Neurofibroma Involving a Bifid Median Nerve in a Pediatric Patient: A Case Report.

Neurofibromas are benign peripheral nerve sheath tumors that typically develop within cutaneous nerve branches but can involve major nerves as well. They can be sporadic or associated with neurofibromatosis type 1. In this report, we describe the surgical treatment of a pediatric patient with neurofibromatosis type 1 presenting with a neurofibroma of a bifid median nerve. Involvement of the median nerve was not evident on preoperative examination or imaging, therefore altering the risk-benefit ratio of the procedure. After bifid nerve involvement was identified intraoperatively, the patient's parents were counseled on the risks and benefits of surgical excision before resuming the case. Ultimately, the neurofibroma was resected, and the patient experienced no neurological deficits after surgery.

Gut Malrotation in a Human Cadaver: Exploration Into the Prevention and Screening of Undiagnosed Malrotation in Adults.

Malrotation is a congenital anomaly that results from the abnormal rotation of the gut during fetal development. Malrotation may be missed in early life and can present later with non-specific, chronic abdominal symptoms and decreased quality of life and in some cases can lead to serious bowel complications. Most adult cases are discovered incidentally on imaging or during surgery. An 82-year-old male cadaver was identified as having probable malrotation of the intestines. The performance of a previous surgical procedure could not be confirmed due to a lack of medical and surgical history. The cadaver dissection raised the question regarding the screening modalities used to reliably identify malrotations in infants and adults. Implementing a standardized reliable screening tool in infants or adults complaining of chronic abdominal pain could largely reduce the incidence of undiagnosed malrotation. Along with the development of a screening tool, increasing understanding of the clinical presentation of malrotation in adults could help identify undiagnosed cases earlier, which can reduce morbidity and mortality in these patients.

Carbon dots as dual inhibitors of tau and amyloid-beta aggregation for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of senile dementia, presenting a significant challenge for the development of effective treatments. AD is characterized by extracellular amyloid plaques and intraneuronal neurofibrillary tangles. Therefore, targeting both hallmarks through inhibition of amyloid beta (Aß) and tau aggregation presents a promising approach for drug development. Carbon dots (CD), with their high biocompatibility, minimal cytotoxicity, and blood-brain barrier (BBB) permeability, have emerged as promising drug nanocarriers. Congo red, an azo dye, has gathered significant attention for inhibiting amyloid-beta and tau aggregation. However, Congo red's inability to cross the BBB limits its potential to be used as a drug candidate for central nervous system (CNS) diseases. Furthermore, current studies only focus on using Congo red to target single disease hallmarks, without investigating dual inhibition capabilities. In this study, we synthesized Congo red-derived CD (CRCD) by using Congo red and citric acid as precursors, resulting in three variants, CRCD1, CRCD2 and CRCD3, based on different mass ratios of precursors. CRCD2 and CRCD3 exhibited sustained low cytotoxicity, and CRCD3 demonstrated the ability to traverse the BBB in a zebrafish model. Moreover, thioflavin T (ThT) aggregation assays and AFM imaging revealed CRCD as potent inhibitors against both tau and Aß aggregation. Notably, CRCD1 emerged as the most robust inhibitor, displaying IC50 values of 0.2 ± 0.1 and 2.1 ± 0.5 µg/mL against tau and Aß aggregation, respectively. Our findings underscore the dual inhibitory role of CRCD against tau and Aß aggregation, showcasing effective BBB penetration and positioning CRCD as potential nanodrugs and nanocarriers for the CNS. Hence, CRCD-based compounds represent a promising candidate in the realm of multi-functional AD therapeutics, offering an innovative formulation component for future developments in this area. STATEMENT OF SIGNIFICANCE: This article reports Congo red-derived carbon dots (CRCD) as dual inhibitors of tau and amyloid-beta (Aß) aggregation for the treatment of Alzheimer's disease (AD). The CRCD are biocompatible and show strong fluorescence, high stability, the ability to cross the blood-brain barrier, and the function of addressing two major pathological features of AD.

High incidence of dural tears with 3-column osteotomies: a systematic review of adult spinal deformity surgery literature for the past decade.

PURPOSE: Dural tear (DT) is a well-known complication of spinal surgery. We aimed to systematically review the literature from the past decade and determine the incidence and risk factors for DT in the adult spinal deformity (ASD) population to improve both the surgical strategy and counseling of patients undergoing ASD correction. METHODS: A systematic review from 2013 to 2023 utilizing PRISMA guidelines was performed. The MEDLINE database was used to collect primary English language articles. The inclusion criterion for patients was degenerative ASD. Pediatric studies, animal studies, review articles, case reports, studies investigating minimally invasive surgery (MIS), studies lacking data on DT incidence, and articles pertaining to infectious, metastatic or neoplastic, traumatic, or posttraumatic etiologies of ASD were excluded. RESULTS: Our results demonstrate that the incidence of DT in ASD surgery ranges from 2.0% to 35.7%, which is a much broader range than the reported incidence for non deformity surgery. Moreover, the average rate of DT during ASD surgery stratified by surgical technique was greater for osteotomy overall (19.5% +/- 7.9%), especially for 3-column osteotomy (3CO), and lower for interbody fusion (14.3% +/- 9.9%). Risk factors for DT in the ASD surgery cohort included older age, revision surgery, chronic severe compression, higher-grade osteotomy, complexity of surgery, rheumatoid arthritis (RA), and higher Anesthesiology Society of America (ASA) grade. CONCLUSION: To our knowledge, this is the first systematic review discussing the incidence of and risk factors for DT in the ASD population. We found that the risk factors for DT in ASD patients were older age, revision surgery, chronic severe compression, a greater degree of osteotomy, complexity of surgery, RA, and a higher ASA grade. These findings will help guide spine surgeons in patient counseling as well as surgical planning.

Return to play and athletic performance in division I female volleyball players following anterior cruciate ligament injury.

OBJECTIVES: The purpose of this study is to examine NCAA Division I volleyball players' return to play rates and performance statistics compared to pre-injury levels following ACL injury. METHODS: Female volleyball players that sustained ACL injuries from 2008 to 2020 and competed in one of seven collegiate conferences (n = 99) were identified via an internet search algorithm. Players were categorized by position, academic year, and playing time pre- and post-injury. Post-injury performance statistics were gathered for a subset of outside hitters and middle blockers that played in ≥35 sets in a single season for up to 3 years following injury (mean 1.7 seasons). A control group (n = 512) was generated for demographic and statistical comparison. Mean pre-injury and post-injury statistics were compared for players that did not change positions and played ≥35 sets before and after injury. RESULTS: Volleyball attackers were 54.7% of the control population but sustained 78.8% of identified injuries. Following ACL injury, 6.1% of players registered no in-game statistics, 16.2% played in <35 sets, 65.7% played in ≥35 sets, and 12.1% graduated. Mean performance statistics increased linearly the more years players were from ACL injury. CONCLUSIONS: Female collegiate volleyball players return to play following ACL injury at high rates (93.1%) and maintain pre-injury performance levels. Volleyball attackers sustain ACL injuries more commonly than setters and libero/defensive specialists.

Ethnicity-related differences in mitochondrial regulation by insulin stimulation in diabetes.

Mitochondrial dysfunction has long been implicated in the development of insulin resistance, which is a hallmark of type 2 diabetes. However, recent studies reveal ethnicity-related differences in mitochondrial processes, underscoring the need for nuance in studying mitochondrial dysfunction and insulin sensitivity. Furthermore, the higher prevalence of type 2 diabetes among African Americans and individuals of African descent has brought attention to the role of ethnicity in disease susceptibility. In this review, which covers existing literature, genetic studies, and clinical data, we aim to elucidate the complex relationship between mitochondrial alterations and insulin stimulation by considering how mitochondrial dynamics, contact sites, pathways, and metabolomics may be differentially regulated across ethnicities, through mechanisms such as single nucleotide polymorphisms (SNPs). In addition to achieving a better understanding of insulin stimulation, future studies identifying novel regulators of mitochondrial structure and function could provide valuable insights into ethnicity-dependent insulin signaling and personalized care.

Call me by your name: Considerations of DNA sequences as types within wider discussions on fungal nomenclature.

This paper discusses the interaction between two substantial debates in taxonomy and nomenclature: The potential introduction of DNA-only types into fungal taxonomy and whether certain species names are offensive and should be changed. It argues that the acceptance of DNA sequences as types will likely lead to a proliferation of eponyms (species named after a person or persons) and that this will render them more likely to censure thus creating a point of instability in the fungal nomenclature. More fundamentally, it seeks to highlight the cultural and aesthetic attraction of names and to promote wider conversation on why we consider the Latin binomial central in our description of species.

D-ꞵ-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance.

The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KBs) when less glucose is available. Neuronal KB uptake, which does not rely on glucose transporter 4 (GLUT4) or insulin, has shown promising clinical applicability in alleviating the neurological and cognitive effects of disorders with hypometabolic components. However, the specific mechanisms by which such interventions affect neuronal functions are poorly understood. In this study, we pharmacologically blocked GLUT4 to investigate the effects of exogenous KB D-ꞵ-hydroxybutyrate (D-ꞵHb) on mouse brain metabolism during acute insulin resistance (AIR). We found that both AIR and D-ꞵHb had distinct impacts across neuronal compartments: AIR decreased synaptic activity and long-term potentiation (LTP) and impaired axonal conduction, synchronization, and action potential properties, while D-ꞵHb rescued neuronal functions associated with axonal conduction, synchronization, and LTP.

Characterization of natural product inhibitors of quorum sensing in Pseudomonas aeruginosa reveals competitive inhibition of RhlR by ortho-vanillin.

Quorum sensing (QS) is a cell-cell signaling system that enables bacteria to coordinate population density-dependent changes in behavior. This chemical communication pathway is mediated by diffusible N-acyl L-homoserine lactone signals and cytoplasmic signal-responsive LuxR-type receptors in Gram-negative bacteria. As many common pathogenic bacteria use QS to regulate virulence, there is significant interest in disrupting QS as a potential therapeutic strategy. Prior studies have implicated the natural products salicylic acid, cinnamaldehyde and other related benzaldehyde derivatives as inhibitors of QS in the opportunistic pathogen Pseudomonas aeruginosa, yet we lack an understanding of the mechanisms by which these compounds function. Herein, we evaluate the activity of a set of benzaldehyde derivatives using heterologous reporters of the P. aeruginosa LasR and RhlR QS signal receptors. We find that most tested benzaldehyde derivatives can antagonize LasR or RhlR reporter activation at micromolar concentrations, although certain molecules also caused mild growth defects and nonspecific reporter antagonism. Notably, several compounds showed promising RhlR or LasR specific inhibitory activities over a range of concentrations below that causing toxicity. Ortho-Vanillin, a previously untested compound, was the most promising within this set. Competition experiments against the native ligands for LasR and RhlR revealed that ortho-vanillin can interact competitively with RhlR but not with LasR. Overall, these studies expand our understanding of benzaldehyde activities in the LasR and RhlR receptors and reveal potentially promising effects of ortho-vanillin as a small molecule QS modulator against RhlR.

Changes in an enzyme ensemble during catalysis observed by high-resolution XFEL crystallography.

Enzymes populate ensembles of structures necessary for catalysis that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography at an x-ray free electron laser to observe catalysis in a designed mutant isocyanide hydratase (ICH) enzyme that enhances sampling of important minor conformations. The active site exists in a mixture of conformations, and formation of the thioimidate intermediate selects for catalytically competent substates. The influence of cysteine ionization on the ICH ensemble is validated by determining structures of the enzyme at multiple pH values. Large molecular dynamics simulations in crystallo and time-resolved electron density maps show that Asp17 ionizes during catalysis and causes conformational changes that propagate across the dimer, permitting water to enter the active site for intermediate hydrolysis. ICH exhibits a tight coupling between ionization of active site residues and catalysis-activated protein motions, exemplifying a mechanism of electrostatic control of enzyme dynamics.

Damage Control Laparotomy and Management of the Open Abdomen.

Management of the open abdomen has been used for decades by general surgeons. Techniques have evolved over those decades to improve control of infection, fluid loss, and improve the ability to close the abdomen to avoid hernia formation. The authors explore the history, indications, and techniques of open abdomen management in multiple settings. The most important considerations in open abdomen management include the reason for leaving the abdomen open, prevention and mitigation of ongoing organ dysfunction, and eventual plans for abdominal closure.

Quantifying the effects of exceptional fossil preservation on the global availability of phylogenetic data in deep time.

Fossil deposits with exceptional preservation ("lagerstätten") provide important details not typically preserved in the fossil record, such that they hold an outsized influence on our understanding of biodiversity and evolution. In particular, the potential bias imparted by this so-called "lagerstätten effect" remains a critical, but underexplored aspect of reconstructing evolutionary relationships. Here, we quantify the amount of phylogenetic information available in the global fossil records of 1,327 species of non-avian theropod dinosaurs, Mesozoic birds, and fossil squamates (e.g., lizards, snakes, mosasaurs), and then compare the influence of lagerstätten deposits on phylogenetic information content and taxon selection in phylogenetic analyses to other fossil-bearing deposits. We find that groups that preserve a high amount of phylogenetic information in their global fossil record (e.g., non-avian theropods) are less vulnerable to a "lagerstätten effect" that leads to disproportionate representation of fossil taxa from one geologic unit in an evolutionary tree. Additionally, for each taxonomic group, we find comparable amounts of phylogenetic information in lagerstätten deposits, even though corresponding morphological character datasets vary greatly. Finally, we unexpectedly find that ancient sand dune deposits of the Late Cretaceous Gobi Desert of Mongolia and China exert an anomalously large influence on the phylogenetic information available in the squamate fossil record, suggesting a "lagerstätten effect" can be present in units not traditionally considered lagerstätten. These results offer a phylogenetics-based lens through which to examine the effects of exceptional fossil preservation on biological patterns through time and space, and invites further quantification of evolutionary information in the rock record.

Disparities in funding for Nobel Prize awards in medicine and physiology across nationalities, races, and gender.

Since 1901, the Nobel Prize in Physiology and Medicine has been awarded to numerous individuals for their outstanding contributions. This article presents a comprehensive analysis of the Nobel Prize recipients, focusing on gender, race, and nationality. We observe that an alarming disparity emerges when we examine the underrepresentation of Black scientists among Nobel laureates. Furthermore, trends in nationalities show how Americans make up the majority of Nobel Prize winners, while there is a noticeable lack of gender and racial minority winners of the Nobel Prize in Physiology and Medicine. Together, this highlights the importance of diversity and inclusion in scientific achievement. We offer suggestions and techniques, including funding opportunities and expanding nominators, to improve the gender, racial, and geographical diversity of Nobel Prizes.

History in the pub: The historiography of J.D. Wetherspoon.

J. D. Wetherspoon is a popular pub chain in the United Kingdom. Despite its prominence in British cultural life and active and deliberate engagement with history, it has received scant academic attention. Here, this engagement with history is explored with a particular focus on how Wetherspoon approaches the history of science. This paper highlights the focus of Wetherspoon on local history and, in particular, on local exceptionalism, before discussing how such an understanding of history informs wider debates-such as Wetherspoon's support of Brexit (the UK's withdrawal from the European Union). It contributes to understandings of what constitutes popular history and, through doing so, emphasises the need for historians to engage with historical narratives outside the academy.

D-ß-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance.

1.The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KBs) when less glucose is available. Neuronal KB uptake, which does not rely on glucose transporter 4 (GLUT4) or insulin, has shown promising clinical applicability in alleviating the neurological and cognitive effects of disorders with hypometabolic components. However, the specific mechanisms by which such interventions affect neuronal functions are poorly understood. In this study, we pharmacologically blocked GLUT4 to investigate the effects of exogenous KB D-P-hydroxybutyrate (D-ßHb) on mouse brain metabolism during acute insulin resistance (AIR). We found that both AIR and D-ßHb had distinct impacts across neuronal compartments: AIR decreased synaptic activity and long-term potentiation (LTP) and impaired axonal conduction, synchronization, and action potential (AP) properties, while D- PHb rescued neuronal functions associated with axonal conduction, synchronization and LTP.

Global patterns of plumage color evolution in island-living passeriform birds.

Island environments have the potential to change evolutionary trajectories of morphological traits in species relative to their mainland counterparts due to habitat and resource differences, or by reductions in the intensity of social or sexual selection. Latitude, island size, and isolation may further influence trait evolution through biases in colonization rates. We used a global dataset of passerine plumage color as a model group to identify selective pressures driving morphological evolution of island animals using phylogenetically-controlled analyses. We calculated chromaticity values from red and blue scores extracted from images of the majority of Passeriformes and tested these against the factors hypothesized to influence color evolution. In contrast to predictions based on sexual and social selection theory, we found consistent changes in island female color (lower red and higher blue chromaticity), but no change in males. Instead, island size and distance from mainland and other islands influenced color in both sexes, reinforcing the importance of island physiognomy in shaping evolutionary processes. Interactions between ecological factors and latitude also consistently influenced color for both sexes, supporting a latitudinal gradient hypothesis. Finally, patterns of color evolution varied among families, indicating taxon-specific microevolutionary processes in driving color evolution. Our results show island residency influences color evolution differently between sexes, but the patterns in both sexes are tempered by ecological, island characteristics, and phylogenetic effects that further vary in their importance among families. The key role of environmental factors in shaping bird plumage on islands further suggests a reduced importance of sexual and social factors in driving color evolution.

MitoTracker: A useful tool in need of better alternatives.

The fluorescence viewing of mitochondria is commonly performed by MitoTracker, a lipophilic cationic dye that is taken up by the mitochondria. In this forum, we highlight several issues that may occur with MitoTracker, including staining of other organelles. Our aim is to offer alternative dyes and discuss their advantages and disadvantages. We also offer options for software with alternatives to MitoTracker to expedite future experimental design.

Development of the ARENA training programme for resilient performance in defense and security settings.

Defense and Security Personnel (DSP) often have to operate in the presence of stressful demands. Prior research has identified factors and processes associated with DSP being able to perform resiliently in demanding situations and settings. The aim of the present study was to develop a resilient performance training programme for UK defense and security operators. An intervention mapping (IM) method was used to guide the development of the programme. Typically, IM follows six sequential phases. In the present work, these phases were shaped by insights from prior research (e.g. systematic review and end user interviews), the input of a dedicated working group (N = 13) and from practitioner focus groups. During the IM process, the importance of programme flexibility was emphasized by practitioners. As such, the enAbling REsilieNt performAnce (ARENA) training programme was designed to be agile and include both face-to-face training and online learning modules. Theoretical behavior change principles, closely aligned to findings of earlier work on resilient defense and security performance, were used to underpin programme content and delivery. Future research should seek to gather data on the impact of the ARENA programme, in the targeted biological, psychological and social factors that previously been associated with resilient performances.

Diversity, Equity and Inclusion in the Laboratory: Strategies to Enhance Inclusive Laboratory Culture.

Building a diverse laboratory that is equitable is critical for the retention of talent and the growth of trainees professionally and personally. Here, we outline several strategies including enhancing understanding of cultural competency and humility, establishing laboratory values, and developing equitable laboratory structures to create an inclusive laboratory environment to enable trainees to achieve their highest success.

X-ray-driven chemistry and conformational heterogeneity in atomic resolution crystal structures of bacterial dihydrofolate reductases.

Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate. Bacterial DHFRs are targets of several important antibiotics as well as model enzymes for the role of protein conformational dynamics in enzyme catalysis. We collected 0.93 Å resolution X-ray diffraction data from both Bacillus subtilis (Bs) and E. coli (Ec) DHFRs bound to folate and NADP+. These oxidized ternary complexes should not be able to perform chemistry, however electron density maps suggest hydride transfer is occurring in both enzymes. Comparison of low- and high-dose EcDHFR datasets show that X-rays drive partial production of tetrahydrofolate. Hydride transfer causes the nicotinamide moiety of NADP+ to move towards the folate as well as correlated shifts in nearby residues. Higher radiation dose also changes the conformational heterogeneity of Met20 in EcDHFR, supporting a solvent gating role during catalysis. BsDHFR has a different pattern of conformational heterogeneity and an unexpected disulfide bond, illustrating important differences between bacterial DHFRs. This work demonstrates that X-rays can drive hydride transfer similar to the native DHFR reaction and that X-ray photoreduction can be used to interrogate catalytically relevant enzyme dynamics in favorable cases.