Upper-limb neurovascular compression, pectoralis minor and quadrilateral space syndromes: A narrative review of current literature.

Pectoralis minor syndrome (PMS) and quadrilateral space syndrome (QSS) are uncommon neurovascular compression disorders affecting the upper extremity. PMS involves compression under the pectoralis minor muscle, and QSS results from compression in the quadrilateral space-both are classically observed in overhead-motion athletes. Diagnosing PMS and QSS may be challenging due to variable presentations and similarities with other, more common, upper-limb pathologies. Although there is no gold standard diagnostic, local analgesic muscle-block response in a patient with the appropriate clinical context is often all that is required for an accurate diagnosis after excluding more common etiologies. Treatment ranges from conservative physical therapy to decompressive surgery, which is reserved for refractory cases or severe, acute vascular presentations. Decompression generally yields favorable outcomes, with most patients experiencing significant relief and restored baseline function. In conclusion, PMS and QSS, although rare, can cause debilitating upper-extremity symptoms; accurate diagnosis and appropriate treatment offer excellent outcomes, alleviating pain and disability.

Geospatial Analysis of the Proportion of Persons Defined as Underrepresented in Medicine for Each Medical School and Their Surrounding Core-Based Statistical Area.

Background: The current approach to increasing diversity in medical education fails to consider local community demographics when determining medical school matriculation. Purpose: We propose that medical schools better reflect their surrounding community, both because racially/ethnically concordant physicians have been shown to provide better care and to repair the historical and current racist impacts of these institutions that have criminalized, displaced, and excluded local Black and Brown communities. Methods and Results: In this study, we used geospatial analysis to determine that medical school enrollments generally fail to reflect their surrounding community, represented as their core-based statistical area, within which the individual medical schools reside.

Chronic nicotine exposure is associated with electrophysiological and sympathetic remodeling in the intact rabbit heart.

Nicotine is the primary addictive component of tobacco products. Through its actions on the heart and autonomic nervous system, nicotine exposure is associated with electrophysiological changes and increased arrhythmia susceptibility. To assess the underlying mechanisms, we treated rabbits with transdermal nicotine (NIC, 21 mg/day) or control (CT) patches for 28 days before performing dual optical mapping of transmembrane potential (RH237) and intracellular Ca2+ (Rhod-2 AM) in isolated hearts with intact sympathetic innervation. Sympathetic nerve stimulation (SNS) was performed at the first to third thoracic vertebrae, and ß-adrenergic responsiveness was additionally evaluated following norepinephrine (NE) perfusion. Baseline ex vivo heart rate (HR) and SNS stimulation threshold were higher in NIC versus CT (P = 0.004 and P = 0.003, respectively). Action potential duration alternans emerged at longer pacing cycle lengths (PCL) in NIC versus CT at baseline (P = 0.002) and during SNS (P = 0.0003), with similar results obtained for Ca2+ transient alternans. SNS shortened the PCL at which alternans emerged in CT but not in NIC hearts. NIC-exposed hearts tended to have slower and reduced HR responses to NE perfusion, but ventricular responses to NE were comparable between groups. Although fibrosis was unaltered, NIC hearts had lower sympathetic nerve density (P = 0.03) but no difference in NE content versus CT. These results suggest both sympathetic hypoinnervation of the myocardium and regional differences in ß-adrenergic responsiveness with NIC. This autonomic remodeling may contribute to the increased risk of arrhythmias associated with nicotine exposure, which may be further exacerbated with long-term use.NEW & NOTEWORTHY Here, we show that chronic nicotine exposure was associated with increased heart rate, increased susceptibility to alternans, and reduced sympathetic electrophysiological responses in the intact rabbit heart. We suggest that this was due to sympathetic hypoinnervation of the myocardium and diminished ß-adrenergic responsiveness of the sinoatrial node following nicotine treatment. Though these differences did not result in increased arrhythmia propensity in our study, we hypothesize that prolonged nicotine exposure may exacerbate this proarrhythmic remodeling.

Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets.

BACKGROUND: Vestibular schwannomas (VSs) remain a challenge due to their anatomical location and propensity to growth. Macrophages are present in VS but their roles in VS pathogenesis remains unknown. OBJECTIVES: The objective was to assess phenotypic and functional profile of macrophages in VS with single-cell RNA sequencing (scRNAseq). METHODS: scRNAseq was carried out in three VS samples to examine characteristics of macrophages in the tumour. RT-qPCR was carried out on 10 VS samples for CD14, CD68 and CD163 and a panel of macrophage-associated molecules. RESULTS: scRNAseq revealed macrophages to be a major constituent of VS microenvironment with three distinct subclusters based on gene expression. The subclusters were also defined by expression of CD163, CD68 and IL-1ß. AREG and PLAUR were expressed in the CD68+CD163+IL-1ß+ subcluster, PLCG2 and NCKAP5 were expressed in CD68+CD163+IL-1ß- subcluster and AUTS2 and SPP1 were expressed in the CD68+CD163-IL-1ß+ subcluster. RT-qPCR showed expression of several macrophage markers in VS of which CD14, ALOX15, Interleukin-1ß, INHBA and Colony Stimulating Factor-1R were found to have a high correlation with tumour volume. CONCLUSIONS: Macrophages form an important component of VS stroma. scRNAseq reveals three distinct subsets of macrophages in the VS tissue which may have differing roles in the pathogenesis of VS.

Enhanced Ca2+-Driven Arrhythmias in Female Patients with Atrial Fibrillation: Insights from Computational Modeling.

BACKGROUND AND AIMS: Substantial sex-based differences have been reported in atrial fibrillation (AF), with female patients experiencing worse symptoms, increased complications from drug side effects or ablation, and elevated risk of AF-related stroke and mortality. Recent studies revealed sex-specific alterations in AF-associated Ca2+ dysregulation, whereby female cardiomyocytes more frequently exhibit potentially proarrhythmic Ca2+-driven instabilities compared to male cardiomyocytes. In this study, we aim to gain a mechanistic understanding of the Ca2+-handling disturbances and Ca2+-driven arrhythmogenic events in males vs females and establish their responses to Ca2+-targeted interventions. METHODS AND RESULTS: We incorporated known sex differences and AF-associated changes in the expression and phosphorylation of key Ca2+-handling proteins and in ultrastructural properties and dimensions of atrial cardiomyocytes into our recently developed 3D atrial cardiomyocyte model that couples electrophysiology with spatially detailed Ca2+-handling processes. Our simulations of quiescent cardiomyocytes show increased incidence of Ca2+ sparks in female vs male myocytes in AF, in agreement with previous experimental reports. Additionally, our female model exhibited elevated propensity to develop pacing-induced spontaneous Ca2+ releases (SCRs) and augmented beat-to-beat variability in action potential (AP)-elicited Ca2+ transients compared with the male model. Parameter sensitivity analysis uncovered precise arrhythmogenic contributions of each component that was implicated in sex and/or AF alterations. Specifically, increased ryanodine receptor phosphorylation in female AF cardiomyocytes emerged as the major SCR contributor, while reduced L-type Ca2+ current was protective against SCRs for male AF cardiomyocytes. Furthermore, simulations of tentative Ca2+-targeted interventions identified potential strategies to attenuate Ca2+-driven arrhythmogenic events in female atria (e.g., t-tubule restoration, and inhibition of ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase), and revealed enhanced efficacy when applied in combination. CONCLUSIONS: Our sex-specific computational models of human atrial cardiomyocytes uncover increased propensity to Ca2+-driven arrhythmogenic events in female compared to male atrial cardiomyocytes in AF, and point to combined Ca2+-targeted interventions as promising approaches to treat AF in female patients. Our study establishes that AF treatment may benefit from sex-dependent strategies informed by sex-specific mechanisms.

Validation of image-derived input function using a long axial field of view PET/CT scanner for two different tracers.

BACKGROUND: Accurate image-derived input function (IDIF) from highly sensitive large axial field of view (LAFOV) PET/CT scanners could avoid the need of invasive blood sampling for kinetic modelling. The aim is to validate the use of IDIF for two kinds of tracers, 3 different IDIF locations and 9 different reconstruction settings. METHODS: Eight [18F]FDG and 10 [18F]DPA-714 scans were acquired respectively during 70 and 60 min on the Vision Quadra PET/CT system. PET images were reconstructed using various reconstruction settings. IDIFs were taken from ascending aorta (AA), descending aorta (DA), and left ventricular cavity (LV). The calibration factor (CF) extracted from the comparison between the IDIFs and the manual blood samples as reference was used for IDIFs accuracy and precision assessment. To illustrate the effect of various calibrated-IDIFs on Patlak linearization for [18F]FDG and Logan linearization for [18F]DPA-714, the same target time-activity curves were applied for each calibrated-IDIF. RESULTS: For [18F]FDG, the accuracy and precision of the IDIFs were high (mean CF ≥ 0.82, SD ≤ 0.06). Compared to the striatum influx (Ki) extracted using calibrated AA IDIF with the updated European Association of Nuclear Medicine Research Ltd. standard reconstruction (EARL2), Ki mean differences were < 2% using the other calibrated IDIFs. For [18F]DPA714, high accuracy of the IDIFs was observed (mean CF ≥ 0.86) except using absolute scatter correction, DA and LV (respectively mean CF = 0.68, 0.47 and 0.44). However, the precision of the AA IDIFs was low (SD ≥ 0.10). Compared to the distribution volume (VT) in a frontal region obtained using calibrated continuous arterial sampler input function as reference, VT mean differences were small using calibrated AA IDIFs (for example VT mean difference = -5.3% using EARL2), but higher using calibrated DA and LV IDIFs (respectively + 12.5% and + 19.1%). CONCLUSIONS: For [18F]FDG, IDIF do not need calibration against manual blood samples. For [18F]DPA-714, AA IDIF can replace continuous arterial sampling for simplified kinetic quantification but only with calibration against arterial blood samples. The accuracy and precision of IDIF from LAFOV PET/CT system depend on tracer, reconstruction settings and IDIF VOI locations, warranting careful optimization.

A meta-analysis of the effect of visiting zoos and aquariums on visitors' conservation knowledge, beliefs, and behavior.

Zoos and aquariums are well placed to connect visitors with the issues facing biodiversity globally and many deliver interventions that seek to influence visitors' beliefs and behaviors with respect to conservation. However, despite primary studies evaluating the effect of such interventions, the overall effect of engaging with zoos and the factors that influence this effect remain unclear. We conducted a systematic review to investigate the effect of zoo-led interventions on knowledge, beliefs (attitudes, intentions, self-efficacy, and social norms), and behavior among zoo visitors. These outcomes were identified using the Theory of Planned Behavior as a theoretical lens. We identified and described the nature of zoo-led interventions in 56 studies and used the behavior change technique (BCT) taxonomy to identify 6 specific BCTs used in interventions to date. Multilevel meta-analyses revealed a small to medium positive effect of engaging with zoo-led interventions on outcomes (d+  = 0.40, 95% confidence interval = 0.28-0.51). Specifically, visitors were more knowledgeable about conservation issues, held more favorable attitudes toward conservation, and reported being more likely to act for the benefit of biodiversity. No evidence of publication bias was present. Effect sizes were, however, heterogeneous and subgroup analyses revealed that the nature of the intervention or type of outcome did not explain this variance. Larger effects were, however, found in studies conducted at a single institution relative to research at multiple institutions and studies that used within-participant designs relative to between-participant designs. Taken together, these findings demonstrate how behavior change frameworks can be used to describe zoo-led interventions and supports the assertion that zoos and aquariums can promote changes in beliefs and behaviors that may help protect biodiversity.

Metaanálisis del efecto de la visita a acuarios y zoológicos sobre el conocimiento, creencias y comportamientos de conservación de los visitantes © 2024 by John Wiley & Sons, Inc. Resumen Los zoológicos y los acuarios están bien posicionados para conectar a los visitantes con temas mundiales de biodiversidad y varios cuentan con intervenciones que buscan influir las creencias y el comportamiento de los visitantes con respecto a la conservación. Sin embargo, con todo y los estudios primarios que evalúan el efecto de dichas intervenciones, aún no está claro el efecto general de participar en los zoológicos y los factores que influyen sobre este efecto. Realizamos una revisión sistemática para investigar el efecto de las intervenciones en los zoológicos sobre el conocimiento, creencias (actitud, intención, autosuficiencia y normas sociales) y comportamiento de sus visitantes. Usamos la teoría del comportamiento planeado como lente teórico para identificar los resultados. Identificamos y describimos la naturaleza de las intervenciones en los zoológicos en 56 estudios y usamos la taxonomía de las técnicas de modificación de conducta (TMC) para identificar seis TMC específicas que se usan hoy en día en dichas intervenciones. Los metaanálisis multinivel revelaron un efecto positivo de pequeño a mediano sobre los resultados causado por la participación en las intervenciones de los zoológicos (d+ = 0.40, 95% CI = 0.28 - 0.51). En específico, los visitantes fueron más conocedores sobre los temas de conservación, tuvieron actitudes más favorables hacia la conservación y reportaron tener mayor probabilidad de actuar en beneficio de la biodiversidad. No hubo evidencias de sesgos en las publicaciones. Sin embargo, el tamaño de los efectos fue heterogéneo y el análisis de los subgrupos reveló que la naturaleza de la intervención o el tipo de resultados no explicaban esta varianza. A pesar de esto, encontramos efectos más grandes en los estudios realizados en una sola institución en relación con la investigación realizada en varias instituciones y los estudios que usaron diseños intraparticipantes en relación a los que usaron diseños interparticipantes. Nuestra revisión demuestra cómo los marcos de modificación conductual pueden usarse para describir las intervenciones en los zoológicos y acuarios y respalda la aseveración de que estas instituciones pueden promover cambios en las creencias y el comportamiento que pueden ayudar a proteger la biodiversidad.

Endocannabinoid levels in plasma and neurotransmitters in the brain: a preliminary report on patients with a psychotic disorder and healthy individuals.

BACKGROUND: Interactions between the endocannabinoid system (ECS) and neurotransmitter systems might mediate the risk of developing a schizophrenia spectrum disorder (SSD). Consequently, we investigated in patients with SSD and healthy controls (HC) the relations between (1) plasma concentrations of two prototypical endocannabinoids (N-arachidonoylethanolamine [anandamide] and 2-arachidonoylglycerol [2-AG]) and (2) striatal dopamine synthesis capacity (DSC), and glutamate and y-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC). As anandamide and 2-AG might reduce the activity of these neurotransmitters, we hypothesized negative correlations between their plasma levels and the abovementioned neurotransmitters in both groups. METHODS: Blood samples were obtained from 18 patients and 16 HC to measure anandamide and 2-AG plasma concentrations. For all subjects, we acquired proton magnetic resonance spectroscopy scans to assess Glx (i.e. glutamate plus glutamine) and GABA + (i.e. GABA plus macromolecules) concentrations in the ACC. Ten patients and 14 HC also underwent [18F]F-DOPA positron emission tomography for assessment of striatal DSC. Multiple linear regression analyses were used to investigate the relations between the outcome measures. RESULTS: A negative association between 2-AG plasma concentration and ACC Glx concentration was found in patients (p = 0.008). We found no evidence of other significant relationships between 2-AG or anandamide plasma concentrations and dopaminergic, glutamatergic, or GABAergic measures in either group. CONCLUSIONS: Our preliminary results suggest an association between peripheral 2-AG and ACC Glx levels in patients.

Predictors of Functional Decline Among Critically Ill Surgical Patients: A National Analysis.

INTRODUCTION: Functional decline is associated with critical illness, though this relationship in surgical patients is unclear. This study aims to characterize functional decline after intensive care unit (ICU) admission among surgical patients. METHODS: We performed a retrospective analysis of surgical patients admitted to the ICU in the Cerner Acute Physiology and Chronic Health Evaluation database, which includes 236 hospitals, from 2007 to 2017. Patients with and without functional decline were compared. Predictors of decline were modeled. RESULTS: A total of 52,838 patients were included; 19,310 (36.5%) experienced a functional decline. Median ages of the decline and nondecline groups were 69 (interquartile range 59-78) and 63 (interquartile range 52-72) years, respectively (P < 0.01). The nondecline group had a larger proportion of males (59.1% versus 55.3% in the decline group, P < 0.01). After controlling for sociodemographic covariates, comorbidities, and disease severity upon ICU admission, patients undergoing pulmonary (odds ratio [OR] 6.54, 95% confidence interval [CI] 2.67-16.02), musculoskeletal (OR 4.13, CI 3.51-4.87), neurological (OR 2.67, CI 2.39-2.98), gastrointestinal (OR 1.61, CI 1.38-1.88), and skin and soft tissue (OR 1.35, CI 1.08-1.68) compared to cardiovascular surgeries had increased odds of decline. CONCLUSIONS: More than one in three critically ill surgical patients experienced a functional decline. Pulmonary, musculoskeletal, and neurological procedures conferred the greatest risk. Additional resources should be targeted toward the rehabilitation of these patients.

PHF6-altered T-ALL Harbor Epigenetic Repressive Switch at Bivalent Promoters and Respond to 5-Azacitidine and Venetoclax.

PURPOSE: To assess the impact of PHF6 alterations on clinical outcome and therapeutical actionability in T-cell acute lymphoblastic leukemia (T-ALL). EXPERIMENTAL DESIGN: We described PHF6 alterations in an adult cohort of T-ALL from the French trial Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/2005 and retrospectively analyzed clinical outcomes between PHF6-altered (PHF6ALT) and wild-type patients. We also used EPIC and chromatin immunoprecipitation sequencing data of patient samples to analyze the epigenetic landscape of PHF6ALT T-ALLs. We consecutively evaluated 5-azacitidine efficacy, alone or combined with venetoclax, in PHF6ALT T-ALL. RESULTS: We show that PHF6 alterations account for 47% of cases in our cohort and demonstrate that PHF6ALT T-ALL presented significantly better clinical outcomes. Integrative analysis of DNA methylation and histone marks shows that PHF6ALT are characterized by DNA hypermethylation and H3K27me3 loss at promoters physiologically bivalent in thymocytes. Using patient-derived xenografts, we show that PHF6ALT T-ALL respond to the 5-azacytidine alone. Finally, synergism with the BCL2-inhibitor venetoclax was demonstrated in refractory/relapsing (R/R) PHF6ALT T-ALL using fresh samples. Importantly, we report three cases of R/R PHF6ALT patients who were successfully treated with this combination. CONCLUSIONS: Overall, our study supports the use of PHF6 alterations as a biomarker of sensitivity to 5-azacytidine and venetoclax combination in R/R T-ALL.

Mitigating SUV uncertainties using total body PET imaging.

PURPOSE: Standardised uptake values (SUV) are commonly used to quantify 18F-FDG lesion uptake. However, SUVs may suffer from several uncertainties and errors. Long-axial field-of-view (LAFOV) PET/CT systems might enable image-based quality control (QC) by deriving 18F-FDG activity and weight from total body (TB) 18F-FDG PET images. In this study, we aimed to develop these image-based QC to reduce errors and mitigate SUV uncertainties. METHODS: Twenty-five out of 81 patient scans from a LAFOV PET/CT system were used to determine regression fits for deriving of image-derived activity and weight. Thereafter, the regression fits were applied to 56 independent 18F-FDG PET scans from the same scanner to determine if injected activity and weight could be obtained accurately from TB and half-body (HB) scans. Additionally, we studied the impact of image-based values on the precision of liver SUVmean and lesion SUVpeak. Finally, 20 scans were acquired from a short-axial field-of-view (SAFOV) PET/CT system to determine if the regression fits also applied to HB scans from a SAFOV system. RESULTS: Both TB and HB 18F-FDG activity and weight significantly predicted reported injected activity (r = 0.999; r = 0.984) and weight (r = 0.999; r = 0.987), respectively. After applying the regression fits, 18F-FDG activity and weight were accurately derived within 4.8% and 3.2% from TB scans and within 4.9% and 3.1% from HB, respectively. Image-derived values also mitigated liver and lesion SUV variability compared with reported values. Moreover, 18F-FDG activity and weight obtained from a SAFOV scanner were derived within 6.7% and 4.5%, respectively. CONCLUSION: 18F-FDG activity and weight can be derived accurately from TB and HB scans, and image-derived values improved SUV precision and corrected for lesion SUV errors. Therefore, image-derived values should be included as QC to generate a more reliable and reproducible quantitative uptake measurement.

A class of their own? Water-soluble polymer pollution impacting a freshwater host-pathogen system.

While the inclusion of synthetic polymers such as primary microplastics within personal care products have been widely restricted under EU/UK Law, water-soluble polymers (WSPs) have so far slipped the net of global chemical regulation despite evidence that these could be polluting wastewater effluents at concentrations greatly exceeding those of microplastics. Polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) represent WSPs with common industry and household uses, down-the-drain disposal and a direct route to wastewater treatment plants, conveying high risk of environmental leaching into freshwater ecosystems. The current study is the first investigating the impacts of predicted environmental concentrations of these WSPs on life-history traits of two freshwater species also constituting a disease model (fish - Poecilia reticulata and parasite - Gyrodactylus turnbulli). Single effects of WSPs on fish as well as their interactive effects with infection of the ectoparasite were determined over a 45-day exposure. Generally, WSPs reduced fish growth and increased routine metabolic rate of fish implying a depleted energetic budget, however these effects were dose, exposure time and polymer dependent. Parasitic infection alone caused a significant reduction in fish growth and enhanced fish routine metabolic rate. In contrast, a non-additive effect on metabolic rate was evident in fish experiencing simultaneous infection and WSP exposure, suggesting a protective effect of the two WSPs for fish also exposed to a metazoan ectoparasite. Off-host parasite survival was significantly lowered by both WSPs; however, parasite counts of infected fish also exposed to WSP were not significantly different from the control, implying more complex mechanisms may underpin this stressor interaction. Distinct detrimental impacts were inflicted on both organisms implying environmental leaching of WSPs may be causing significant disruption to interspecies interactions within freshwater ecosystems. Additionally, these results could contribute to sustainable development in industry, as we conclude PVA represents a less harmful alternative to PVP.

Systematic review exploring the clinical features of optic neuritis after SARS-CoV infection and vaccination.

BACKGROUND: This study aims to characterise the symptoms and clinical features of optic neuritis (ON) following SARS-CoV-2 infection and vaccination. METHOD: A literature search was conducted in four databases (PubMed, Medline, Embase and Google Scholar) to identify relevant case reports and case series. The records were screened and articles adhering to the inclusion criteria were critically appraised. RESULTS: Sixty-eight studies were found to be eligible for inclusion, including 34 reporting ON following SARS-CoV-2 infection and an equal number reporting cases postvaccination. In total 93 patients and 125 eyes were included. The infection cohort included 42 patients and 56 eyes, 51.2% were female and 33.3% experienced bilateral ON. The mean visual acuity was 1.64 log of minimum angle of resolution (LogMAR), while pain was present in 77.8%. Oligoclonal bands were present in 3 patients, myelin oligodendrocyte glycoprotein (MOG) antibodies in 18 patients and AQP-4 antibodies in 4 patients. The vaccination cohort included 51 patients and 69 eyes. 60.8% were female and 35.3% had a bilateral ON. The mean visual acuity was 0.93 LogMAR. Oligoclonal bands were present in 46.7%, MOG antibodies in nine patients and AQP-4 antibodies in three patients. CONCLUSION: Patients with ON post-SARS-CoV infection were more likely to experience severe visual impairment than in cases following vaccination. Further research is required to outline the clinical features of ON after COVID-19 infection and vaccination, and establish causality.

Maternal-child consumption of ultra-processed foods and sugar-sweetened beverages in informal settlements in Mumbai, India.

BACKGROUND: The global nutrition transition is associated with increased consumption of ultra-processed snack foods and sugar-sweetened beverages (UPF/SSB), contributing to the double burden of child obesity and undernutrition. METHODS: This cross-sectional study describes the prevalence of maternal and child UPF/SSB consumption and the factors associated with frequent consumption in a convenience sample of 749 children ages 6 months through 6 years and their mothers participating in a community-based child oral health program in five informal settlement communities in Mumbai, India. Mothers were interviewed regarding maternal and child oral health and nutrition characteristics, including consumption of beverages and foods associated with tooth decay-milk, soda, tea with sugar, sweets, and chips/biscuits-using standardized questionnaires. Spearman correlations were used to assess for associations between various social factors and the frequency of maternal and child consumption of the five food categories. Chi-square tests were used to assess differences in child consumption patterns by age groups. RESULTS: Though reported soda consumption was low among both mothers and children, nearly 60% of children consumed sweets and chips/biscuits daily, four to five times the rate of mothers. Factors associated with children's frequent consumption of UPF/SSB included lower maternal education level, frequent maternal consumption of UPF/SSB, greater number of household members, greater amount of money given to the child, and closer proximity to a store. CONCLUSION: Our findings demonstrate social factors that may promote UPF/SSB consumption. The nutritional dangers of sugary drinks and non-nutritious snacks for mothers and young children should be addressed across maternal-child health, education, and social service programs. Early childhood nutrition interventions should involve the entire family and community and emphasize the need to limit children's consumption of unhealthy foods and beverages from an early age.

Chronic nicotine exposure is associated with electrophysiological and sympathetic remodeling in the intact rabbit heart.

Nicotine is the primary addictive component in tobacco products. Through its actions on the heart and autonomic nervous system, nicotine exposure is associated with electrophysiological changes and increased arrhythmia susceptibility. However, the underlying mechanisms are unclear. To address this, we treated rabbits with transdermal nicotine (NIC, 21 mg/day) or control (CT) patches for 28 days prior to performing dual optical mapping of transmembrane potential (RH237) and intracellular Ca 2+ (Rhod-2 AM) in isolated hearts with intact sympathetic innervation. Sympathetic nerve stimulation (SNS) was performed at the 1 st - 3 rd thoracic vertebrae, and ß-adrenergic responsiveness was additionally evaluated as changes in heart rate (HR) following norepinephrine (NE) perfusion. Baseline ex vivo HR and SNS stimulation threshold were increased in NIC vs. CT ( P = 0.004 and P = 0.003 respectively). Action potential duration alternans emerged at longer pacing cycle lengths (PCL) in NIC vs. CT at baseline ( P = 0.002) and during SNS ( P = 0.0003), with similar results obtained for Ca 2+ transient alternans. SNS reduced the PCL at which alternans emerged in CT but not NIC hearts. NIC exposed hearts also tended to have slower and reduced HR responses to NE perfusion. While fibrosis was unaltered, NIC hearts had lower sympathetic nerve density ( P = 0.03) but no difference in NE content vs. CT. These results suggest both sympathetic hypo-innervation of the myocardium and diminished ß-adrenergic responsiveness with NIC. This autonomic remodeling may underlie the increased risk of arrhythmias associated with nicotine exposure, which may be further exacerbated with continued long-term usage. NEW & NOTEWORTHY: Here we show that chronic nicotine exposure was associated with increased heart rate, lower threshold for alternans and reduced sympathetic electrophysiological responses in the intact rabbit heart. We suggest that this was due to the sympathetic hypo-innervation of the myocardium and diminished ß- adrenergic responsiveness observed following nicotine treatment. Though these differences did not result in increased arrhythmia propensity in our study, we hypothesize that prolonged nicotine exposure may exacerbate this pro-arrhythmic remodeling.

Utilizing Virtual Reality for Gender-Affirming Voice Training: Surveying the Attitudes and Perspectives of Potential Consumers.

BACKGROUND: Undertaking voice and communication training is an important part of the gender-affirming journey for many trans, gender-diverse and non-binary individuals. Training supports the alignment of voice with gender identity helping to reduce gender dysphoria as individuals are better able to connect with their voices. However, for training to be effective, regular practice is needed and the demands of training can often be difficult to meet. AIMS: To investigate the interest, attitudes and perspectives on the use of immersive virtual reality (VR) to support gender-affirming voice and communication training by transgender, gender non-binary and gender-diverse people, and speech-language pathologists providing gender-affirming voice and communication training. METHODS & PROCEDURES: A mixed-methods survey (i.e., collecting quantitative data through multiple-choice question and qualitative data through free text questions) was hosted online from 23 August to 21 September 2021. A total of 17 questions asked about technology use, and attitudes and perspectives towards VR. The survey included video examples of three different voice-activated VR applications to prompt participant responses about the technology. OUTCOMES & RESULTS: A total of 70 survey responses were included in the analysis. All participants had previous experience using smart phones, but only 27.2% had previously used VR. Four key themes were identified relating to potential uptake of VR in gender-affirming voice and communication training: (1) general audience appeal, (2) perceived therapeutic value, (3) exposure to or protection from harm and (4) relatability to real life. CONCLUSIONS & IMPLICATIONS: VR games may represent a viable option to support practice of voice exercises. Gamification through VR is likely to motivate some to increase frequency of practice. VR applications that are used in voice training need to be fit-for-purpose, and detailed co-design is necessary to build appropriate applications for future use. This study provides a foundation to inform the design, development and implementation of VR applications to be used in gender-affirming voice training. WHAT THIS PAPER ADDS: What is already known on the subject? Speech-language pathologists work closely with transgender and gender-diverse individuals to help them achieve gender congruent voice and communication. Clients need to undertake regular and ongoing practice outside of training sessions to achieve and maintain their ideal voice. Motivation and adherence to regular practice sessions remain an ongoing challenge. What this study adds to the existing knowledge This study explores the use of immersive VR technologies to create safe, motivating and enjoyable environments to encourage regular practice of gender-affirming voice and communication exercises. It engages stakeholders in an early-stage participant-involved design to gauge interest in, and perspectives on, VR and technology-based training support tools. The results suggest that voice-activated VR applications would highly motivate some individuals if they were appropriately designed but would not be ideal for all. What are the actual and clinical implications of this work? Immersion in VR can be a highly motivating tool to enhance adherence to practice schedules for some individuals. However, tools need to be specifically designed with outcomes in mind to be fit-for-purpose, to support individual goals and to minimize the risk of harm. The few existing VR voice-activated applications that are available require further assessment, and redesign through co-design with users to functionally and safely support gender-affirming voice and communication training.

Developing balloon dilatation sizing guidance for anastomotic stricture dilatation following oesophageal atresia repair.

PURPOSE: To develop guidance for the selection of balloon catheter size when performing an oesophageal dilatation for a stricture post oesophageal atresia repair. METHODS: This was a single centre retrospective study at a paediatric tertiary centre. Dilatations were performed between 2015 and 2020. All dilatations were performed under general anaesthesia using balloon catheters under fluoroscopic guidance. Outliers were excluded using ROUT method and descriptive analysis was calculated to 1SD or IQR depending on the normality of data distribution. RESULTS: 97 patients underwent 341 dilatations. Median age was 19 months (37 weeks corrected gestation-17 years), median weight was 10.7 kg (2.6-72 kg). Balloon catheter sizes ranged from 6-8 mm to 18-20 mm. There was strong correlation between weight and balloon size (r = 0.8, p < 0.0001). There were 2 perforations (0.6%), both diagnosed intra-operatively and treated conservatively. From the results, weight recommendations were created for each balloon size. CONCLUSION: Fluoroscopic balloon dilatation is a safe and effective method to treat anastomotic stricture following oesophageal atresia repair. Previous studies have shown correlation between patient weight and oesophageal diameter. We propose guidance for using an appropriate balloon size based on patient's weight with the aim to reduce complication.

TREC mediated oncogenesis in human immature T lymphoid malignancies preferentially involves ZFP36L2.

The reintegration of excised signal joints resulting from human V(D)J recombination was described as a potent source of genomic instability in human lymphoid cancers. However, such molecular events have not been recurrently reported in clinical patient lymphoma/leukemia samples. Using a specifically designed NGS-capture pipeline, we here demonstrated the reintegration of T-cell receptor excision circles (TRECs) in 20/1533 (1.3%) patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). Remarkably, the reintegration of TREC recurrently targeted the tumor suppressor gene, ZFP36L2, in 17/20 samples. Thus, our data identified a new and hardly detectable mechanism of gene deregulation in lymphoid cancers providing new insights in human oncogenesis.