Sex disparity in liver allocation within Eurotransplant.

In Eurotransplant, relatively more females than males die while waiting for a liver transplantation, and relatively fewer females are transplanted. With adult liver transplantation candidates listed between 2007 and 2019 (n=21,170), we study whether sex disparity is inherent to the Model for End-stage Liver Disease (MELD) scoring system, or the indirect result of a small candidate body size limiting access to transplantation. Cox proportional hazards models are used to quantify the direct effect of sex on waitlist mortality, independent of sex's effect through MELD scores, and the direct effect of sex on the transplantation rate, independent of sex's effect through MELD and candidate body size. Adjusted waitlist mortality hazard ratios for female sex are insignificant (HR: 1.03, 95%-CI: 0.88-1.20). We thus lack evidence that MELD systematically underestimates waitlist mortality rates for females. Transplantation rates are 25% lower for females than males in unadjusted analyses (HR: 0.74, 95%-CI: 0.71-0.77), but hazard ratios become insignificant with adjustment for mediators (HR: 0.98, 95%-CI: 0.93-1.04), most importantly candidate body size. Sex disparity in Eurotransplant thus appears to be largely a consequence of lower transplantation rates for females, which are explained by sex differences in body size.

Preference for daily (1HP) vs. weekly (3HP) isoniazid-rifapentine among people living with HIV in Uganda.

BACKGROUND: Both 1 month of daily (1HP) and 3 months of weekly (3HP) isoniazid-rifapentine are recommended as short-course regimens for TB prevention among people living with HIV (PLHIV). We aimed to assess acceptability and preferences for 1HP vs. 3HP among PLHIV. METHODS: In a cross-sectional survey among PLHIV at an HIV clinic in Kampala, Uganda, participants were randomly assigned to a hypothetical scenario of receiving 1HP or 3HP. Participants rated their level of perceived intention and confidence to complete treatment using a 0-10 Likert scale, and chose between 1HP and 3HP. RESULTS: Among 429 respondents (median age: 43 years, 71% female, median time on ART: 10 years), intention and confidence were rated high for both regimens. Intention to complete treatment was rated at least 7/10 by 92% (189/206 randomized to 1HP) and 93% (207/223 randomized to 3HP). Respectively 86% (178/206) and 93% (208/223) expressed high confidence to complete treatment. Overall, 81% (348/429) preferred 3HP over 1HP. CONCLUSIONS: Both 1HP and 3HP were highly acceptable regimens, with 3HP preferred by most PLHIV. Weekly, rather than daily, dosing appears preferable to shorter duration of treatment, which should inform scale-up and further development of short-course regimens for TB prevention.

CONTEXTE: L'association isoniazide-rifapentine est recommandée comme traitement de courte durée pour la prévention de la TB chez les personnes vivant avec le VIH (PVVIH), à raison d'un mois de traitement quotidien (1HP) et de 3 mois de traitement hebdomadaire (3HP). Nous avons cherché à évaluer l'acceptabilité et les préférences des PVVIH pour le traitement 1HP par rapport au traitement 3HP. MÉTHODES: Dans le cadre d'une enquête transversale menée auprès de PVVIH dans une clinique VIH de Kampala, en Ouganda, les participants ont été assignés de manière aléatoire à un scénario hypothétique de réception de 1HP ou de 3HP. Les participants ont évalué leur niveau d'intention perçue et de confiance pour terminer le traitement en utilisant une échelle de Likert de 0 à 10 et ont choisi entre 1HP et 3HP. RÉSULTATS: Parmi les 429 répondants (âge médian : 43 ans, 71% de femmes, durée médiane de la thérapie antirétrovirale : 10 ans), l'intention et la confiance ont été jugées élevées pour les deux schémas. L'intention de terminer le traitement a été évaluée à au moins 7/10 par 92% (189/206 randomisés pour 1HP) et 93% (207/223 randomisés pour 3HP). Respectivement 86% (178/206) et 93% (208/223) ont exprimé une grande confiance dans le fait de terminer le traitement. Dans l'ensemble, 81% (348/429) ont préféré la 3HP à la 1HP. CONCLUSION: Les schémas 1HP et 3HP étaient tous deux très acceptables, le schéma 3HP étant préféré par la plupart des PVVIH. L'administration hebdomadaire, plutôt que quotidienne, semble préférable à une durée de traitement plus courte, ce qui devrait inspirer l'extension et le développement de schémas thérapeutiques de courte durée pour la prévention de la TB.

An adjustable acoustic metamaterial cell using a magnetic membrane for tunable resonance.

Acoustic metamaterials are growing in popularity for sound applications including noise control. Despite this, there remain significant challenges associated with the fabrication of these materials for the sub-100 Hz regime, because acoustic metamaterials for such frequencies typically require sub-mm scale features to control sound waves. Advances in additive manufacturing technologies have provided practical methods for rapid fabrication of acoustic metamaterials. However, there is a relatively high sensitivity of their resonant characteristics to sub-mm deviations in geometry, pushing the limits of additive manufacturing. One way of overcoming this is via active control of device resonance. Here, an acoustic metamaterial cell with adjustable resonance is demonstrated for the sub-100 Hz regime. A functionally superparamagnetic membrane-devised to facilitate the fabrication process by eliminating magnetic poling requirements-is engineered using stereolithography, and its mechanical and acoustic properties are experimentally measured using laser Doppler vibrometry and electret microphone testing, with a mathematical model developed to predict the cell response. It is demonstrated that an adjustable magnetic acoustic metamaterial can be fabricated at ultra-subwavelength dimensions ( ≤ λ /77.5), exhibiting adjustable resonance from 88.73 to 86.63 Hz. It is anticipated that this research will drive new innovations in adjustable metamaterials, including wider frequency ranges.

Characterizing hepatitis B virus infection in children in the Democratic Republic of Congo to inform elimination efforts.

Objective: Despite global reductions in hepatitis B virus (HBV) prevalence, an estimated 6.2 million children are infected, two-thirds of whom live in the WHO Africa region. We sought to characterize childhood HBV to inform elimination efforts in the Democratic Republic of Congo (DRC), one of the largest and most populous African countries. Methods: Using the most recent (2013-14) nationally representative Demographic and Health Survey in the DRC, we analyzed HBV surface antigen (HBsAg) on dried blood spots and associated survey data from children aged 6-59 months. We estimated HBsAg-positivity prevalence nationally, regionally, and by potential correlates of infection. We evaluated spatial variation in HBsAg-positivity prevalence, overall and by age, sex, and vaccination status. Findings: Using data from 5,679 children, we found national HBsAg-positivity prevalence was 1.3% (95% CI: 0.9%-1.7%), but ranged from 0.0% in DRC's capital city province, Kinshasa, to 5.6% in northwestern Sud-Ubangi Province. Prevalence among boys (1.8%, 95% CI: 1.2%-2.7%) was double that among girls (0.7%, 95%CI: 0.4%-1.3%). Tetanus antibody-negativity, rurality, and lower household wealth were also significantly associated with higher HBsAg-positivity prevalence. We observed no difference in prevalence by age. Children had higher HBsAg-positivity odds if living with ≥1 HBsAg-positive adult household member (OR: 2.3, 95%CI: 0.7-7.8), particularly an HBsAg-positive mother (OR: 7.2, 95%CI:1.6-32.2). Conclusion: In the largest national survey of HBV among children and household contacts in the DRC, we found that childhood HBV prevalence was 10-60 times the global target of 0.1%. We highlight specific regions and populations for further investigation and focused prevention efforts.

[Safety of umeclidinium/vilanterol in Chinese patients in a real-world setting: a prospective, multicenter, single-arm, observational study].

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.

Crystalloid volume versus catecholamines for management of hemorrhagic shock during esophagectomy - assessment of microcirculatory tissue oxygenation of the gastric conduit in a porcine model using hyperspectral imaging - an experimental study.

INTRODUCTION: Oncologic esophagectomy is a two-cavity procedure with considerable morbidity and mortality. Complex anatomy and the proximity to major vessels constitute a risk for massive intraoperative hemorrhage. Currently, there is no conclusive consensus on the ideal anesthesiologic countermeasure in case of such immense blood loss. The objective of this work was to identify the most promising anesthesiologic management in case of intraoperative hemorrhage with regards to tissue perfusion of the gastric conduit during esophagectomy using hyperspectral imaging (HSI). MATERIAL AND METHODS: An established live porcine model (n=32) for esophagectomy was used with gastric conduit formation and simulation of a linear stapled side-to-side esophagogastrostomy. After a standardized procedure of controlled blood loss of about 1 L per pig, the four experimental groups (n=8 each) differed in anesthesiologic intervention i.e. (I) permissive hypotension, (II) catecholamine therapy using noradrenaline, (III) crystalloid volume supplementation and (IV) combined crystalloid volume supplementation with noradrenaline therapy. HSI tissue oxygenation (StO2) of the gastric conduit was evaluated and correlated with systemic perfusion parameters. Measurements were conducted before (T0) and after (T1) laparotomy, after hemorrhage (T2) and 60 minutes (T3) and 120 minutes (T4) after anesthesiologic intervention. RESULTS: StO2 values of the gastric conduit showed significantly different results between the four experimental groups with 63.3% (±7.6%) after permissive hypotension (I), 45.9% (±6.4%) after catecholamine therapy (II), 70.5% (±6.1%) after crystalloid volume supplementation (III) and 69.0% (±3.7%) after combined therapy (IV). StO2 values correlated strongly with systemic lactate values (r=-0.67; CI -0.77 to -0.54), which is an established prognostic factor. CONCLUSION: Crystalloid volume supplementation (III) yields the highest StO2 values and lowest systemic lactate values and therefore appears to be the superior primary treatment strategy after hemorrhage during esophagectomy with regards to microcirculatory tissue oxygenation of the gastric conduit.

Depression: an individual-level early warning indicator of virologic failure in HIV patients in South Africa.

OBJECTIVE: To identify individual-level early warning indicators of virologic failure in HIV patients receiving antiretroviral therapy (ART) in South Africa. DESIGN: A matched case-control study of individuals with and without virologic failure (VF) (>5 months on ART and HIV-1 plasma viral load >1,000 copies/mL) was conducted between June 2014 and June 2018. Of the 1,000 participants enrolled in the parent cohort, 96 experienced VF, and 199 additional controls were identified from the parent cohort and matched 1:2 (some matched 1:3) for sex, age, ART duration, and site. Participants were interviewed while clinical, pharmacy refill, laboratory, and objective pharmacological data were obtained. Multivariate conditional logistic regression models were constructed using model selection to identify factors associated with VF. Significant determinants of VF were identified using an alpha level of 0.05. RESULTS: In a full conditional model, higher cumulative ART adherence, quantified using tenofovir-diphosphate concentrations in dried blood spots (OR 0.26) and medication possession ratio (OR 0.98) were protective against VF, whereas an increase in total depression score (OR 1.20) was predictive of VF. CONCLUSION: This analysis demonstrates the importance of depression as a key individual-level early warning indicator of VF. Efforts to address mental health concerns among patients with people living with HIV could improve virologic suppression.

OBJECTIF: Identifier les indicateurs d'alerte précoce au niveau individuel de l'échec virologique chez les patients séropositifs recevant un traitement antirétroviral (TAR) en Afrique du Sud. MÉTHODE: Une étude cas-témoins appariée de personnes avec et sans échec virologique (FV, pour l'anglais « virologic failure ¼) (>5 mois sous ART et charge virale plasmatique du VIH-1 >1 000 copies/ml) a été menée entre juin 2014 et juin 2018. Sur les 1 000 participants inscrits dans la cohorte parente, 96 ont présenté une FV et 199 témoins supplémentaires ont été identifiés dans la cohorte parentale et appariés 1:2 (certains appariés 1:3) pour le sexe, l'âge, la durée du TAR et le site. Les participants ont été interrogés pendant que des données cliniques, de renouvellement de pharmacie, de laboratoire et pharmacologiques objectives ont été obtenues. Des modèles de régression logistique conditionnelle multivariée ont été construits à l'aide d'une sélection de modèles pour identifier les facteurs associés à la FV. Les déterminants significatifs de la FV ont été identifiés à l'aide d'un niveau alpha de 0,05. RÉSULTATS: Dans un modèle conditionnel complet, une observance cumulative plus élevée du TAR, quantifiée à l'aide des concentrations de ténofovir-diphosphate dans les gouttes de sang séché (OR 0,26) et du ratio de possession de médicaments (OR 0,98) protégeait contre la FV, tandis qu'une augmentation du score de dépression totale (OR 1,20) était prédictive de la FV. CONCLUSION: Cette analyse démontre l'importance de la dépression en tant qu'indicateur précoce clé au niveau individuel de la FV. Les efforts visant à résoudre les problèmes de santé mentale chez les personnes vivant avec le VIH pourraient améliorer la suppression virologique.

[The origin and development of Huanglong Decoction].

"Different prescriptions with the same name" is a common phenomenon clinically in traditional Chinese medicine prescriptions. Huanglong Decoction can be regarded as a representative example of this phenomenon with many changes to the contents of the decoction during its development. To clarify and identify the typology of Huanglong Decoction, this paper attempts to explore the origins and evolution of almost all types of Huanglong Decoction with an archival method examining data before 1911. It was found that Huanglong Decoction has at least seven main types: Fecal Liquid, Xiaochaihu Decoction Plus or Minus, Tao's, Taiping Shenghui Fang, Shengji Zonglu, Fu's and Zhulin Gynecology Treatment. Xiaochaihu Decoction Plus or Minus (Xiao Chai Hu Tang Jia Jian) includes four subcategories: Yao's Huanglong Decoction, Gujin Luyan Huanglong Decoction, Leizheng Huorenshu Huanglong Decoction, and Qian's Huanglong Decoction. It was also found that Xinjia Huanglong Decoction is derived from Tao's Huanglong Decoction.

Consistency, completeness and external validity of ethnicity recording in NHS primary care records: a cohort study in 25 million patients' records at source using OpenSAFELY.

BACKGROUND: Ethnicity is known to be an important correlate of health outcomes, particularly during the COVID-19 pandemic, where some ethnic groups were shown to be at higher risk of infection and adverse outcomes. The recording of patients' ethnic groups in primary care can support research and efforts to achieve equity in service provision and outcomes; however, the coding of ethnicity is known to present complex challenges. We therefore set out to describe ethnicity coding in detail with a view to supporting the use of this data in a wide range of settings, as part of wider efforts to robustly describe and define methods of using administrative data. METHODS: We describe the completeness and consistency of primary care ethnicity recording in the OpenSAFELY-TPP database, containing linked primary care and hospital records in > 25 million patients in England. We also compared the ethnic breakdown in OpenSAFELY-TPP with that of the 2021 UK census. RESULTS: 78.2% of patients registered in OpenSAFELY-TPP on 1 January 2022 had their ethnicity recorded in primary care records, rising to 92.5% when supplemented with hospital data. The completeness of ethnicity recording was higher for women than for men. The rate of primary care ethnicity recording ranged from 77% in the South East of England to 82.2% in the West Midlands. Ethnicity recording rates were higher in patients with chronic or other serious health conditions. For each of the five broad ethnicity groups, primary care recorded ethnicity was within 2.9 percentage points of the population rate as recorded in the 2021 Census for England as a whole. For patients with multiple ethnicity records, 98.7% of the latest recorded ethnicities matched the most frequently coded ethnicity. Patients whose latest recorded ethnicity was categorised as Other were most likely to have a discordant ethnicity recording (32.2%). CONCLUSIONS: Primary care ethnicity data in OpenSAFELY is present for over three quarters of all patients, and combined with data from other sources can achieve a high level of completeness. The overall distribution of ethnicities across all English OpenSAFELY-TPP practices was similar to the 2021 Census, with some regional variation. This report identifies the best available codelist for use in OpenSAFELY and similar electronic health record data.

Primary Headache Relief in Paediatric Patients Following Rapid Maxillary Expansion: a Prospective Study and Cephalometric Changes Analysis.

BACKGROUND: Primary headaches (PH) are a group of disorders greatly impairing quality of life, highly prevalent in growing population. Previous studies suggested a rhinogenic involvement in PH episodes. Modifications of nasal cavities and septum take place during rapid maxillary expansion (RME). This study aims to investigate the role of skeletal modifications due to RME on PH episodes. METHODS: Sixty-eight growing patients (30/38 MF 7-12 y.o 9.2 ± 1.3 SD) were enrolled. All the selected sample patients reported at least 12 PH episodes in the previous year and were diagnosed with maxillary constriction to be treated with RME. Changes in PH episodes before and after this orthodontic procedure were analysed using paired t-tests. Correlations between age and PH episodes were assessed using Spearman correlation coefficients. Correlations between cephalometric changes and PH episodes were investigated using paired t-tests. CONCLUSION: RME produces significant modifications in maxillary and nasal width and lower nasal length and decreased monthly episodes of PH significantly. It can be supposed and inferred that RME has beneficial effects on PH in growing patients.

Effects of bench press technique variations on musculoskeletal shoulder loads and potential injury risk.

While shoulder injuries resulting from the bench press exercise are commonly reported, no biomechanical evidence for lowering injury risk is currently available. Therefore, the aim of the present study was to compare musculoskeletal shoulder loads and potential injury risk during several bench press variations. Ten experienced strength athletes performed 21 technical variations of the barbell bench press, including variations in grip width of 1,1.5 and 2 bi-acromial widths (BAW), shoulder abduction angles of 45°, 70° and 90°, and scapula poses including neutral, retracted, and released conditions. Motions and forces were recorded by an opto-electronic measurement system and an instrumented barbell. An OpenSim musculoskeletal shoulder model was employed to estimate joint reaction forces in the glenohumeral and acromioclavicular joints. Time-series of joint reaction forces were compared between techniques by statistical non-parametric mapping. Results showed that narrower grip widths of < 1.5 BAW decreased acromioclavicular compression (p < 0.05), which may decrease the risk for distal clavicular osteolysis. Moreover, scapula retraction, as well as a grip width of < 1.5 BAW (p < 0.05), decreased glenohumeral posterior shear force components and rotator cuff activity and may decrease the risk for glenohumeral instability and rotator cuff injuries. Furthermore, results showed that mediolaterally exerted barbell force components varied considerably between athletes and largely affected shoulder reaction forces. It can be concluded that the grip width, scapula pose and mediolateral exerted barbell forces during the bench press influence musculoskeletal shoulder loads and the potential injury risk. Results of this study can contribute to safer bench press training guidelines.

Reversal of insulin resistance in people with obesity by lifestyle-induced weight loss does not impact the proportion of circulating 12α-hydroxylated bile acids.

AIM: Bile acids (BAs) are implicated in the pathogenesis of several metabolic syndrome-related diseases, including insulin resistance (IR) and type 2 diabetes (T2D). It has been reported that IR and T2D are associated with an increased ratio of 12α/non-12α-hydroxylated BAs in the circulating BA pool. It is, however, unknown whether the improvement of insulin sensitivity inversely affects BA composition in humans. Therefore, we assessed whether lifestyle-induced weight loss induces changes in BA metabolism in people with obesity, with or without T2D, and if these changes are associated with metabolic parameters. MATERIALS AND METHODS: Individual BAs and C4 were quantified by ultra-high-performance liquid chromatography-tandem mass spectrometry in plasma samples collected from two cohorts of people with obesity (OB) and with T2D and obesity (T2D), before and after a lifestyle intervention. RESULTS: Lifestyle-induced weight loss improved glycaemic control in both cohorts, with plasma BA concentrations not affected by the lifestyle interventions. The ratio of 12α/non-12α-hydroxylated BAs remained unchanged in OB (p = .178) and even slightly increased upon intervention in T2D (p = .0147). Plasma C4 levels were unaffected in OB participants (p = .20) but significantly reduced in T2D after intervention (p = .0003). There were no significant correlations between the ratio of 12α/non-12α-hydroxylated BAs and glucose, insulin, or homeostatic model assessment-IR, nor in plasma triglycerides, low-density lipoprotein cholesterol, lipoprotein (a) in the T2D cohort. CONCLUSIONS: Lifestyle-induced weight loss did improve glycaemic control but did not affect BA concentrations. Improvements in insulin sensitivity were not associated with changes in BA parameters in people with obesity, with or without T2D.

Unsaturated fatty acid perturbation combats emerging triazole antifungal resistance in the human fungal pathogen Aspergillus fumigatus.

Contemporary antifungal therapies utilized to treat filamentous fungal infections are inhibited by intrinsic and emerging drug resistance. Consequently, there is an urgent need to develop novel antifungal compounds that are effective against drug-resistant filamentous fungi. Here, we utilized an Aspergillus fumigatus cell-based high-throughput screen to identify small molecules with antifungal activity that also potentiated triazole activity. The screen identified 16 hits with promising activity against A. fumigatus. A nonspirocyclic piperidine, herein named MBX-7591, exhibited synergy with triazole antifungal drugs and activity against pan-azole-resistant A. fumigatus isolates. MBX-7591 has additional potent activity against Rhizopus species and CO2-dependent activity against Cryptococcus neoformans. Chemical, genetic, and biochemical mode of action analyses revealed that MBX-7591 increases cell membrane saturation by decreasing oleic acid content. MBX-7591 has low toxicity in vivo and shows good efficacy in decreasing fungal burden in a murine model of invasive pulmonary aspergillosis. Taken together, our results suggest MBX-7591 is a promising hit with a novel mode of action for further antifungal drug development to combat the rising incidence of triazole-resistant filamentous fungal infections.IMPORTANCEThe incidence of infections caused by fungi continues to increase with advances in medical therapies. Unfortunately, antifungal drug development has not kept pace with the incidence and importance of fungal infections, with only three major classes of antifungal drugs currently available for use in the clinic. Filamentous fungi, also called molds, are particularly recalcitrant to contemporary antifungal therapies. Here, a recently developed Aspergillus fumigatus cell reporter strain was utilized to conduct a high-throughput screen to identify small molecules with antifungal activity. An emphasis was placed on small molecules that potentiated the activity of contemporary triazole antifungals and led to the discovery of MBX-7591. MBX-7591 potentiates triazole activity against drug-resistant molds such as A. fumigatus and has activity against Mucorales fungi. MBX-7591's mode of action involves inhibiting the conversion of saturated to unsaturated fatty acids, thereby impacting fungal membrane integrity. MBX-7591 is a novel small molecule with antifungal activity poised for lead development.

Trauma-Informed Undergraduate Medical Education: A Pathway to Flourishing with Adversity by Enhancing Psychological Safety.

We describe the Life Experiences Curriculum (LEC), which attempts to integrate medical student well-being with trauma-informed medical education. The long-term goal of LEC is to help medical students flourish with adversity and trauma, where flourishing refers to having a sense of purpose that arises from awareness of one's strengths and limitations, shaped by life experiences. The short-term goal of LEC is to develop students' relational capacities, such as acceptance and awareness of self and others, while building and maintaining students' psychological safety. We describe the conceptual rationale for these goals and the curriculum's development, implementation, evaluation, and limitations. The curriculum extends over four years and involves a preclinical seminar and students' individual and group reflection sessions with LEC faculty. The seminar addresses the coexistence of trauma and flourishing across life experiences, as well as how safety in relationships is impaired by traumatic experiences and must be restored for healing and growth. The physician faculty have no role in student evaluation and co-lead all LEC activities. LEC is intended to provide students with new language for understanding the process of trauma and flourishing in both individuals and systems and to build and sustain students' relational capacities. There are ongoing efforts to re-imagine self-care as communal-care in which care and support are given and received in a community of students and faculty. Such a model may help build the relational capacities needed to deliver trauma-informed care and also promote flourishing with adversity in healers and in those seeking to be healed.

Complete genome sequence of Serratia ureilytica KML.E1, a copper-tolerant strain isolated from a disused tungsten mine.

Serratia ureilytica KML.E1 was recovered from a disused tungsten mine in Hong Kong and can tolerate copper(II) concentrations up to 90 mM. Its complete genome, a single chromosome of 5,094,661 bp (59.68% G+ C), was established through hybrid assembly.

Do newborn lambs with black and white hair-coats in an equatorial semi-arid environment maintain homeothermy?

We assessed newborn lambs from two hair-coat sheep breeds, the black Santa Ines (n = 29) and white Dorper (n = 26), to determine how they behaviourally and physiologically respond to the prevailing thermal conditions in an equatorial semi-arid environment. Measurements of hair-coat surface temperature, rectal temperature and the lambs' exposure to sun were recorded across the first 24 h of life every hour, after the lambs had received colostrum. Lambs and ewes were kept in a lambing pen and could freely move between a shaded area or be exposed to sun. During the study period, the air temperature ranged between 20 ºC and 34 ºC. When exposed to sun, lambs and ewes could experience as much as 1200 W m-2 of solar irradiance. Santa Ines lambs exhibited higher (highest density interval at 95%, HDI) hair-coat surface temperatures than did Dorper lambs. Overall, both Santa Ines and Dorper lambs sustained homeothermy, with a mean rectal temperature ranging from 38.7 ºC to 39.1 ºC between night and daytime phase, and a mean amplitude of ~ 0.8 ºC. Nevertheless, from 10:00 to 15:00, some lambs were found to be moderately hyperthermic. Five Santa Ines and three Dorper lambs had rectal temperatures above 40 ºC, and one Santa Ines lamb, while exposed to sun, had a rectal temperature of 41.3 ºC. Over this time period, lambs were more likely to move to shade (HDI at 95%). From 00:00 to 06:00, despite the air temperature being lower than the hair-coat surface, favouring high rates of sensible heat loss to the environment, no lamb exhibited signs of hypothermia (rectal temperature < 37.5 ºC). In conclusion, haired newborn lambs coped well with high levels of radiant heat during the daytime and lower temperatures at night. However, providing access to shade during the daytime is important to improve the welfare of newborn lambs delivered in equatorial semi-arid regions.

Ten-Year Efficacy of Transoral Surgery for Squamous Carcinoma of the Lateral Oropharynx.

OBJECTIVES: To document the 10-year results of transoral mandibular preservation surgery for patients with T1-2 squamous cell carcinoma (SCC) arising from the lateral oropharynx. METHODS: This was a retrospective 30-year review using STROBE guidelines at an academic, tertiary referral center. A total of 294 patients with T1-2 SCC of the lateral oropharynx were reviewed. Only 19% of patients were never-smokers, suggesting a predominantly HPV-negative population. All patients had transoral mandibular preservation surgery. Follow-up therapy included neck dissection (76.5%), induction chemotherapy (57.8%), and postoperative radiation therapy (31.6%) Local control, survival, and functional endpoints, as well as the consequences of local recurrence, were analyzed. RESULTS: The 10-year local disease control was 88.3%. Local recurrence was salvaged in 50% of cases, resulting in an overall 94.5% local control rate. The overall 10-year survival was 50%. Mortality was related to metachronous second primary cancer (MSPC) (29.2%), medical comorbidities (25.7%), uncontrolled local recurrence (10%), and complications following transoral resection (4.2%). In multivariate analysis, the development of an MSPC significantly increased (p < 0.005) the risk of death. Overall, 95.2% of patients achieved mandibular preservation. However, gastrostomy and tracheostomy dependence occurred in 1% and 0.3% of cases, respectively. CONCLUSIONS: For a patient population with a significant percentage of tobacco-associated oropharyngeal cancer (OPC), transoral surgery was associated with long-term minimal postoperative complications and a high rate of local control. MSPC was the main cause of death during the first 10 postoperative years. Such long-term figures support transoral surgery as an effective first-line treatment for early-stage predominantly tobacco-related OPC. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Magnesium enhances aurintricarboxylic acid's inhibitory action on the plasma membrane Ca2+-ATPase.

Our research aimed to elucidate the mechanism by which aurintricarboxylic acid (ATA) inhibits plasma membrane Ca2+-ATPase (PMCA), a crucial enzyme responsible for calcium transport. Given the pivotal role of PMCA in cellular calcium homeostasis, understanding how it is inhibited by ATA holds significant implications for potentially regulating physiopathological cellular processes in which this pump is involved. Our experimental findings revealed that ATA employs multiple modes of action to inhibit PMCA activity, which are influenced by ATP but also by the presence of calcium and magnesium ions. Specifically, magnesium appears to enhance this inhibitory effect. Our experimental and in-silico results suggest that, unlike those reported in other proteins, ATA complexed with magnesium (ATA·Mg) is the molecule that inhibits PMCA. In summary, our study presents a novel perspective and establishes a solid foundation for future research efforts aimed at the development of new pharmacological molecules both for PMCA and other proteins.