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Meralgia paresthetica is a compressive neuropathy of the lateral femoral cutaneous nerve. Surgery is the gold standard for severe cases. However, no high-quality evidence exists on which strategy is best: decompression or neurectomy. Data of a consecutive series of 52 patients treated for meralgia paresthetica over 25 years (1997–2022) were retrospectively collected from medical records and telephone interviews. In total, 27 women and 25 men were operated on; 11 patients had iatrogenic meralgia paresthetica. Decompression was performed on 47 patients, and neurectomy in 8 cases (5 primary neurectomies plus 3 failed neurolysis). Out of the patients who underwent decompression, 41 (87.2%) benefited from the treatment; 3 had pain relief, but no benefit on paresthesia; and 3 reported pain persistence. The latter required neurectomy to resolve symptoms. The eight patients who underwent neurectomy experienced symptom relief but had an obvious anesthetic area persisting over years. Complications were rare (3.8%): a groin hematoma in the post-operative course and an inguinal herniation 6 months after surgery. Surgery, be it neurolysis or neurectomy, offers excellent results with low risks. Decompression has been proven to be adequate in almost all patients, avoiding the side effects of neurectomy. The latter should be confined to failed decompression or to iatrogenic meralgia.

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical phenotypes. The missense variants in individuals with CDH are located within the actin-binding domains of the protein but are not predicted to affect protein structure, whereas the variants in individuals with osteoporosis are predicted to result in loss of function. A mouse knockin model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Both the mouse model and one adult human male with a CDH-associated PLS3 variant were observed to have increased rather than decreased bone mineral density. Together, these clinical and functional data in humans and mice reveal that specific missense variants affecting the actin-binding domains of PLS3 might have a gain-of-function effect and cause a Mendelian congenital disorder.

Abstract The lamb meat tenderness acceptance threshold has been little studied and has never been evaluated for the Brazilian population. So, this study aimed to find the maximum acceptable shear force for Brazilian lamb meat consumers. Three muscles were previously tested and chosen Longissimus thoracis et lumborum (LTL), psoas major and semimembranosus muscles received different treatments in the post-slaughter period (Hot deboning followed by cooling on ice, Standard carcass cooling and Ageing), aiming to create samples with varying levels of tenderness, which were evaluated by acceptance tests and descriptive analysis of tenderness by a trained team. Sarcomere length, myofibril fragmentation index, proximate composition, weight loss and pH analyses were performed to observe the biochemical phenomena in each treatment's meats. Variations caused in samples by treatments were more significant than differences inherent to the different muscles. Pearson and Multiple Factor correlation analyses indicated positive correlations between sarcomere length, myofibril fragmentation index and the scores assigned in sensory tests by 140 panelists and a trained team. Both groups noted that the differences between the meats in terms of tenderness and the sarcomere length also influenced the perception of juiciness observed by the groups. The maximum shear force indicated as acceptable for lamb meat was 44.1 N. The results obtained are important to guide the lamb meat producer for certain practices in the post-slaughter moments, avoiding actions that lead to sarcomere shortening and encouraging the production of aged meats.

This theoretical paper presents the development and analysis of an inclusive educational framework designed to manage cognitive load for neurodivergent students in online learning environments. Drawing from cognitive load theory and neurodiversity studies, the framework is based on existing literature, empirical work conducted by the authors, and iterative feedback from a participatory research advisory board. Taking a neurodiversity-informed perspective that focuses on interventions addressing challenges common across a range of conditions, it identifies six critical areas that might impact cognitive load in online learning for neurodivergent students: format, environment, delivery, instruction, support, and research (FEDIS+R). To assess the external factors influencing the potential implementation of the framework and its place within the broader landscape of inclusive education, a PESTEL (Political, Economic, Social, Technological, Environmental, and Legal) analysis was conducted. The analysis highlights challenges such as resource disparities, institutional commitment to inclusion, and legal requirements for accessibility, which may affect the adoption of the framework. Given the evolving nature of both cognitive load theory and neurodiversity studies, future research directions are suggested to evaluate its effectiveness across diverse educational contexts. This paper contributes to the growing body of knowledge on neurodiversity in education and offers practical recommendations for educators and policymakers seeking to create inclusive online learning environments.

Background/Objectives: Otosclerosis is a relatively uncommon condition that causes conductive hearing loss in children. The preferred treatment for adults is stapedotomy, while for individuals under 18 years old, there is an ongoing discussion about the best treatment approach. Thus, the surgical procedure for the stapes in pediatric patients continues to be a subject of debate. This study aimed to evaluate the results of stapes surgery in children, trying to understand, based on our results, whether this is actually the most suitable option. Methods: The study included 18 patients who underwent surgery between January 2013 and December 2023. The patients’ ages ranged from 11 to 18 years, with an average age of 14.7. Out of the total 21 surgeries, three patients opted for bilateral surgery. Pre- and post-operative data were compared, focusing on the mean air conduction (AC) and bone conduction (BC) thresholds at frequencies of 0.5, 1, 2, and 4 kHz. Additionally, pre-operative thresholds and the post-operative air–bone gap (ABG) were examined. Results: After a year, the air–bone gap was effectively reduced to 10 dB or less in 94% of the 21 cases, and to 20 dB or less in 98% of all cases. Conclusions: Our results and research in the field have consistently shown that stapedotomy, when conducted by skilled otosurgeons, is a reliable and successful procedure for a considerable number of patients. The outcomes it generates are similar to those achieved through the procedure conducted during adulthood.

A finite element method is employed to examine the impact of a magnetic field on the development of plaque in an artery with stenotic bifurcation. Consistent with existing literature, blood flow is characterized as a Newtonian fluid that is stable, incompressible, biomagnetic, and laminar. Additionally, it is assumed that the arterial wall is linearly elastic throughout. The hemodynamic flow within a bifurcated artery, influenced by an asymmetric magnetic field, is described using the arbitrary Lagrangian–Eulerian (ALE) method. This technique incorporates the fluid–structure interaction coupling. The nonlinear system of partial differential equations is discretized using a stable P2P1 finite element pair. To solve the resulting nonlinear algebraic equation system, the Newton-Raphson method is employed. Magnetic fields are numerically modeled, and the resulting displacement, velocity magnitude, pressure, and wall shear stresses are analyzed across a range of Reynolds numbers (Re = 500, 1000, 1500, and 2000). The numerical analysis reveals that the presence of a magnetic field significantly impacts both the displacement magnitude and the flow velocity. In fact, introducing a magnetic field leads to reduced flow separation, an expanded recirculation area near the stenosis, as well as an increase in wall shear stress.

Summary: Efficient long-range axonal transport is essential for maintaining neuronal function, and perturbations in this process underlie severe neurological diseases. Nodes of Ranvier (NoR) are short, specialized unmyelinated axonal domains with a unique molecular and structural composition. Currently, it remains unresolved how the distinct molecular structures of the NoR impact axonal transport dynamics. Using intravital time-lapse microscopy of sciatic nerves in live, anesthetized mice, we reveal (1) similar morphologies of the NoR in fast and slow motor axons, (2) signaling endosomes and mitochondria accumulate specifically at the distal node, and (3) unique axonal transport profiles of signaling endosomes and mitochondria transiting through the NoR. Collectively, these findings provide important insights into the fundamental physiology of peripheral nerve axons, motor neuron subtypes, and diverse organelle dynamics at the NoR. Furthermore, this work has relevance for several pathologies affecting peripheral nerves and the NoR.

This review delves into the potential of manipulating the microbiome to enhance oral tolerance in food allergy, focusing on food allergen-specific immunotherapy (FA-AIT) and the use of adjuvants, with a significant emphasis on probiotics. FA-AIT, including oral (OIT), sublingual (SLIT), and epicutaneous (EPIT) immunotherapy, has shown efficacy in desensitizing patients and achieving sustained unresponsiveness (SU). However, the long-term effectiveness and safety of FA-AIT are still under investigation. Probiotics, particularly strains of Lactobacillus, play a crucial role in enhancing immune tolerance by promoting regulatory T cells (Tregs) and modulating cytokine profiles. These probiotics can induce semi-mature dendritic cells, enhance CD40 expression, inhibit IL-4 and IL-5, and promote IL-10 and TGF-β, thus contributing to mucosal defense and immunological tolerance. Clinical trials combining probiotics with FA-AIT have demonstrated improved desensitization rates and immune tolerance in food-allergic patients. For example, the combination of Lactobacillus rhamnosus with peanut OIT resulted in a significantly higher rate of SU compared to the placebo group, along with notable immune changes such as reduced peanut-specific IgE and increased IgG4 levels. The review also explores other adjuvants in FA-AIT, such as biologic drugs, which target specific immune pathways to improve treatment outcomes. Additionally, nanoparticles and herbal therapies like food allergy herbal formula 2 (FAHF-2) are discussed for their potential to enhance allergen delivery and immunogenicity, reduce adverse events, and improve desensitization. In conclusion, integrating probiotics and other adjuvants into FA-AIT protocols could significantly enhance the safety and efficacy of FA-AIT, leading to better patient outcomes and quality of life.

A clinical research requires a systematic approach with diligent planning, execution and sampling in order to obtain reliable and validated results, as well as an understanding of each research methodology is essential for researchers. Indeed, selecting an inappropriate study type, an error that cannot be corrected after the beginning of a study, results in flawed methodology. The results of clinical research studies enhance the repertoire of knowledge regarding a disease pathogenicity, an existing or newly discovered medication, surgical or diagnostic procedure or medical device. Medical research can be divided into primary and secondary research, where primary research involves conducting studies and collecting raw data, which is then analysed and evaluated in secondary research. The successful deployment of clinical research methodology depends upon several factors. These include the type of study, the objectives, the population, study design, methodology/techniques and the sampling and statistical procedures used. Among the different types of clinical studies, we can recognize descriptive or analytical studies, which can be further categorized in observational and experimental. Finally, also pre-clinical studies are of outmost importance, representing the steppingstone of clinical trials. It is therefore important to understand the types of method for clinical research. Thus, this review focused on various aspects of the methodology and describes the crucial steps of the conceptual and executive stages.

Animal experimentation is widely used around the world for the identification of the root causes of various diseases in humans and animals and for exploring treatment options. Among the several animal species, rats, mice and purpose-bred birds comprise almost 90% of the animals that are used for research purpose. However, growing awareness of the sentience of animals and their experience of pain and suffering has led to strong opposition to animal research among many scientists and the general public. In addition, the usefulness of extrapolating animal data to humans has been questioned. This has led to Ethical Committees' adoption of the 'four Rs' principles (Reduction, Refinement, Replacement and Responsibility) as a guide when making decisions regarding animal experimentation. Some of the essential considerations for humane animal experimentation are presented in this review along with the requirement for investigator training. Due to the ethical issues surrounding the use of animals in experimentation, their use is declining in those research areas where alternative in vitro or in silico methods are available. However, so far it has not been possible to dispense with experimental animals completely and further research is needed to provide a road map to robust alternatives before their use can be fully discontinued.

Pasireotide-LAR is recommended as a second-line treatment for patients with acromegaly. Although the effects of pasireotide-LAR have been well characterized in clinical studies, real-practice evidence is scant, especially in the long term and within the individualization of therapy in patients with comorbidities. To provide additional insight on the individualized approach to acromegaly management, six clinical cases of complex acromegaly treated with pasireotide-LAR for more than 5 years were reported. Pasireotide-LAR allowed the normalization of insulin-like growth factor 1 (IGF1) values in all patients and reduced tumour residue volume where present. A good safety profile and long-term tolerability were also reported.

Hyperventilation induces metabolic changes that can elicit nystagmus (hyperventilation-induced nystagmus, HVIN) in various vestibular disorders, revealing vestibular imbalance and bringing out central or peripheral asymmetries. In acute unilateral vestibulopathy (AUVP, namely vestibular neuritis), hyperventilation can induce different patterns of nystagmus (excitatory, inhibitory, or negative), disclosing or modifying existing static vestibular asymmetries through its ability to invalidate compensation or increase peripheral excitability. In this context, we followed the evolutionary stages of HVIN in AUVP across 35 consecutive patients, with the goal of assessing alterations in the oculomotor pattern caused by hyperventilation over time. In the acute phase, the incidence of the excitatory pattern (and the strongly excitatory one, consisting of a reversal nystagmus evoked by hyperventilation) was significantly higher compared to the inhibitory pattern; then, a progressive reduction in the incidence of the excitatory pattern and a concomitant gradual increase in the incidence of the inhibitory one were observed in the follow-up period. Assuming the role of the ephaptic effect and the transient loss of vestibular compensation as opposing mechanisms, i.e., excitatory and inhibitory, respectively, the oculomotor pattern evoked by hyperventilation is the result of the interaction of these two factors. The data obtained allowed us to hypothesize an interpretative model regarding the pathogenetic aspects of responses evoked by hyperventilation and the etiologies of the disease: according to our hypotheses, the excitatory pattern implies a neuritic (viral) form of AUVP; instead, the inhibitory (and negative) one can be an expression of both the neuritic (viral) and vascular forms of the disease.

BACKGROUND: Hyperventilation-induced nystagmus test (HINT) is capable of generating a response in 77.2% of cases of acute unilateral vestibulopathy (AUVP); both nystagmus toward the affected side (excitatory pattern) and toward the healthy side (inhibitory pattern) have been described. The aim of the study is to investigate the clinical and prognostic role of the test by evaluating its correlation with vestibulo-ocular reflex (VOR) gain. METHODS: We evaluated 33 AUVP patients by performing the HINT and video head impulse test (V-HIT) during the acute phase and then at 15 and 90 days after the onset of the symptoms. The correlation between the VOR gain of the affected side and test responses was evaluated first, phase by phase, and then considering the pattern shown during the first assessments. RESULTS: Patients with a negative HINT had a higher mean VOR gain than patients with a positive test at both 15 and 90 days. Patients who showed an inhibitory pattern at the first assessment had a continuous improvement in V-HIT performance, while patients with an initial excitatory response had a transient decrease in gain at the subsequent evaluation (P=.001). No difference between these 2 groups emerged at 90 days (P=.09). CONCLUSION: The finding of a negative HINT during the follow-up correlates with good V-HIT performance and could be an indicator of good recovery. The inhibitory pattern is associated with a subsequent improvement; and it would be indicative of compensation. but, despite this, the prognostic value of the test is limited.

The discovery of a multi-target scaffold in medicinal chemistry is an important goal for the development of new drugs with different biological effects. Azobenzene is one of the frameworks in medicinal chemistry used for its simple synthetic methods and for the possibility to obtain a great variety of derivatives by simple chemical modifications or substitutions. Phenyldiazenyl-containing compounds show a wide spectrum of pharmacological activities, such as antimicrobial, anti-inflammatory, anti-neurodegenerative, anti-cancer, and anti-enzymatic. The aim of this review is to highlight the importance of azobenzene as a scaffold in medicinal chemistry, with particular attention to the chemical modifications and structure–activity relationships (SARs). This review emphasizes the main therapeutic applications of phenyldiazenyl derivatives, with a particular focus on structural modification and its influence on activity, with the aim of inspiring medicinal chemists to obtain new, increasingly powerful azobenzenes useful in therapy.

IntroductionArthrogryposis multiplex congenita (AMC) is an umbrella term including hundreds of conditions with the common clinical manifestation of multiple congenital contractures. AMC affects 1 in 3000 live births and is caused by lack of movement in utero. To understand the long-term needs of individuals diagnosed with a rare condition, it is essential to know the prevalence, aetiology and functional outcomes in a large sample. The development and implementation of a multicentre registry is critical to gather this data. This registry aims to improve health through genetic and outcomes research, and ultimately identify new therapeutic targets and diagnostics for treating children with AMC.Methods and analysisParticipants for the AMC registry will be recruited from seven orthopaedic hospitals in North America. Enrollment occurs in two phases; Part 1 focuses on epidemiology, aetiology and interventions. For this part, retrospective and cross-sectional data will be collected using a combination of patient-reported outcomes and clinical measures. Part 2 focuses on core subset of the study team, including a geneticist and bioinformatician, identifying causative genes and linking the phenotype to genotype via whole genome sequencing to identify genetic variants and correlating these findings with pedigree, photographs and clinical information. Descriptive analyses on the sample of 400 participants and logistic regression models to evaluate relationships between outcomes will be conducted.Ethics and disseminationEthical approval has been granted from corresponding governing bodies in North America. Dissemination of findings will occur via traditional platforms (conferences, manuscripts) for the scientific community. Other modalities will be employed to ensure that all stakeholders, including youth, families and patient support groups, may be provided with findings derived from the registry. Ensuring the findings are circulated to a maximum amount of interested parties will ensure that the registry can continue to serve as a platform for hypothesis-driven research and further advancement for AMC.

In 2020, King's College London introduced HyFlex teaching as a means to supplement online and face-to-face teaching and to respond to COVID-19 restrictions. This enabled teaching to a mixed cohort of students (both online and on campus). This article provides an outline of how such an approach was conceptualized and implemented in a higher-education institution during an intense three-month period over that summer and prior to the limited re-opening of the university campus. This was a new approach that offers a number of pointers for reflection and provides key insights in on this novel learning environment and the physical and pedagogical contexts in which learning can occur. Technical implementation factors are detailed, along with both reflections on challenges and solutions. Pedagogical issues such as cognitive load, social presence, and resolving the issues of a cohort spread across two locations are discussed. While we should be mindful of the limitations of this relatively-specific research, and shouldn't therefore over-extrapolate our findings, one key finding is that delivering Hyflex is associated with a higher cognitive load. Further, the audio quality of our implementation enhanced the feeling of presence in the learning environment. We recommend providing appropriate technical and pedagogical training, as well as audio-visual and digital education support.