De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ~30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.

Insights into eye genetics and recent advances in ocular gene therapy.

The rapid advancements in the field of genetics have significantly propelled the development of gene therapies, paving the way for innovative treatments of various hereditary disorders. This review focuses on the genetics of ophthalmologic conditions, highlighting the currently approved ophthalmic gene therapy and exploring emerging therapeutic strategies under development. Inherited retinal dystrophies represent a heterogeneous group of genetic disorders that manifest across a broad spectrum from infancy to late middle age.

Influence of meteorological changes on the occurrence of cerebral aneurysm rupture in the Montpellier region: A retrospective study.

Background/context: Aneurysmal subarachnoid hemorrhage (aSAH) is a sudden and potentially serious event. Recognized risk factors of aSAH include smoking, high blood pressure, and alcohol consumption. Some studies have reported associations between risk of aSAH and climatic conditions, but no consensus exists.

Dynamic and quasi static stiffness characterization of a lamination stack of an electric motor.

The development of electric motors for automotive applications requires precise material models to simulate structural strength and NVH (Noise, Vibration, and Harshness) properties. Modeling the behavior of lamination stacks, composed of stacked steel plates, presents significant challenges. This study conducted dynamic and quasi-static experiments at various preload levels on an unmodified automotive lamination stack.

Validation of artificial intelligence application for dental caries diagnosis on intraoral bitewing and periapical radiographs.

Objectives: This study aimed to assess the reliability of AI-based system that assists the healthcare processes in the diagnosis of caries on intraoral radiographs.

Methods: The proximal surfaces of the 323 selected teeth on the intraoral radiographs were evaluated by two independent observers using an AI-based (Diagnocat) system. The presence or absence of carious lesions was recorded during Phase 1.

Loss-of-function variants in UBAP1L cause autosomal recessive retinal degeneration.

Purpose: Inherited retinal diseases (IRDs) are a group of monogenic conditions that can lead to progressive blindness. Their missing heritability is still considerable, due in part to the presence of disease genes that await molecular identification. The purpose of this work was to identify novel genetic associations with IRDs.

Missing Heritability in Albinism: Deep Characterization of a Hungarian Albinism Cohort Raises the Possibility of the Digenic Genetic Background of the Disease.

Albinism is characterized by a variable degree of hypopigmentation affecting the skin and the hair, and causing ophthalmologic abnormalities. Its oculocutaneous, ocular and syndromic forms follow an autosomal or X-linked recessive mode of inheritance, and 22 disease-causing genes are implicated in their development. Our aim was to clarify the genetic background of a Hungarian albinism cohort.

Whole-brain characterization of apoptosis after sevoflurane anesthesia reveals neuronal cell death patterns in the mouse neonatal neocortex.

In the last two decades, safety concerns about general anesthesia (GA) arose from studies documenting brain cell death in various pharmacological conditions and animal models. Nowadays, a thorough characterization of sevoflurane-induced apoptosis in the entire neonatal mouse brain would help identify and further focus on underlying mechanisms. We performed whole-brain mapping of sevoflurane-induced apoptosis in post-natal day (P) 7 mice using tissue clearing and immunohistochemistry.

Human pancreatic ductal organoids with controlled polarity provide a novel ex vivo tool to study epithelial cell physiology.

Epithelial ion and fluid secretion determine the physiological functions of a broad range of organs, such as the lung, liver, or pancreas. The molecular mechanism of pancreatic ion secretion is challenging to investigate due to the limited access to functional human ductal epithelia. Patient-derived organoids may overcome these limitations, however direct accessibility of the apical membrane is not solved.

Fatigue Resistance of Dissected Lower First Molars Restored with Direct Fiber-Reinforced Bridges-An In Vitro Pilot Study.

The aim of this research was to evaluate the mechanical impact of utilizing different fiber-reinforced composite (FRC) systems to reinforce inlay-retained bridges in dissected lower molars with different levels of periodontal support. A total of 24 lower first molars and 24 lower second premolars were included in this study. The distal canal of all molars received endodontic treatment.

Thiopurines impair the apical plasma membrane expression of CFTR in pancreatic ductal cells via RAC1 inhibition.

Background And Aims: Thiopurine-induced acute pancreatitis (TIP) is one of the most common adverse events among inflammatory bowel disease patients treated with azathioprine (AZA), representing a significant clinical burden. Previous studies focused on immune-mediated processes, however, the exact pathomechanism of TIP is essentially unclear.

Methods: To model TIP in vivo, we triggered cerulein-induced experimental pancreatitis in mice receiving a daily oral dose of 1.

Impaired regulation of PMCA activity by defective CFTR expression promotes epithelial cell damage in alcoholic pancreatitis and hepatitis.

Alcoholic pancreatitis and hepatitis are frequent, potentially lethal diseases with limited treatment options. Our previous study reported that the expression of CFTR Cl channel is impaired by ethanol in pancreatic ductal cells leading to more severe alcohol-induced pancreatitis. In addition to determining epithelial ion secretion, CFTR has multiple interactions with other proteins, which may influence intracellular Ca signaling.

The biomechanical effect of root amputation and degree of furcation involvement on intracoronally splinted upper molar teeth - An in vitro study.

Objectives: The aim of this study was to evaluate the effect of the amount of periodontal support and the presence or absence of root amputation on the fracture resistance of intracoronally splinted maxillary molar teeth.

Materials And Methods: 48 extracted human upper first molars and 48 s premolars were included in the study. All teeth underwent standard mesio-occluso-distal (MOD) (molars) and standard occluso-distal (OD) (premolars) cavity preparation.

[Minimally invasive and O-arm assisted en bloc spinal tumor resections].

Background And Purpose: The en bloc resection of spinal tumors is required in primary spine tumors and in selected cases of secondary spine tumors, where the primary disease is under control and long survival time is expected. Three cases are presented, applying O-arm assisted navigation or minimally invasive anterior approaches for en bloc tumor removal.

Methods: O-arm navigation assisted osteotomies were carried out to remove a Th.

Bile acid- and ethanol-mediated activation of Orai1 damages pancreatic ductal secretion in acute pancreatitis.

Regardless of its aetiology, sustained intracellular Ca overload is a well-known hallmark of acute pancreatitis (AP). Toxic Ca elevation induces pancreatic ductal cell damage characterized by impaired ion and fluid secretion - essential to wash out the protein-rich fluid secreted by acinar cells while maintaining the alkaline intra-ductal pH under physiological conditions - and mitochondrial dysfunction. While prevention of ductal cell injury decreases the severity of AP, no specific drug target has yet been identified in the ductal cells.

Percutaneous Spine Fusion Combined with Whole-Body Traction in the Acute Surgical Treatment of AO A- and C-Type Fractures: A Technical Note.

Background: A diminished level of pain following the operation and shortened hospitalization are the distinct advantages of minimally invasive spine surgery (MISS). However, manipulating the spine with additional MISS tools (e.g.

Cerebral Microbleeds May Be Less Detectable by Susceptibility Weighted Imaging MRI From 24 to 72 Hours After Traumatic Brain Injury.

A former rodent study showed that cerebral traumatic microbleeds (TMBs) may temporarily become invisible shortly after injury when detected by susceptibility weighted imaging (SWI). The present study aims to validate this phenomenon in human SWI. In this retrospective study, 46 traumatic brain injury (TBI) patients in various forms of severity were included and willingly complied with our strict selection criteria.

Long-term outcome in patients with aneurysmal subarachnoid hemorrhage requiring mechanical ventilation.

Background: Patients affected with aneurysmal subarachnoid hemorrhage (aSAH) often require intensive care, and then present distinctive outcome from less severe patients. We aimed to specify their long-term outcome and to identify factors associated with poor outcome.

Methods: We conducted a retrospective study in a French university hospital intensive care unit.

Immunological biomarkers of the vitreous responsible for proliferative alteration in the different forms of retinal detachment.

Background: The purpose of the study was to explore the immunological components that are responsible for the proliferative alterations in the different forms of retinal detachment (RD).

Methods: Vitreous fluids were collected during 23G pars plana vitrectomy from 54 eyes of 54 patients with different RD types, such as rhegmatogenous RD (RRD) without proliferative vitreoretinopathy (PVR) (n = 30), PVR (n = 16) and proliferative diabetic retinopathy (PDR) with tractional RD (n = 8). Vitreous fluids were obtained from 19 eyes with epiretinal membrane (ERM), which were used as control samples.

Phenotypic characterisation of early COPD: a prospective case-control study.

The phenotypic characteristics of chronic obstructive pulmonary disease (COPD) in individuals younger than 50 years of age (early COPD) are not well defined. This prospective, multicentre, case-control study sought to describe these characteristics and compare them with those of smokers (≥10 pack-years) of similar age with normal spirometry (controls). We studied 92 cases (post-bronchodilator forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC) <0.