Sense of direction in vestibular disorders.

BACKGROUND: Our sense of direction (SOD) ability relies on the sensory integration of both visual information and self-motion cues from the proprioceptive and vestibular systems. Here, we assess how dysfunction of the vestibular system impacts perceived SOD in varying vestibular disorders, and secondly, we explore the effects of dizziness, migraine and psychological symptoms on SOD ability in patient and control groups. METHODS: 87 patients with vestibular disorder and 69 control subjects were assessed with validated symptom and SOD questionnaires (Santa Barbara Sense of Direction scale and the Object Perspective test). RESULTS: While patients with vestibular disorders performed significantly worse than controls at the group level, only central and functional disorders (vestibular migraine and persistent postural perceptual dizziness), not peripheral disorders (benign-paroxysmal positional vertigo, bilateral vestibular failure and Meniere's disease) showed significant differences compared to controls on the level of individual vestibular groups. Additionally, orientational abilities associated strongly with spatial anxiety and showed clear separation from general dizziness and psychological factors in both patient and control groups. CONCLUSIONS: SOD appears to be less affected by peripheral vestibular dysfunction than by functional and/or central diagnoses, indicating that higher level disruptions to central vestibular processing networks may impact SOD more than reductions in sensory peripheral inputs. Additionally, spatial anxiety is highly associated with orientational abilities in both patients and control subjects.

Left ventricular to left arial volume ratio in the assessment of filling pressure in patients with dyspnoea and preserved ejection fraction.

Introduction: Assessing filling pressure (FP) remains a clinical challenge despite advancements in non-invasive imaging techniques. This study investigates the utility of echocardiographic left ventricular (LV) to left atrial (LA) volume ratio in estimating the resting FP in patients with dyspnoea and preserved ejection fraction (EF). Methods: This study is a prospective, single-centre analysis of 53 consecutive patients with dyspnoea (New York Heart Association grade 2 or 3) and LVEF of ≥50% (mean age 71 ± 10 years) who underwent cardiac catheterisation, including direct measurement of LA pressure at rest using retrograde technique. Echocardiographic data were obtained 1.5 ± 1.0 h after cardiac catheterisation. The patients were divided into two groups: Group 1 consisted of individuals with elevated FP, indicated by a mean LA pressure or mean pulmonary capillary wedge pressure of >12 mmHg, and Group 2 comprised of patients with normal FP. The LV and LA volumes were measured at three specific points: the minimum volume (LVES, LAmin), the volume during diastasis (LVdias, LAdias), and the maximum volume (LVED, LAmax). The corresponding LV/LA volume ratios were analysed: end-systole (LVES/LAmax), diastasis (LVdias/LAdias), and end-diastole (LVED/LAmin). Results: The patients in Group 1 exhibited lower LV/LA volume ratios compared with those in Group 2 (LVES/LAmax 0.44 ± 0.12 vs. 0.60 ± 0.23, P = 0.0032; LVdias/LAdias 1.13 ± 0.30 vs. 1.56 ± 0.49, P = 0.0007; LVED/LAmin 2.71 ± 1.57 vs. 4.44 ± 1.70, P = 0.0004). The LV/LA volume ratios correlated inversely with an increased FP (LVES/LAmax, r = -0.40, P = 0.0033; LVdias/LAdias, r = -0.45, P = 0.0007; LVED/LAmin, r = -0.55, P < 0.0001). Among all the measurements, the LVdias/LAdias ratio demonstrated the highest discriminatory power to distinguish patients with elevated FP from normal FP, with a cut-off value of ≤1.24 [area under the curve (AUC) = 0.822] for the entire group, encompassing both sinus rhythm and atrial fibrillation. For patients in sinus rhythm specifically, the cut-off value was ≤1.28 (AUC = 0.799), with P < 0.0001 for both. The LVdias/LAdias index demonstrated non-inferiority to the E/e' ratio [ΔAUC = 0.159, confidence interval (CI) = -0.020-0.338; P = 0.0809], while surpassing the indices of LA reservoir function (ΔAUC = 0.249, CI = 0.044-0.454; P = 0.0176), LA reservoir strain (ΔAUC = 0.333, CI = 0.149-0.517; P = 0.0004), and LAmax index (ΔAUC = 0.224, CI = 0.043-0.406; P = 0.0152) in diagnosing patients with elevated FP. Conclusion: The study presents a straightforward and reproducible method for non-invasive estimation of FP using routine TTE in patients with dyspnoea and preserved EF. The LVdias/LAdias index emerges as a promising indicator for identifying elevated FP, demonstrating comparable or even superior performance to established parameters.

Understanding patient preferences for student clinician attire: a cross-sectional study of a student chiropractic clinic in Australia.

Objectives: Previous studies have investigated the role of clinical attire in establishing patient-held perceptions of professionalism and knowledgeability across various healthcare settings. This study aimed to understand patients' preferences for chiropractic student attire. Methods: Three hundred and twenty patients were recruited from a university chiropractic clinic and asked to complete an online questionnaire. The patients' preferences for five different attires were rated and calculated as the composite score of five domains (knowledgeable, trustworthy, caring, professional, and comfortable). Results: While 71.9% of participants indicated that how students dress was important to them, most (63.4%) disagreed that wearing a white coat was essential for chiropractic student clinicians. The most preferred form of attire was the current clinic shirt. Conclusion: The attire worn by chiropractic student clinicians at a single institution was found to be an influential attribute. Student chiropractic clinicians should dress professionally to make a good first impression. This study provided some guidance with the ongoing debate around students' dress code.

Objectif: Des études antérieures ont examiné le rôle de la tenue vestimentaire en clinique dans l'établissement des perceptions des patients quant au professionnalisme et à la compétence dans divers environnements de soins de santé. Cette étude visait à comprendre les préférences des patients en matière de tenue vestimentaire des étudiants en chiropratique. Méthodologie: Trois cent vingt patients ont été recrutés dans une clinique chiropratique universitaire et invités à remplir un questionnaire en ligne. Les préférences des patients pour cinq tenues différentes ont été évaluées et calculées en tant que score composite de cinq domaines (bien informé, digne de confiance, attentionné, professionnel et confortable). Résultats: Si 71,9 % des participants ont indiqué que la tenue vestimentaire des étudiants était importante pour eux, la plupart (63,4 %) n'étaient pas d'accord avec le fait que le port d'une blouse blanche était essentiel pour les étudiants cliniciens en chiropratique. La tenue vestimentaire la plus appréciée était la chemise de clinique actuelle. Conclusion: La tenue vestimentaire des étudiants cliniciens en chiropratique d'un même établissement s'est révélée être un attribut influent. Les étudiants en chiropratique doivent s'habiller de manière professionnelle pour faire une bonne première impression. Cette étude a permis d'éclairer le débat en cours sur le code vestimentaire des étudiants.

Organizational benefits of neurodiversity: Preliminary findings on autism and the bystander effect.

Although the bystander effect is one of the most important findings in the psychological literature, researchers have not explored whether autistic individuals are prone to the bystander effect. The present research examines whether autistic employees are more likely to report issues or concerns in an organization's systems and practices that are inefficient or dysfunctional. By bringing attention to these issues, autistic employees may foster opportunities to improve organizational performance, leading to the development of a more adaptive, high performing, and ethical culture. Thirty-three autistic employees and 34 nonautistic employees completed an online survey to determine whether employees on the autism spectrum (1) are more likely to report they would voice concerns about organizational dysfunctions, (2) are less likely to report they were influenced by the number of other witnesses to the dysfunction, (3) if they do not voice concerns, are more likely to acknowledge the influence of other people on the decision, (4) are less likely to formulate "elaborate rationales" for their decisions to intervene or not, and (5) whether any differences between autistic and nonautistic employees with regards to the first two hypotheses, intervention likelihood and degree of influence, are moderated by individual differences in camouflaging. Results indicate that autistic employees may be less susceptible to the bystander effect than nonautistic employees. As a result, autistic employees may contribute to improvements in organizational performance because they are more likely to identify and report inefficient processes and dysfunctional practices when they witness them. These preliminary findings suggesting potential benefits of neurodiversity in the workplace are promising. However, further research is required.

XGBoost, A Novel Explainable AI Technique, in the Prediction of Myocardial Infarction: A UK Biobank Cohort Study.

We wanted to assess if "Explainable AI" in the form of extreme gradient boosting (XGBoost) could outperform traditional logistic regression in predicting myocardial infarction (MI) in a large cohort. Two machine learning methods, XGBoost and logistic regression, were compared in predicting risk of MI. The UK Biobank is a population-based prospective cohort including 502 506 volunteers with active consent, aged 40 to 69 years at recruitment from 2006 to 2010. These subjects were followed until end of 2019 and the primary outcome was myocardial infarction. Both models were trained using 90% of the cohort. The remaining 10% was used as a test set. Both models were equally precise, but the regression model classified more of the healthy class correctly. XGBoost was more accurate in identifying individuals who later suffered a myocardial infarction. Receiver operator characteristic (ROC) scores are class size invariant. In this metric XGBoost outperformed the logistic regression model, with ROC scores of 0.86 (accuracy 0.75 (CI ±0.00379) and 0.77 (accuracy 0.77 (CI ± 0.00369) respectively. Secondly, we demonstrate how SHAPley values can be used to visualize and interpret the predictions made by XGBoost models, both for the cohort test set and for individuals. The XGBoost machine learning model shows very promising results in evaluating risk of MI in a large and diverse population. This model can be used, and visualized, both for individual assessments and in larger cohorts. The predictions made by the XGBoost models, points toward a future where "Explainable AI" may help to bridge the gap between medicine and data science.

The EMS Modified Early Warning Score (EMEWS): A Simple Count of Vital Signs as a Predictor of Out-of-Hospital Cardiac Arrests.

Objective: For patients at risk for out-of-hospital cardiac arrest (OHCA) after Emergency Medical Services (EMS) arrival, outcomes may be mitigated by identifying impending arrests and intervening before they occur. Tools such as the Modified Early Warning Score (MEWS) have been developed to determine the risk of arrest, but involve relatively complicated algorithms that can be impractical to compute in the prehospital environment. A simple count of abnormal vital signs, the "EMS Modified Early Warning Score" (EMEWS), may represent a more practical alternative. We sought to compare to the ability of MEWS and EMEWS to identify patients at risk for EMS-witnessed OHCA.Methods: We conducted a retrospect analysis of the 2018 ESO Data Collaborative database of EMS encounters. Patients without cardiac arrest before EMS arrival were categorized into those who did or did not have an EMS-witnessed arrest. MEWS was evaluated without its temperature component (MEWS-T). The performance of MEWS-T and EMEWS in predicting EMS witnessed arrest was evaluated by comparing receiver-operating characteristic curves.Results: Of 369,064 included encounters, 4,651 were EMS witnessed arrests. MEWS-T demonstrated an area under the curve (AUC) of 0.79 (95% CI: 0.79 - 0.80), with 86.8% sensitivity and 51.0% specificity for MEWS-T ≥ 3. EMEWS demonstrated an AUC of 0.74 (95% CI: 0.73 - 0.75), with 81.3% sensitivity and 53.9% specificity for EMEWS ≥ 2.Conclusions: EMEWS showed a similar ability to predict EMS-witnessed cardiac arrest compared to MEWS-T, despite being significantly simpler to compute. Further study is needed to evaluate whether the implementation of EMEWS can aid EMS clinicians in anticipating and preventing OHCA.

rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans.

Injured axons must regenerate to restore nervous system function, and regeneration is regulated in part by external factors from non-neuronal tissues. Many of these extrinsic factors act in the immediate cellular environment of the axon to promote or restrict regeneration, but the existence of long-distance signals regulating axon regeneration has not been clear. Here we show that the Rab GTPase rab-27 inhibits regeneration of GABAergic motor neurons in C. elegans through activity in the intestine. Re-expression of RAB-27, but not the closely related RAB-3, in the intestine of rab-27 mutant animals is sufficient to rescue normal regeneration. Several additional components of an intestinal neuropeptide secretion pathway also inhibit axon regeneration, including NPDC1/cab-1, SNAP25/aex-4, KPC3/aex-5, and the neuropeptide NLP-40, and re-expression of these genes in the intestine of mutant animals is sufficient to restore normal regeneration success. Additionally, NPDC1/cab-1 and SNAP25/aex-4 genetically interact with rab-27 in the context of axon regeneration inhibition. Together these data indicate that RAB-27-dependent neuropeptide secretion from the intestine inhibits axon regeneration, and point to distal tissues as potent extrinsic regulators of regeneration.

Apneic oxygenation via nasal cannula for intubation of a premature neonate with multiple airway anomalies.

Intubating a neonate under non-emergent conditions may be quite stressful, even for experienced providers, due to the potential for rapid oxygen desaturation. Pulmonary physiology and increased metabolic oxygen demand in this patient population contribute to accelerated oxygen desaturation during induction of anaesthesia and intubation. Using a nasal cannula, placed prior to induction of anaesthesia and left in place until the airway is secured, is a simple and effective way to provide apneic oxygenation and may help maintain adequate oxygen saturation. This technique may be particularly useful for patients who require additional time for intubation, including those with suspected difficult airways.

Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration.

Axonal regrowth is crucial for recovery from CNS injury but is severely restricted in adult mammals. We used a genome-wide loss-of-function screen for factors limiting axonal regeneration from cerebral cortical neurons in vitro. Knockdown of 16,007 individual genes identified 580 significant phenotypes. These molecules share no significant overlap with those suggested by previous expression profiles. There is enrichment for genes in pathways related to transport, receptor binding, and cytokine signaling, including Socs4 and Ship2. Among transport-regulating proteins, Rab GTPases are prominent. In vivo assessment with C. elegans validates a cell-autonomous restriction of regeneration by Rab27. Mice lacking Rab27b show enhanced retinal ganglion cell axon regeneration after optic nerve crush and greater motor function and raphespinal sprouting after spinal cord trauma. Thus, a comprehensive functional screen reveals multiple pathways restricting axonal regeneration and neurological recovery after injury.

Anisotropy and Strain Localization in Dynamic Impact Experiments of Tantalum Single Crystals.

Deformation mechanisms in bcc metals, especially in dynamic regimes, show unusual complexity, which complicates their use in high-reliability applications. Here, we employ novel, high-velocity cylinder impact experiments to explore plastic anisotropy in single crystal specimens under high-rate loading. The bcc tantalum single crystals exhibit unusually high deformation localization and strong plastic anisotropy when compared to polycrystalline samples. Several impact orientations - [100], [110], [111] and [[Formula: see text]] - are characterized over a range of impact velocities to examine orientation-dependent mechanical behavior versus strain rate. Moreover, the anisotropy and localized plastic strain seen in the recovered cylinders exhibit strong axial symmetries which differed according to lattice orientation. Two-, three-, and four-fold symmetries are observed. We propose a simple crystallographic argument, based on the Schmid law, to understand the observed symmetries. These tests are the first to explore the role of single-crystal orientation in Taylor impact tests and they clearly demonstrate the importance of crystallography in high strain rate and temperature deformation regimes. These results provide critical data to allow dramatically improved high-rate crystal plasticity models and will spur renewed interest in the role of crystallography to deformation in dynamics regimes.

Characterization of exposure to byproducts from firing lead-free frangible ammunition in an enclosed, ventilated firing range.

U.S. Air Force small arms firing ranges began using copper-based, lead-free frangible ammunition in the early 2000s due to environmental and health concerns related to the use of lead-based ammunition. Exposure assessments at these firing ranges have routinely detected chemicals and metals in amounts much lower than their mass-based occupational exposure limits, yet, instructors report work-related health concerns including respiratory distress, nausea, and headache. The objective of this study at one firing range was to characterize the aerosol emissions produced by weapons during firing events and evaluate the ventilation system's effectiveness in controlling instructor exposure to these emissions. The ventilation system was assessed by measuring the range static air pressure differential and the air velocity at the firing line. Air flow patterns were near the firing line. Instructor exposure was sampled using a filter-based air sampling method for metals and a wearable, real-time ultrafine particle counter. Area air sampling was simultaneously performed to characterize the particle size distribution, morphology, and composition. In the instructor's breathing zone, the airborne mass concentration of copper was low (range = <1 µg/m3 to 16 µg/m3), yet the ultrafine (nanoscale) particle number concentration increased substantially during each firing event. Ultrafine particles contained some copper and were complex in morphology and composition. The ventilation assessment found that the average velocity across all shooting lanes was acceptable compared to the recommended guideline (20% of the ideal 0.38 m/s (75 ft/min). However, uniform, downrange airflow pattern requirements were not met. These results suggest that the mass-based occupational exposure limits, as applied to this environment, may not be protective enough to eliminate health complaints reported by instructors whose full-time job involves training personnel on weapons that fire lead-free frangible ammunition. Using an ultrafine particle counter appears to be an alternative method of assessing ventilation effectiveness in removing ultrafine particulate produced during firing events.

Synthesis of 3-substituted isoindolin-1-ones via a tandem desilylation, cross-coupling, hydroamidation sequence under aqueous phase-transfer conditions.

A simple and expedient method for the synthesis of 3-methylene-isoindolin-1-ones 4 under aqueous phase-transfer conditions has been developed. Starting from 2-iodobenzamides 1 and (silyl)alkynes, the products are obtained in high yields and short reaction times (30 min) with the use of inexpensive CuCl/PPh3 catalyst system in the presence of n-Bu4NBr (TBAB) as a phase-transfer agent. Terminal alkynes are conveniently "unmasked" upon in situ desilylation under the reaction conditions. Alkynes possessing heterocyclic moieties were also found as amenable substrates. Furthermore, a one-pot process starting from 2-iodobenzamides 1, aryl halides (bromides or iodides) and trimethylsilylacetylene (TMSA) as a convenient acetylene surrogate was also shown to be feasible under Pd/Cu catalysis.

The role of folate metabolism in orofacial development and clefting.

Folate deficiency has been associated with numerous diseases and birth defects including orofacial defects. However, whether folate has a role in the face during early orofacial development has been unclear. The present study reveals that pharmacological and antisense oligonucleotide mediated inhibition of DHFR, an integral enzyme in the folate pathway, results in specific changes in the size and shape of the midface and embryonic mouth. Such defects are accompanied by a severe reduction in the muscle and cartilage jaw elements without significant change in neural crest pattern or global levels of methylation. We propose that the orofacial defects associated with DHFR deficient function are the result of decreased cell proliferation and increased cell death via DNA damage. In particular, localized apoptosis may also be depleting the cells of the face that express crucial genes for the differentiation of the jaw structures. Folate supplementation is widely known to reduce human risk for orofacial clefts. In the present study, we show that activating folate metabolism can reduce median oral clefts in the primary palate by increasing cell survival. Moreover, we demonstrate that a minor decrease in DHFR function exacerbates median facial clefts caused by RAR inhibition. This work suggests that folate deficiencies could be a major contributing factor to multifactorial orofacial defects.

RNA ligation in neurons by RtcB inhibits axon regeneration.

Activity of the RNA ligase RtcB has only two known functions: tRNA ligation after intron removal and XBP1 mRNA ligation during activation of the unfolded protein response. Here, we show that RtcB acts in neurons to inhibit axon regeneration after nerve injury. This function of RtcB is independent of its basal activities in tRNA ligation and the unfolded protein response. Furthermore, inhibition of axon regeneration is independent of the RtcB cofactor archease. Finally, RtcB is enriched at axon termini after nerve injury. Our data indicate that neurons have co-opted an ancient RNA modification mechanism to regulate specific and dynamic functions and identify neuronal RtcB activity as a critical regulator of neuronal growth potential.

Programmed evolution for optimization of orthogonal metabolic output in bacteria.

Current use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields - evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization. Our approach is called Programmed Evolution to capture two concepts. First, a population of cells is programmed with DNA code to enable it to compute solutions to a chosen optimization problem. As analog computers, bacteria process known and unknown inputs and direct the output of their biochemical hardware. Second, the system employs the evolution of bacteria toward an optimal metabolic solution by imposing fitness defined by metabolic output. The current study is a proof-of-concept for Programmed Evolution applied to the optimization of a metabolic pathway for the conversion of caffeine to theophylline in E. coli. Introduced genotype variations included strength of the promoter and ribosome binding site, plasmid copy number, and chaperone proteins. We constructed 24 strains using all combinations of the genetic variables. We used a theophylline riboswitch and a tetracycline resistance gene to link theophylline production to fitness. After subjecting the mixed population to selection, we measured a change in the distribution of genotypes in the population and an increased conversion of caffeine to theophylline among the most fit strains, demonstrating Programmed Evolution. Programmed Evolution inverts the standard paradigm in metabolic engineering by harnessing evolution instead of fighting it. Our modular system enables researchers to program bacteria and use evolution to determine the combination of genetic control elements that optimizes catabolic or anabolic output and to maintain it in a population of cells. Programmed Evolution could be used for applications in energy, pharmaceuticals, chemical commodities, biomining, and bioremediation.

An estrogen-responsive module in the ventromedial hypothalamus selectively drives sex-specific activity in females.

Estrogen-receptor alpha (ERα) neurons in the ventrolateral region of the ventromedial hypothalamus (VMHVL) control an array of sex-specific responses to maximize reproductive success. In females, these VMHVL neurons are believed to coordinate metabolism and reproduction. However, it remains unknown whether specific neuronal populations control distinct components of this physiological repertoire. Here, we identify a subset of ERα VMHVL neurons that promotes hormone-dependent female locomotion. Activating Nkx2-1-expressing VMHVL neurons via pharmacogenetics elicits a female-specific burst of spontaneous movement, which requires ERα and Tac1 signaling. Disrupting the development of Nkx2-1(+) VMHVL neurons results in female-specific obesity, inactivity, and loss of VMHVL neurons coexpressing ERα and Tac1. Unexpectedly, two responses controlled by ERα(+) neurons, fertility and brown adipose tissue thermogenesis, are unaffected. We conclude that a dedicated subset of VMHVL neurons marked by ERα, NKX2-1, and Tac1 regulates estrogen-dependent fluctuations in physical activity and constitutes one of several neuroendocrine modules that drive sex-specific responses.

Osteocutaneous radial forearm free flap in subtotal nasal reconstruction.

A 66-year-old man presented with a large squamous cell carcinoma of the right nasal vestibule. He underwent partial rhinectomy and medial maxillectomy followed by staged reconstruction. Reconstruction of a full-thickness nasal defect requires repair of three distinct layers: the skin-soft tissue envelope, subsurface framework and intranasal lining. We report the first use in the UK of an osteocutaneous radial forearm free flap in the reconstruction of a subtotal nasal deficit. The skin of the radial forearm free flap was tubed to recreate the nasal lining and the radial bone reconstructed the dorsal contour of the nose. A full-thickness paramedian forehead flap supplied external coverage. The osteocutaneous radial forearm free flap and forehead flap is a viable option for large nasal defects requiring reconstruction of framework, nasal lining and external covering.