demographic data were assessed.

A multinational study exploring adolescent perception of school climate and mental health.

School climate is a topic of increasing importance internationally. The current study investigated the established measurement invariance of an eight-factor school climate scale using a multinational sample of secondary students. School climate factor means across 14 international groups were compared and findings on the association between school climate factors and mental health were also investigated.

Propelling Healthcare with Advanced Therapy Medicinal Products: A Policy Discussion.

Recent advances in biomedicine are opening the door to new approaches, and treatment and prevention are being transformed by novel medicines based on genetic engineering, innovative cell-based therapies and tissue-engineered products, and combinations of a medical device with embedded cell or tissue components. These advanced therapy medicinal products (ATMPs) hold one of the keys to making a reality of genuinely personalised medicine. There are an estimated 450 companies across the globe working on the development of gene therapies and more than 1,000 clinical trials underway worldwide, and some 20-30 new ATMPs filings are expected in Europe annually over the next 5 years.

Recommendations by the European Network of Paediatric Research at the European Medicines Agency (Enpr-EMA) Working Group on preparedness of clinical trials about paediatric medicines process.

Conduct of clinical trials in babies, children and young people is often hindered by issues that could have been foreseen before the trial opened; that is, some clinical trials are often underprepared. In order to identify a good approach to trial preparedness, the European Network of Paediatric Research at the European Medicines Agency formed a working group. The Working Group included representation from regulators, industry, academics, paediatric clinical research networks and parents.

Global Collaborative Social Network (Share4Rare) to Promote Citizen Science in Rare Disease Research: Platform Development Study.

Background: Rare disease communities are spread around the globe and segmented by their condition. Little research has been performed on the majority of rare diseases. Most patients who are affected by a rare disease have no research on their condition because of a lack of knowledge due to absence of common groups in the research community.

Association of Soluble Suppression of Tumorigenesis-2 (ST2) with Endothelial Function in Patients with Ischemic Heart Failure.

Soluble suppression of tumorigenesis-2 (sST2) has been introduced as a marker associated with heart failure (HF) pathophysiology and status. Endothelial dysfunction is a component underlying HF pathophysiology. Therefore, we examined the association of arterial wall properties with sST2 levels in patients with HF of ischemic etiology.

High-Intensity Endurance and Strength Training in Water Polo Olympic Team Players: Impact on Arterial Wall Properties.

Introduction: Regular physical activity is recommended to minimize health risk. However, the upper intensity threshold associated with the best health outcomes is difficult to be determined. Water polo (WP) Olympic athletes present unique characteristics such as high-intensity exercise, long training sessions, and a combination of endurance and strength training.

AAV-mediated ERdj5 overexpression protects against P23H rhodopsin toxicity.

Rhodopsin misfolding caused by the P23H mutation is a major cause of autosomal dominant retinitis pigmentosa (adRP). To date, there are no effective treatments for adRP. The BiP co-chaperone and reductase ERdj5 (DNAJC10) is part of the endoplasmic reticulum (ER) quality control machinery, and previous studies have shown that overexpression of ERdj5 in vitro enhanced the degradation of P23H rhodopsin, whereas knockdown of ERdj5 increased P23H rhodopsin ER retention and aggregation.

Unmet Medical Need: An Introduction to Definitions and Stakeholder Perceptions.

Background: Despite increasing informal and formal use of unmet medical need (UMN) in drug development, regulation, and assessment, there is no insight into its definitions in use. This study aims to provide insight into the current definitions in use and to provide a starting point for a multi-stakeholder discussion on alignment.

Methods: A scoping and a gray literature review were performed to locate definitions of UMN in literature and on stakeholder websites.

Seasonal Toxicity Observed with Amphipods (Eohaustorius estuarius) at Paleta Creek, San Diego Bay, USA.

To assess potential impacts on receiving systems, associated with storm water contaminants, laboratory 10-d amphipod (Eohaustorius estuarius) survival toxicity tests were performed using intact sediment cores collected from Paleta Creek (San Diego Bay, CA, USA) on 5 occasions between 2015 and 2017. The approach included deposition-associated sediment particles collected from sediment traps placed at each of 4 locations during the 2015 to 2016 wet seasons. The bioassays demonstrated wet season toxicity, especially closest to the creek mouth, and greater mortality associated with particles deposited in the wet season compared with dry season samples.

European regulators' views on a wearable-derived performance measurement of ambulation for Duchenne muscular dystrophy regulatory trials.

Development of novel therapies for Duchenne muscular dystrophy (DMD) are driving the need for more efficient ways of detecting changes in disease- progression in DMD [1]. However, medicines' approval must be based on outcome measures that are acceptable from a regulatory perspective. In this article, European regulators provide an update on the recent regulatory consideration of a new endpoint (Stride Velocity 95th Centile (SV95C)) that could be used in therapeutic DMD trials.