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Factors associated with high milk production levels have been linked to alterations in the endometrial epidermal growth factor (EGF) profile, a cause of reduced fertility in dairy cows. Therefore, we examined the leptin system that connects nutritional status and reproduction in dairy cattle related to reduced fertility in repeat breeder cows. Plasma leptin concentrations were measured in 18 heifers, 20 high-yielding control cows, and 26 repeat breeder cows, showing an altered EGF profile. Then, all repeat breeder cows were infused with seminal plasma (SP) into the vagina at the next estrus to normalize the EGF profile, while heifers and control cows were infused with vehicle alone. All animals were examined for EGF profiles. Eighteen repeat breeder cows, nine heifers, and nine control cows were also determined for leptin receptor (Ob-R) expression levels in the estrous cycle before and after the infusion. SP normalized the EGF profile in 53.8% of the repeat breeder cows. Leptin concentrations were similar in all groups, regardless of the treatment results for the EGF profile. In contrast, Ob-R levels in repeat breeder and control cows were similar and higher than those in heifers before SP treatment. Ob-R in repeat breeders showing a normal EGF profile after treatment decreased to an intermediate level between heifers and control cows and may provide a clue to take measures against repeat breeding in dairy cows.

Summary: Background: The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods: In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings: In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1–9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3–25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation: There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained. Funding: Bill & Melinda Gates Foundation.

With the increased life expectancies of people with severe haemophilia A, diagnoses of disorders associated with increased age are likely to become more common. Multiple myeloma is a commonly diagnosed plasma cell dyscrasia, with incidence strongly related to age. Both the disease itself and specific myeloma therapies are associated with a significant increase in rates of venous thromboembolism (VTE). Management of VTE prophylaxis can be challenging, especially in patients with a bleeding disorder. In this case report, we describe the management of a patient with concurrent diagnosis of multiple myeloma and severe haemophilia A, undergoing first line myeloma chemotherapy. The patient was successfully managed on standard of care myeloma treatment, with use of emicizumab and venous thromboprophylaxis. This case demonstrates the successful management of a haematological malignancy and a bleeding disorder using integrated and multidisciplinary patient-focused care.

Research Findings: A growing number of stakeholders in early childhood education (ECE) rely on self-assessment to assess and improve the quality of ECE. In this systematic review, we investigated the reliability and validity of self-assessment in ECE, summarizing findings from 27 publications. We meta-analytically synthesized findings from 25 publications for 1,882 groups and 79,163 children aged 0-72 months in center-based childcare. Most studies reported high internal consistency, but one study reported a lower consistency. Inter-rater reliability was generally high. A three-level meta-analysis (k = 13, ES = 45) revealed a positive association between self-assessment ratings and ratings with validated measures of ECE quality (r = 0.38), indicating a moderate convergent validity. Studies with lower methodological quality and published "peer reviewed" studies reported somewhat higher correlations between self-assessment ratings and ratings with validated measures. The meta-analytic correlation remained significant after removal of studies with lower methodological quality (r = 0.33) or studies from the "grey" literature (r = 0.44). A second meta-analysis (k = 16, ES = 71) with a focus on the predictive validity of self-assessment ratings showed a small significant association between self-assessed ECE quality and child outcomes (r = 0.09); there were no significant moderators. Practice or Policy: Despite empirical evidence for the validity of self-assessment, further studies are needed to investigate potential bias in self-assessment. Future studies should further explore the validity and reliability of self-assessment measures in ECE, including countries outside the United States.

Lipids perform multiple biological functions and reflect the physiology and pathology of cells, tissues, and organs. Here, we sought to understand lipid content in relation to tumor pathology by characterizing phospholipids and sphingolipids in the orthotopic mouse glioma using MALDI MS imaging (MSI) and LC-MS/MS. Unsupervised clustering analysis of the MALDI-MSI data segmented the coronal tumoral brain section into 10 histopathologically salient regions. Heterogeneous decrease of the common saturated phosphatidylcholines (PCs) in the tumor was accompanied by the increase of analogous PCs with one or two additional fatty acyl double bonds and increased lyso-PCs. Polyunsaturated fatty acyl-PCs and ether PCs highlighted the striatal tumor margins, whereas the distributions of other PCs differentiated the cortical and striatal tumor parenchyma. We detected a reduction of SM d18:1/18:0 and the heterogeneous mild increase of SM d18:1/16:0 in the tumor, whereas ceramides accumulated only in a small patch deep in the tumoral parenchyma. LC-MS/MS analyses of phospholipids and sphingolipids complemented the MALDI-MSI observation, providing a snapshot of these lipids in the tumor. Finally, the proposed mechanisms responsible for the tumoral lipid changes were contrasted with our interrogation of gene expression in human glioma. Together, these lipidomic results unveil the aberrant and heterogeneous lipid metabolism in mouse glioma where multiple lipid-associated signaling pathways underline the tumor features, promote the survival, growth, proliferation, and invasion of different tumor cell populations, and implicate the management strategy of a multiple-target approach for glioma and related brain malignancies.

Background. The objective of this study was to compare the long-term outcomes of older (50–65 y) type 1 diabetics with body mass index

BackgroundMost people with autism spectrum disorder (ASD) present at least one form of challenging behavior (CB), causing reduced life quality, social interactions, and community-based service inclusion.ObjectivesThe current study had two objectives: (1) to assess the differences in physiological reaction to stressful stimuli between adults with and without high-functioning ASD; (2) to develop a system able to predict the incoming occurrence of a challenging behaviors (CBs) in real time and inform the caregiver that a CB is about to occur; (3) to evaluate the acceptability and usefulness of the developed system for users with ASD and their caregivers.MethodsComparison between physiological parameters will be conducted by enrolling two groups of 20 participants with and without ASD monitored while watching a relaxing and disturbing video. To understand the variations of the parameters that occur before the CB takes place, 10 participants with ASD who have aggressive or disruptive CBs will be monitored for 7 days. Then, an ML algorithm capable of predicting immediate CB occurrence based on physiological parameter variations is about to be developed. After developing the application-based algorithm, an efficient proof of concept (POC) will be carried out on one participant with ASD and CB. A focus group, including health professionals, will test the POC to identify the strengths and weaknesses of the developed system.ResultsHigher stress level is anticipated in the group of people with ASD looking at the disturbing video than in the typically developed peers. From the obtained data, the developed algorithm is used to predict CBs that are about to occur in the upcoming 1 min. A high level of satisfaction with the proposed technology and useful consideration for further developments are expected to emerge from the focus group.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT05340608].

Protein tyrosine phosphatase receptor-type kappa (PTPRK) is a transmembrane receptor that links extracellular homophilic interactions to intracellular catalytic activity. Previously we showed that PTPRK promotes cell–cell adhesion by selectively dephosphorylating several cell junction regulators including the protein Afadin (Fearnley et al, 2019). Here, we demonstrate that Afadin is recruited for dephosphorylation by directly binding to the PTPRK D2 pseudophosphatase domain. We mapped this interaction to a putative coiled coil (CC) domain in Afadin that is separated by more than 100 amino acids from the substrate pTyr residue. We identify the residues that define PTP specificity, explaining how Afadin is selectively dephosphorylated by PTPRK yet not by the closely related receptor tyrosine phosphatase PTPRM. Our work demonstrates that PTP substrate specificity can be determined by protein–protein interactions distal to the active site. This explains how PTPRK and other PTPs achieve substrate specificity despite a lack of specific sequence context at the substrate pTyr. Furthermore, by demonstrating that these interactions are phosphorylation-independent and mediated via binding to a non-catalytic domain, we highlight how receptor PTPs could function as intracellular scaffolds in addition to catalyzing protein dephosphorylation.

Background: Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to have a diagnosis. Untreated coeliac disease may lead to malnutrition, anaemia, osteoporosis and lymphoma. Objectives: The objectives were to define at-risk groups and determine the cost-effectiveness of active case-finding strategies in primary care. Design: (1) Systematic review of the accuracy of potential diagnostic indicators for coeliac disease. (2) Routine data analysis to develop prediction models for identification of people who may benefit from testing for coeliac disease. (3) Systematic review of the accuracy of diagnostic tests for coeliac disease. (4) Systematic review of the accuracy of genetic tests for coeliac disease (literature search conducted in April 2021). (5) Online survey to identify diagnostic thresholds for testing, starting treatment and referral for biopsy. (6) Economic modelling to identify the cost-effectiveness of different active case-finding strategies, informed by the findings from previous objectives. Data sources: For the first systematic review, the following databases were searched from 1997 to April 2021: MEDLINE® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), Cochrane Library, Web of Science™ (Clarivate™, Philadelphia, PA, USA), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and the National Institutes of Health Clinical Trials database. For the second systematic review, the following databases were searched from January 1990 to August 2020: MEDLINE, Embase, Cochrane Library, Web of Science, Kleijnen Systematic Reviews (KSR) Evidence, WHO ICTRP and the National Institutes of Health Clinical Trials database. For prediction model development, Clinical Practice Research Datalink GOLD, Clinical Practice Research Datalink Aurum and a subcohort of the Avon Longitudinal Study of Parents and Children were used; for estimates for the economic models, Clinical Practice Research Datalink Aurum was used. Review methods: For review 1, cohort and case–control studies reporting on a diagnostic indicator in a population with and a population without coeliac disease were eligible. For review 2, diagnostic cohort studies including patients presenting with coeliac disease symptoms who were tested with serological tests for coeliac disease and underwent a duodenal biopsy as reference standard were eligible. In both reviews, risk of bias was assessed using the quality assessment of diagnostic accuracy studies 2 tool. Bivariate random-effects meta-analyses were fitted, in which binomial likelihoods for the numbers of true positives and true negatives were assumed. Results: People with dermatitis herpetiformis, a family history of coeliac disease, migraine, anaemia, type 1 diabetes, osteoporosis or chronic liver disease are 1.5–2 times more likely than the general population to have coeliac disease; individual gastrointestinal symptoms were not useful for identifying coeliac disease. For children, women and men, prediction models included 24, 24 and 21 indicators of coeliac disease, respectively. The models showed good discrimination between patients with and patients without coeliac disease, but performed less well when externally validated. Serological tests were found to have good diagnostic accuracy for coeliac disease. Immunoglobulin A tissue transglutaminase had the highest sensitivity and endomysial antibody the highest specificity. There was little improvement when tests were used in combination. Survey respondents (n = 472) wanted to be 66% certain of the diagnosis from a blood test before starting a gluten-free diet if symptomatic, and 90% certain if asymptomatic. Cost-effectiveness analyses found that, among adults, and using serological testing alone, immunoglobulin A tissue transglutaminase was most cost-effective at a 1% pre-test probability (equivalent to population screening). Strategies using immunoglobulin A endomysial antibody plus human leucocyte antigen or human leucocyte antigen plus immunoglobulin A tissue transglutaminase with any pre-test probability had similar cost-effectiveness results, which were also similar to the cost-effectiveness results of immunoglobulin A tissue transglutaminase at a 1% pre-test probability. The most practical alternative for implementation within the NHS is likely to be a combination of human leucocyte antigen and immunoglobulin A tissue transglutaminase testing among those with a pre-test probability above 1.5%. Among children, the most cost-effective strategy was a 10% pre-test probability with human leucocyte antigen plus immunoglobulin A tissue transglutaminase, but there was uncertainty around the most cost-effective pre-test probability. There was substantial uncertainty in economic model results, which means that there would be great value in conducting further research. Limitations: The interpretation of meta-analyses was limited by the substantial heterogeneity between the included studies, and most included studies were judged to be at high risk of bias. The main limitations of the prediction models were that we were restricted to diagnostic indicators that were recorded by general practitioners and that, because coeliac disease is underdiagnosed, it is also under-reported in health-care data. The cost-effectiveness model is a simplification of coeliac disease and modelled an average cohort rather than individuals. Evidence was weak on the probability of routine coeliac disease diagnosis, the accuracy of serological and genetic tests and the utility of a gluten-free diet. Conclusions: Population screening with immunoglobulin A tissue transglutaminase (1% pre-test probability) and of immunoglobulin A endomysial antibody followed by human leucocyte antigen testing or human leucocyte antigen testing followed by immunoglobulin A tissue transglutaminase with any pre-test probability appear to have similar cost-effectiveness results. As decisions to implement population screening cannot be made based on our economic analysis alone, and given the practical challenges of identifying patients with higher pre-test probabilities, we recommend that human leucocyte antigen combined with immunoglobulin A tissue transglutaminase testing should be considered for adults with at least a 1.5% pre-test probability of coeliac disease, equivalent to having at least one predictor. A more targeted strategy of 10% pre-test probability is recommended for children (e.g. children with anaemia). Future work: Future work should consider whether or not population-based screening for coeliac disease could meet the UK National Screening Committee criteria and whether or not it necessitates a long-term randomised controlled trial of screening strategies. Large prospective cohort studies in which all participants receive accurate tests for coeliac disease are needed. Study registration: This study is registered as PROSPERO CRD42019115506 and CRD42020170766. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 44. See the NIHR Journals Library website for further project information.

Nanothermites have been employed as fuel additives in energetic formulations due to their higher energy density over CHNO energetics. Nevertheless, sintering and degradation of nanoparticles significantly limit the practical use of nanothermites. In this work, combustion characteristic and aging behavior of aluminum/iron oxide (Al/Fe2O3) nanothermite mixtures were investigated in the presence of micron-scale nickel aimed to produce bimetal thermite powders. The results showed that the alumina content in the combustion residue increased from 88.3% for Al/Fe2O3 nanothermite to 96.5% for the nanothermite mixture containing 20 wt% nickel. Finer particle sizes of combustion residue were obtained for the nanothermite mixtures containing nickel, indicative of the reduced agglomeration. Both results suggested a more complete combustion in the bimetal thermite powders. Aging behavior of the nanothermite mixture was also assessed by measuring the heat of combustion of the mixture before and after aging process. The reduction in heat of combustion of nanothermite mixtures containing nickel was less severe as compared to a significant decrease for the nanothermite mixture without nickel, indicating better aging resistance of the bimetal thermite powders.

The Iberian Peninsula represents a diversity hotspot for the genus Dicranopalpus. However, most taxa are insufficiently defined. Our revision of the Dicranopalpus pyrenaeus species group reveals two hidden species: D. catariegensis sp. nov. and D. gallaecicus sp. nov. Two species, D. pyrenaeus from the Spanish and French Pyrenees and D. insignipalpis from Corsica, are redescribed. Dicranopalpus cantabricus Dresco, 1953 is resurrected as a valid species. Three new synonyms of D. martini (Simon, 1878) are proposed: Fagea bolivari Dresco, 1949 (including D. bolivari sensu Rambla 1975), Egaenasser extraordinarius Roewer, 1953 and Dicranopalpus dispar Rambla, 1967. With these additions, the Iberian Peninsula harbours four species of the Dicranopalpus pyrenaeus species group. They largely have allopatric distributions, ranging from the Pyrenees and the Cantabrian mountain range to the west coast of Galicia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency affects 500 million people globally, affecting red blood cell (RBC) antioxidant pathways and increasing susceptibility to hemolysis under oxidative stress. Despite the systemic generation of reactive oxygen species during exercise, the effects of exercise on individuals with G6PD deficiency remain poorly understood This study used humanized mouse models expressing the G6PD Mediterranean variant (S188F, with 10% enzymatic activity) to investigate exercise performance and molecular outcomes. Surprisingly, despite decreased enzyme activity, G6PD-deficient mice have faster critical speed than mice expressing human canonical G6PD. After exercise, deficient mice did not exhibit differences in RBC morphology or hemolysis, but had improved cardiac function, including cardiac output, stroke volume, sarcomere length, and mitochondrial content. Proteomics analyses of cardiac and skeletal muscles (gastrocnemius, soleus) from G6PD-deficient compared with sufficient mice revealed improvements in mitochondrial function and increased protein turnover via ubiquitination, especially for mitochondrial and structural myofibrillar proteins. Mass spectrometry-based metabolomics revealed alterations in energy metabolism and fatty acid oxidation. These findings challenge the traditional assumptions regarding hemolytic risk during exercise in G6PD deficiency, suggesting a potential metabolic advantage in exercise performance for individuals carrying noncanonical G6PD variants.

Introduction Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) has become a popular regimen for adults with acute lymphoblastic leukemia (ALL). We assessed the efficacy and tolerability of hyper-CVAD in the treatment of adult ALL. Material and methods We retrospectively reviewed ALL patients aged 18 or above receiving the hyper-CVAD regimen. We assessed complete remission rate and overall survival, as well as hepatitis B carrier rate and hepatitis flare due to hepatitis B virus (HBV) reactivation. Results Fifty-two patients were treated with the hyper-CVAD regimen. The median age at diagnosis was 42 years; 27% of patients were Philadelphia (Ph) chromosome positive. The complete remission (CR) rate was 90.4% after the first cycle of chemotherapy. The induction mortality rate was 1.9%. Three patients required two cycles of hyper-CVAD to achieve CR. The median overall survival was 39.6 months and the 5-year overall survival was 50%. Age over 30 years and white blood cell count of more than 30 × 109/l were found to be prognostic for poor overall survival in multivariate analysis. The hepatitis B carrier rate was 17% in our cohort, and the rate of hepatitis flare due to HBV reactivation was 11% in patients with current infection. Conclusions Hyper-CVAD is feasible and tolerable with a good CR rate in the treatment of adult ALL patients. It is an option for the treatment of ALL. Antiviral prophylaxis should be considered in ALL patients with HBV infection to reduce the risk of HBV reactivation.

Background and purpose — Congenital pseudarthrosis of the tibia (CPT) is caused by local periosteal disease that can lead to bowing, fracturing, and pseudarthrosis. Current most successful treatment methods are segmental bone transport and vascularized and non-vascularized bone grafting. These methods are commonly hampered by discomfort, reoperations, and long-term complications. We report a combination of a vascularized fibula graft and large bone segment allograft, to improve patient comfort with similar outcomes. Patients and methods — 7 limbs that were operated on in 6 patients between November 2007 and July 2018 with resection of the CPT and reconstruction with a vascularized fibula graft in combination with a bone allograft were retrospectively studied. The mean follow-up time was 5.4 years (0.9–9.6). Postoperative endpoints: time to discharge, time to unrestricted weight bearing, complications within 30 days, consolidation, number of fractures, and secondary deformities. Results — The average time to unrestricted weight bearing with removable orthosis was 3.5 months (1.2–7.8). All proximal anastomoses consolidated within 10 months (2–10). 4 of the 7 grafts fractured at the distal anastomosis between 6 and 14 months postoperatively. After reoperation, consolidation of the distal anastomosis was seen after 2.8 months (2–4). 1 patient required a below-knee amputation. Interpretation — This case series showed favorable results of the treatment of CPT through a combination of a vascularized fibula graft and large bone segment allograft, avoiding the higher reintervention rate and discomfort with ring frame bone transport, and the prolonged non-weight bearing with vascularized fibula transfer without reinforcement with a massive large bone segment allograft.

Abstract Hepatic steatosis is strongly associated with chronic liver disease and systemic metabolic disorder. Adipose lipolysis is a recognized principal source of intrahepatic fat in various metabolic disorders, including non-alcoholic fatty liver disease. We hypothesized that, in the premorbid state, hepatic de novo lipogenesis (DNL) driven by excess carbohydrates abundance might play a more significant role. We employed a novel nutritional model in sheep of two distinct carbohydrates abundances. During 4 months of the dietary treatment, lambs were monitored for metabolic and terminal liver parameters. Lambs grown on the high-calorie (HC) diet were consistently more hyperglycemic and hyperinsulinemic than lambs grown on the lower-calorie (LC) diet (P

Perceptions of program safety for youth might include such features as physical safety, psychological safety, and social-relational safety. A holistic sense of safety, or one that inclusively encompasses and integrates features of, and relations with, the ecology in which youth develop, could be engendered through programmatic designs that attend to the dynamic relations among physical, psychological, and social-relational safety. Having a better understanding of the phenomenology of safety among program participants, and how such perceptions function in youth programs would enable positive youth development (PYD) program practitioners to better align their conceptions -- that is, their "objective" definitions -- of program safety with the phenomenological experiences of youth and, in so doing, better promote PYD and thriving outcomes. The present study was informed by preliminary quantitative findings emerging from the broader Compassion International (CI) Study of PYD (Lerner et al., 2019; Tirrell et al., 2021; Tirrell, Gansert, et al., 2019; Tirrell, Geldhof, et al., 2019). As described in this article, youth who engaged in CI-supported programs in El Salvador reported feeling safe at the CI programs, but also reported feeling generally unsafe, and worrying about their safety, in the broader contexts of their lives.

Work-integrated learning (WIL), as an educational approach, is facilitated through relationships between Higher Education Institutions (HEIs) and external 'host' organizations. Responsible host organizations should recognize that students undertaking WIL come from a range of different cultures, socio-economic backgrounds, and have varying academic, physical, and other capabilities. An inclusive workplace will seek to facilitate a positive and rewarding experience for all WIL students. Recent WIL literature has seen a strong focus on inclusive access to WIL. This article examines key elements that can contribute to host organizations providing an inclusive environment for students. Socio-cultural theories related to learning in the workplace are used as a theoretical lens. An Inclusive WIL Workplace Framework is proposed, highlighting principles, practices, and supervisor and co-worker characteristics, that can be utilized by workplaces to assess their inclusivity and address any gaps, and by students to understand the expectations of HEIs on host organizations.

BackgroundPsychological distress is a common occurrence among women during the perinatal period. Maternal psychological distress (MPS) can also have a negative influence on neonatal outcomes such as infant health, child development or mother-child interaction. Hence, interventions to improve mental wellbeing during this period are vital. Mindfulness based intervention (MBI) has been found to be effective in reducing psychological distress. Delivery of MBI via the internet, making it accessible and inexpensive, is showing a promising positive effect in reducing psychological distress. A randomized control trial with sufficient power is required to confirm its positive effect among pregnant women. The positive effects of MBI have been found to be associated with heart rate variability (HRV) biofeedback; however, the efficacy of MBI on HRV has been rarely studied among pregnant women. Also, the potential association of HRV with MBI and psychological wellbeing needs further examination. This research aims to test the effectiveness of guided mobile-based perinatal mindfulness intervention (GMBPMI) among pregnant women experiencing psychological distress during the pre- and post-natal period, as well as examining the efficacy of GMBPMI on HRV.MethodThis study is a randomized controlled trial that follows a parallel design. Consenting pregnant women in their second trimester (between 12th and 20th week gestation) will be randomly assigned to an intervention group (GMBPMI) or a control group (psychoeducation). The intended sample size is 198, with 99 participants in each group. Three levels of outcomes will be measured at baseline, post intervention in both the intervention and control groups, and at 36-week gestation and five-week postpartum. The primary outcomes include maternal psychological stress, mindfulness and positive appraisal HRV. Secondary outcomes are psychological and physical wellbeing. Tertiary outcomes include obstetric and neonatal outcomes, and social support. Analyses will follow an intention-to-treat method and repeated measures MANOVA will be conducted to compare changes in primary and secondary outcomes. A series of mixed-effects models will be fitted to assess the mediation effects.DiscussionThis trial expects to increase understanding of GMBPMI on HRV and psychological wellbeing for pregnant women, with extended support in both pre-and post-natal periods. The study could also potentially provide evidence for delivery of cost-effective and accessible services to pregnant women.Trial registrationClinicalTrials.gov: NCT04876014, registered on 30 March 2021. Protocol Version 1.0., 10 May 2021.

There are limited data regarding bone health in older people living with HIV (PWH), especially those of Asian ethnicity. We aimed to determine whether BMD in well-suppressed HIV-infected men and women aged ≥ 50 years are different from HIV-uninfected controls. In a cross-sectional study, BMD by dual-energy X-ray absorptiometry and calciotropic hormones were measured. A total of 481 participants were consecutively enrolled (209 HIV+ men, 88 HIV- men, 126 HIV+ women and 58 HIV- women). PWH were on average 2.5 years younger [men: 55.0 vs. 57.5 yr; women: 54.0 vs. 58.0 yr] and had lower body mass index (BMI) [men: 23.2 vs. 25.1 kg/m2; women: 23.1 vs. 24.7 kg/m2] compared to the controls. The median duration since HIV diagnosis was 19 (IQR 15–21) years in men and 18 (IQR 15–21) years in women. Three-quarters of PWH had been treated with tenofovir disoproxil fumarate-containing antiretroviral therapy for a median time of 7.4 (IQR 4.5–8.9) years in men and 8.2 (IQR 6.1–10) years in women. In an unadjusted model, HIV+men had significantly lower BMD (g/cm2) at the total hip and femoral neck whereas there was a tend toward lower BMD in HIV+women. After adjusting for age, BMI, and other traditional osteoporotic risk factors, BMD of virologically suppressed older PWH did not differ from participants without HIV (P>0.1). PWH had lower serum 25(OH)D levels but this was not correlated with BMD. In conclusion, BMD in well-suppressed PWH is not different from non-HIV people, therefore, effective control of HIV infection and minimization of other traditional osteoporosis risk factors may help maintain good skeletal health and prevent premature bone loss in Asian PWH. Clinical trial registration: Clinicaltrials.gov # NCT00411983.

Rice is the major staple food crop for more than 50% of the world’s total population, and its production is of immense importance for global food security. As a photophilic plant, its yield is governed by the quality and duration of light. Like all photosynthesizing plants, rice perceives the changes in the intensity of environmental light using phytochromes as photoreceptors, and it initiates a morphological response that is termed as the shade-avoidance response (SAR). Phytochromes (PHYs) are the most important photoreceptor family, and they are primarily responsible for the absorption of the red (R) and far-red (FR) spectra of light. In our endeavor, we identified the morphological differences between two contrasting cultivars of rice: IR-64 (low-light susceptible) and Swarnaprabha (low-light tolerant), and we observed the phenological differences in their growth in response to the reduced light conditions. In order to create genomic resources for low-light tolerant rice, we constructed a subgenomic library of Swarnaprabha that expedited our efforts to isolate light-responsive photoreceptors. The titer of the library was found to be 3.22 × 105 cfu/mL, and the constructed library comprised clones of 4–9 kb in length. The library was found to be highly efficient as per the number of recombinant clones. The subgenomic library will serve as a genomic resource for the Gramineae community to isolate photoreceptors and other genes from rice.

Background: To better understand the intricate science of reading development, both cognitive and affective factors must be taken into consideration. This developmental study aims to enrich the literature by exploring how reading motivation -- an affective factor -- contributes to reading comprehension in Chinese elementary schoolers, beyond well-accepted cognitive-based reading skills, such as decoding and vocabulary. Methods: We used a cross-sectional design with 420 native Mandarin-Chinese-speaking students (Grade 2: N = 95; Grade 3: N = 216; Grade 4: N = 109), with age-appropriate materials to measure their decoding skills, vocabulary knowledge, reading motivation, and reading comprehension. Three sets of hierarchical regression analyses were run for the three grade samples to examine the unique contributions of reading motivation to reading comprehension while controlling children's demographic profiles, such as age and gender, and two cognitive-based reading skills. Results: We replicated previous findings: children's decoding and vocabulary are robust predictors of reading achievement across Grades 2 to 4. Importantly, reading motivation contributed uniquely to reading comprehension in all three grades and explained an increasing amount of the variances in reading comprehension from Grades 2 to 4. Intrinsic reading motivation was critical in Grade 3, while extrinsic reading motivation became important in Grade 4. Conclusions: Taken together, our findings reveal the complexity of reading development and advance the existing cognitive-based reading theories by including affective dimensions.

Abstract: Red blood cells (RBCs) are the most numerous cell type in the body and serve a vital purpose of delivering oxygen to essentially all tissues. In addition to the central role of RBCs in health and disease, RBC storage is a requirement for the >90 million units of RBC transfusions given to millions of recipients each year, worldwide. It is well known that there is genetic donor-to-donor variability in how human RBCs store, rendering blood a nonstandardized therapeutic with a wide range of biological properties from unit to unit, by the time it is transfused. As with humans, genetic variation exists in how murine RBCs, from different strains of mice, store and perform after transfusion. The genetic mechanisms for variation, in humans and mice, both remain obscure. Combining advanced metabolomics, genetics, and molecular and cellular biology approaches, we identify genetic variation in six-transmembrane epithelial antigen of prostate 3 (Steap3) expression as a critical and previously unrecognized mechanism of oxidative damage of RBCs during storage. Increased levels of Steap3 result in degradation of cellular membrane through lipid peroxidation, leading to failure of RBC homeostasis and hemolysis/clearance of RBCs. This article is the first report of a role of Steap3 in mature RBCs; it defines a new mechanism of redox biology in RBCs with a substantial effect upon RBC function and provides a novel mechanistic determinant of genetic variation of RBC storage.

The main purpose of this study was to select the appropriate ultrasound parameters that support the freezing process of Bo Chinh ginseng. This process involves placing Bo Chinh ginseng in an open-air environment and ensuring that the transducer does not come into contact with the material. The research results show that the ultrasound power, ultrasound irradiation temperature and intermittency ratio all affect the freezing time, nucleation temperature, color and microstructure of the materials. When the ultrasound continuously operated during the freezing process, at a frequency of 20 kHz, there was a 29.1% reduction in the freezing time at a power level of 100 W as compared to freezing without the help of ultrasound irradiation. The irradiation temperature and nucleation temperature have a linear relationship (y=−0.35x−0.93) which can help to control the nucleation temperature, thereby changing the ice crystal size. Ultrasound-assisted freezing at a 0.6 intermittency ratio had the shortest freezing time. The microstructure of the material changed after ultrasound-assisted freezing and many microchannels and holes were generated. When frozen at a wave rate of 0.4, the microchannels that were created in the material effectively supported the process of water drainage in the drying sublimation stage. At the same time, ultrasound irradiation did not affect the color of the post-freezing material when compared to the color of the frozen material that did not undergo ultrasound irradiation.

Prior MALDI mass spectrometry imaging (MALDI-MSI) studies reported significant changes in phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), and sphingomyelins (SMs) in ischemic rat brains yet overlooked the information on other classes of PLs and SLs and provided very little or no validation on the detected lipid markers. Relative quantitation of four classes of PLs and two classes of SLs in the ischemic and normal temporal cortex (TCX), parietal cortex (PCX), and striatum (ST) of rats was performed with hydrophilic interaction chromatography (HILIC)–tandem mass spectrometry (MS/MS) analyses, and the marker lipid species was identified by multivariate data analysis and validated with additional tissue cohorts. The acquired lipid information was sufficient in differentiating individual anatomical regions under different pathological states, identifying region-specific ischemic brain lipid markers and revealing additional PL and SL markers not reported previously. Validation of orthogonal partial least square discriminating analysis (OPLS-DA) identified ischemic brain lipid markers yielded much higher classification accuracy, precision, specificity, sensitivity, and lower false positive and false negative rates than those from the volcano plot analyses using conventional statistical significance and a fold change of two as the cutoff and provided a wider prospective to ischemia-associated brain lipid changes.

This study focused on the experimental drying of Bo Chinh ginseng by the ultrasound-assisted heat pump drying method, in which the effects of drying air temperature (T), ultrasonic power (P), intermittency ratio of ultrasound generator (A) on the moisture effective diffusion coefficient (Deff), saponin content (Sp) and color change (dE) during the drying process were determined. The results showed that the drying time was reduced from 12.5 h at 35 °C to 8.9 h at 40 °C and greatly reduced to 5.8 h at 55 °C. The moisture diffusion coefficient Deff and color change index increased with the increase in drying temperature. Meanwhile, from 35 °C to 45 °C, the saponin content after drying tended to increase gradually, but when the temperature continued to rise from 45 °C to 55 °C, the saponin content decreased. The effect of ultrasonic power in the drying process was in particular as follows. The drying time of 8.8 h at 40 W ultrasonic power reduced to 7.8 h at 80 W ultrasonic power, and reduced to 7 h at 160 W ultrasonic power. The remaining saponin content after drying tended to increase gradually at the power level of 40–120 W (from 89.2% to 95.2%) and decrease when the power increased from 120 to 160 W (from 95.2% to 90.5%). The moisture diffusion coefficient Deff also increased with the increase in ultrasonic power. Meanwhile, the color change of dried products decreased as the ultrasonic power increased in the range of 40–120 W but increased with the ultrasonic power range from 120 to 160 W. Additionally, the experimental method and Box–Behnken design were used for optimizing the drying process with the optimal drying conditions such as drying air temperature of 45.2 °C, ultrasonic power of 127.7 W and intermittency ratio of ultrasound generator of 0.18.

Fungal infections are an extremely serious health problem, particularly in patients with compromised immune systems. Most antifungal agents have low aqueous solubility, which may hamper their bioavailability. Their complexation with cyclodextrins (CDs) could increase the solubility of antifungals, facilitating their antifungal efficacy. Nanoparticulate systems are promising carriers for antifungal delivery due to their ability to overcome the drawbacks of conventional dosage forms. CD-based nanocarriers could form beneficial combinations of CDs and nanoparticulate platforms. These systems have synergistic or additive effects regarding improved drug loading, enhanced chemical stability, and enhanced drug permeation through membranes, thereby increasing the bioavailability of drugs. Here, an application of CD in antifungal drug formulations is reviewed. CD-based nanocarriers, such as nanoparticles, liposomes, nanoemulsions, nanofibers, and in situ gels, enhancing antifungal activity in a controlled-release manner and possessing good toxicological profiles, are described. Additionally, the examples of current, updated CD-based nanocarriers loaded with antifungal drugs for delivery by various routes of administration are discussed and summarized.