Search

Older adults are vulnerable to glucocorticoid‐induced muscle atrophy and weakness, with sex potentially influencing their susceptibility to those effects. Aerobic exercise can reduce glucocorticoid‐induced muscle atrophy in young rodents. However, it is unknown whether aerobic exercise can prevent glucocorticoid myopathy in aged muscle. The objectives of this study were to define the extent to which sex influences the development of glucocorticoid myopathy in aged muscle, and to determine the extent to which aerobic exercise training protects against myopathy development. Twenty‐four‐month‐old female (n = 30) and male (n = 33) mice were randomized to either sedentary or aerobic exercise groups. Within their respective groups, mice were randomized to either daily treatment with dexamethasone (DEX) or saline. Upon completing treatments, the contractile properties of the triceps surae complex were assessed in situ. DEX marginally lowered muscle mass and soluble protein content in both sexes, which was attenuated by aerobic exercise only in females. DEX increased sub‐tetanic force and rate of force development only in females, which was not influenced by aerobic exercise. Muscle fatigue was higher in both sexes following DEX, but aerobic exercise prevented fatigue induction only in females. The sex‐specific differences to muscle function in response to DEX treatment coincided with sex‐specific changes to the content of proteins related to calcium handling, mitochondrial quality control, reactive oxygen species production, and glucocorticoid receptor in muscle. These findings define several important sexually dimorphic changes to aged skeletal muscle physiology in response to glucocorticoid treatment and define the capacity of short‐term aerobic exercise to protect against those changes. Key points: There are sexually dimorphic effects of glucocorticoids on aged skeletal muscle physiology.Glucocorticoid‐induced changes to aged muscle contractile properties coincide with sex‐specific differences in the content of calcium handling proteins.Aerobic exercise prevents glucocorticoid‐induced fatigue only in aged females and coincides with differences in the content of mitochondrial quality control proteins and glucocorticoid receptors. [ABSTRACT FROM AUTHOR]

Younger women rely on altering cardiac output (Q̇$\dot{Q}$) to regulate blood pressure (BP). In contrast, older women rely more on altering vascular tone. However, evidence suggests that the ability to alter systemic vascular conductance (SVC) is diminished in older women. In the present study, cardioselective β‐blockade was utilized to diminish the relative contribution of Q̇$\dot{Q}$ to BP regulation and thereby evaluate age‐related vascular limitations in women at rest and during large muscle dynamic exercise. Younger (n = 13, mean age 26.0 years) and older (n = 14, mean age 61.8 years) healthy women performed submaximal bouts of semi‐recumbent cycling exercise at varying intensities while receiving an intravenous infusion of esmolol, a β1‐antagonist, or saline control in a repeated‐measures crossover design. Q̇$\dot{Q}$ was attenuated during esmolol infusion, with greater reductions during exercise (moderate, –1.0 (95% CI, –1.6 to –0.5) L/min, P < 0.001; heavy, –2.0 (95% CI, –2.6 to –1.5) L/min, P < 0.001) than seated rest (–0.5 (95% CI, –1.1 to 0.0) L/min, P = 0.048), and this reduction was not significantly different between age groups (P = 0.122). Older women exhibited a greater attenuation in mean arterial pressure (MAP) during esmolol (–7 (95% CI, –9 to –4) mmHg, P < 0.001) relative to younger women (–2 (95% CI, –5 to 0) mmHg, P = 0.071). These changes coincided with a greater reduction of SVC in the younger women during esmolol (–15 (95% CI, –20 to –10) mL/min/mmHg, P < 0.001) compared to older women (–3 (95% CI, –9 to 2) mL/min/mmHg, P = 0.242). Together, these findings provide evidence that older, postmenopausal women have a diminished ability to adjust SVC in order to regulate MAP. What is the central question of this study?Will older women have a greater reduction in mean arterial pressure during cardioselective β‐blockade compared to younger women? And will older women exhibit a smaller reduction in systemic vascular conductance in response to cardioselective β‐blockade relative to younger women?What is the main finding and its importance?Cardioselective β‐blockade revealed a limitation in the systemic vasoconstrictor capacity of older women to maintain blood pressure both at rest and during dynamic exercise. These findings may have significant clinical implications, particularly during hypotensive stressors such as heat stress, hypovolemia and orthostatic hypotension. [ABSTRACT FROM AUTHOR]

Data published on the oral clavulanic acid pharmacokinetics in the pediatric population is lacking. This research aimed to describe clavulanic acid disposition following oral and intravenous administration and to provide insights into clavulanic acid exposure based on threshold concentrations for (pre‐)term neonates and infants. This pooled population pharmacokinetic study combined four datasets for analysis in NONMEM v7.4.3. Clavulanic acid exposure was simulated using the percentage of time above the threshold concentrations (%fT > CT). Multiple dosage regimens and amoxicillin/clavulanic acid dosage ratios were evaluated. The cohort consisted of 89 (42 oral, 47 intravenous) subjects (403 samples) with a median (range) postnatal age 54.5 days (0–365), gestational age 37.4 weeks (23.0–41.7), and current bodyweight 3.9 kg (0.6–9.0). A one‐compartment model with first‐order absorption best described clavulanic acid pharmacokinetics with postnatal age as a covariate on the inter‐individual variability of clearance. Oral bioavailability was 24.4% in neonates up to 10 days of age. An oral dosing regimen 90 mg/kg/day amoxicillin/clavulanic acid (4:1 ratio) resulted in 40.2% of simulated patients achieving 100% fT > CT,2mg/L. An amoxicillin/clavulanic acid ratio of 4:1 is preferred for neonatal oral regimens due to the higher exposure along the entire %fT > CT range (0–100%) as ratios higher than 4:1 might result in inadequate exposure. Our results highlight substantial exposure differences (%fT > CT) when using threshold concentrations of 1 mg/L vs. 2 mg/L. This first population pharmacokinetic model for clavulanic acid in neonates may serve as a foundational step for future research, once more precise clavulanic acid targets become available. [ABSTRACT FROM AUTHOR]

Spontaneous tumor regression is a recognized phenomenon across various cancer types. Recent research emphasizes the alterations in autoantibodies against carbonic anhydrase I (CA I) (anti‐CA I) levels as potential prognostic markers for various malignancies. Particularly, autoantibodies targeting CA I and II appear to induce cellular damage by inhibiting their respective protein's catalytic functions. Our study illuminates the profound impact of anti‐CA I autoantibodies from patient serum on the esterase activity of human CA I, exhibiting inhibitory effects akin to the acetazolamide inhibitor. Concurrently, our newly synthesized mouse monoclonal IgG antibody, mAb 2B8, against human CA I showcased a potent inhibitory action. An in‐depth exploration into mAb 2B8′s binding dynamics with its target enzyme was undertaken. Leveraging epitope extraction and phage display library techniques, we identified the amino acid sequence DFWTYP (positions 191–196 of CA I) as crucial for mAb 2B8′s interaction. In 3‐D structural analysis, this sequence is spatially adjacent to a previously identified epitope (DFWTYP) that interacts with patient‐derived autoantibodies. Critically, mAb 2B8 demonstrated an ability to infiltrate eukaryotic cells, engaging specifically with its intracytoplasmic target. This positions mAb 2B8 as a promising model for future studies aimed at tumor cell eradication. [ABSTRACT FROM AUTHOR]

Vibrational Strong Coupling (VSC) has been reported to change the rate of organic reactions. However, a lack of convenient and reliable methods to measure reaction kinetics under VSC makes it challenging to obtain mechanistic insight into its influence, hindering progress in the field. Here, we use recently developed fixed‐width optical cavities to obtain large kinetic datasets under VSC with small errors (±1–5 %) in an operationally simple manner using UV/Vis spectroscopy. The setup is used to test whether VSC changes a fundamental kinetic property of polar reactions, nucleophilicity, for water and alcohols, species commonly used in VSC‐modified chemistry. We determined the rate constants for nucleophilic capture with a library of benzhydrilium ions as reference electrophiles with and without strong coupling of the nucleophile's key vibrations. For all investigated combinations of electrophiles and nucleophiles, only minor changes in the observed rate constants of the reactions were observed independently of the coupled bands. These results indicate that VSC does not substantially alter the nucleophilicity of water and alcohols, suggesting that polar reactions are modified through other, presently unknown mechanisms. Fixed‐width cavities allow for convenient and reproducible UV/Vis kinetics, facilitating mechanistic studies of VSC‐modified chemistry. [ABSTRACT FROM AUTHOR]

ABSTRACT Arrhythmogenic cardiomyopathy (ACM) is a genetically heterogeneous inherited cardiomyopathy with an estimated prevalence of 1:5000–10 000 that predisposes patients to life‐threatening ventricular arrhythmias (VA) and sudden cardiac death (SCD). ACM diagnostic criteria and risk prediction models, particularly for arrhythmogenic right ventricular cardiomyopathy (ARVC), the most common form of ACM, are typically genotype‐agnostic, but numerous studies have established clinically meaningful genotype‐phenotype associations. Early signs of ACM onset differ by genotype indicating the need for genotype‐specific diagnostic criteria and family screening paradigms. Likewise, risk factors for SCD vary by genetic subtype, indicating that genotype‐specific guidelines for management are also warranted. Of particular importance, genotype‐specific therapeutic approaches are being developed. Results from a randomized controlled trial for flecainide use in ARVC patients are currently pending. Research in a plakophilin‐2‐deficient mouse model suggests this antiarrhythmic drug may be particularly useful for patients with likely pathogenic or pathogenic (LP/P) PKP2 variants. Additionally, the first gene therapy clinical trials in ARVC patients harboring LP/P PKP2 variants are currently underway. This review aims to provide clinicians caring for ACM patients with an up‐to‐date overview of the current literature in genotype‐specific natural history of disease and management of ACM patients and describe scientific advances that have led to upcoming clinical trials. [ABSTRACT FROM AUTHOR]

The validity of sorting as rapid method for sensory characterization of food has been demonstrated, however, research on its effectiveness to profile complex products, especially when using trained assessors, is limited. In this study, directed sorting based on aroma (sortingAROMA), palate (sortingPALATE) and both aroma and palate attributes (sortingGLOBAL) were conducted by trained assessors to categorize honeybush tea prepared from five Cyclopia species. Descriptive sensory analysis provided a detailed sensory profile of the same samples for comparison. SortingAROMA and sortingPALATE resulted in similar sample configurations. SortingGLOBAL was less effective at grouping samples per species. Despite the use of trained assessors, three replicate sessions were needed to ensure consistent results, particularly for sortingAROMA. Both DISTATIS, combined with Barycentric Text Projection (BTP), and Correspondence Analysis (CA) produced similar correspondences between attributes and sample groupings. The bootstrap ratios of DISTATIS‐BTP confirmed significant sample‐attribute associations, thereby providing additional information. [ABSTRACT FROM AUTHOR]

Dexamethasone is a synthetic glucocorticoid approved for treating disorders of various organ systems in both adult and pediatric populations. Currently, approved pediatric dosing recommendations are weight‐based, but it is unknown whether differences in dexamethasone drug disposition and exposure exist for children with obesity. This study aimed to develop a population pharmacokinetic (PopPK) model for dexamethasone with data collected from children with obesity. Dexamethasone was given as either IV or oral/enteral administration, and a salt factor correction was used for dexamethasone sodium phosphate injection. A PopPK analysis using dexamethasone plasma concentration versus time was performed using the software NONMEM. A virtual population of 1000 children with obesity across three age groups was generated for dosing simulations. Data from 59 study participants with 82 PK plasma samples were used in the PopPK analysis. A one‐compartment model with first‐order absorption and the inclusion of total body weight as a covariate characterized the data. No other covariates were included in the PopPK model. Single and multiple IV dose(s) of 0.5 and 1 mg/kg every 8 h resulted in 68% or more of virtual children with obesity attaining simulated exposures that were within exposure ranges previously reported in adult studies. In conclusion, this was the first study to characterize dexamethasone's PopPK in children with obesity. Simulation results suggest that virtual children with obesity receiving oral doses of 0.5 and 1 mg/kg had generally comparable dexamethasone exposures as adult estimates. Additional studies are needed to characterize the dexamethasone's target exposure in children. [ABSTRACT FROM AUTHOR]

An 8‐year‐old male cross‐Labrador retriever was presented for a progressive appearance of folds all over the body of the dog. Scleromyxoedema was diagnosed based on clinical signs and histopathological features. Clinical signs were characterised by a papular and vesicular eruption and severe skin thickening causing exuberant folds along with concurrent severe osteoarthritis of the coxofemoral joints. Thyroid disorders were excluded and the condition was not associated with monoclonal gammopathy. Histopathological features consisted of mucin deposition, fibroblast proliferation and fibrosis. Prednisolone was prescribed to decrease mucin synthesis which allowed a marked clinical improvement. Due to the progressive inability to walk, the dog was euthanased 6 months after the first consultation. [ABSTRACT FROM AUTHOR]

An 11‐month‐old female, neutered domestic short‐haired cat was presented for non‐pruritic alopecia of the dorso‐lumbar area which had appeared 1 month after a road accident. After the trauma, a fracture of the left hind limb was demonstrated without dermatological lesions on the dorso‐lumbar area. One month later, hair loss was observed in this area. Four months later, clinical examination revealed dorso‐lumbar alopecia. Histopathological findings included an absence of all adnexae, a mild fibroplasia and fibrosis without oriented collagen deposition, individual to coalescing pyogranulomas at the dermo‐hypodermal junction and a moderately stenotic hypodermal artery. Clinical history, physical examination and histopathological findings were compatible with post‐traumatic dorso‐lumbar alopecia. Special features of this case include the location of the fracture and the more developed histopathological lesions with pyogranulomas at the dermo‐hypodermal junction, the absence of hair follicles and a stenosing arteriopathy. [ABSTRACT FROM AUTHOR]

The article discusses the classification of borderline melanocytic lesions by dermatopathologists and artificial intelligence in an Australian cohort study. The study highlights the potential of AI in dermatology for diagnosing melanocytic lesions accurately. However, it also emphasizes the need for pathologist consensus in training data to reduce misdiagnosis risks. The study's findings suggest that AI models may struggle with challenging lesions, indicating the importance of balancing AI's role in reducing unnecessary biopsies without compromising sensitivity. [Extracted from the article]

Among 50 environments in the United States, we screened 35 hairy vetch (Vicia villosa Roth.) lines for traits of interest to cover cropping. We analyzed the influence of genotype, environment, and the genotype‐by‐environment interaction (G × E) on biomass, vigor, winter survival, emergence, flowering time, and nitrogen fixation. To explore how environments and G × E impacted each trait, we associated environment predictions and G × E loadings with weather and soil parameters. Environment had the largest influence on all traits, representing more than half of the variance. Environment predictions were significantly associated with weather and/or soil parameters for each trait. Biomass was associated with growing degree days, winter survival with freezing degree days without snow cover, growth stage with shortwave radiation, and emergence with soil texture. The G × E interaction was larger than genotypic variance for all traits except for winter survival and flowering time. The G × E interaction loadings were associated with soil sand content for biomass, air temperature for fall vigor and emergence, and snow cover for winter survival. Although it represented the smallest proportion of total variance, genetic effects were significant for all traits except for emergence, Ndfa, %N, and C:N. New hairy vetch breeding lines were superior to all commercially available lines for biomass and winter survival. Biomass harvest timing did not significantly change line rank, indicating that top‐performing lines can be used in diverse management systems. To select for high nitrogen contribution to subsequent crops, breeding programs can indirectly select for biomass rather than expensively evaluating symbiotic nitrogen fixation. Core Ideas: New hairy vetch varieties have higher biomass and winter survival than check cultivars.Genotype‐by‐environment interactions were larger than genetic effects for biomass, vigor, and emergence.Weather and soil parameters that were associated with G × E could be used to optimize selection.There are few tradeoffs in selecting multiple cover crop traits in hairy vetch.Across our sites, aboveground biomass accurately predicted total fixed nitrogen (N). [ABSTRACT FROM AUTHOR]

Objectives: Patients' interactions with health care providers influence back pain–related outcomes. The Health Care Providers' Pain and Impairment Relationship Scale (HC‐PAIRS) is an instrument that assesses providers' attitudes and beliefs about patients with persistent back pain, with lower scores implying that persistent pain does not indicate disability or limitation of activities. This scoping review aims to explore the extent of research involving the HC‐PAIRS. Literature Survey: PubMed, Embase, and PEDro databases were searched from inception to April 2022. Methods: Extracted HC‐PAIRS scores were standardized to 15‐item scores and categorized by profession, student or professional status, and pre/post‐educational intervention to evaluate scores. Psychometric properties and educational interventions of the HC‐PAIRS were described. Results: After screening, 51 studies representing 10,416 participants were included. Student and professional scores were investigated in 24 and 29 studies, respectively. Twenty‐one studies included educational interventions, with heterogenous follow‐up. Psychometric properties of the HC‐PAIRS were assessed in 10 studies and demonstrated acceptable reliability and validity. The overall baseline mean score among all participants was 55.34 (95% CI: 53.54–57.14) (students: 56.54 [56.54–60.87]; professionals: 51.67 [49.08–54.27]). Nurses (61.99 [55.66–68.31]) and non–health care professionals (65.30 [57.33–73.28]) had the highest overall baseline mean scores, whereas chiropractors (51.69 [33.73–69.66]), MDs/PAs (52.64 [47.27–58.00]), physical therapists (53.42 [50.67–56.17]), and exercise professionals (57.36 [49.39–65.33]) had lower scores. Conclusions: The HC‐PAIRS has been used across many disciplines in both students and professionals and demonstrated acceptable reliability and validity. Professionals commonly treating back pain had lower HC‐PAIRS scores. Future research could benefit from standardization of interventions and timing of follow‐up assessments. [ABSTRACT FROM AUTHOR]

Long‐term agricultural field experiments (LTFEs) have been conducted for nearly 150 years. Yet lack of coordination means that synthesis across such experiments remains rare, constituting a missed opportunity for deriving general principles of agroecosystem structure and function. Here, we introduce the Diverse Rotations Improve Valuable Ecosystem Services (DRIVES) project, which uses legacy data from North American LTFEs to address research questions about the multifunctionality of agriculture. The DRIVES Project is a network of researchers who have compiled a database of primary (i.e., observations) and secondary (i.e., transformed observations or modeling results) data from participating sites. It comprises 21 LTFEs that evaluate how crop rotational diversity impacts cropping system performance. The Network consists of United States Department of Agriculture, university, and International Maize and Wheat Improvement Center scientists (20 people) who manage and collect primary data from LTFEs and a core team (nine people) who organize the network, curate network data, and synthesize cross‐network findings. As of 2024, the DRIVES Project database contains 495 site‐years of crop yields, daily weather, soil analysis, and management information. The DRIVES database is findable, accessible, interoperable, and reusable, which allows integration with other public datasets. Initial research has focused on how rotational diversity impacts resilience in the face of adverse weather, nutritional quality, and economic feasibility. Our collaborative approach in handling LTFE data has established a model for data organization that facilitates broader synthesis studies. We openly invite other sites to join the DRIVES network and share their data. Core Ideas: Long‐term agricultural field experiments are critical for understanding the multifunctionality of agroecosystems.The DRIVES (Diverse Rotations Improve Valuable Ecosystem Services) network synthesizes data across long‐term experiments to understand the role of crop rotation diversity.The DRIVES Network has constructed a publicly available database containing daily weather and crop yield observations. [ABSTRACT FROM AUTHOR]

Background: This Intensive Care Medicine Rapid Practice Guideline (ICM‐RPG) provides an evidence‐based recommendation to address the question: in adult patients in intensive care units (ICUs), should we use small‐volume or conventional blood collection tubes? Methods: We included 23 panelists in 8 countries and assessed and managed financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. We conducted a systematic review, including evidence from observational and randomized studies. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, we evaluated the certainty of evidence and developed recommendations using the Evidence‐to‐Decision framework. Results: We identified 8 studies (1 cluster and 2 patient‐level randomized trials; 5 observational studies) comparing small‐volume to conventional tubes. We had high certainty evidence that small‐volume tubes reduce daily and cumulative blood sampling volume; and moderate certainty evidence that they reduce the risk of transfusion and mean number of red blood cell units transfused, but these estimates were limited by imprecision. We had high certainty that small‐volume tubes have a similar rate of specimens with insufficient quantity. The panel considered that the desirable effects of small‐volume tubes outweigh the undesirable effects, are less wasteful of resources, and are feasible, as demonstrated by successful implementation across multiple countries, although there are upfront implementation costs to validate small‐volume tubes on laboratory instrumentation. Conclusion: This ICM‐RPG panel made a strong recommendation for the use of small‐volume sample collection tubes in adult ICUs based on overall moderate certainty evidence. [ABSTRACT FROM AUTHOR]

Toxicokinetic–toxicodynamic (TKTD) modeling has received increasing attention in terms of the regulatory environmental risk assessment of chemicals. This type of mechanistic model can integrate all available data from individual‐level bioassays into a single framework and enable refined risk assessments by extrapolating from laboratory results to time‐variable exposure scenarios, based, for instance, on surface water exposure modeling (e.g., FOCUS). Dynamic energy budget (DEB) models coupled with TKTD modules (DEB–TKTD) constitute the leading approach to assess and predict sublethal effects of chemicals on individual organisms. However, thorough case studies are rare. We provide a state‐of‐the‐art example with the standard aquatic test species Ceriodaphnia dubia and the fungicide azoxystrobin, including all steps, from bespoke laboratory toxicity tests to model calibration and validation, through to environmental risk assessment. Following the framework proposed in the European Food Safety Authority Scientific Opinion from 2018, we designed bespoke good laboratory practice–compliant laboratory toxicity studies based on test guideline 211 of the Organisation for Economic Co‐operation and Development and then identified robust parameter values from those data for all relevant model parameters through model calibration. The DEB–TKTD model, DEBtox2019, then informed the design of the validation experiment. Once validated, the model was used to perform predictions for a time‐variable exposure scenario generated by FOCUS. A moving time‐window approach was used to perform the environmental risk assessment. This assessment method reduces uncertainty in the risk assessment while maintaining consistency with the traditional measures of risk. Environ Toxicol Chem 2024;43:2409–2421. © 2024 Syngenta Crop Protection AG. ibacon GmbH and The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Aim: Bi‐directional associations between loneliness and psychotic experiences (PEs) have been reported, but the mechanisms underlying these associations are unknown. This study aims to explore associations between daily reports of loneliness and PEs, and test differences in this association across young adult individuals at different levels of risk for psychosis. Methods: We analysed 90‐day diary data on loneliness and PEs from N = 96 participants (mean age 24.7, range 18–35, 77% female) divided into 4 subgroups, each indexing increased levels of risk for psychosis according to the clinical staging model: 'psychometric' (n = 25), 'low' (n = 27), 'mild' (n = 24), and 'ultra‐high'(n = 20) risk. Multilevel vector autoregressive models examined within‐day (contemporaneous) and between‐day (temporal) associations between loneliness and PEs for the total sample. Next, these associations were compared across subgroups. Results: Loneliness and PEs were significantly associated contemporaneously (partial correlation B = 0.14) but not temporally. Subgroup membership moderated both contemporaneous and temporal associations. The contemporaneous association between loneliness and PEs was stronger in the low‐risk subgroup compared to the mild‐risk (B = −0.35, p <.01) and ultra‐high‐risk (B = −0.36, p <.01) subgroups. The temporal association between loneliness on the previous day and PEs on the current day was stronger in mild‐risk subgroup compared to the ultra‐high‐risk subgroup (B = −0.03, p =.03). After adjusting for multiple testing, only the contemporaneous—but not the temporal—associations remained statistically significant. Conclusions: Loneliness is associated with PEs in individuals at risk for psychosis, particularly in those with low to mild symptoms. Our findings tentatively suggest that especially individuals with low expressions of PEs may be more sensitive to social context, but future studies are needed to replicate and further unravel the potentially stage‐specific interplay between social context and PEs. [ABSTRACT FROM AUTHOR]

The article focuses on the potential impact of emerging technologies like artificial intelligence, virtual reality, and the metaverse on cardiovascular imaging. Topics include the role of artificial intelligence in enhancing diagnostic accuracy and workflow, the limited practical applications of virtual reality in clinical practice, and the challenges facing the metaverse in transforming patient care and clinician collaboration.

Background: Because of controversial results from clinical studies comparing different dental local anesthesia methods in children, the primary objective of this randomized, split‐mouth, crossover, controlled trial was to compare pain intensity during local anaesthesia (LA) performed with a computer‐controlled LA delivery system (C‐CLADS) versus a conventional syringe (CONV). Secondary objectives included comparisons during dental treatment. Methods: Participants (4–8 years) with tooth pair requiring similar treatment were recruited from five French hospitals. The right primary molar, which was treated at the first visit, was randomly allocated to one of the anaesthesia groups (either intraosseous with C‐CLADS or infiltration with CONV), whereas the contralateral molar (treated at the second visit) was assigned to the other group. Pain intensity and behaviour outcomes, assessed with the Faces Pain and Venham revised scales, respectively, were compared between groups using Proc mixed. Stratified analyses were performed on dentition and location. Results: Among 107 participants, the analysis revealed reduced pain perception during LA in the C‐CLADS group compared with the CONV group (−0.72, 95% CI: −1.43, −0.006), but not during dental treatment. Stratified analyses showed that this effect was observed only in primary dentition (p =.006) and mandibular molars (p =.005). Behavioural issues were fewer in the C‐CLADS group than in the CONV group (p =.05) only during injection. Conclusion: C‐CLADS emerged as the preferable system in primary dentition. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) Infection remains a public health problem and a threat to blood transfusion safety. The aim of this study was to summarise the scientific literature on the seroprevalence of HBV and occult HBV among blood donors in Africa. Searches were carried out in PubMed, Science Direct, Global Index Medicus and African Journals Online from 2012 to 2022. Dersimonian and Laird's random‐effects model‐based method was used for statistical analyses to estimate pooled seroprevalence at a 95% confidence interval (CI) using STATA version 14 software. Heterogeneity was assessed on the basis of Cochran's Q test and quantified by the I2 index. The methodological quality of the articles was assessed using the Joanna Brigg Institute's critical appraisal checklist. Among 90 articles included, 86 reported data in serological test that a pooled HBV seroprevalence of 5.53% (95% CI: 4.56–6.58; I2 = 99.94%) and 14 provided occult hepatitis B data. A high prevalence of 9.69% (95% CI: 8.42–11.03) was observed in the West African region. Lowest prevalence was 1.22% (95% CI: 0.74–1.83) in South Africa region. Prevalence in Africa among men was: 5.18% (95% CI: 3.97–6.54) and in women: 3.50% (95% CI: 2.45–4.71) (I2 = 99.76% and p < 0.01). While the overall pooled prevalence of occult hepatitis B was 3.18% (95% CI: 1.29–5.81). HBV seroprevalence is high in low‐resource areas of Africa, and the data generated by this situation calls for constant epidemiological surveillance. Emphasis must be placed on building blood donor loyalty and integrating molecular testing into the biological qualification of blood donations. [ABSTRACT FROM AUTHOR]

Optical antenna resonators enable control of light‐matter interactions on the nano‐scale via electron–photon hybrid states in strong coupling. Specifically, mid‐infrared (MIR) nano‐antennas coupled to saturable intersubband transitions in multi‐quantum‐well (MQW) semiconductor heterostructures allow for the coupling strength to be tuned through antenna resonance and field intensity. Here, tip‐enhanced nano‐scale variation of antenna‐MQW coupling across the antenna is demonstrated, with a spatially‐dependent coupling strength gaq$g_{\rm aq}$ varying from 73 (strong coupling) to 24 cm−1$\rm {cm}^{-1}$ (weak coupling). This behavior is modeled based on the spatially dependent local constructive and destructive interference between tip and antenna fields. Using a quantum‐mechanical density‐matrix model of the MQW system with its designed values of transition dipole moment, doping density, and population decay time, the picosecond IR pulse coupling to intersubband transitions and the associated tip induced strong‐field saturation effects are described. These results present a new regime of nonlinear IR light‐matter control based on the dynamic manipulation of quantum hybrid states on the nanoscale and in the infrared, with a perspective regarding extension to molecular vibrations. [ABSTRACT FROM AUTHOR]

The binuclear paddle‐wheel copper(II) complex tetrakis(μ‐3,4‐diethoxybenzoato‐κ2O:O′)bis[(ethanol‐κO)copper(II)], [Cu2(C11H13O4)4(C2H6O)2], has been synthesized and characterized. In each molecule, two CuII centres are bridged in a syn–syn fashion by four equatorial 3,4‐diethoxybenzoate ligands, the two axial positions being occupied by ethanol molecules. The thermal stability has been studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. The magnetic behaviour, studied by SQUID magnetometry, shows a CuII–CuII antiferromagnetic exchange interaction with 2J = −288 cm−1, a value that fits with a magnetic structure correlation established for compounds of this kind. [ABSTRACT FROM AUTHOR]

Tracking of animal migrations using telemetry technologies needs to take into consideration the burden that the tag exerts on the animal. Here, we examined the potential impacts of acoustic tags of two sizes (nominally a 'V6' [smaller] and 'V7' [larger]) on the downstream riverine migration success and behaviour of wild Atlantic salmon (Salmo salar L.) smolts. One hundred fish were tagged with either a V6 or V7 tag. Tag burden (tag: fish weight) ranged from 1.88% to 7.39% and differed significantly between fish tagged with the V6 (mean [SD] = 3.63% [0.51%]) and the V7 tags (mean [SD] = 5.84% [0.95%]). There was no significant difference in the in‐river migration failure between the two groups when tested with a time‐to‐event analysis. There were also no differences in other elements of the migratory behaviour (rate of movement, time of detection and residency time) between the two tagging groups. These data support the use of acoustic tracking for monitoring smolt migration and highlight that tagging of smaller smolts at up to 7.39% tag burden to gain a more representative understanding of migration success and behaviours across a smolt population. [ABSTRACT FROM AUTHOR]

Background: Trio exome sequencing can be used to investigate congenital abnormalities identified on pregnancy ultrasound, but its use in an Australian context has not been assessed. Aims: Assess clinical outcomes and changes in management after expedited genomic testing in the prenatal period to guide the development of a model for widespread implementation. Materials and methods: Forty‐three prospective referrals for whole exome sequencing, including 40 trios (parents and pregnancy), two singletons and one duo were assessed in a tertiary hospital setting with access to a state‐wide pathology laboratory. Diagnostic yield, turn‐around time (TAT), gestational age at reporting, pregnancy outcome, change in management and future pregnancy status were assessed for each family. Results: A clinically significant genomic diagnosis was made in 15/43 pregnancies (35%), with an average TAT of 12 days. Gestational age at time of report ranged from 16 + 5 to 31 + 6 weeks (median 21 + 3 weeks). Molecular diagnoses included neuromuscular and skeletal disorders, RASopathies and a range of other rare Mendelian disorders. The majority of families actively used the results in pregnancy decision making as well as in management of future pregnancies. Conclusions: Rapid second trimester prenatal genomic testing can be successfully delivered to investigate structural abnormalities in pregnancy, providing crucial guidance for current and future pregnancy management. The time‐sensitive nature of this testing requires close laboratory and clinical collaboration to ensure appropriate referral and result communication. We found the establishment of a prenatal coordinator role and dedicated reporting team to be important facilitators. We propose this as a model for genomic testing in other prenatal services. [ABSTRACT FROM AUTHOR]

Post‐release monitoring is critical for assessing translocation outcomes. Yet the quality of information gained from monitoring can vary greatly, and perceived monitoring costs often results in reduced monitoring effort. Selecting cost‐effective monitoring strategies that provide high quality data are therefore important for assessing translocation outcomes and making informed management decisions.To compare how monitoring strategy affects information gained, we monitored a toutouwai/North Island robin (Petroica longipes) reintroduction in Aotearoa New Zealand, based on monitoring objectives of determining survival, site fidelity and whether the extent of management was large enough to protect dispersing individuals. We compared how these objectives were met through four monitoring strategies: (1) comprehensive surveys with ground radio telemetry and playback; (2) aerial drone telemetry; (3) dedicated playback by trained surveyors and (4) opportunistic playback by predator control contractors. We undertook a viewshed analysis to determine search coverage of each strategy and compared detection rates, efficiency and cost.Comprehensive ground telemetry and playback, while costly, covered the largest area and provided the most accurate data on dispersal, survival and the translocation outcome. In comparison, opportunistic playback monitoring detected substantially fewer individuals, giving a false impression of low site fidelity and survival and a failed translocation. Although drone telemetry had considerable site‐specific limitations, which limited its effectiveness during our study, it was the most cost‐effective with a high detection rate and low search effort.Synthesis and applications: Our study shows the value of intensive monitoring in facilitating management decisions for wildlife translocations. Comprehensive telemetry and playback, while costly, were invaluable for gaining high quality information on the translocation outcome. Without suitable monitoring, reintroduction outcomes can be difficult to assess and potentially result in unnecessary, ineffective or overly expensive management actions. We recommend that monitoring intensity and methodology should reflect the site, species and level of uncertainty regarding the translocation outcome. Prioritising monitoring can help reduce long‐term costs, increase quality of information gained and allow for more informed management decisions that can improve subsequent translocation outcomes. [ABSTRACT FROM AUTHOR]

Background: The α‐Gal syndrome (AGS) is characterized by the presence of specific IgE‐antibodies to the carbohydrate galactose‐α‐1,3‐galactose (α‐Gal). Sensitization to α‐Gal has been associated with tick bites and individuals exposed to ticks have an elevated risk of sensitization. The aim of this study was to analyze IgG and IgE antibody responses to α‐Gal in a high‐risk cohort of forestry employees (FE) in Luxembourg. Methods: Questionnaires and serum samples of FE from Luxembourg (n = 219) were retrospectively analyzed. α‐Gal specific IgE was quantified by ImmunoCAP, α‐Gal specific IgG and subclasses IgG1–4 were determined by ELISA. Additionally, sera from population‐based controls (n = 150) and two groups of food‐allergic patients, patients with AGS (n = 45) and fish‐allergic patients (n = 22) were assessed for IgG antibody responses to α‐Gal and cod extract. Results: Twenty‐one percent of FE was sensitized to α‐Gal (sIgE ≥ 0.1 kUA/L). Both sensitized and non‐sensitized FE exhibited high levels of α‐Gal specific IgG, IgG1 and IgG3 compared with controls, indicating a stimulation of IgG responses by recurrent tick bites, independent of the sensitization status. AGS patients had the highest levels of IgG1 and IgG2 antibodies, whereas the profile of fish‐allergic patients was similar to the profile of the controls for which anti‐α‐Gal responses were dominated by IgG2 antibodies. α‐Gal sIgG4 levels were either very low or undetectable in all groups. Conclusion: Our study provides evidence for a continuous stimulation of α‐Gal related immune responses by repeated tick bites, translating into highly elevated levels of IgG1 antibodies directed against α‐Gal. [ABSTRACT FROM AUTHOR]

Hydrazone‐type Schiff bases have been widely explored owing to their therapeutic properties. These compounds are known to have antibacterial, antifungal, anticancer, and antioxidant properties, among others. In the present study, six hydrazone‐based Schiff bases (BB1–BB6) were synthesized by the reaction between derivatives of benzaldehyde and benzo hydrazide in methanolic medium in the presence of catalytic amount of formic acid. The synthesized compounds were characterized using various spectroscopic techniques such as NMR (1H, 13C, COSY, DEPT, HSQC, HMBC, and NOESY), FTIR, UV‐Vis, elemental (CHN) analysis, and high‐resolution mass spectroscopy. In addition, single crystal structures of BB2, BB4, and BB6 were obtained. In vitro antidiabetic and antioxidant potential of the compounds was evaluated on glucosidase, amylase, NO, FRAP, and DPPH assays, respectively. In all the assays, compounds BB6, BB4, and BB2 showed higher activity than the others. To further explore the chemical reactivity properties and their mechanism of action against the tested assays, DFT and molecular docking study were performed, and the results obtained reinforce the experimental study data. [ABSTRACT FROM AUTHOR]

Aims: The 2021 European Society of Cardiology (ESC) screening recommendations for individuals carrying a pathogenic transthyretin amyloidosis variant (ATTRv) are based on expert opinion. We aimed to (i) determine the penetrance of ATTRv cardiomyopathy (ATTRv‐CM) at baseline; (ii) examine the value of serial evaluation; and (iii) establish the yield of first‐line diagnostic tests (i.e. electrocardiogram, echocardiogram, and laboratory tests) as per 2021 ESC position statement. Methods and results: We included 159 relatives (median age 55.6 [43.2–65.9] years, 52% male) at risk for ATTRv‐CM from 10 centres. The primary endpoint, ATTRv‐CM diagnosis, was defined as the presence of (i) cardiac tracer uptake in bone scintigraphy; or (ii) transthyretin‐positive cardiac biopsy. The secondary endpoint was a composite of heart failure (New York Heart Association class ≥II) and pacemaker‐requiring conduction disorders. At baseline, 40/159 (25%) relatives were diagnosed with ATTRv‐CM. Of those, 20 (50%) met the secondary endpoint. Indication to screen (≤10 years prior to predicted disease onset and absence of extracardiac amyloidosis) had an excellent negative predictive value (97%). Other pre‐screening predictors for ATTRv‐CM were infrequently identified variants and male sex. Importantly, 13% of relatives with ATTRv‐CM did not show any signs of cardiac involvement on first‐line diagnostic tests. The yield of serial evaluation (n = 41 relatives; follow‐up 3.1 [2.2–5.2] years) at 3‐year interval was 9.4%. Conclusions: Screening according to the 2021 ESC position statement performs well in daily clinical practice. Clinicians should adhere to repeating bone scintigraphy after 3 years, as progressing to ATTRv‐CM without signs of ATTRv‐CM on first‐line diagnostic tests or symptoms is common. [ABSTRACT FROM AUTHOR]

Objective: Rare cases of monogenic obesity, which may respond to specific therapeutics, can remain undetected in populations in which polygenic obesity is prevalent. This study examined rare DNA variation in established monogenic obesity genes within a community using whole‐exome sequence data from 6803 longitudinally studied individuals. Methods: Exome data across 15 monogenic obesity genes were analyzed for nonsynonymous variants observed in any child with a maximum BMI z score > 2 (N = 279) but not observed in a child with a maximum BMI z score ≤ 0 (n = 1542) or that occurred in adults in the top 5th percentile of BMI (n = 263) but not in adults below the median BMI (n = 2629). Variants were then functionally analyzed using luciferase assays. Results: The comparisons between cases of obesity and controls identified eight missense variants in six genes: DYRK1B, KSR2, MC4R, NTRK2, PCSK1, and SIM1. Among these, MC4R p.A303P and p.R165G were previously shown to impair MC4R function. Functional analyses of the remaining six variants suggest that KSR2 p.I402F and p.T193I and NTRK2 p.S249Y alter protein function. Conclusions: In addition to MC4R, rare missense variants in KSR2 and NTRK2 may potentially explain the severe obesity observed for the carriers. [ABSTRACT FROM AUTHOR]

In tropical forests, trees strategically balance growth patterns to optimise fitness amid multiple environmental stressors. Wind poses the primary risk to a tree's mechanical stability, prompting developments such as thicker trunks to withstand the bending forces. Therefore, a trade‐off in resource allocation exists between diameter growth and vertical growth to compete for light. We explore this trade‐off by measuring the relative wind mortality risk for 95 trees in a tropical forest in Panama and testing how it varies with tree size, species and wind exposure. Surprisingly, local wind exposure and tree size had minimal impact on wind mortality risk; instead, species wood density emerged as the crucial factor. Low wood density species exhibited a significantly greater wind mortality risk, suggesting a prioritisation of competition for light over biomechanical stability. Our study highlights the pivotal role of wind safety in shaping the life‐history strategy of trees and structuring diverse tropical forests. [ABSTRACT FROM AUTHOR]

The autosomal dominant Okur–Chung neurodevelopmental syndrome (OCNDS: OMIM #617062) is a rare neurodevelopmental disorder first described in 2016. Features include developmental delay (DD), intellectual disability (ID), behavioral problems, hypotonia, language deficits, congenital heart abnormalities, and non‐specific dysmorphic facial features. OCNDS is caused by heterozygous pathogenic variants in CSNK2A1 (OMIM *115440; NM_177559.3). To date, 160 patients have been diagnosed worldwide. The number will likely increase due to the growing use of exome sequencing (ES) and genome sequencing (GS). Here, we describe a novel OCNDS patient carrying a CSNK2A1 variant (NM_177559.3:c.140G>A; NP_808227.1:p.Arg47Gln). Phenotypically, he presented with DD, ID, generalized hypotonia, speech delay, short stature, microcephaly, and dysmorphic features such as low‐set ears, hypertelorism, thin upper lip, and a round face. The patient showed several signs not yet described that may extend the phenotypic spectrum of OCNDS. These include prenatal bilateral clubfeet, exotropia, and peg lateral incisors. However, unlike the majority of descriptions, he did not present sleep disturbance, seizures or gait difficulties. A literature review shows phenotypic heterogeneity for OCNDS, whether these patients have the same variant or not. This case report is an opportunity to refine the phenotype of this syndrome and raise the question of the genotype–phenotype correlation. [ABSTRACT FROM AUTHOR]

Background: Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear. Objective: Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear. To assess changes in the circulating metabolome produced by ocrelizumab treatment in people with relapsing–remitting MS (RRMS). Methods: Thirty‐one individuals with RRMS eligible for beginning treatment with ocrelizumab were recruited and followed with demographic, clinical, quality‐of‐life, and global metabolomics data collected at each visit. Modules of highly correlated metabolites were identified using the weighted correlation network analysis approach. Changes in each module's eigenmetabolite values and individual metabolites during the study were evaluated using linear mixed‐effects models. Results: Patients with a mean age of 40.8 (SD = 10.30) years, and median disease duration of 4.0 (IQR = 8.5) years, were monitored for a median of 3.36 (IQR = 1.43) years. Two out of twelve identified sets of metabolites were altered significantly. The first module mainly contained androgenic and pregnenolone steroids (p‐value <0.001, coefficient: −0.10). The second module primarily consisted of several lysophospholipids, arachidonic acid, some endocannabinoids, and monohydroxy fatty acid metabolites (p‐value = 0.016, coefficient: −0.12), which its reduction was significantly associated with improvement based on overall disability response score (OR 3.09e‐01, 95% CI: 6.83e‐02, 9.09e‐01, p‐value = 3.15E‐02). Interpretation: In this longitudinal observational study, using a global untargeted metabolomics approach, we showed significant alteration in circulating metabolome in RRMS patients undergoing ocrelizumab treatment. In particular, we observed a significant reduction in metabolites involved in the lysophospholipid pathway, which was associated with patients' improvement. [ABSTRACT FROM AUTHOR]

Recent research has unveiled the pervasiveness with which Indigenous patients are subjected to racialized stereotypes within the Canadian health system. Because discrimination in health care is associated with poor health outcomes and undertreated illness, there is a need to better understand how racism is perpetuated systemically in order to rectify the policies, practices, and attitudes that enable it. This article outlines a moral economy of care in emergency departments in western Canada by exploring the discourses that medical professionals employ when discussing cases of medical racism. While these discourses respond to the everyday realities of working in hospitals, they are also rooted in the colonial genealogy of health care in Canada and perpetuated by neoliberal shifts in health care services. By exploring the moral economy of care, this article sheds light on the way pervasive discourses contribute to reproducing and circulating Indigenous‐specific racism and its role in decision‐making. [ABSTRACT FROM AUTHOR]

As an emerging topic in human resource management (HRM) research, organizational citizenship behavior for the environment (OCBE) and workgroup green advocacy (WGGA) have been studied as a proxy of the environmental performance of organizations as well as a potential way for companies to assess the impact of their environmental strategies and initiatives. Viewing OCBE and WGGA as green‐focused knowledge, skills, abilities, and other characteristics and building on leader‐member exchange theory, we examined the effects of leaders' OCBE and WGGA, person‐supervisor fit (PSF), and person‐group fit (PGF) as well as their potential interactions on members' OCBE and WGGA. To minimize the potential impact of different company strategies, the study was conducted in one MNC using a sample of 269 members from 64 teams. The results revealed that PSF and especially PGF were associated with members' OCBE and WGGA, but leaders' OCBE was a stronger predictor of members' OCBE and WGGA than leaders' WGGA. Contrary to our prediction, no moderating effect of PSF or PGF was found for the associations between leaders' and members' WGGA and OCBE. Together, these findings shed light on the differential trickle‐down effects of leaders' perceptions and behaviors in the context of environmental management. As for the implications for HRM practitioners, our findings suggest companies may focus on leaders' OCBE and WGGA as well as on PSF and PGF independently as the means to shaping team members' OCBE and WGGA to support environmental strategies. [ABSTRACT FROM AUTHOR]

The Mediterranean region is experiencing pronounced aridification and in certain areas higher occurrence of intense precipitation. In this work, we analyze the evolution of the precipitation probability distribution in terms of precipitating days (or "wet‐days") and all‐days quantile trends, in Europe and the Mediterranean, using the ERA5 reanalysis. Looking at the form of wet‐days quantile trends curves, we identify four regimes. Two are predominant: in most of northern Europe the precipitation quantiles all intensify, while in the Mediterranean the low‐medium quantiles are mostly decreasing as extremes intensify or decrease. The wet‐days distribution is then modeled by a Weibull law with two parameters, whose changes capture the four regimes. Assessing the significance of the parameters' changes over 1950–2020 shows that a signal on wet‐days distribution has already emerged in northern Europe (where the distribution shifts to more intense precipitation), but not yet in the Mediterranean, where the natural variability is stronger. We extend the results by describing the all‐days distribution change as the wet‐days' change plus a contribution from the dry‐days frequency change, and study their relative contribution. In northern Europe, the wet‐days distribution change is the dominant driver, and the contribution of dry‐days frequency change can be neglected for wet‐days percentiles above about 50%. In the Mediterranean, however, the change of precipitation distribution comes from the significant increase of dry‐days frequency instead of an intensity change during wet‐days. Therefore, in the Mediterranean the increase of dry‐days frequency is crucial for all‐days trends, even for heavy precipitation. Plain Language Summary: The Mediterranean region is facing increased dryness alongside more intense rainfall in certain areas. We delved into the change of precipitation frequency and intensity across Europe and the Mediterranean using ERA5 reanalysis data from 1950 to 2020. Our analysis revealed four distinct patterns in how rainfall is evolving. In much of northern Europe, heavy rainfall events are becoming more frequent, while in the Mediterranean, lighter precipitation is decreasing while heavy rain is either increasing or decreasing. To understand these changes better, we used a mathematical model with two parameters. This model helped us track the types of changes in precipitation patterns. We found that in northern Europe, the increase in rainfall intensity is the primary driver of change, while in the Mediterranean, it's more about the increase of the dry‐days frequency. These findings underscore the importance of considering both the frequency and intensity of precipitation when studying climate change impacts. By understanding these shifts, we can better prepare for future weather extremes in these regions and adapt to the changing climate. Key Points: Four regimes of change for daily precipitation distribution are identified, and are captured by a two parameters analytical modelIn northern Europe, a signal of increasing mean and extreme precipitation has emergedIn the Mediterranean, the changes of precipitation appears dominated by changes in dry‐days frequency [ABSTRACT FROM AUTHOR]

Background. Postpartum haemorrhage is the leading cause of preventable maternal mortality worldwide. Early identification and prompt management of postpartum haemorrhage improve outcomes. Objective assessment of postpartum blood loss is an important step in identifying postpartum haemorrhage. The Brass‐V drape and MaternaWell tray have been designed for routine measurement of postpartum blood loss. The perceived utility and acceptability of these devices to the parturients and birth attendants still begged exploring. Objective. To assess the perceived usefulness and ease of use of a Brass‐V drape versus a MaternaWell tray for the collection of postpartum blood loss. Methods. We conducted a prospective parallel randomised trial, employing a questionnaire to assess the experiences of birth attendants and birthing women who used these devices. The study was conducted at site B midwife obstetric unit in Khayelitsha Cape Town. Pregnant women presenting in early labour were approached for voluntary participation. After informed consent was obtained, participants were randomly assigned to the Brass‐V drape or the MaternaWell tray, which the birth attendant placed after the birth of the baby. Results. There were 63 participants, of which 33 were assigned to the MaternaWell tray and 30 to the Brass‐V drape. Birth attendants indicated a desire to use the MaternaWell tray (30 (90%)) or Brass‐V drape (26 (87%)) in future deliveries. The parturients were also in favour of the future use of MaternaWell tray (33 (100%)) and Brass‐V drape (28 (93%)). Ease of measurement favoured the Brass V‐drape, and ease of placement favoured the MaternaWell tray. Five (8%) participants experienced postpartum haemorrhage, two with the MaternaWell tray and three with the Brass‐V drape. One parturient required hospital transfer. Conclusion. The responses of the birth attendants and parturients were positive. The MaternaWell tray has the benefit of reuse and lower cost and is an acceptable alternative to the Brass‐V drape. Both devices aid in the early recognition of postpartum haemorrhage. [ABSTRACT FROM AUTHOR]

Introduction: Hyperpigmentation disorders are very frequent, affect the quality of life and may become a psychological burden for afflicted patients. Many anti‐pigmenting or depigmenting agents are available with various efficacy and almost no comparative data. 2‐mercaptonicotinoyl glycine (2‐MNG) was recently proposed as a viable candidate showing safe and effective results on hyperpigmentation control in vitro and in vivo. Objectives: A Bayesian network meta‐analysis (BNMA) was conducted to map and rank the anti‐pigmenting and depigmenting efficacy of 2‐MNG 0.5% on UV daylight (UVDL)‐induced pigmentation together with 13 other reference molecules. A comparison in the kinetics of 2‐MNG 0.5% was also performed. Methodology: Fourteen studies were conducted, for each, on 15–30 women of skin phototype III in Shanghai, China and Paris, France. The products were applied on mini zone, in randomized and blinded protocol, on the back, 5 days a week during 6 weeks, at a dose of 4 mg/cm2. During the second week, volunteers were exposed under to varying minimum erythemal dose of UVDL during 4 consecutive days—adapted to obtain a similar induction of skin pigmentation regardless of the population. Assessments were performed instrumentally using Chromameter®. Ascorbic acid 7% was used as a positive control for all experiments. A Bayesian network meta‐analysis was then established to map and follow the kinetics of 2‐MNG 0.5% performance with 13 reference molecules (glutathione 2%, kojic acid 1%, hydroquinone 4%, ascorbyl glucoside 2%, niacinamide 4%, etc.). Results: 2‐MNG 0.5% dominated the ranking at all time points with a significant high probability of strong efficacy against UVDL‐induced pigmentation. Ascorbic acid 7% ranks second after 4 days of irradiations (D12) whereas hydroquinone 4% ranks second 1 month after irradiations (D40). In the kinetics, 2‐MNG at 0.5% was effective as from the end of irradiations (D12) to the study endpoint (D40). This suggested an immediate and persistent efficacy across all timepoints evaluated. Conclusion: The BNMA revealed a rapid and lasting efficacy of 2‐MNG 0.5% on the anti‐pigmenting and depigmenting phases of the clinical protocol. 2‐MNG 0.5% ranked first, with immediate and lasting effect compared to 13 other references. This study is the first allowing comparison between reference anti‐pigmenting and depigmenting agents and will help clinicians for proposing the most effective approach for their patients. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The understanding of the pathological events in Alzheimer's disease (AD) has advanced dramatically, but the successful translation from rodent models into efficient human therapies is still problematic. METHODS: To examine how tau pathology can develop in the primate brain, we injected 12 macaques with a dual tau mutation (P301L/S320F) into the entorhinal cortex (ERC). An investigation was performed using high‐resolution microscopy, magnetic resonance imaging (MRI), positron emission tomography (PET), and fluid biomarkers to determine the temporal progression of the pathology 3 and 6 months after the injection. RESULTS: Using quantitative microscopy targeting markers for neurodegeneration and neuroinflammation, as well as fluid and imaging biomarkers, we detailed the progression of misfolded tau spreading and the consequential inflammatory response induced by glial cells. DISCUSSION: By combining the analysis of several in vivo biomarkers with extensive brain microscopy analysis, we described the initial steps of misfolded tau spreading and neuroinflammation in a monkey model highly translatable to AD patients. Highlights: Dual tau mutation delivery in the entorhinal cortex induces progressive tau pathology in rhesus macaques.Exogenous human 4R‐tau coaptates monkey 3R‐tau during transneuronal spread, in a prion‐like manner.Neuroinflammatory response is coordinated by microglia and astrocytes in response to tau pathology, with microglia targeting early tau pathology, while astrocytes engaged later in the progression, coincident with neuronal death.Monthly collection of CSF and plasma revealed a profile of changes in several AD core biomarkers, reflective of neurodegeneration and neuroinflammation as early as 1 month after injection. [ABSTRACT FROM AUTHOR]

Aim: This aim of this study was to detail maternal and fetal anomalies observed on a national scale in a large French cohort of patients presenting high hCG values (≥10 multiple of the median [MoM]) at Down syndrome screening in order to define clear and optimal guidelines. Methods: This is a retrospective multicenter study based on a French annual database of all trisomy 21 screenings. Our study targeted and studied cases with hCG or hCGβ values ≥10 MoM. Complementary exams and outcomes were analyzed. Results: The calculated frequency was 0.05% for hCGβ ≥10 MoM in unselected patients. For this series of 289 cases, a complication of the pregnancy or a poor outcome was observed in 145 cases (51%) as follows: 96 (66%) cases of fetal disease, 23 (16%) of maternal disease, 5 (3.5%) of placental anomalies and 21 (14.5%) of systemic disease concerning mother, fetus and placenta. Conclusion: This study establishes the frequency of hCG or hCGβ values ≥10 MoM, presents a flow chart that optimizes follow‐up, and gives clear information for patients presenting with such abnormal values at trisomy 21 screening. Key points: What's already known about this topic? High hCG or hCGβ values have been previously reported to be associated with poor prognosis, when over 2.5 multiple of the median (MoM). What does this study add? This study specifies maternal and fetal anomalies observed in patients presenting high hCG values (≥10 MoM) at Down syndrome screening in order to define clear and optimal guidelines. We calculate the frequency of this abnormal value of hCGβ, detail the outcomes, present a flow chart that optimizes follow‐up and provide clear information for patients. [ABSTRACT FROM AUTHOR]

Delimiting salt inclusions from migrated images during the velocity model building flow is a time‐consuming activity that depends on highly human‐curated analysis and is subject to interpretation errors or limitations of the images and methods available. We propose a supervised deep learning based method to include three‐dimensional salt geometries in the velocity models. We compare two convolutional networks – based on the U‐Net architecture – which can process three‐dimensional seismic data. One architecture uses three‐dimensional convolutional kernels, and the other has convolutional long short‐term memory units. Each architecture requires specific preprocessing steps which affects their training and predictive performance. Both proposed architectures use subsurface offset gathers obtained from reverse time migration with an extended imaging condition as input and are trained to predict the salt inclusions. The velocity model used in migration is a reasonable approximation of sediment velocity but without salt inclusions. Thus, the migration model and, consequently, the migrated images are inaccurate due to the absence of the salt inclusion in the model using just the sediment velocity information for the segmentation. A similar salt inclusion methodology was previously validated for two‐dimensional approaches; we extend it to the three‐dimensional case. Our approach relies on subsurface common image gathers to focus the sediments' reflections around the zero offset and spread salt reflections' energy over large subsurface offsets. The results show that both proposed network models can accurately delineate the salt bodies in the test models, but when evaluating the trained networks for the three‐dimensional SEG/EAGE salt model, the architecture with convolutional long short‐term memory units has proven to generalize better. [ABSTRACT FROM AUTHOR]

Unchecked antimicrobial resistance is lethal and carries a high economic burden on the global economy. Primary care is central to the success of health service antibiotic stewardship programmes, as most of these infections are managed in the community. This article examines a pioneering programme that aims to reduce resistance to antibiotics commonly used to treat lower urinary tract infections. [ABSTRACT FROM AUTHOR]

During symbiosis, C that rhizobia respire to power N fixation can be stored as polyhydroxybutyrate (PHB), shown to support rhizobia survival under laboratory starvation. We collected soil in 2015 from four replicate plots per treatment in two long‐term experiments at Waseca, MN. Treatments differed in the intervals between soybean [Glycine max (L.) Merr.] hosts. We measured PHB accumulation in eight nodules per plant from four soybean (cv. MN0095) trap plants per soil sample. Trap plants were arranged in a greenhouse, common‐garden experiment, and PHB accumulation was measured using flow cytometry. Treatments sampled after long intervals without soybean (greater than 2 years) showed a greater relative abundance of high‐PHB strains. Treatments sampled after the first year of soybean following 5 years of a non‐host crop showed a decreased relative abundance of high‐PHB strains, compared to treatments sampled after long intervals without soybean. The latter result is consistent with the hypothesis (not tested directly here) that some high‐PHB strains were "sanctioned" by plants as less beneficial. Our results suggest that rhizobia strains with the tendency to allocate more C to N fixation at the expense of PHB accumulation may be less likely to persist where soybean is grown infrequently or where soil conditions make PHB particularly valuable. However, with typical 2‐year rotations in Minnesota, differences in PHB storage are unlikely to have a major effect on the relative survival of strains. Core Ideas: By supporting their more beneficial root nodules, soybeans may enrich the soil with better rhizobia.To benefit future crops, these more beneficial rhizobia strains must survive in soil between soybean crops.We found that strains that hoard more of the lipid, polyhydroxybutyrate (PHB), survive longer in the field.Hoarding more PHB could divert carbon from nitrogen fixation, a possible tradeoff.But differences in strain survival mainly occurred beyond the usual 2‐year gap between soybean crops. [ABSTRACT FROM AUTHOR]

The gasotransmitter hydrogen sulfide (H2S) is thought to be involved in the post‐translational modification of cysteine residues to produce reactive persulfides. A persulfide‐specific chemoselective proteomics approach with mammalian cells has identified a broad range of zinc finger (ZF) proteins as targets of persulfidation. Parallel studies with isolated ZFs show that persulfidation is mediated by ZnII, O2, and H2S, with intermediates involving oxygen‐ and sulfur‐based radicals detected by mass spectrometry and optical spectroscopies. A small molecule ZnII complex exhibits analogous reactivity with H2S and O2, giving a persulfidated product. These data show that ZnII is not just a biological structural element, but also plays a critical role in mediating H2S‐dependent persulfidation. ZF persulfidation appears to be a general post‐translational modification and a possible conduit for H2S signaling. This work has implications for our understanding of H2S‐mediated signaling and the regulation of ZFs in cellular physiology and development. [ABSTRACT FROM AUTHOR]

Control of multicomponent alloys during welding is challenging because it lacks a real‐time understanding of composition. The optical emissions of plasma formed during laser‐induced metal welding correlate with the composition of particles ejected from the melt pool. Plasma emissions observed in this study contain large iron, manganese, chrome, and copper signatures, which match the composition of emitted particles. Particles recovered closest to the melt pool exhibit a core–shell morphology that is composed of iron‐manganese‐chrome intermetallic cores within copper shells. Particles collected farther from the melt pool, do not share this core–shell morphology, though similar elemental compositions are observed. The correlation between plasma optical emissions and particle composition can be used to predict the composition of the melt pool, allowing for real‐time welding and sintering control. [ABSTRACT FROM AUTHOR]