A Missense Variant in HACE1 Is Associated with Intellectual Disability, Epilepsy, Spasticity, and Psychomotor Impairment in a Pakistani Kindred.

Intellectual disability (ID), which affects around 2% to 3% of the population, accounts for 0.63% of the overall prevalence of neurodevelopmental disorders (NDD). ID is characterized by limitations in a person's intellectual and adaptive functioning, and is caused by pathogenic variants in more than 1000 genes. Here, we report a rare missense variant (c.350T>C; p.(Leu117Ser)) in HACE1 segregating with NDD syndrome with clinical features including ID, epilepsy, spasticity, global developmental delay, and psychomotor impairment in two siblings of a consanguineous Pakistani kindred. HACE1 encodes a HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1), which is involved in protein ubiquitination, localization, and cell division. HACE1 is also predicted to interact with several proteins that have been previously implicated in the ID phenotype in humans. The p.(Leu117Ser) variant replaces an evolutionarily conserved residue of HACE1 and is predicted to be deleterious by various in silico algorithms. Previously, eleven protein truncating variants of HACE1 have been reported in individuals with NDD. However, to our knowledge, p.(Leu117Ser) is the second missense variant in HACE1 found in an individual with NDD.

Computing edge version of metric dimension of certain chemical networks.

In the modern digital sphere, graph theory is a significant field of research that has a great deal of significance. It finds widespread application in computer science, robotic directions, and chemistry. Additionally, graph theory is used in robot network localization, computer network problems and the formation of various chemical structures for networks. Moreover, it finds uses in exploring diffusion mechanisms and scheduling aircraft as well. The present research project examines and concentrates on the edge version of metric dimension of the Concealed Non-Kekuléan Benzenoid Hydrocarbon, Polythiophene, Backbone DNA network and Bakelite networks. All the mentioned networks have constant edge metric dimension except Bakelite network, as demonstrated by the results. If we talk about the applications of these networks, Polythiophene are used to treat prion disorders. It is also capable of detecting metal ions. The concept of Bakelite, which finds applications in the jewelry, electrical, cookware, sports, and clock industries, had an impact on the invention of modern polymers. The functions of DNA include information encoding, replication, mutation, and recombination gene expression.

A shared group of bacterial taxa in the duodenal microbiota of undernourished Pakistani children with environmental enteric dysfunction.

Environmental enteric dysfunction (EED) is a subclinical syndrome of altered small intestinal function postulated to be an important contributor to childhood undernutrition. The role of small intestinal bacterial communities in the pathophysiology of EED is poorly defined due to a paucity of studies where there has been a direct collection of small intestinal samples from undernourished children. Sixty-three members of a Pakistani cohort identified as being acutely malnourished between 3 and 6 months of age and whose wasting (weight-for-length Z-score [WLZ]) failed to improve after a 2-month nutritional intervention underwent esophagogastroduodenoscopy (EGD). Paired duodenal luminal aspirates and duodenal mucosal biopsies were obtained from 43 children. Duodenal microbiota composition was characterized by sequencing bacterial 16S rRNA gene amplicons. Levels of bacterial taxa (amplicon sequence variants [ASVs]) were referenced to anthropometric indices, histopathologic severity in biopsies, expression of selected genes in the duodenal mucosa, and fecal levels of an immunoinflammatory biomarker (lipocalin-2). A "core" group of eight bacterial ASVs was present in the duodenal samples of 69% of participants. Streptococcus anginosus was the most prevalent, followed by Streptococcus sp., Gemella haemolysans, Streptococcus australis, Granulicatella elegans, Granulicatella adiacens, and Abiotrophia defectiva. At the time of EGD, none of the core taxa were significantly correlated with WLZ. Statistically significant correlations were documented between the abundances of Granulicatella elegans and Granulicatella adiacens and the expression of duodenal mucosal genes involved in immune responses (dual oxidase maturation factor 2, serum amyloid A, and granzyme H). These results suggest that a potential role for members of the oral microbiota in pathogenesis, notably Streptococcus, Gemella, and Granulicatella species, warrants further investigation.IMPORTANCEUndernutrition among women and children is a pressing global health problem. Environmental enteric dysfunction (EED) is a disease of the small intestine (SI) associated with impaired gut mucosal barrier function and reduced capacity for nutrient absorption. The cause of EED is ill-defined. One emerging hypothesis is that alterations in the SI microbiota contribute to EED. We performed a culture-independent analysis of the SI microbiota of a cohort of Pakistani children with undernutrition who had failed a standard nutritional intervention, underwent upper gastrointestinal tract endoscopy, and had histologic evidence of EED in their duodenal mucosal biopsies. The results revealed a shared group of bacterial taxa in their duodenums whose absolute abundances were correlated with levels of the expression of genes in the duodenal mucosa that are involved in inflammatory responses. A number of these bacterial taxa are more typically found in the oral microbiota, a finding that has potential physiologic and therapeutic implications.

Epidemiology, Pathophysiology, and Treatment Strategies of Concussions: A Comprehensive Review.

A concussion is a particular manifestation of a traumatic brain injury, which is the leading cause of mortality and disabilities across the globe. The global prevalence of traumatic brain injury is estimated to be 939 instances per 100,000 individuals, with approximately 5.48 million people per year experiencing severe traumatic brain injury. Epidemiology varies amongst different countries by socioeconomic status with diverse clinical manifestations. Additionally, classifying concussions is an ambiguous process as clinical diagnoses are the only current classification method, and morbidity rates differ by demographic location as well as populations examined. In this article, we critically reviewed the pathophysiology of concussions, classification methods, treatment options available including both pharmacologic and nonpharmacologic intervention methods, etiologies as well as global etiologic differences associated with them, and clinical manifestations along with their associated morbidities. Furthermore, analysis of the current research regarding the incidence of concussion based traumatic brain injuries and future directions are discussed. Investigation on the efficacy of new therapeutic-related interventions such as exosome therapy and electromagnetic field stimulation are warranted to properly manage and treat concussion-induced traumatic brain injury.

Primary Circumscribed Meningeal Melanoma Involving the Meckel's Cave: A Report of a Rare Case and Review of Literature.

Primary intracranial meningeal melanomas are rare. Diagnosing primary meningeal melanomas mostly involves comprehensive assessment through clinical and radiological means. This evaluation should encompass a detailed dermal and ophthalmic examination. Any suspicious lesion must be biopsied and examined microscopically. This is crucial not only to differentiate primary intracranial melanoma from other brain tumors but also to rule out metastases from potential sources of primary cutaneous or non-cutaneous melanomas. Surgery is considered the mainstay of treatment. Despite melanomas being generally considered radio- and chemo-resistant tumors, adjuvant radiotherapy and chemotherapy still play a crucial role in their management. The treatment landscape for primary meningeal melanoma is continually evolving, with ongoing research aiming to improve outcomes for patients with this challenging disease.

Investigations of Limeum Indicum Plant for Diabetes Mellitus and Alzheimer's Disease Dual Therapy: Phytochemical, GC-MS Chemical Profiling, Enzyme Inhibition, Molecular Docking and In-Vivo Studies.

Limeum indicum has been widely utilized in traditional medicine but no experimental work has been done on this herb. The primary objective of this study was to conduct a phytochemical analysis and assess the multifunctional capabilities of aforementioned plant in dual therapy for Alzheimer's disease (AD) and Type 2 diabetes (T2D). The phytochemical screening of ethanol, methanol extract, and their derived fractions of Limeum indicum was conducted using GC-MS, HPLC, UV-analysis and FTIR. The antioxidant capacity was evaluated by DPPH method. The inhibitory potential of the extracts/fractions against α-, ß-glucosidase acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoaminine oxidases (MAO-A & B) was evaluated. Results revealed that acetonitrile fraction has highest inhibitory potential against α-glucosidase (IC50=68.47±0.05 µg/mL), methanol extract against ß-glucosidase (IC50=91.12±0.07 µg/mL), ethyl acetate fraction against AChE (IC50=59.0±0.02 µg/mL), ethanol extract against BChE (28.41±0.01 µg/mL), n-hexane fraction against MAO-A (IC50=150.5±0.31 µg/mL) and methanol extract for MAO-B (IC50=75.95±0.13 µg/mL). The docking analysis of extracts\fractions suggested the best binding scores within the active pocket of the respective enzymes. During the in-vivo investigation, ethanol extract produced hypoglycemic effect (134.52±2.79 and 119.38±1.40 mg/dl) after 21 days treatment at dose level of 250 and 500 mg/Kg. Histopathological findings further supported the in-vivo studies.

Synergism of Anti-CGRP Monoclonal Antibodies and OnabotulinumtoxinA in the Treatment of Chronic Migraine: A Real-World Retrospective Chart Review.

BACKGROUND: Many patients with chronic migraine do not achieve clinically meaningful improvement in their headache frequency with monotherapy. The burden associated with chronic migraine calls for a multifaceted treatment approach targeting multiple aspects of migraine pathophysiology. OBJECTIVE: The aim of this study was to evaluate the effect of concurrent anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) and onabotulinumtoxinA (onabot) treatment on median monthly migraine days (MMD) in patients with chronic migraine, through a retrospective study. METHODS: The electronic medical records of Cleveland Clinic patients either concurrently (dual therapy) or consecutively (monotherapy) treated with anti-CGRP mAbs and onabot between June 2018 and November 2021 were extracted. Only adult patients (≥ 18 years of age) were included in this study. MMDs for 194 concurrently treated (86.6% female and a median [interquartile range] age of 51 [41-61] years) and 229 consecutively treated (88.2% female and median age of 47 [IQR 39-57] years) patients were examined at baseline, after first therapy of either anti-CGRP mAb or onabot, and following dual therapy for 3 consecutive months. The reduction of MMDs for each treatment group were compared. The same approach was utilized to compare consecutive monotherapy at separate times (n = 229) and dual-therapy groups. RESULTS: The initial treatment of the dual-therapy group reduced the median (IQR) MMDs from 30 (30-30) to 15 (12-30) [p < 0.0001]. After initiation of dual therapy, the median MMDs was further decreased from 15 (12-30) to 8 (3-22) [p < 0.0001]. A majority [132/194 (68.0%)] of the dual-therapy patients reported a ≥ 50% reduction in MMD and 90/194 (46.4%) reported a ≥ 75% reduction. For the consecutive monotherapy group, median MMDs changed from a baseline of 30 (25-30) to 15 (8-25) from onabot monotherapy and decreased from 25 (15-30) to 12 (4-25) after anti-CGRP mAb monotherapy. Almost half (113/229 [49.3%] from onabot, and 104/229 [45.4%] from anti-CGRP mAb) of these patients achieved a ≥ 50% reduction in MMDs and a minority (38/229 [16.6%] from onabot, and 45/229 [19.7%] from anti-CGRP mAb) achieved a reduction of ≥ 75%. Additionally, dual therapy showed significant improvement in MMDs compared with monotherapy of either treatment (p < 0.0001). CONCLUSION: Dual therapy of anti-CGRP mAbs and onabot may be more efficacious than monotherapy, possibly due to their synergistic mechanisms of action.

Neurotrauma-From Injury to Repair: Clinical Perspectives, Cellular Mechanisms and Promoting Regeneration of the Injured Brain and Spinal Cord.

Traumatic injury to the brain and spinal cord (neurotrauma) is a common event across populations and often causes profound and irreversible disability. Pathophysiological responses to trauma exacerbate the damage of an index injury, propagating the loss of function that the central nervous system (CNS) cannot repair after the initial event is resolved. The way in which function is lost after injury is the consequence of a complex array of mechanisms that continue in the chronic phase post-injury to prevent effective neural repair. This review summarises the events after traumatic brain injury (TBI) and spinal cord injury (SCI), comprising a description of current clinical management strategies, a summary of known cellular and molecular mechanisms of secondary damage and their role in the prevention of repair. A discussion of current and emerging approaches to promote neuroregeneration after CNS injury is presented. The barriers to promoting repair after neurotrauma are across pathways and cell types and occur on a molecular and system level. This presents a challenge to traditional molecular pharmacological approaches to targeting single molecular pathways. It is suggested that novel approaches targeting multiple mechanisms or using combinatorial therapies may yield the sought-after recovery for future patients.

Design of liposomal nanocarriers with a potential for combined dexamethasone and bevacizumab delivery to the eye.

Clinicians face numerous challenges when delivering medications to the eyes topically because of physiological barriers, that can inhibit the complete dose from getting to the intended location. Due to their small size, the ability to deliver drugs of different polarities simultaneously, and their biocompatibility, liposomes hold great promise for ocular drug delivery. This study aimed to develop and characterise a dual loaded liposome formulation encapsulating Bevacizumab (BEV) and Dexamethasone (DEX) that possessed the physicochemical attributes suitable for topical ocular delivery. Liposomes were prepared by using thin film hydration followed by extrusion, and the formulations were optimised using a design of experiments approach. Physicochemical characterisation along with cytocompatibility and bioactivity of the formulations were assessed. Liposomes were successfully prepared with a particle size of 139 ± 2 nm, PDI 0.03 ± 0.01 and zeta potential -2 ± 0.7 mV for the optimised formulation. BEV and DEX were successfully encapsulated into the liposomes with an encapsulation efficiency of 97 ± 0.5 % and 26 ± 0.5 %, respectively. A sustained release of BEV was observed from the liposomes and the bioactivity of the formulation was confirmed using a wound healing assay. In summary, a potential topical eye drop drug delivery system, which can co-load DEX and BEV was developed and characterised for its potential to be used in ocular drug delivery.

Delaying Suspension Syndrome Onset in Aerially Suspended Victims Through Leg Raising.

INTRODUCTION: Suspension syndrome (SS) develops when venous blood pools in extremities of passively suspended individuals, resulting in presyncopal symptoms and potential unconsciousness or death independent of additional injuries. We investigated use of leg raising to delay onset of SS, as it can decrease venous pooling and increase cardiac return and systemic perfusion. METHODS: Participants were suspended in rock climbing harnesses at an indoor climbing wall in a legs-dangling control position or a legs-raised interventional position to compare physiological outcomes between groups. Participants were suspended for a maximum of 45 min. Onset of 2 or more symptoms of SS, such as vertigo, lightheadedness, or nausea, halted suspension immediately. We recorded each participant's heart rate, blood pressure, oxygen saturation, lower leg oxygen saturation, pain rating, and presyncope scores presuspension, midsuspension, and postsuspension, as well as total time suspended. RESULTS: There were 24 participants. There was a significant difference in total time suspended between groups (43.05±6.7 min vs 33.35±9.02 min, p=0.007). There was a significant difference in heart rate between groups overall (p=0.012), and between groups, specifically at the midsuspension time interval (80±11 bpm vs 100±17 bpm, p=0.003). Pain rating was significantly different between groups (p=0.05). Differences in blood pressure, oxygen saturation, lower leg oxygen saturation, and presyncope scores were not significant. CONCLUSION: Leg raising lengthened the time individuals tolerated passive suspension and delayed symptom onset.

Soret Effect on MHD Casson Fluid over an Accelerated Plate with the Help of Constant Proportional Caputo Fractional Derivative.

Non-Newtonian fluid flow is significant in engineering and biomedical applications such as thermal exchangers, electrical cooling mechanisms, nuclear reactor cooling, drug delivery, blood flow analysis, and tissue engineering. The Caputo operator has emerged as a prevalent tool in fractional calculus, garnering widespread recognition. This research aims to introduce a novel derivative by merging the proportional and Caputo operators, resulting in the fractional operator known as the constant proportional Caputo. In order to demonstrate this newly defined operator's dynamic qualities, it was employed in the analysis of the unsteady Casson flow model. In addition, the current work shows an analytical analysis to determine the Soret effect on the fractionalized MHD Casson fluid over an oscillating vertical plate. Fractional partial differential equations (PDEs) are used to formulate the problem along with IBCs. The introduction of appropriate nondimensional variables converts the PDEs into dimensionless form. The precise solutions to the fractional governing PDEs are then determined by the Laplace transform method. Velocity, concentration, and temperature profiles; the impacts of the Prandtl number; fractional parameter ß and γ; and Soret and Schmidt numbers are graphically depicted. The profiles of temperature, concentration, and velocity rise with rising time and fractional parameters. Interestingly, as the Casson flow parameter is higher, fluid velocity decreases closest to the plate but increases away from the plate. Tables showing the findings for the skin-friction coefficient, Sherwood, and Nusselt numbers for a range of flow-controlling parameter values are provided. Furthermore, an investigation is undertaken to compare fractionalized and ordinary velocity fields. The results suggest that the fractional model employing a constant proportional derivative exhibits a quicker decay than the model incorporating conventional Caputo and Caputo-Fabrizio operators.

Diagnosis and management of subarachnoid haemorrhage.

Aneurysmal subarachnoid haemorrhage (aSAH) presents a challenge to clinicians because of its multisystem effects. Advancements in computed tomography (CT), endovascular treatments, and neurocritical care have contributed to declining mortality rates. The critical care of aSAH prioritises cerebral perfusion, early aneurysm securement, and the prevention of secondary brain injury and systemic complications. Early interventions to mitigate cardiopulmonary complications, dyselectrolytemia and treatment of culprit aneurysm require a multidisciplinary approach. Standardised neurological assessments, transcranial doppler (TCD), and advanced imaging, along with hypertensive and invasive therapies, are vital in reducing delayed cerebral ischemia and poor outcomes. Health care disparities, particularly in the resource allocation for SAH treatment, affect outcomes significantly, with telemedicine and novel technologies proposed to address this health inequalities. This article underscores the necessity for comprehensive multidisciplinary care and the urgent need for large-scale studies to validate standardised treatment protocols for improved SAH outcomes.

Heteroleptic samarium complexes with high quantum yields for temperature sensing applications.

Two new crystallographically characterized samarium complexes, [Sm(fod)3(L1)] (1) and [Sm(fod)3(L2)] (2) {L1 = 4,7-diphenyl-1,10-phenanthroline (bath), L2 = 2,2':6',2''-terpyridine and fod = anion of 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedione (Hfod)}, were synthesized and thoroughly characterized. Single-crystal (SC) analysis shows that complex 1 is an eight-coordinate structure with a distorted square antiprism geometry (D4d), whereas complex 2 possesses a nine-coordinate structure with distorted muffin geometry (Cs). The NMR results are in line with SC-XRD analysis, which further validate that the complexes remain intact in solutions. The photophysical characteristics of the complexes were studied in both visible and near infra-red (NIR) regions. The PLQY values of the present complexes were found to be higher than those reported in the literature except for a tetrakis Sm complex. This result indicates that both the ligands act as effective antennas for the present systems. A comparison of PLQY and emission lifetime values within the present complexes (in solid state) reveals that energy transfer from terpy to Sm3+ is more effective than that from the bath ligand. Various color parameters of the complexes were calculated, and the determined CCT values suggest that the complexes may be used as warm light sources. The determined band gap values for the complexes are in the range of those for semiconductors, which suggest the application of present systems in the field of optoelectronics. The curve between the emission intensity and temperature for complex 1 shows a perfect linearity (χ2 = 0.99), which suggests that this complex can have potential application as a temperature sensor in the range 60-350 K.

Wnt7a Decreases Brain Endothelial Barrier Function Via ß-Catenin Activation.

The blood-brain barrier consists of tightly connected endothelial cells protecting the brain's microenvironment from the periphery. These endothelial cells are characterized by specific tight junction proteins such as Claudin-5 and Occludin, forming the endothelial barrier. Disrupting these cells might lead to blood-brain barrier dysfunction. The Wnt/ß-catenin signaling pathway can regulate the expression of these tight junction proteins and subsequent barrier permeability. The aim of this study was to investigate the in vitro effects of Wnt7a mediated ß-catenin signaling on endothelial barrier integrity. Mouse brain endothelial cells, bEnd.3, were treated with recombinant Wnt7a protein or XAV939, a selective inhibitor of Wnt/ß-catenin mediated transcription to modulate the Wnt signaling pathway. The involvement of Wnt/HIF1α signaling was investigated by inhibiting Hif1α signaling with Hif1α siRNA. Wnt7a stimulation led to activation and nuclear translocation of ß-catenin, which was inhibited by XAV939. Wnt7a stimulation decreased Claudin-5 expression mediated by ß-catenin and decreased endothelial barrier formation. Wnt7a increased Hif1α and Vegfa expression mediated by ß-catenin. However, Hif1α signaling pathway did not regulate tight junction proteins Claudin-5 and Occludin. Our data suggest that Wnt7a stimulation leads to a decrease in tight junction proteins mediated by the nuclear translocation of ß-catenin, which hampers proper endothelial barrier formation. This process might be crucial in initiating endothelial cell proliferation and angiogenesis. Although HIF1α did not modulate the expression of tight junction proteins, it might play a role in brain angiogenesis and underlie pathogenic mechanisms in Wnt/HIF1α signaling in diseases such as cerebral small vessel disease.

How safe and effective are paediatric virtual fracture clinics? A systematic review.

Introduction: Virtual fracture clinics (VFC) involve a consultant-led multidisciplinary team meeting where cases are reviewed before a telephone consultation with the patient. VFCs have the advantages of reducing waiting times, outpatient appointments and time off school compared to face-to-face (F2F) fracture clinics. There has been a surge in VFC use since the COVID-19 pandemic but there are still concerns over safety in the paediatric population. Fractures make up a large burden of paediatric injuries, therefore research is required on the safety and efficacy of paediatric VFCs. This systematic review will look at the safety and effectiveness of paediatric VFCs, as well as determine the cost-effectiveness and parent preferences. Methods: As per the PRISMA guidelines two independent reviewers searched the following databases: Medline, Embase and Web of Science. Studies were included if children under 18 years old presented to A&E with a suspected or confirmed simple un-displaced fracture and were referred to a VFC. The primary outcomes assessed were effectiveness and safety, with the secondary outcomes of cost-effectiveness and parent satisfaction. Results: Six studies met the inclusion criteria for this systematic review. There was a high rate of direct discharge from the VFC leading to reduced outpatient appointments. All patients were seen within 72 h of presentation. There were limited incidences of missed fractures and the rates of re-presentation were similar to that of F2F orthopaedic clinics. There were significant cost savings for the hospitals and high parent satisfaction. Discussion: VFCs have shown to be safe and effective at managing most stable, low operative risk paediatric fractures. Safety must be ensured with a telephone helpline and an open return to fracture clinic policy. More research is needed into specific paediatric fracture types to be managed in the VFC. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier: CRD42023423795.

E-scooter attitudes and risk-taking behaviours: an international systematic literature review and survey responses in the West Midlands, United Kingdom.

Introduction: Micromobility initiatives, including electric scooters (e-scooters), are part of the United Kingdom government's sustainability drive. Since summer 2020, multiple trials have been conducted across the United Kingdom. Safety concerns have been raised around e-scooters joining other vehicles on United Kingdom roads, alongside the numerous private e-scooters illegally ridden on public land. Although literature has been published abroad on perceptions, risk-taking behaviours and attitudes surrounding e-scooters, independent United Kingdom research has concentrated on analysing trauma. Our aim was to identify common themes and recommendations to form conclusions on factors affecting e-scooter trauma hospital admissions. Methods: A systematic literature search in June 2023 extracted studies focused on the primary outcomes of risk factors, perceptions, and attitudes surrounding e-scooters globally from the EMBASE, PubMed, and Web of Sciences databases. Two independent reviewers conducted a critical appraisal to extract potential biases and study characteristics. A critical appraisal skills programme (CASP) analysis was also completed. Two online surveys distributed in Birmingham and Wolverhampton focused on: public perception towards e-scooters, and road user attitudes around e-scooters. The target population was residents of the West Midlands who were both riders and non-riders of e-scooters. The surveys were opened in late-March 2023 and closed in late-July 2023. Results: 443 studies were retrieved with 13 studies being eligible according to our inclusion and exclusion criteria. CASP assessment concluded that the studies were of good quality, however heterogeneity meant sample sizes could not be meaningfully aggregated. Many studies focused on safety concerns whilst others observed risk-taking behaviour, non-rider perceptions, and infrastructure. Our surveys received 299 responses and respondents reported risk-taking behaviours such as pavement riding, alcohol consumption, and minimal helmet use. However, positive opinions were expressed on e-scooter convenience but concerns were raised regarding rider and non-rider safety. Discussion: Whilst global literature had investigated e-scooter attitudes, risk-taking behaviours and perceptions, there was no comparable independent United Kingdom literature. Our literature review and analysis of survey responses concluded that e-scooters were perceived as a sustainable form of transport; however, safety concerns were raised. Our study points to risk-taking behaviours by riders being associated with admissions into hospital emergency departments. We conclude that well maintained infrastructure could improve the safety of both e-scooter riders and vulnerable pedestrians, whilst education and enforcement of clear rules may reduce risk-taking behaviour. The recommendations found in the PACTS reports, and documents from the RNIB confirm our findings. We recommend that hospital data and future studies should differentiate between private and rental e-scooters for robust conclusions to be made.

Dual AAV-based PCDH15 gene therapy achieves sustained rescue of visual function in a mouse model of Usher syndrome 1F.

Mutations in the PCDH15 gene, encoding protocadherin-15, are among the leading causes of Usher syndrome type 1 (USH1F), and account for up to 12% USH1 cases worldwide. A founder truncating variant of PCDH15 has a ∼2% carrier frequency in Ashkenazi Jews accounting for nearly 60% of their USH1 cases. Although cochlear implants can restore hearing perception in USH1 patients, presently there are no effective treatments for the vision loss due to retinitis pigmentosa. We established a founder allele-specific Pcdh15 knockin mouse model as a platform to ascertain therapeutic strategies. Using a dual-vector approach to circumvent the size limitation of adeno-associated virus, we observed robust expression of exogenous PCDH15 in the retinae of Pcdh15KI mice, sustained recovery of electroretinogram amplitudes and key retinoid oxime, substantially improved light-dependent translocation of phototransduction proteins, and enhanced levels of retinal pigment epithelium-derived enzymes. Thus, our data raise hope and pave the way for future gene therapy trials in USH1F subjects.

Exploring the effectiveness of artificial intelligence, machine learning and deep learning in trauma triage: A systematic review and meta-analysis.

Background: The development of artificial intelligence (AI), machine learning (ML) and deep learning (DL) has advanced rapidly in the medical field, notably in trauma medicine. We aimed to systematically appraise the efficacy of AI, ML and DL models for predicting outcomes in trauma triage compared to conventional triage tools. Methods: We searched PubMed, MEDLINE, ProQuest, Embase and reference lists for studies published from 1 January 2010 to 9 June 2022. We included studies which analysed the use of AI, ML and DL models for trauma triage in human subjects. Reviews and AI/ML/DL models used for other purposes such as teaching, or diagnosis were excluded. Data was extracted on AI/ML/DL model type, comparison tools, primary outcomes and secondary outcomes. We performed meta-analysis on studies reporting our main outcomes of mortality, hospitalisation and critical care admission. Results: One hundred and fourteen studies were identified in our search, of which 14 studies were included in the systematic review and 10 were included in the meta-analysis. All studies performed external validation. The best-performing AI/ML/DL models outperformed conventional trauma triage tools for all outcomes in all studies except two. For mortality, the mean area under the receiver operating characteristic (AUROC) score difference between AI/ML/DL models and conventional trauma triage was 0.09, 95% CI (0.02, 0.15), favouring AI/ML/DL models (p = 0.008). The mean AUROC score difference for hospitalisation was 0.11, 95% CI (0.10, 0.13), favouring AI/ML/DL models (p = 0.0001). For critical care admission, the mean AUROC score difference was 0.09, 95% CI (0.08, 0.10) favouring AI/ML/DL models (p = 0.00001). Conclusions: This review demonstrates that the predictive ability of AI/ML/DL models is significantly better than conventional trauma triage tools for outcomes of mortality, hospitalisation and critical care admission. However, further research and in particular randomised controlled trials are required to evaluate the clinical and economic impacts of using AI/ML/DL models in trauma medicine.

Pure red-light emitting europium based complexes as efficient UV light converters: synthesis, crystal structure and photoluminescence properties.

This paper reports three new crystallographically characterized europium complexes with composition as follows: [Eu(fod)3(L1)] (1), [Eu(fod)3(L2)] (2) and [Eu(fod)3(L3)] (3) {L1 = benzimidazole (bzi), L2 = 4,7-diphenyl-1,10-phenanthroline (bath), L3 = 2-(2-pyridyl) benzimidazole (py-im) and fod = anion of 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedione (Hfod)}. The single crystal (SC) XRD analysis shows that complex 1 is seven-coordinated while complexes 2 and 3 are eight-coordinated with the geometrical structures of a mono-capped octahedron and a trigonal dodecahedron, respectively. The NMR spectra of the complexes validate the SC-XRD results in solution. The complexes are stable in solution as no dissociation of any ligand was observed in the NMR spectra of the complexes. The photophysical properties of the complexes in solution, solid state, and PMMA thin films were studied. The hypersensitive transition 5D0 → 7F2 dominates the emission spectra in all phases, showing the highly asymmetric environment around the Eu(III) ion. The bath ligand is found to be the best sensitizer of the Eu ion and hence complex 2 shows the strongest luminescence properties with the highest absolute quantum yield among the three complexes. The CIE coordinate analysis shows that pure red-luminescence is emitted by the Eu complexes in the solid state since the coordinates found in this phase are closer to the standard NTSC 1987 values. The optical band gaps were determined for the complexes and the observed values suggest that the complexes can have possible applications in the field of semiconductor materials.

Preparation of Retinal Explant Cultures.

Organotypic retinal explants are routinely used as alternatives to in vitro cell culture and to replace the use of animals in modelling retinal neurodegenerative diseases. Retinal explants fill the gap between in vivo which are expensive, time consuming, and complex due to inaccessibility of target tissues. However, organotypic retinal explants are less expensive and rapid and retinal cell types in the explant maintain their morphologic interactions with other cells in the retina. Therefore, retinal explants have high potential to be used as tools to assess the pharmacological and other therapies prior to in vivo validation, reducing the use of live animals.