A venom peptide-induced NaV channel modulation mechanism involving the interplay between fixed channel charges and ionic gradients.

Venoms are used by arthropods either to immobilise prey or as defence against predators. Our study focuses on the venom peptide, Ta3a, from the African ant species, Tetramorium africanum and its effects on voltage-gated sodium (NaV) channels, which are ion channels responsible for the generation of electrical signals in electrically excitable cells, such as neurons. Using the NaV1.7 isoform as our model NaV channel we show that Ta3a prolongs single channel active periods with increased open probability and induces non-inactivating whole-cell currents. Ta3a-affected NaV1.7 channels exhibit a leftward (hyperpolarising) shift in activation threshold, constitutive activity even in the absence of an activating voltage stimulus, and at cell membrane voltages where channels are normally silent. Current-voltage experiments show that Ta3a shifts the voltage at which NaV current changes direction (reversal potential) by altering the local ionic concentration of permeant ions (Na+) rather than changing the channel's preference for ionic species. We propose a model where Ta3a maintains the positively charged voltage-sensing (S4) domains of the channel in the activated configuration where their electric field is exposed to the extracellular membrane surface to create an ionic bilayer comprising S4 domains and mobile anions (Cl-). This bilayer has a depolarising effect on the cell membrane, thus reducing the amount of externally applied voltage required for channel activation.

Binomial models uncover biological variation during feature selection of droplet-based single-cell RNA sequencing.

Effective analysis of single-cell RNA sequencing (scRNA-seq) data requires a rigorous distinction between technical noise and biological variation. In this work, we propose a simple feature selection model, termed "Differentially Distributed Genes" or DDGs, where a binomial sampling process for each mRNA species produces a null model of technical variation. Using scRNA-seq data where cell identities have been established a priori, we find that the DDG model of biological variation outperforms existing methods. We demonstrate that DDGs distinguish a validated set of real biologically varying genes, minimize neighborhood distortion, and enable accurate partitioning of cells into their established cell-type groups.

The Influence of Preimplant Balancing on Manipulation under Anesthesia Rates Following Imageless Robotic-assisted Total Knee Arthroplasty.

BACKGROUND: Acquired Idiopathic Stiffness (AIS) following total knee arthroplasty (TKA) often requires manipulation under anesthesia (MUA). Robotic-assisted TKA (R-TKA) systems provide gap balance templates for objective correlation with the rate of AIS. The purpose of this study was to assess intraoperative balancing parameters that were associated with MUA utilizing an "anatomic" implant design. METHODS: We performed a retrospective chart review of 265 imageless R-TKA procedures performed by two senior surgeons between 2018 to 2020. The primary outcome for AIS or clinically significant "arthrofibrosis" was MUA. Patient intraoperative gap planning data was examined for association. RESULTS: The rate of MUA was 8.7% (23/265), which was performed at a mean follow-up time of 75.9 ± 32.2 days. The lateral to medial gap difference in extension was significantly less in patients requiring MUA (OR = 0.86, 95% CI, 0.75 - 0.99) (p = 0.034). Significantly less pre-operative varus mechanical axis was associated with knees requiring MUA (1.83° vs 4.04°, OR 1.09 95% CI 1.00-1.19). Decreased templated mechanical axis correction was associated with MUA (2.09° vs 4.75° p <0.0001). CONCLUSIONS: Tighter lateral to medial gap in extension, less pre-operative varus, and smaller templated mechanical axis corrections were associated with increased rates of manipulation under anesthesia.

Evaluation of a host-protein signature score for differentiating between bacterial and viral infections: real-life evidence from a German tertiary hospital.

PURPOSE: A host-protein signature score, consisting of serum-concentrations of C-reactive protein, tumour necrosis factor-related apoptosis-inducing ligand, and interferon gamma-induced protein 10, was validated for distinguishing between bacterial and viral infections as an antimicrobial stewardship measure for routine clinical practice among adult patients in a German tertiary hospital. METHODS: This single-centre, explorative study prospectively assessed the host-protein signature score, comparing it with serum procalcitonin (PCT) in patients with blood stream infections (BSI) and evaluating its efficacy in patients with viral infections against the standard of care (SOC) to assess the need for antibiotics due to suspected bacterial super/coinfection. Manufacturer-specified threshold scores were used to differentiate viral (< 35) and bacterial (> 65) infections. RESULTS: Ninety-seven patients (BSI [n = 56]; viral infections [n = 41]) were included. The score (cut-off score > 65) tended to detect BSI with higher sensitivity than did PCT (cut-off > 0.5 ng/mL) (87.5% vs. 76.6%). Three patients (5.4%) with BSI had a score < 35. One patient with BSI did not receive antibiotic treatment following SOC prior to positive blood culture results. Among patients with viral infections, 29 (70.7%) had scores > 65, indicating bacterial superinfections. Additionally, 11 patients (26.8%) had scores < 35, indicating no bacterial superinfections. In total, the antibiotic treatment discrepancy in the viral group between the SOC and a host-protein signature score guided approach was 2/41 patients (4.9%). CONCLUSION: The score tended towards a higher sensitivity in detecting BSI than that with PCT. However, its impact on reducing antibiotic use in viral infections was minor compared with that of SOC.

Clinical Considerations for Integrating Ethical Principles of Beneficence in the Development of Evidence-Based Interventions: The case of Pediatric Misophonia.

Misophonia is a condition involving decreased tolerance and intense responses to specific sounds, often those that are human-generated and repetitive in nature. Misophonia frequently onsets during childhood and is associated with significant distress, impairment, and diminished quality of life. While misophonia research remains nascent and no definitive practice guidelines exist at present, extant studies offer several promising potential avenues in intervention development for adults with misophonia. However, such research is comparatively limited for youth. Before widespread adoption of promising treatments, it is important to consider the potential for harm or non-beneficence that may arise from the mis-informed application of such treatments. In this article, we identify several potential pitfalls within intervention development for pediatric misophonia and provide recommendations to circumvent them. To that end, we focus on the following three topic areas: (a) challenges arising when psychological mechanisms are not considered in intervention development, (b) importation of a cognitive-behavior therapy (CBT) framework for obsessive-compulsive spectrum disorders without nuanced tailoring to misophonia, and (c) neglecting to include individuals with lived experience in the process of intervention development research. Considering these key areas within misophonia intervention development will be critical for upholding beneficence and minimizing harm in treatment of misophonia across the lifespan.

Evaluating the accuracy of the MBT Lipid Xtract Kit for assessing colistin resistance in comparison to broth microdilution.

Colistin resistance testing methods such as broth microdilution (BMD) are time-consuming and labour intensive for clinical laboratories. MBT Lipid Xtract Kit on MALDI Biotyper Sirius System (Bruker, Billerica, MA, USA) utilizes lipidomic analysis to identify specific cell wall modifications associated with colistin resistance. We compared MBT to BMD (ComASP Colistin, Liofilchem) across 36 Gram-negative isolates (non-resistant MIC ≤2 µg ml-1, resistant MIC ≥4 µg ml-1). All samples were tested twice on MBT with discrepant results repeated before assessing categorical agreement between MBT and BMD. 44.4% (16/36) of isolates were colistin resistant via BMD. MBT Lipid Xtract had 80.6% agreement (29/36) with BMD, with 5/7 discrepancies corrected to match upon repeat testing. There was 100% agreement for Escherichia coli isolates (n=16). The whole-genome sequencing was completed on the two discrepant Klebsiella pneumoniae isolates, with variants within colistin resistance-associated loci identified (MIC 0.5 µg ml-1: arnC S30T, pmrB T246A, lapB N212T, lpxM S253G, crrB Q287K and MIC >16 µg ml-1: arnC S30T, pmrB R90insRN, pmrB T246A, pmrA E57G, lpxM S253G). Further evaluation, particularly for non-E. coli, of MBT is required prior to implementation in clinical laboratories.

Screening, diagnosis, and monitoring of interstitial lung disease in autoimmune rheumatic diseases: A narrative review.

Interstitial lung disease (ILD) is a common and serious manifestation of autoimmune rheumatic diseases. While the prevalence of ILD differs among the individual autoimmune rheumatic diseases, ILD remains an important cause of morbidity and mortality in systemic sclerosis, systemic lupus erythematosus, mixed connective tissue disease, primary Sjögren's disease, rheumatoid arthritis, and idiopathic inflammatory myositis. The present review summarizes recent literature on autoimmune-associated ILD with a focus on screening and monitoring for ILD progression. Reflecting on the currently available evidence, the authors propose a guideline for monitoring for progression in patients with newly diagnosed autoimmune-associated ILD. This review also highlights clinical and biological predictors of progressive pulmonary fibrosis and describes opportunity for further study in the rapidly evolving area of rheumatology and pulmonology.

La enfermedad pulmonar intersticial (EPI) es una manifestación común y seria de las enfermedades autoinmunes. Aunque la prevalencia de EPI difiere de acuerdo a cada enfermedad, continúa siendo una causa importante de morbilidad y mortalidad en la esclerosis sistémica, la artritis reumatoide, el síndrome de Sjögren, la enfermedad mixta del tejido conjuntivo y las miopatías inflamatorias. Este artículo de revisión resume la literatura reciente sobre la EPI asociada con autoinmunidad, con enfoque en la búsqueda y el monitoreo de la progresión de la EPI. Con base en la evidencia disponible, los autores proponen una guía para el monitoreo de la progresión en pacientes con la EPI asociada con autoinmunidad de reciente diagnóstico. Esta revisión también aborda los predictores clínicos y biológicos de la fibrosis pulmonar progresiva y resalta la oportunidad para estudios adicionales en áreas de rápida evolución como la reumatología y la neumología.

Characterizing Revascularization after Encephalo-Duro-Arterio-Synangiosis (EDAS) in Adult Patients with Moyamoya Disease Using the Orbital Grading System.

BACKGROUND: The Matsushima Grade has traditionally been used to evaluate vessel ingrowth from the STA after EDAS for MMD-patients. However, this grading is subjective and prone to measurement variability. Herein, we propose the orbital grading system quantifying leptomeningeal and burr hole-related vessel-ingrowth from the STA and/or MMA to the middle and anterior cerebral arteries post-EDAS in MMD patients. METHODS: An anatomical classification was developed by reference to two parallel vertical lines from the bony landmarks of the orbit, categorized from Grade 0-3. Regression models were used to compare clinical and functional outcomes of our grading system with the Matsushima scale. RESULTS: Forty MMD patients, with median age of 48 years, mostly females (72.5%), were included. Presentation included ischemic events (65.0%), hemorrhage (22.5%), and seizures (7.5%). Most patients were categorized as Suzuki ≥ IV (69.5%). Fifty EDAS (89.9%) had concurrent burr holes placed (parietal and frontal regions). At a median follow-up of 13.7 months, collateral growth was graded as follows: grade 0 (6;10.8%), grade 1 (12;21.4%), grade 2 (23;41.1%) and grade 3 (15;26.8%). Linear regression showed similarities in the distribution between the orbital grading system and Matsushima grading (r=0.86;p<0.01). Ischemic events were fewer in hemispheres categorized as grade 2-3 compared to grade 0-1 (p=0.047) as well as in Matsushima grading A or B compared to C (p=0.047). CONCLUSION: The orbital grading system demonstrated agreement in identifying postoperative ischemic events as the Matsushima grade and provides a more practical and objective evaluation of collateral vessel ingrowth after EDAS with and without burr-holes.

CNS Embryonal Tumor with PLAGL Amplification, a New Tumor Type in Children and Adolescents: Insights from a Comprehensive MRI Analysis.

BACKGROUND AND PURPOSE: CNS embryonal tumor with PLAGL1/PLAGL2 amplification (ET, PLAGL) is a newly identified, highly malignant pediatric tumor. Systematic MRI descriptions of ET, PLAGL are currently lacking. MATERIALS AND METHODS: MRI data from 19 treatment-naïve patients with confirmed ET, PLAGL were analyzed. Evaluation focused on anatomical involvement, tumor localization, MRI signal characteristics, DWI behavior, and the presence of necrosis and hemorrhage. Descriptive statistics (median, interquartile range, percentage) were assessed. RESULTS: Ten patients had PLAGL1 and nine PLAGL2 amplifications. The solid components of the tumors were often multinodular with heterogeneous enhancement (mild to intermediate in 47% and intermediate to strong in 47% of cases). Non-solid components included cysts in 47% and necrosis in 84% of the cases. The tumors showed heterogeneous T2WI hyper-and isointensity (74%), relatively little diffusion restriction (ADC values < contralateral normal-appearing WM in 36% of cases with available DWI), and tendencies towards hemorrhage/calcification (42%). No reliable distinction was found between PLAGL1-and PLAGL2-amplified tumors or compared to other embryonal CNS tumors. CONCLUSIONS: The study contributes to understanding the imaging characteristics of ET, PLAGL. It underscores the need for collaboration in studying rare pediatric tumors and advocates for the use of harmonized imaging protocols for better characterization. ABBREVIATIONS: ATRT= atypical teratoid/rhabdoid tumor; ETMR= embryonal tumor with multilayered rosettes; ET, PLAGL= CNS embryonal tumor with PLAGL amplification; EVD= external ventricular drain; IQR: interquartile range; PLAGL1= pleomorphic adenoma gene-like 1; PLAGL2= pleomorphic adenoma gene-like 2; WHO= World Health Organization.

Covid-19 Impacts on Physical Activity among Community-dwelling Older Adults with Memory Problems: The Moderating Role of Walkable Neighborhood Destinations.

BACKGROUND AND OBJECTIVES: The number of people with memory problems who desire or are forced to age in place has been growing rapidly. COVID-19 has brought significant challenges to the ability of those with memory problems to stay active and age in place. This study investigated the roles of neighborhood environments in helping community-dwelling people with memory problems maintain physical activity during the COVID-19 pandemic. RESEARCH DESIGN AND METHODS: We used retrospective online survey data from 75 caregivers who responded on behalf of their care recipients with memory problems living in Texas communities. We used difference-in-difference (DID) estimations based on zero-inflated negative binomial regression models to examine the changes in recreational walking and moderate-to-strenuous exercise before and during the COVID-19 pandemic and whether such changes vary by diversity of walkable neighborhood destinations. RESULTS: In the total sample, there was a significant reduction in both recreational walking (Δ change=-45.16 min/week, p<0.001) and exercise (Δ change=-36.28 min/week, p=0.03) after the COVID-19 outbreak. The pandemic's impact on exercise varied by diversity of neighborhood destinations (DID=0.81, p=0.03). Those living in neighborhoods with diverse walkable destinations experienced less decline in physical activity compared to those living in areas with limited destinations. DISCUSSION AND IMPLICATIONS: These findings suggest that the impact of the COVID-19 pandemic on physical activity among people with memory problems may be partially explained by neighborhood land use characteristics. Destination-rich, mixed-use neighborhood environments can help people with memory problems stay active even during pandemics such as COVID-19 in the U.S. and potentially elsewhere.

Types of high-riding vertebral artery: a classification system for preoperative planning of C2 instrumentation based on 908 potential screw insertion sites.

BACKGROUND CONTEXT: Our recent studies indicated that a high-riding vertebral artery (HRVA) is a common variant posing a risk of injuring the vessel during C2 instrumentation. However, several different types fit in the current definition of HRVA, which may require a different strategy for C2 screw placement. PURPOSE: To classify HRVA and provide a clinical aid for preoperative planning of C2 instrumentation. A secondary goal was to estimate coexistence of each HRVA type with the ipsilateral narrow C2 pedicle (NP). STUDY DESIGN: A retrospective observational study involving radiologic measurements of the estimated number of anonymized cervical computed tomography (CT) scans. STROBE checklist was applied. PATIENT SAMPLE: 908 potential screw insertion sites (PSIS) of 454 consecutive cervical CT scans were analyzed. The sample size was estimated using ScalaR SP function in RStudio. OUTCOME MEASURES: Three types of HRVA based on a series of C2 vertebral morphological parameters including the C2 isthmus height (C2IsH) and C2 internal height (C2InH). Also, the prevalences of each HRVA type and coexisting NP based on the C2 pedicle width (C2PW). METHODS: HRVA was defined as C2IsH of ≤ 5 mm and/or C2InH of ≤ 2 mm measured 3 mm lateral to the lateral border of the spinal canal. A narrow pedicle was defined as C2PW of ≤ 4 mm. Measurements were done using Syn.govia software. Interobserver, intraobserver, and inter-software agreement coefficients for C2IsH, C2InH, and C2PW parameters were adopted from our previous study. K-means cluster analysis was applied. RESULTS: Prevalence of at least one HRVA was 24.9% (n = 113 subjects) and 16.2% of PSIS (n = 147 sites). Based on the measurements and K-means clustering, the following three types of HRVA have been distinguished: type 1 - isthmic with only C2IsH being reduced and normal C2InH; type 2 - internal with only C2InH being reduced and C2IsH within normal limits; type 3 - isthmo-internal with both C2IsH and C2InH being reduced. Kruskal-Wallis test followed by unadjusted and Bonferroni-adjusted post-hoc multiple comparison analysis detected significant differences across the types. The prevalences of the newly identified types were as follows: 78.2%, 8.8%, and 12.9% for type 1, type 2, and type 3, respectively. 73.9% of type 1 HRVA, 53.8% of type 2 HRVA, and 100% of type 3 HRVA had a concomitant ipsilateral NP. Prediction of the HRVA types by the K-means clustering has been evaluated. Screw placement techniques for each type are proposed and discussed. CONCLUSION: We present the first classification system for the high-riding vertebral artery distinguishing three types based on the large homogenous cohort, which may serve as an adjunct to preoperative planning of C2 instrumentation. External validation of this classification scheme shall determine its further clinical utility.

On-call simulation: Evaluating cost and impact.

BACKGROUND: On-call simulation has been shown to improve the confidence of prospective junior doctors in undertaking on-call shifts. Despite this, it is not mandated in UK medical school curricula, leading to variations in provision. Barriers to widespread implementation may include doubts surrounding effectiveness, feasibility of delivering on-call simulation across multiple sites and unknown costs. To address these gaps in the literature, we designed and implemented a multi-site on-call simulation programme. We aimed to evaluate it both educationally, using student preparedness to complete on-call shifts as our outcome, and economically, by performing a cost-outcome description. APPROACH: An on-call simulation programme, 'Bleep 101', was developed and implemented at eight hospitals. Students were 'bleeped' around a circuit of written scenarios including clinical emergencies, prescribing and distractor tasks. Students could escalate to their facilitator on the phone for advice at any time. Sessions concluded with a 30-minute debrief focusing on prioritisation and communication skills. EVALUATION: Between 2018 and 2023, 217 students took part and completed feedback forms. Post-session feedback using Likert scales demonstrated a significant increase in preparedness to complete an on-call shift (pre-4/10, post-7/10, p < 0.01) with outcomes consistent across sites. A cohort of 20 students completed paired pre- and post-session feedback to evaluate the impact of the session on specific skills. This demonstrated increased confidence in using a bleep, prioritisation, gathering information and handing over. The costs of implementation at one site were reported, demonstrating a cost of £1.99/student/year or £99.48/student/year excluding costs saved by volunteers and room hire. IMPLICATIONS: This study indicates that on-call simulation can be delivered at a low cost using existing medical education infrastructure within hospitals. Results suggested an improvement in medical students' preparedness for on-call practice. We therefore recommend on-call simulation be available to all medical students as part of medical school curricula.

Humans use local spectrotemporal correlations to detect rising and falling pitch.

To discern speech or appreciate music, the human auditory system detects how pitch increases or decreases over time. However, the algorithms used to detect changes in pitch, or pitch motion, are incompletely understood. Here, using psychophysics, computational modeling, functional neuroimaging, and analysis of recorded speech, we ask if humans detect pitch motion using computations analogous to those used by the visual system. We adapted stimuli from studies of vision to create novel auditory correlated noise stimuli that elicited robust pitch motion percepts. Crucially, these stimuli possess no persistent features across frequency or time, but do possess positive or negative local spectrotemporal correlations in intensity. In psychophysical experiments, we found clear evidence that humans judge pitch direction based on both positive and negative spectrotemporal correlations. The observed sensitivity to negative correlations is a direct analogue of illusory "reverse-phi" motion in vision, and thus constitutes a new auditory illusion. Our behavioral results and computational modeling led us to hypothesize that human auditory processing employs pitch direction opponency. fMRI measurements in auditory cortex supported this hypothesis. To link our psychophysical findings to real-world pitch perception, we analyzed recordings of English and Mandarin speech and discovered that pitch direction was robustly signaled by the same positive and negative spectrotemporal correlations used in our psychophysical tests, suggesting that sensitivity to both positive and negative correlations confers ecological benefits. Overall, this work reveals that motion detection algorithms sensitive to local correlations are deployed by the central nervous system across disparate modalities (vision and audition) and dimensions (space and frequency).

Altered Use of Context During Visual Perception in Psychotic Psychopathology: A Neurophysiological Investigation of Tuned and Untuned Suppression During Contrast Perception.

BACKGROUND AND HYPOTHESIS: The human visual system streamlines visual processing by suppressing responses to textures that are similar to their surrounding context. Surround suppression is weaker in individuals with schizophrenia (ISZ); this altered use of visuospatial context may relate to the characteristic visual distortions they experience. STUDY DESIGN: To understand atypical surround suppression in psychotic psychopathology, we investigated neurophysiological responses in ISZ, healthy controls (HC), individuals with bipolar disorder (IBP), and first-degree relatives (ISZR/IBPR). Participants performed a contrast judgment task on a circular target with annular surrounds, with concurrent electroencephalography. Orientation-independent (untuned) suppression was estimated from responses to central targets with orthogonal surrounds; the orientation-dependence of suppression was estimated by fitting an exponential function to the increase in suppression as surrounds became more aligned with the center. RESULTS: ISZ exhibited weakened untuned suppression coupled with enhanced orientation-dependence of suppression. The N1 visual evoked potential was associated with the orientation-dependence of suppression, with ISZ and ISZR (but not IBP or IBPR) showing enhanced orientation-dependence of the N1. Collapsed across orientation conditions, the N1 for ISZ lacked asymmetry toward the right hemisphere; this reduction in N1 asymmetry was associated with reduced untuned suppression, real-world perceptual anomalies, and psychotic psychopathology. The overall amplitude of the N1 was reduced in ISZ and IBP. CONCLUSIONS: Key measures of symptomatology for ISZ are associated with reductions in untuned suppression. Increased sensitivity for ISZ to the relative orientation of suppressive surrounds is reflected in the N1 VEP, which is commonly associated with higher-level visual functions such as allocation of spatial attention or scene segmentation.

Ultrasonographic liver nodules are more often benign lesions in dogs with hemoperitoneum secondary to splenic tumor rupture.

OBJECTIVE: To evaluate the reliability of preoperative abdominal ultrasonography as a staging tool for dogs with hemoperitoneum due to presumed splenic tumor rupture, focusing on the detection of metastatic lesions in the liver. ANIMALS: 99 dogs from 20 emergency and specialty hospitals across the US. METHODS: Dogs with nontraumatic hemoperitoneum secondary to splenic tumor rupture were included. A post hoc analysis was conducted on data from a nationwide prospective trial investigating novel treatments for canine hemangiosarcoma. The accuracy of preoperative staging was assessed by comparing ultrasonographic findings with intraoperative observations and histologic findings. RESULTS: On preoperative ultrasonography, there was a 20% incidence of liver lesions identified, with no association to liver lesions seen during operation. Notably, 22% of liver lesions observed during operation were missed on preoperative ultrasonography. The presence of liver lesions on preoperative ultrasonography was associated with a higher likelihood of a benign splenic tumor diagnosis. There was no association between the identification of liver lesions on preoperative ultrasonography and the presence of metastatic disease on liver biopsy, with a sensitivity and specificity of 19% and 82%, respectively. Additionally, ultrasound had low sensitivity in detecting intra-abdominal lesions beyond the liver and spleen, with 82% of these lesions missed preoperatively. CLINICAL RELEVANCE: This study challenges conventional perceptions around the approach to staging in dogs with hemoperitoneum. These findings advocate for a reevaluation of the staging approach, with more comprehensive modalities like whole-body CT or MRI potentially being more warranted.

Benefits and Risks Associated With Antibiotic Prophylaxis for Thyroid Operations.

INTRODUCTION: Prophylactic antibiotics (pABX) are commonly used prior to thyroid operations despite clean case classification. The objective of this study was to assess the association of antibiotic prophylaxis with the incidence of surgical site infection (SSI) among patients undergoing thyroidectomy. METHODS: We performed a cohort study of all adults undergoing thyroid operations at a tertiary referral center from 2010 to 2019. The primary outcome was 30-d SSI, based on diagnosis codes and/or antibiotic use and further classified based on whether wound aspiration or operative washout were required. The association between pABX and SSI was determined using propensity score matching based on patient demographics and comorbidities likely to influence SSI risk. RESULTS: We identified 2411 patients who underwent thyroid operations, of whom 1358 (56.3%) received pABX. Patients who received pABX had a higher mean Charlson-Deyo Comorbidity Index score than patients who did not (3.6 versus 2.9). The unadjusted incidence of SSI was higher in patients who received pABX than those who did not (6.1% versus 3.4%, P < 0.001). Few patients with SSI required aspiration or operative washout (0.29% who received pABX versus 0.19% who did not). After propensity score matching, pABX use showed no association with overall 30-d SSI (odds ratio 1.38, 95% confidence interval 0.84-2.26) or SSI requiring procedural intervention (odds ratio 3.01, 95% confidence interval 0.24-158). CONCLUSIONS: In a large cohort of patients with a high prevalence of comorbidity, use of pABX was not associated with a decreased incidence of SSI following thyroid surgery. Efforts should be made to deimplement low-value pABX use in thyroid surgery.

Influence of Electron Donors on the Charge Transfer Dynamics of Carbon Nanodots in Photocatalytic Systems.

Carbon nanodots (CNDs) are nanosized light-harvesters emerging as next-generation photosensitizers in photocatalytic reactions. Despite their ever-increasing potential applications, the intricacies underlying their photoexcited charge carrier dynamics are yet to be elucidated. In this study, nitrogen-doped graphitic CNDs (NgCNDs) are selectively excited in the presence of methyl viologen (MV2+, redox mediator) and different electron donors (EDs), namely ascorbic acid (AA) and ethylenediaminetetraacetic acid (EDTA). The consequent formation of the methyl viologen radical cation (MV•+) is investigated, and the excited charge carrier dynamics of the photocatalytic system are understood on a 0.1 ps-1 ms time range, providing spectroscopic evidence of oxidative or reductive quenching mechanisms experienced by optically excited NgCNDs (NgCNDs*) depending on the ED implemented. In the presence of AA, NgCNDs* undergo oxidative quenching by MV2+ to form MV•+, which is short-lived due to dehydroascorbic acid, a product of photoinduced hole quenching of oxidized NgCNDs. The EDTA-mediated reductive quenching of NgCNDs* is observed to be at least 2 orders of magnitude slower due to screening by EDTA-MV2+ complexes, but the MV•+ population is stable due to the irreversibly oxidized EDTA preventing a back reaction. In general, our methodology provides a distinct solution with which to study charge transfer dynamics in photocatalytic systems on an extended time range spanning 10 orders of magnitude. This approach generates a mechanistic understanding to select and develop suitable EDs to promote photocatalytic reactions.

Alterations of cerebrovascular reactivity following pediatric mild traumatic brain injury are independent of neurodevelopmental changes.

Cerebrovascular dysfunction following mild traumatic brain injury (mTBI) is understudied relative to other microstructural injuries, especially during neurodevelopment. The blood-oxygen level dependent response was used to investigate cerebrovascular reactivity (CVR) in response to hypercapnia following pediatric mTBI (pmTBI; ages 8-18 years), as well as pseudocontinuous arterial spin labeling to measure cerebral blood flow (CBF). Data were collected ∼1-week (N = 107) and 4 months (N = 73) post-injury. Sex- and age-matched healthy controls (HC) underwent identical examinations at comparable time points (N = 110 and N = 91). Subtle clinical and cognitive deficits existed at ∼1 week that resolved for some, but not all domains at 4 months post-injury. At both visits, pmTBI showed an increased maximal fit between end-tidal CO2 regressor and the cerebrovascular response across multiple regions (primarily fronto-temporal), as well as increased latency to maximal fit in independent regions (primarily posterior). Hypoperfusion was also noted within the bilateral cerebellum. A biphasic relationship existed between CVR amplitude and age (i.e., positive until 14.5 years, negative thereafter) in both gray and white matter, but these neurodevelopment effects did not moderate injury effects. CVR metrics were not associated with post-concussive symptoms or cognitive deficits. In conclusion, cerebrovascular dysfunction may persist for up to four months following pmTBI.

Tixagevimab/Cilgavimab for COVID-19 Pre-Exposure Prophylaxis in Hematologic Patients-A Tailored Approach Based on SARS-CoV-2 Vaccine Response.

Patients with hematologic malignancies still face a significant risk of severe coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-neutralizing monoclonal antibody combination tixagevimab/cilgavimab (TIX/CGB) could be administered to immunocompromised patients for pre-exposure prophylaxis (PrEP) before the emergence of TIX/CGB-resistant COVID-19 Omicron variants. TIX/CGB application could be carried out regardless of the host's immune response to previous active SARS-CoV-2 vaccinations or infections. Because the efficacy of COVID-19 PrEP remains unclear, especially in SARS-CoV-2-seropositive patients, German national guidelines recommended TIX/CGB PrEP only for SARS-CoV-2-seronegative patients in addition to an intensified active vaccination schedule. Having followed these guidelines, we now report the characteristics and outcomes of 54 recipients of TIX/CGB PrEP in SARS-CoV-2-seronegative patients with hematological disease from a German tertiary medical center and compare them to 125 seropositive patients who did not receive any PrEP. While the number of patients with B-cell lymphomas was significantly higher in the seronegative cohort (33 (61%) vs. 18 (14%) cases, p < 0.01), patients with myeloid diseases were significantly more frequent in the seropositive cohort (51 (41%) vs. 5 (9%) cases, p < 0.01). Strikingly, patients who had undergone allogeneic hematopoietic stem cell transplantation were significantly more likely (forty-nine (39%) vs. six (11%) cases, p < 0.01) to be SARS-CoV-2 seropositive. We observed that prophylactic application of TIX/CGB PrEP to a highly vulnerable group of SARS-CoV-2-seronegative patients resulted in a similar number of COVID-19 breakthrough infections compared to the untreated seropositive control group (16 (32%) vs. 39 (36%), p = 0.62) and comparable COVID-19-related outcomes like hospitalization and oxygen requirement throughout an extended follow-up period of 12 months. In conclusion, our results support the tailored approach of administering TIX/CGB PrEP only to SARS-CoV-2-seronegative patients during the COVID-19 pandemic and might provide a rationale for similar strategies during future outbreaks/diseases, especially in times of initial limited availability and/or financial constraints.

The Application of Paclobutrazol to GA3-Treated Seed Tuber Potato Fields Does Not Shorten the Growth Cycle or Mitigate Tuber Elongation.

Potato seed tubers are a valuable product in potato agriculture. Over the years, studies have been conducted to increase the fraction of mid-size tubers, which are used as a planting material, within the general pool of tuber sizes. Gibberellic acid has been a central component of such studies and has successfully increased the seed-size pool. However, in many cases, misshapen tubers were formed, and the practice has not become widespread. The use of the gibberellic acid inhibitor paclobutrazol has been examined for its ability to increase seed tuber number and tuber growth and to overcome the heat inhibition of tuberization in warm climates. Paclobutrazol has been shown to increase tuber yield and growth rate. In this study, we aimed to test whether the combination of gibberellic acid and paclobutrazol can increase the seed tuber pool, reduce the number of misshapen tubers, and shorten the growth cycle, thus avoiding end-of-season elevated heat conditions and reducing agricultural inputs. Our findings suggest that gibberellic acid on its own can lead to an increase in the number of seed tubers at earlier stages of growth; however, the sequential addition of paclobutrazol was not able to drive even earlier growth or lower the number of misshapen tubers.