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Abstract The epitranscriptome embodies many new and largely unexplored functions of RNA. A significant roadblock hindering progress in epitranscriptomics is the identification of more than one modification in individual transcript molecules. We address this with CHEUI (CH3 (methylation) Estimation Using Ionic current). CHEUI predicts N6-methyladenosine (m6A) and 5-methylcytosine (m5C) in individual molecules from the same sample, the stoichiometry at transcript reference sites, and differential methylation between any two conditions. CHEUI processes observed and expected nanopore direct RNA sequencing signals to achieve high single-molecule, transcript-site, and stoichiometry accuracies in multiple tests using synthetic RNA standards and cell line data. CHEUI’s capability to identify two modification types in the same sample reveals a co-occurrence of m6A and m5C in individual mRNAs in cell line and tissue transcriptomes. CHEUI provides new avenues to discover and study the function of the epitranscriptome.

Insecticidal interventions at critical stages of maize are an important strategy for managing invasive insect pest fall armyworm (FAW) Spodoptera frugiperda (J.E. Smith). Conventional spraying systems cannot be used over larger areas, and the insecticide application using unmanned aerial vehicles is becoming popular among peasants. As the FAW resides inside the maize whorls, targeted insecticide application is necessary for effective management. The efficacy of (UAV) spray with different types of nozzles was compared with the conventional spray system, namely high-volume spray and Control droplet applicator. The other spray systems' droplet density, efficacy, and residues of insecticides in plants, soil and water were studied. The UAV droplet density up to 5 m swath recorded no significant variation for both nozzles. A UAV with an atomizer nozzle was as effective as a high-volume spray in reducing the FAW infestation. The residue analysis of leaf samples from the study area revealed more residues in the control droplet applicator and UAV atomizer nozzle. The per cent reduction of initial deposits in the top, middle and bottom maize leaves was least in the UAV atomizer nozzle. The insecticide residues in the study sample area were also below the detectable limit. UAV usage in maize saves time and reduces FAW damage as that of high-volume sprayers.

An experiment was conducted during 2021–22 and 2022–23 at the research farm of Punjab Agricultural University, Ludhiana, Punjab to optimize organic nutrition and planting geometry for improved productivity and profitability of sesame (Sesamum indicum L.)-chickpea (Cicer arietinum L.) organic cropping system. The experiment was conducted in a split-plot design (SPD) with three organic nutrition management practices in main plots, viz. Application of farmyard manure (FYM) to supply recommended doses of nitrogen (RDN) i.e. 52.5 kg/ha for sesame and 15 kg/ha for chickpea; Application of FYM to supply RDN + natural farming concoctions (NFCs) i.e. beejamrit, ghanjeevamrit and jeevamrit; and Control i.e. without application of FYM and NFCs. In sub-plots, four planting geometries were evaluated for sesame (30 cm × 15 cm, 45 cm × 10 cm, 60 cm × 10 cm, and paired rows) and chickpea (30 cm × 10 cm, 45 cm × 7 cm, 60 cm × 7 cm, and bed planting). Application of FYM significantly improved growth, yield attributes and seed yield of sesame and chickpea compared to the control, whereas the addition of NFCs along with FYM did not further enhance these parameters significantly during both the years. Paired row sowing followed by (fb) bed formation led to notably higher seed yield in sesame, while chickpea sown at 30 cm × 10 cm spacing achieved the highest seed yield, statistically equivalent to sowing at 45 cm × 7 cm and bed planting. The most productive system, recorded a sesame equivalent yield of 18.1 q/ha, net returns of ₹1,06,224/ha, and a benefit cost (B:C) ratio of 1.51, achieved through paired row sowing of sesame and bed planting of chickpea. Conclusively, the optimized organic nutrition and planting geometry significantly enhanced the productivity and profitability of the sesame-chickpea cropping system, with paired row sowing and bed planting emerging as the most effective strategies.

IntroductionThe economic importance of quinoa is not only due to the possibility of using the seeds as a food product characterized by a similar composition and use as consumer cereals but the species can also be managed as a leafy vegetable with high nutritional value and similar uses, such as, for example, spinach. Drought is another environmental stressor for plants subjected to severe water stress, especially in semi-arid and arid environments. Water scarcity poses a considerable challenge to crop production, leading to a notable reduction in crop yield. Quinoa, however, boasts low water requirements and demonstrates resilience in drought conditions. Even during dry periods, quinoa can effectively sustain leaf area and regulate photosynthetic activity. This resilience is facilitated by structural characteristics such as small, thin-walled cells, tissue flexibility, low osmotic potential, and controlled leaf area reduction through dehiscence. Other quinoa features for sustaining turgor pressure through osmotic adjustment during drought stress include inorganic ion buildup (e.g., Ca, K, and Na) and improved organic element synthesis (carotenoids and proline). Quinoa genotypes have several drought-resistance mechanisms, enabling this crop to grow and develop under severe drought conditions. Materials and MethodsTo evaluate the effect of moisture levels on some quinoa cultivars biochemical traits, four separate experiments were conducted in a factorial layout based on randomized complete block design with three replications in two regions (Birjand and Sarbisheh) and two planting dates (March and July/August) in 2018-2019. The experimental factors included five moisture levels (25, 50, 75, 100, and 125% of crop water requirement) and three quinoa cultivars (Titicaca, Giza1, and Redcarina). Some quinoa physiological and biochemical traits were evaluated by composite analysis at the 50% flowering stage and the effects of planting date and location were considered fixed.Results and DiscussionThe results showed that in August/July cultivation, the characteristics of RWC, electrolyte leakage, sodium percentage, potassium percentage, chlorophyll a, carotenoids, proline content, and total soluble carbohydrate of leaves were increased by 17.10, 74.62, 95.51, 31.9, 3.53, 38.65, 94.19 and 9.30% respectively and chlorophyll b content decreased by 13.15% compared to March culture. Also, in Sarbisheh, RWC, electrolyte leakage, potassium percentage, and leaf carotenoids are respectively 3.53, 38.65, 94.19 and 9.30% more than Birjand, but sodium percentage, chlorophyll a, chlorophyll b, proline and total soluble carbohydrates of leaves were 4, 1.88, 15.67, 51.02 and 30.41% less than Birjand, respectively. In most of the studied traits, the Giza1 cultivar had higher quality traits. Severe water scarcity resulted in an elevation of certain biochemical traits in quinoa leaves. Specifically, as moisture levels decreased from 125% to 25% of the water requirement, there was a significant increase in electrolyte leakage, sodium and potassium percentages, chlorophyll a and b, carotenoids, proline, and total leaf soluble carbohydrates by 24.50%, 37.84%, 35.89%, 24.83%, 59.12%, 48.75%, 51.58%, and 36.71%, respectively. However, the relative water content (RWC) decreased by 17.70%. Notably, there were no significant differences observed between the 125% and 100% levels of water requirement for most of the analyzed traits.ConclusionIn general, with the significance of the triple interaction of planting date × location × cultivar, as a result, the reaction of each variety depends on the planting date and location of its planting. But in general, most of the quinoa leaf physiological and biochemical traits increased in August/July cultivation. In Birjand, due to the higher average temperature and other climatic parameters compared to Sarbisheh, and probably understanding the heat stress, traits such as photosynthetic pigments, proline, and soluble carbohydrates had higher values. In this research, the Giza1 was superior to the other two cultivars, and moisture stress caused a significant decrease in the water content of the leaves and a significant increase in quinoa leaves quality traits.

Introduction Obstructive sleep apnoea (OSA) is a common, but underdiagnosed, sleep disorder. If untreated, it leads to poor health outcomes, including Alzheimer’s disease, cancer, cardiovascular disease and all-cause mortality. Our aim is to determine the feasibility and cost-effectiveness of moving the testing for OSA into general practice and how general practitioner (GP)-based screening affects overall detection rates.Methods and analysis Randomised controlled trial of case finding of OSA in general practice using a novel Medicines and Healthcare products Regulatory Agency-registered device (AcuPebble SA100) compared with usual care with internal feasibility phase. A diverse sample of general practices (approximately 40) from across the West Midlands Clinical Research Network will identify participants from their records. Eligible participants will be aged 50–70 years with body mass index >30 kg/m2 and diabetes (type 1 or 2) and/or hypertension (office blood pressure >145/90 mm Hg or on treatment). They will exclude individuals with known OSA or chronic obstructive pulmonary disease, or those they deem unable to take part. After eligibility screening, consent and baseline assessment, participants will be randomised to either the intervention or control group. Participants in the intervention arm will receive by post the AcuPebble sleep test kit. Those in the control arm will continue with usual care. Follow-up questionnaires will be completed at 6 months. The study is powered (90%) to detect a 5% difference and will require 606 patients in each arm (713 will be recruited to each arm to allow for attrition). Due to the nature of the intervention, participants and GPs will not be blinded to the allocation.Outcomes Primary: Detection rate of moderate-to-severe OSA in the intervention group versus control group. Secondary: Time to diagnosis and time to treatment for intervention versus control group for mild, moderate and severe OSA; cost-effectiveness analysis comparing the different testing pathways.Ethics and dissemination The trial started on 1 November 2022. Ethical approval was granted from the South Central Oxford A Research Ethics Committee on 9 June 2023 (23/SC/0188) (protocol amendment version 1.3; update with amendment and approval to renumber to V2.0 on 29 August 2023). Patient recruitment began on 7 January 2024; initial planned end date will be on 31 April 2025.Results will be uploaded to the ISRCTN register within 12 months of the end of the trial date, presented at conferences, submitted to peer-reviewed journals and distributed via our patient and public involvement networks.The University of Warwick will act as the trial sponsor. The trial will be conducted in accordance with the Sponsor and Primary Care Clinical Trials Unit standard operating procedures.Trial registration number ISRCTN 16982033.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 has accumulated a series of point mutations and evolved into several variants of concern (VOCs), some of which are more transmissible and potentially more severe than the original strain. The most notable VOCs are Alpha, Beta, Gamma, Delta, and Omicron, which have spread to various parts of the world. This study conducted surveillance in Jashore, Bangladesh to identify the prevalence of SARS-CoV-2 coinfected with dengue virus and their genomic effect on the emergence of VOCs. A hospital-based COVID-19 surveillance from June to August, 2021 identified 9 453 positive patients in the surveillance area. The study enrolled 572 randomly selected COVID-19-positive patients, of which 11 (2%) had dengue viral coinfection. Whole genome sequences of SARS-CoV-2 were analyzed and compared between coinfection positive and negative group. In addition, we extracted 185 genome sequences from GISAID to investigate the cross-correlation function between SARS-CoV-2 mutations and VOC; multiple ARIMAX(p,d,q) models were developed to estimate the average number of amino acid (aa) substitution among different SARS-CoV-2 VOCs. The results of the study showed that the coinfection group had an average of 30.6 (±1.7) aa substitutions in SARS-CoV-2, whereas the dengue-negative COVID-19 group had that average of 25.6 (±1.8; P

Background: Type 2 Diabetes mellitus (T2DM) may affect the musculoskeletal (MSK) system in a variety of ways. The impacts can be debilitating enough to impair functional ability and quality of life. MSK complications are the most common endocrine arthropathies which are often under-recognized and poorly treated. This study was done to evaluate the prevalence of MSK complications and its correlation with microvascular complications of T2DM given the paucity of similar studies in India particularly South India. Materials and Methods: A cross-sectional study was conducted on 130 diabetic patients at a tertiary care hospital in Bengaluru. The patient's demographic details, clinical profile including history, general physical examination, systemic examination, and relevant investigations were done to record microvascular complications. A thorough MSK system examination along with imaging of bones and joints was also performed. Results: Out of 130 diabetic patients, 21 patients (16.2%) had MSK complications of which 47.6% (n = 10) of them had carpal tunnel syndrome and 42.8% (n = 9) had frozen shoulder and 9.5% (n = 2) had diabetic amyotrophy. It was also noted that patients who were on oral hypoglycemic agents alone were more likely to develop MSK complications (57.14%) than patients solely on insulin (14.2%). Poor glycemic control, existing microvascular complications, and low high-density lipoprotein were found to be associated with increased risk of MSK complications. Conclusion: The prevalence of MSK complications in T2DM patients is quite significant and is also associated with microvascular complications. Improved glycemic control in T2DM was found to reduce the burden of such complications. Early identification of MSK complications can improve the quality of life in diabetic patients and hence demands proper screening and follow-up.

This scrutiny encounters the hydrothermal approach of binary nanocomposites V2O5/TiO2 (VT). The XRD pattern substantiated the formation of the binary composites with 18 nm of the crystallite size without any extraneous impurities. Whereas, HR-SEM implies the efficient bonding and homogeneous distribution between V2O5 and TiO2 nanoparticles, which provokes high electrochemical performances. Additionally, the BET analysis exposes the specific surface area to be 251 m2 g−1 with an average pore size of 3.14 nm for the VT nanocomposite. The electrochemical performances of the binary VT nanocomposite exhibit high specific capacitance of 443.7 Fg−1 at a current density of 1 Ag−1 with an excellent cyclic retention of 90 % even after successive 5000 cycles at 5 Ag−1. Therefore, the results obtained in this study clearly demonstrates that the binary nanocomposite VT would be a favorable electrode material for the commercial energy storage applications.

IntroductionDeficit irrigation offers a solution for optimizing crop production under water stress conditions, albeit with an initial reduction in yield per unit area. Employing deficit irrigation aids in farm management in scenarios where land availability isn’t constrained, enabling the determination of optimal cultivation patterns while conserving water consumption. However, deficit irrigation may influence plant growth and development by inducing drought stress. Due to several capabilities, quinoa shows resistance to solar radiation, temperature, water availability, and atmospheric CO2 concentration, which makes it possible to cultivate it in different agricultural areas. Quinoa also has a great capacity for cultivation in dry and low-water soils. Although growth analysis sometimes provides valuable clues, it does not provide any physicochemical information related to the environmental reactions of plants; in other words, the main benefit of many quantities involved in growth analysis is to provide an accurate estimate of the ability and efficiency of the plant in the community at certain time intervals. In general, growth analysis evaluates the system based on the results of physiological manifestations. The purpose of this research was to evaluate the physiological growth analyses of three quinoa cultivars under different moisture levels in summer and spring planting dates in the South Khorasan region.Materials and MethodsTo evaluate the physiological traits of three quinoa cultivars under deficit irrigation conditions, four separate experiments were conducted using a factorial layout based on a randomized complete block design. These experiments included three replications and were carried out in two regions (Birjand and Sarbisheh) during two planting dates (March and July) in 2018-2019. The experimental factors consisted of five moisture levels (ranging from 25% to 125% of crop water requirement) and three quinoa cultivars (Titicaca, Giza1, and Redcarina). To compare the cultivars and assess the impact of humidity levels, several physiological indices—such as leaf area index (LAI), crop growth rate (CGR), relative growth rate (RGR), and net assimilation rate (NAR)—were studied. Regression curves were fitted to the data from all four experiments separately, and separate analyses of variance were also performed for each sampling time.Results and DiscussionThe trend of changes in the leaf area index (LAI) showed that the time needed to reach the maximum LAI was observed between 106 to 107 days after emergence in March and between 73 to 76 days after emergence in July in Birjand, respectively. In Sarbisheh, the maximum LAI was observed on day 104 after emergence in March and between 65 to 72 days after emergence in July. In March, in both studied areas, Redcarina had the highest LAI values (4.5 in Birjand and 6.7 in Sarbisheh), along with the maximum crop growth rate (CGR) of 17.93 g m-2 day-1 in Birjand and 20.63 g m-2 day-1 in Sarbisheh. Conversely, in July, Giza1 exhibited the highest LAI (6.4 in Birjand and 6 in Sarbisheh), along with the maximum CGR of 19.32 g m-2 day-1 in Birjand and 18.11 g m-2 day-1 in Sarbisheh. Additionally, the highest relative growth rate (RGR) and net assimilation rate (NAR) at the beginning of the growing season in March were observed for Redcarina, while in July, Giza1 demonstrated the highest RGR and NAR in both studied areas. Considering the effect of humidity levels, the highest levels of LAI, CGR, RGR, and NAR indices were observed at the 125% water requirement level. Specifically, the maximum LAI values in March (in Sarbisheh and Birjand) and August (in Sarbisheh and Birjand) were 8.2, 5.3, 6.5, and 7.2, respectively. The maximum CGR values were 28.78, 23.56, 22.96, and 26.18 g m-2 day-1, respectively. Furthermore, the highest RGR at the beginning of the growing season ranged from 0.189 to 0.214 g g-1 day-1, and the highest NAR at the beginning of the growing season ranged from 6.16 to 10.22 g m-2 day-1. Conversely, the lowest values of these indices were observed at the 25% water requirement level.ConclusionOverall, Redcarina, cultivated in March, and Giza1, cultivated in July, exhibited the most favorable growth analysis indices and grain yield compared to other cultivars. Additionally, deficit irrigation resulted in a decrease in all of these indices and grain yield.

Introduction: Diabetic neuropathy is a common complication, affecting up to half the diabetics. Diabetic peripheral neuropathy (DPN) predominantly affects the hands and lower limbs. It leads to loss of protective sensation, resulting in continuous injury to insensitive feet. The early detection of DPN using an objective screening test followed by its appropriate management is important, as up to 50% of diabetic peripheral neuropathies may be asymptomatic. Objectives: To screen diabetic patients attending a Rural Health and Training Centre of a medical college in Tamil Nadu for DPN. To assess the association between DPN and sociodemographic factors, duration of diabetes, glycemic control, physical activity, body mass index, smoking and habit of alcohol consumption. Materials and Methods: The study was conducted among 206 diabetic patients attending a Rural Health and Training Centre. Participants were assessed using the Michigan Neuropathy Screening Instrument (MNSI), which involves using a questionnaire followed by a physical examination. Results: Of the 206 patients, 61.2% were male, and 38.8% were female. The mean age was 50.86 years (standard deviation [SD] = 12.26 years). The mean duration of diabetes was 8.3 years (SD = 5.5 years). The proportion of diabetics who were screened positive for peripheral neuropathy was 16.5% and 21.8% using the MNSI questionnaire and examination, respectively. Age of 60 years and above was significantly associated with DPN.(OR = 3.982, P value = 0.0001). Duration of more than 5 years of diabetes was also significantly associated with DPN.(OR = 6.01, P value = 0.003). Conclusion: A high proportion of diabetics were screened positive for peripheral neuropathy, and many of them were unaware of having the complication. Many risk factors associated with DPN were reported in this study. Thus, early diagnosis and management with MNSI or any other validated screening tool in health care institutions is essential.

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health.Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86).Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need.Trail registration number ISRCTN10980107.

Summary: Background: Neuroimaging-based brain-age delta has been shown to be a mediator linking cardiovascular risk factors to cognitive function. We aimed to assess the mediating role of brain-age delta in the association between modifiable risk factors of dementia and longitudinal cognitive decline in middle-aged and older individuals who are asymptomatic, stratified by Alzheimer's disease pathology. We also explored whether the mediation effect is specific to cognitive domain. Methods: In this cohort study, we included participants from the ALFA+ cohort aged between 45 years and 65 years who were cognitively unimpaired and who had available structural MRI, cerebrospinal fluid β-amyloid (Aβ)42 and Aβ40 measurements obtained within 1 year of each other, modifiable risk factors assessment, and cognitive evaluation over 3 years. Participants were recruited from the Barcelonaβeta Brain Research Center (Barcelona, Spain). Included individuals underwent a first assessment between Oct 25, 2016, and Jan 28, 2020, and a follow-up cognitive assessment 3·28 (SD 0·27) years later. We computed brain-age delta and composites of different cognitive function domains (preclinical Alzheimer's cognitive composite [PACC], attention, executive function, episodic memory, visual processing, and language). We used partial least squares path modelling to explore mediation effects in the associations between modifiable risk factors (including cardiovascular, mental health, mood, metabolic or endocrine history, and alcohol use) and changes in cognitive composites. To assess the role of Alzheimer's disease pathology, we computed separate models for Aβ-negative and Aβ-positive individuals. Findings: Of the 419 participants enrolled in ALFA+, 302 met our inclusion criteria, of which 108 participants were classified as Aβ-positive and 194 as Aβ-negative. In Aβ-positive individuals, brain-age delta partially mediated (percent mediation proportion 15·73% [95% CI 14·22–16·66]) the association between modifiable risk factors and decline in overall cognition (across cognitive domains). Brain-age delta fully mediated (mediation proportion 28·03% [26·25–29·21]) the effect of modifiable risk factors on the PACC, wherein increased values for risk factors correlated with an older brain-age delta, and, consequently, an older brain-age delta was linked to greater PACC decline. This effect appears to be primarily driven by memory decline. Mediation was not significant in Aβ-negative individuals (3·52% [0·072–4·17]) on PACC, although path coefficients were not significantly different from those in the Aβ-positive group. Interpretation: Our findings suggest that brain-age delta captures the association between modifiable risk factors and longitudinal cognitive decline in middle-aged and older people. In asymptomatic middle-aged and older individuals who are Aβ-positive, the pathology might be the strongest driver of cognitive decline, whereas the effect of risk factors is smaller. Our results highlight the potential of brain-age delta as an objective outcome measure for preventive lifestyle interventions targeting cognitive decline. Funding: La Caixa Foundation, the TriBEKa Imaging Platform, and the Universities and Research Secretariat of the Catalan Government. Translation: For the Spanish translation of the abstract see Supplementary Materials section.

BackgroundHIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach.Methods and findingsHPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value ≤0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time.ConclusionsIn this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings.Trial registrationClinicalTrials.gov: NCT01900977.

An experiment was conducted to evaluate the effect of dietary supplementation of Ficus hookeri leaf meal as herbal feed additive on rumen protozoal population, enzyme profile and fermentation characteristics in growing crossbred calves. Ten growing male crossbred (Jersey × Tharparker) calves with similar initial body weight of 91.8+1.37 kg, were randomly divided into two equal groups (T1 and T2) and fed individually under stall feeding for 140 days on a mixed ration containing rice straw and concentrate mixture in 50:50 ratio. Two types (C1 and C2) of iso-nitrogenous concentrate mixtures were prepared. Wheat bran in concentrate mixture (C2) of test group (T2) was partially replaced (4 parts w/w) with Ficus hookeri leaf meal. Daily dry matter intake between two experimental groups was similar. Rumen pH, NH3-N concentration and total rumen protozoal population decreased while ruminal TVFA and propionic acid production increased due to dietary supplementation of Ficus hookeri leaf meal as herbal feed additive. Activity of carboxymethyl cellulase, xylanase and b-glucosidase enzymes were significantly higher in the rumen liquor of calves fed Ficus hookeri leaf meal. It could be concluded that dietary supplementation of Ficus hookeri leaf meals as herbal feed additive have a potential for reducing rumen protozoal population and ammonia nitrogen concentration with improving ruminal TVFA and propionate production in growing crossbred calves.

Delineating spatial boundaries that accurately encompass complex, often cryptic, life histories of highly migratory marine megafauna can be a significant conservation challenge. For example, marine turtles range across vast ocean basins and coastal areas, thus complicating the evaluation of relative impacts of multiple overlapping threats and the creation of coherent conservation strategies. To address these challenges, spatially explicit ‘regional management units’ (RMUs) were developed in 2010 for all marine turtle species, globally. RMUs were intended to provide a consistent framework that organizes conspecific assemblages into units above the level of nesting rookeries and genetic stocks, but below the species level, within regional entities that may share demographic trajectories because they experience similar environmental conditions and other factors. From their initial conception, RMUs were intended to be periodically revised using new information about marine turtle distributions, life history, habitat use patterns, and population structure. Here, we describe the process used to update the 2010 RMU framework by incorporating newly published information and inputs from global marine turtle experts who are members of the IUCN Marine Turtle Specialist Group. A total of 48 RMUs for 6 of 7 marine turtle species and 166 distinct genetic stocks for all 7 species are presented herein. The updated RMU framework reflects a significant advance in knowledge of marine turtle biology and biogeography, and it provides improved clarity about the RMU concept and its potential applications. All RMU products have been made open access to support research and conservation initiatives worldwide.

Objective: The European Registries for Rare Endocrine Conditions (EuRRECa, eurreb. eu) includes an e-reporting registry (e-REC) used to perform surveillance of conditions within the European Reference Network (ERN) for rare endocrine conditions (Endo-ERN). The aim of this study was to report the experience of e-REC over the 3.5 years since its launch in 2018. Methods: Electronic reporting capturing new encounters of Endo-ERN conditions was performed monthly through a bespoke platform by clinicians registered to participate in e-REC from July 2018 to December 2021. Results: The number of centres reporting on e-REC increased to a total of 61 centres from 22 countries. A median of 29 (range 11, 45) paediatric and 32 (14, 51) adult centres had reported cases monthly. A total of 9715 and 4243 new cases were reported in adults (age ≥18 years) and children, respectively. In children, sex development conditions comprised 40% of all reported conditions and transgender cases were most frequently reported, comprising 58% of sex development conditions. The median number of sex development cases reported per centre per month was 0.6 (0, 38). Amongst adults, pituitary conditions comprised 44% of reported conditions and pituitary adenomas (69% of cases) were most commonly reported. The median number of pituitary cases reported per centre per month was 4 (0.4, 33). Conclusions: e-REC has gained increasing acceptability over the last 3.5 years for capturing brief information on new encounters of rare conditions and shows wide variations in the rate of presentation of these conditions to centres within a reference network. Significance statement Endocrinology includes a very wide range of rare conditions and their occurrence is often difficult to measure. By using an electronic platform that allowed monthly reporting of new clinical encounters of several rare endocrine conditions wi thin a defined network that consisted of several reference centres in Europe, the EuRRECa project shows that a programme of e-surveillance is feasible and acceptable. The data that have been collected by the e-reporting of rare endocrine conditions (e-REC) can allow the continuous monitoring of rare conditions and may be used for clinical benchmarking, designing new studies or recruiting to clinical trials.

Enzootic bovine leucosis is caused by bovine leukaemia virus (BLV), a Deltaretrovirus belonging to the family Retroviridae. BLV causes huge economic losses to the dairy industry in the form of decreased milk production, premature culling, and poor reproductive performance of the animals. The aim of the present study was to determine the seroprevalence of BLV infection in buffalo in two districts of Punjab, Pakistan. A total of 384 samples were collected and analysed using a commercial indirect enzyme-linked immunosorbent assay (ELISA) to investigate the seroprevalence of BLV through the detection of the anti-BLV gp51 antibody. A predesigned data questionnaire proforma was employed to find out the association of risk factors with disease. Overall, 18.2% of buffaloes were seropositive for BLV in the study population. The results revealed a significant association (P

The resistance of the Haemonchus contortus, a parasite causing severe anemia in ruminants, to commercial anthelmintics emphasizes the need for alternative bio-anthelmintics. This study aimed to identify the molecular, chemical composition, and in vitro anthelmintic activity of Sargassum duplicatum against H. contortus. Molecular identification employed the Chelex method, with DNA diversity and phylogeny assessed using maximum likelihood in IQ-tree. The analyzed chemical composition included proximate, total flavonoid, and total phenols. Adult worm motility test (AWMT) and egg hatch inhibiting test (EHIT) were conducted at concentrations of 2, 4, and 6 mg/mL of S. duplicatum ethanolic extract. AWMT followed a completely randomized factorial design (5 replications, each with 5 worms), while EHIT used a completely randomized one-way design (5 replications, each with H. contortus egg batches from 3 adult female worms). The cox1 gene sequence revealed the Sargassum sample as S. duplicatum (KP101270.1) with 99.83% similarity. The results indicated that the identified concentrations of S. duplicatum ethanolic extract, and the observation time significantly influenced motility and egg hatchability (p

Introduction SARS-CoV-2 was declared as a global pandemic by World Health Organization (WHO) owing to its high infectivity and pathogenicity that has been quickly entangling the world since its first reported outbreak in China in December, 2019. The main objectives of the present work were to quantify the influence of age, duration of hospitalization, duration of presenting symptoms and comorbidities on the probability of mortality from COVID-19 disease. Methods This was a cohort study involving adult in-patients (30th April to 31st December’20) with laboratory-confirmed (RT-PCR) COVID-19 at Sanjay Gandhi and Gandhi Memorial Hospital, Rewa, Madhya Pradesh, India, whose data was retrospectively extracted from hospital records. These files were selected randomly attributing to 25% of the total number of in-patients fulfilling the inclusion and exclusion criteria. Out of the 131 cases, 26 cases were deceased while 105 cases were recovered. A binary logistic regression analysis was employed to quantify various factors responsible for mortality among COVID-19 patients. Results The result showed that age & duration of presenting symptoms had a positively significant influence on COVID- 19 mortality. Based on the binary logistic regression model, there is an increased risk of COVID-19 mortality of 1.028 per year of age & 1.213 times per day of presenting symptoms. Further analysis also showed that COVID-19 patients who was hospitalized since 10 days, was approximately 8 times less likely to die as compared to a COVID-19 patient who was hospitalized since 1 day. This is explained by the presence of co morbidities among older aged patients as reported in previous literature. Discussion Among several factors contributing to mortality; in particular, older age and duration of presenting symptoms was associated with higher odds of in-hospital death, while duration of hospitalization with lower odds of in hospital death. The current study confirmed that increased age was associated with death in patients with COVID-19.

An experiment was conducted during 2019, 2020 and 2021 at Centre of Excellence in Millets, (Tamil Nadu Agricultural University, Coimbatore, Tamil Nadu), Athiyandal, Tiruvanamalai, Tamil Nadu. to study the performance of little millet (Panicum flexuosum Retz.) based cropping system for rainfed agro ecosystems for north-eastern part of Tamil Nadu. The experiment was laid out in randomized block design (RBD) comprised of 9 treatments, viz. T1, Little millet + Redgram [Cajanus cajan (L.) Millsp.] (4:1)-Moth bean [Vigna aconitifolia (Jacq.) Marechal]; T2, Little millet + Redgram (4:1)-Blackgram [Vigna mungo (L.) Hepper]; T3, Little millet + Redgram (4:1)-Horsegram [Macrotyloma uniflorum (Lam.) Verdc.]; T4, Little millet + Redgram (6:2)-Moth bean; T5, Little millet + Redgram (6:2)-Blackgram; T6, Little millet + Redgram (6:2)-Horsegram; T7, Little millet + Redgram (8:2)- Mothbean; T8, Little millet + Redgram (8:2)-Blackgram; T9, Little millet + Redgram (8:2)- Horsegram, with three replications. The good quality seeds of little millet (CO 4), redgram (Paiyur 2), horsegram (Paiyur 2), blackgram (VBN 3) and mothbean [TMV (Mb) 1] were used. The result shows that the higher yield for little millet and intercropped redgram was recorded in T9 (985 and 362 kg/ha) followed by T7 (853 and 356 kg/ha) and T8 (834 and 337 kg/ ha). The 8:2 row ratio exhibited the highest little millet equivalent yield when compared to 6:2 and 4:1 row ratio. The highest economic return and benefit cost (B:C) ratio was observed in T9 with gross return of ₹60,962/ha, net returns of ₹35,362/ha and B:C ratio (2.38). This was followed by T7 which had gross returns of ₹51,314/ha, net returns of ₹25,989/ha and B:C ratio (2.10).

Objectives This study aims to evaluate the prevalence and associated factors of lower back pain (LBP) among farmers, rickshaw pullers and office workers in Bangladesh, while also investigating potential contributors within these occupational groups.Design This cross-sectional study aimed to determine the prevalence of LBP, associated factors and management procedures among farmers, rickshaw pullers and office workers in Bangladesh through face-to-face interviews.Setting The study was conducted in different parts of the Bogura district in Bangladesh.Participants A total of 396 participants were included in the final analysis, all the participants were men and adult in age.Main outcome measurements Data were collected using a semi-structured questionnaire based on previous research. Bivariate and multivariable logistic regression analyses were performed to identify significant associations.Results The prevalence of LBP was found to be 42.7% among the participants. Farmers and rickshaw pullers had approximately four-times and three-times higher odds of experiencing LBP compared with office workers. Other significant factors associated with LBP included living in a nuclear family, having a normal body weight, lacking professional training, having a chronic disease, having a family history of LBP and experiencing numbness in the legs or feet. The majority of respondents sought medical attention and took medication for their LBP.Conclusion The study underscores occupational differences in LBP prevalence, emphasising the necessity for tailored interventions and occupational health policies. Identifying specific risk factors and management practices in these professions can aid in developing effective prevention strategies and enhancing healthcare services.

Dental casting machine is an electrical device used to extrude molten materials to fabricate dental prostheses such as crowns, bridges, intracoronal and extracoronal restorations, and removable partial dentures. The casting process basically include melting and casting. Firstly, the solid material is heated in a crucible in temperature-controlled conditions to melt the material to its smelled form. The dental casting process is a complex one with multifaceted steps and equipment. Different types of casting machines are available to produce heat using different sources and techniques. It includes Arc melting, Open flame casting, and Electrical resistance. Arc melting involves the application of an electric or gas discharge on tungsten electrodes, causing the metal base to melt utilizing the heat produced by arcing. Open flame casting or induction melting employs water-cooled alternate current induction coils to induce heat. However, resistance heating uses electric current to melt precious metals.

Abstract One‐third of newly diagnosed adult acute myeloid leukaemia (AML) carry FLT3 mutations, which frequently occur together with nucleophosmin (NPM1) mutations and are associated with worse prognosis. FLT3 inhibitors are widely used in clinics with limitations due to drug resistance. AML cells carrying FLT3 mutations in both mouse models and patients present low expression of GATA1, a gene involved in haematopoietic changes preceding AML. Here, we show that FLT3 inhibition induces cellular responses and restores the GATA1 pathway and functions in NPM1/FLT3‐ITD mutated AML, thus providing a new mechanism of action for this drug.

Background & aim: HIV/AIDS is a major health concern globally. Promoting HIV AIDS literacy for everyone is one of the appropriate and required measures in this regard. The present research aimed to improve HIV/AIDS literacy among male teachers in high schools of Ahvaz. Methods: The present field-trial study was conducted on 200 male teachers of the first and second high schools of Ahvaz. The study population was randomly divided into intervention (n=100) and control (n=100) groups. The Iranian HIV/AIDS Literacy Questionnaire was used to collect data. According to easy-to-read texts and alternative communication tools strategies, HIV/AIDS Literacy intervention was developed. The intervention included developing an educational pamphlet and sending SMS to the intervention group. One month after the intervention, the questionnaire was completed again and analyzed by SPSS software using logistic regression and t-test. Results: The age mean and standard deviation of the participants was 41.60 ± 7.80. At the baseline, the mean and standard deviation of HIV/AIDS literacy was 11.1 ± 3.46 in the intervention group and 9.63 ± 2.54 in the comparison group. After the intervention, the score of HIV/AIDS literacy significantly improved in the intervention group (P

To accommodate the changes in the nature and the pattern of electricity consumption with the available resources, utilities have introduced variety of tariffs over the years. This paper develops a comprehensive optimization framework that addresses the challenges associated with the diversity of utility tariffs for commercial loads. Optimization of commercial building net load through Battery Energy Storage System (BESS) and renewable energy resources is modeled and explored for minimizing billing cost for different tariffs. Cost functions are formulated for each possible commercial utility tariff type, engendering the universal cost function format. An algorithm is developed to apply the optimization model and generate the desired optimal outputs (e.g., optimal net load and BESS power, costs and savings, etc.). The results for several building loads and all tariff types are compared and analyzed to present the findings. An impacts analysis is performed to observe how different changes in tariffs affect the optimizations results. Results exhibit that for same building load and renewable generation, the tariff type can have an overwhelming impact on costs and savings. Tariffs without Time of Use (TOU) charges or peak demand charge components offer lower savings opportunity from BESS optimization. Price change sensitivities showed the complicated dynamics among TOU price components on savings and historical trend analysis as an effective tool to predict future savings. Tradeoff between energy and demand charge heavy tariff options are also discussed for user benefit. The recent change in TOU time periods presents limited desired benefits while the modified tariff proposed in this paper exhibit significant improvement in terms of utility operation.

Objective: Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007–2017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model. Methods: Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed. Results: The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model’s performance. Conclusions: The PPV improved significantly (26–48%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.

Abstract Background Stress and mental disorders in pregnancy can adversely affect the developing fetus. Women with a preconception history of mental disorders or of psychosocial vulnerabilities are at increased risk of experiencing perinatal stress or mental health problems. Mindfulness-Based-Stress-Reduction (MBSR) is an acceptable intervention for pregnant women and has a growing evidence-base with meta-analyses consistently pointing to reductions in symptoms of stress, anxiety and depression. This study protocol aim to address the need for a wider array of evidence-based and non-pharmacological options during pregnancy to reduce stress and improve mental health in a psychosocially highly vulnerable group of women. Methods Pregnant women with a preconception history of mental disorders or psychosocial vulnerabilities (n = 240) will be recruited from an obstetric ambulatory clinic at Copenhagen University Hospital, Hvidovre, Denmark. Recruitment for the study began in March 2022 and will continue until the desired number of participants is reached. Consenting pregnant women will be randomized to one of two study arms, an adapted MBSR program as add on to usual care or usual care alone. The primary outcome is mental wellbeing at nine months post-randomization. Secondary and exploratory outcomes include stress, anxiety, depression, and maternal antenatal attachment, experience of childbirth, delivery and mode of delivery. Mindfulness and self-compassion are examined as possible mediators of the effect on outcomes. Discussion Teaching the skills of mindfulness meditation to a psychosocially vulnerable group of pregnant women could prove a viable and non-pharmacological approach to improve mental health and wellbeing during pregnancy, reduce stress and support the transition to parenthood. Mindfulness-Based Stress Reduction does not target a particular group, and results from the study is thus of potential relevance for pregnant women in general as a means of reducing stress and improving perinatal mental health and wellbeing. Trial registration ClinicalTrials.gov: NCT05300646 . Registered March 29, 2022.

Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

Nowadays, hulless barley (Hordeum vulgare L.) is gaining importance as a raw material for food industry due to its highly nutritive value. Non-availability of high yield and disease resistant varieties has restricted its production in marginal areas over the last two decades. Therefore, an experiment was conducted during 2017–18 and 2018–19 at the Seed and Research Farm of ICAR-Indian Institute of Wheat and Barley Research, Karnal, Haryana to characterized 11 exotic hulless barley genotypes and 4 Indian barley cultivars for morpho-physiological characters and stripe rust resistance. Seedling resistant test for stripe rust was done at Regional Station (ICAR-Indian Institute of Wheat and Barley Research), Flowerdale, Shimla, Himachal Pradesh. Highly significant genotypic differences were found for morpho-physiological traits during analysis of variance. Genotype DWRNB28 showed a good combination of desirable traits, viz. early maturity (118 days), dwarf plant height (64.4 cm) and high 1000-grain weight (55.2 g). Maximum number of tillers per meter (149) was observed in DWRNB17. Genotype DWRNB25 was found resistant to maximum pathotypes (6S0, 7S0, and Q) at the seedling stage. DWRNB23 and DWRNB25 with pooled ACI=0 and ACI=0.04 respectively, were found immune to stripe rust in field conditions. These promising genotypes can be utilized as donor parents for the development of high-yielding and stripe-rust-resistant hulless barley varieties.

While numerous studies have assessed the association between temperature and diarrhoea in various locations, evidence of relationship between heat wave and diarrhoea is scarce. We defined elevated daily mean and maximum temperature over the 95th and 99th percentiles lasting for at least one day between March to October 1981-2010 as TAV95 and TAV99 and D95 and D99 heat wave, respectively. We investigated the association between heat wave and daily counts of hospitalisations for all-cause diarrhoea in Dhaka, Bangladesh using time series regression analysis employing constrained distributed lag-linear models. Effects were assessed for all ages and children aged under 5 years of age. Diarrhoea hospitalisation increased by 6.7% (95% CI: 4.6%- 8.9%), 8.3% (3.7-13.1), 7.0 (4.8-9.3) and 7.4 (3.1-11.9) in all ages on a TAV95, TAV99, D95 and D99 heat wave day, respectively. These effects were more pronounced for under-5 children with an increase of 13.9% (95% CI: 8.3-19.9), 24.2% (11.3-38.7), 17.0 (11.0-23.5) and 19.5 (7.7-32.6) in diarrhoea hospitalisations on a TAV95, TAV99, D95 and D99 heat wave day, respectively. At lags of 3 days, we noticed a negative association indicating a 'harvesting' effect. Our findings suggest that heat wave was a significant risk factor for diarrhoea hospitalisation in Dhaka. Further research is needed to elucidate the causal pathways and identify the preventive measures necessary to mitigate the impacts of heat waves on diarrhoea. Given that no heat wave definitions exist for Dhaka, these results may help to define heat waves for Dhaka and trigger public health interventions including heat alerts to prevent heat-related morbidity in Dhaka, Bangladesh.

IntroductionMolecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting.MethodsThis multi-centre prospective study was designed to explore the performance of current clinical practice during the run-in phase using local SoC tissue profiling procedures. The subsequent phase was designed to investigate the extent to which comprehensive molecular profiling (CMP) can be maximized by protocolising tumour profiling. Successful molecular profiling was defined as completion of at least EGFR and ALK testing. Additionally, PD-L1 tumour proportions scores were explored. Lastly, the additional value of centralised plasma-based testing for EGFR and KRAS mutations using droplet digital PCR was evaluated.ResultsTotal accrual was 878 patients, 22.0% had squamous cell carcinoma and 78.0% had non-squamous NSCLC. Stage I-III was seen in 54.0%, stage IV in 46.0%. Profiling of EGFR and ALK was performed in 69.9% of 136 patients included in the run-in phase, significantly more than real-world data estimates of 55% (pConclusionThis study shows a high success rate of tissue-based molecular profiling that was significantly improved by a protocolised approach. Tissue-based profiling remains unfeasible for a substantial proportion of patients. Combined analysis of tumour tissue and circulating tumour DNA is a promising approach to allow adequate molecular profiling of more patients.

ObjectiveTo determine work participation, social roles, and empowerment of QFS patients ≥10-year after infection.MethodsQFS patients ≥10-year after acute infection, who were of working age, participated in a cross-sectional survey study. Work participation, fulfilment of social roles, and empowerment outcomes were studied for the total population, as well as for subgroups based on employment type and current work status. Associations between empowerment, work and social roles were examined.Results291 participants were included. Of the 250 participants who had paid work before Q-fever, 80.4% stopped working or worked less hours due to QFS. For each social role, more than half of the participants (56.6-87.8%) spent less time on the role compared to before Q-fever. The median empowerment score was 41.0 (IQR: 37.0-44.0) out of 60. A higher empowerment score was significantly associated with lower odds of performing all social roles less due to QFS (OR = 0.871-0.933; pConclusionWork participation and fulfilment of social roles is generally low in QFS patients. Many of the participants stopped working or are working less hours due to QFS, and most spent less time on social roles compared to before Q-fever. Minor variation was seen in total empowerment scores of participants; however, these slight differences were associated with the fulfilment of social roles, but not work participation. This new insight should be further explored in future studies.

A simple bedside triage tool is essential to stratify COVID-19 patients in the emergency department (ED). This study aimed to identify an early warning score (EWS) that could best predict the clinical outcomes in COVID-19 patients. Data were obtained from medical records of 219 laboratory-confirmed COVID-19 positive patients. We calculated 13 EWSs based on the admission characteristics of the patients. Receiver operating characteristic (ROC) curve analysis was used to assess the performance of the scores in predicting serious illness and in-hospital mortality. The median patient age was 51 (38, 60) years, and 25 (11.4%) patients died. Among patients admitted with mild to moderate illness (n = 175), 61 (34.9%) developed serious illness. Modified National Early Warning Score (m-NEWS) (AUROC 0.766; 95% CI: 0.693, 0.839) and Rapid Emergency Medicine Score (REMS) (AUROC 0.890; 95% CI: 0.818, 0.962) demonstrated the highest AUROC point estimates in predicting serious illness and in-hospital mortality, respectively. Both m-NEWS and REMS demonstrated good accuracy in predicting both the outcomes. However, no significant difference was found between m-NEWS (p = 0.983) and REMS (p = 0.428) as well as some other EWSs regarding the AUROCs in predicting serious illness and in-hospital mortality. We propose m-NEWS could be used as a triage score to identify COVID-19 patients at risk of disease progression and death especially in resource-poor settings because it has been explicitly developed for risk stratification of COVID-19 patients in some countries like China and Italy. However, this tool needs to be validated by further large-scale prospective studies.

Background Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Future estimations suggest an increase in global burden of AF greater than 60% by 2050. Numerous studies provide growing evidence that AF is not only associated with stroke but also with cognitive impairment and dementia.Aim The main goal is to assess the impact of the combined use of cardiac rhythm monitoring devices, echocardiography, biomarkers and neuroimaging on the early diagnosis of AF, silent strokes and cognitive decline, in subjects at high risk of AF.Methods and analysis Two-year follow-up of a cohort of individuals aged 65–85 years at high risk for AF, with no prior diagnosis of either stroke or dementia. The study involves baseline echocardiography, biomarkers, and neuroimaging, yearly cardiac monitoring, and semiannual clinical assessments. Different parameters from these tests will be analysed as independent variables. Throughout the study period, primary outcomes: new diagnoses of AF, stroke and cognitive impairment, along with any clinical and therapeutic changes, will be registered. A first descriptive and bivariate statistical analysis, appropriate to the types of variables, will be done. The information obtained from the data analysis will encompass adjusted risk estimates along with 95% confidence intervals. Event risk predictions will rely on multivariate Cox proportional hazards regression models. The predictive value of the model will be evaluated through the utilisation of receiver operating characteristic curves for area under the curve calculation. Additionally, time-to-event analysis will be performed using Kaplan-Meier curves.Ethics and dissemination This study protocol has been reviewed and approved by the Independent Ethics Committee of the Foundation University Institute for Primary Health Care Research-IDIAP Jordi Gol (expedient file 22/090-P). The authors plan to disseminate the study results to the general public through various scientific events. Publication in open-access journals and presentations at scientific congresses, seminars and meetings is also foreseen.Trial registration number NCT05772806.

Zanthoxylum rhetsa (ZR) is used traditionally to manage a variety of ailments, including diabetes. Oxidative stress may accelerate the diabetic condition. The available antidiabetic and antioxidant drugs have many shortcomings including resistance, inefficiency, higher dose, side effects and costs. The goal of the current investigation was to assess the antioxidant capacity and antidiabetic activity of an ethanolic extract of Zanthoxylum rhetsa root bark (ZRRB) through in vitro, in vivo, and in silico methods. The antioxidant capacity of the ZRRB extract was measured using both the DPPH radical assay and the total antioxidant activity test. The oral glucose tolerance test (OGTT) and alloxan-induced diabetic mice model were also used to examine in vivo antidiabetic efficacy. Phytochemicals identification was done by GCMS analysis. Additionally, computational methods such as molecular docking, ADMET analysis, and molecular dynamics (MD) modeling were performed to determine the above pharmacological effects. The extract demonstrated significant DPPH scavenging activity (IC50 = 42.65 μg/mL). In the OGTT test and alloxan-induced diabetes mice model, the extract effectively lowered blood glucose levels. Furthermore, in vitro inhibition of pancreatic α-amylase studies demonstrated the ZRRB extract as a good antidiabetic crude drug (IC50 = 81.45 μg/mL). GCMS investigation confirmed that the crude extract contains 16 major phytoconstituents, which were docked with human peroxiredoxin-5, α-amylase, and sulfonylurea receptor 1. Docking and pharmacokinetic studies demonstrated that among 16 phytoconstituents, 6H-indolo[3,2,1-de] [1,5]naphthyridin-6-one (CID: 97176) showed the highest binding affinity to targeted enzymes, and imitated Lipinski's rule of five. Furthermore, MD simulation data confirmed that the aforementioned compound is very steady to the binding site of α-amylase and sulfonylurea receptor 1 receptors. Findings from in vitro, in vivo and in silico investigation suggest that ZRRB extract contains a lead compound that could be a potent source of antidiabetic drug candidate.

BackgroundObsessive-compulsive disorder (OCD) is a highly prevalent neuropsychiatric disorder. Recently, there has been a growing interest in investigating the association between pro-inflammatory cytokines and the pathogenesis of OCD. However, studies targeting interleukin-1β (IL-1β) and interleukin-6 (IL-6) in OCD are limited. Therefore, the present study aimed to explore the potential role of pro-inflammatory cytokines IL-1β and IL-6 in the pathophysiology and development of OCD.MethodsThis study recruited 58 OCD patients and 30 age-sex-matched healthy controls (HCs). A qualified psychiatrist diagnosed OCD patients and assessed HCs based on the Diagnostic and Statistical Manual for Mental Health Disorders, 5th edition (DSM-5) criteria. We measured the severity of OCD using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Serum IL-1β and IL-6 levels were measured using ELISA kits following the appropriate methods.ResultsThe results showed that serum IL-1β levels were significantly elevated in OCD patients compared to HCs (23.68±1.65 pg/ml vs. 15.75±1.02 pg/ml; p = 0.002). Similarly, OCD patients exhibited significantly higher serum IL-6 levels than HCs (44.97±0.73 pg/ml vs. 37.04±0.35 pg/ml; pConclusionThese results suggest that serum IL-1β and IL-6 levels may be associated with the pathophysiology of OCD. Also, these cytokines levels in blood samples can serve as early risk assessment tools for the development of OCD. We recommend further studies in a large and homogeneous population to support these findings.

Musculoskeletal conditions affect an estimated 1.7 billion people worldwide, causing intense pain and disability. These conditions lead to 30 million emergency room visits yearly, and the numbers are only increasing. However, diagnosing musculoskeletal issues can be challenging, especially in emergencies where quick decisions are necessary. Deep learning (DL) has shown promise in various medical applications. However, previous methods had poor performance and a lack of transparency in detecting shoulder abnormalities on X-ray images due to a lack of training data and better representation of features. This often resulted in overfitting, poor generalisation, and potential bias in decision-making. To address these issues, a new trustworthy DL framework has been proposed to detect shoulder abnormalities (such as fractures, deformities, and arthritis) using X-ray images. The framework consists of two parts: same-domain transfer learning (TL) to mitigate imageNet mismatch and feature fusion to reduce error rates and improve trust in the final result. Same-domain TL involves training pre-trained models on a large number of labelled X-ray images from various body parts and fine-tuning them on the target dataset of shoulder X-ray images. Feature fusion combines the extracted features with seven DL models to train several ML classifiers. The proposed framework achieved an excellent accuracy rate of 99.2%, F1Score of 99.2%, and Cohen's kappa of 98.5%. Furthermore, the accuracy of the results was validated using three visualisation tools, including gradient-based class activation heat map (Grad CAM), activation visualisation, and locally interpretable model-independent explanations (LIME). The proposed framework outperformed previous DL methods and three orthopaedic surgeons invited to classify the test set, who obtained an average accuracy of 79.1%. The proposed framework has proven effective and robust, improving generalisation and increasing trust in the final results.

Toxoplasma gondii and Trichinella spp. are critical tissue-dwelling foodborne zoonotic parasites associated with pork consumption and pig rearing. Despite being a major pig-rearing region in the country, Northeastern India has not undergone any investigation regarding the presence of T. gondii and Trichinella spp. in pigs. Therefore, this study aims to determine the seroprevalence of T. gondii and Trichinella spp. and identify associated risk factors in pigs reared by tribal communities and small-holder livestock farmers in the northeastern region of India. In a cross-sectional serological survey, 400 pigs from 400 households across five northeastern states of India underwent testing for the seroprevalence of porcine toxoplasmosis and trichinellosis. Serum samples (80 from each state) were analyzed using commercially available ELISA assays. Data on backyard farm characteristics and various management aspects were collected, and risk factors linked with prevalence were analyzed through univariate and multivariate logistic regression analysis. The findings revealed that the apparent and true prevalence of anti-T. gondii antibodies were 45% (40.12-49.88, 95% CI) and 45.7% (40.7-50.69, 95% CI), respectively. As for anti- Trichinella antibodies, both the apparent and true prevalence were 0.75% (-0.1-1.6, 95% CI). The univariate and multivariate analyses indicated that age above 24 months (OR 7.20, 95% CI 2.45-23.71), exposure to cats (OR = 5.87, 95% CI 2.55-14.05), and farms operating for breeding purposes (OR = 5.60, 95% CI 3.01-11.04) were significant risk factors associated with the seroprevalence of T. gondii. This study marks the initial documentation of the seroprevalence of T. gondii and Trichinella spp. in pigs reared by tribal communities in Northeastern India. The results emphasize the significance of these parasites as foodborne zoonotic threats in the region, potentially posing substantial public health risks, especially within tribal and rural communities. The insights derived from this research could be valuable in formulating targeted preventive and control strategies against T. gondii and Trichinella spp. in pigs, not only in this region but also in areas with similar rearing practices.

Carbon foot prints (CFs) studies based on life cycle assessment between sheep farming systems and green house gases (GHG) emissions is one of the best indicators to quantify the amount of GHG emissions per kg of product. Therefore, a life cycle assessment (LCA) study was conducted for three different sheep farming systems i.e. intensive system (stall fed only), semi-intensive (grazing with supplementation) and extensive system (grazing only) under semiarid region of India to assess the carbon cost of sheep rearing. The total CFs were estimated to be 16.9, 15.8 and 17.1 kg CO2-eq in intensive, semi-intensive and extensive system of grazing indicating semi-intensive system to be most carbon (C) efficient. For 1kg mutton production in semi-intensive and intensive system, around 30% and 24% CFs were contributed from enteric fermentation and feed respectively, whereas, in extensive system, the contribution of enteric fermentation increased up to 50%. The carbon foot prints analysis gives an insight of carbon inputs used but the amount of CO2 sequestered in soil making LCA a holistic approach for estimating GHG emissions from livestock.

During striated muscle development the first periodically repeated units appear in the premyofibrils, consisting of immature sarcomeres that must undergo a substantial growth both in length and width, to reach their final size. Here we report that, beyond its well established role in sarcomere elongation, the Sarcomere length short (SALS) protein is involved in Z-disc formation and peripheral growth of the sarcomeres. Our protein localization data and loss-of-function studies in the Drosophila indirect flight muscle strongly suggest that radial growth of the sarcomeres is initiated at the Z-disc. As to thin filament elongation, we used a powerful nanoscopy approach to reveal that SALS is subject to a major conformational change during sarcomere development, which might be critical to stop pointed end elongation in the adult muscles. In addition, we demonstrate that the roles of SALS in sarcomere elongation and radial growth are both dependent on formin type of actin assembly factors. Unexpectedly, when SALS is present in excess amounts, it promotes the formation of actin aggregates highly resembling the ones described in nemaline myopathy patients. Collectively, these findings helped to shed light on the complex mechanisms of SALS during the coordinated elongation and thickening of the sarcomeres, and resulted in the discovery of a potential nemaline myopathy model, suitable for the identification of genetic and small molecule inhibitors.

Transducin β-like 1 X-linked receptor 1 (TBL1XR1) is a WD40 repeat-containing protein and part of the corepressor complex SMRT/NCoR that binds to the thyroid hormone receptor (TR). We recently described a mutation in TBL1XR1 in patients with Pierpont syndrome. A mouse model bearing this Tbl1xr1 mutation (Tbl1xr1Y446C/Y446C) displays several aspects of the Pierpont phenotype. Although serum thyroid hormone (TH) concentrations were unremarkable in these mice, tissue TH action might be affected due to the role of TBL1XR1 in the SMRT/NCoR corepressor complex. The aim of the present study was to evaluate tissue TH metabolism and action in a variety of tissues of Tbl1xr1Y446C/Y446C mice. We studied the expression of genes involved in TH metabolism and action in tissues of naïve Tbl1xr1Y446C/Y446C mice and wild type (WT) mice. In addition, we measured deiodinase activity in liver (Dio1 and Dio3), kidney (Dio1 and Dio3) and BAT (Dio2). No striking differences were observed in the liver, hypothalamus, muscle and BAT between Tbl1xr1Y446C/Y446C and WT mice. Pituitary TRα1 mRNA expression was lower in Tbl1xr1Y446C/Y446C mice compared to WT, while the mRNA expression of Tshβ and the positively T3-regulated gene Nmb were significantly increased in mutant mice. Interestingly, Mct8 expression was markedly higher in WAT and kidney of mutants, resulting in (subtle) changes in T3-regulated gene expression in both WAT and kidney. In conclusion, mice harboring a mutation in TBL1XR1 display minor changes in cellular TH metabolism and action. TH transport via MCT8 might be affected as the expression is increased in WAT and kidney. The mechanisms involved need to be clarified.

Thyroid hormone (TH) is indispensable for brain development in utero and during the first 2–3 years of life, and the negative effects of TH deficiency on brain development are irreversible. Detection of TH deficiency early in life by neonat al screening allows early treatment, thereby preventing brain damage. Inborn shortage of TH, also named congenital hypothyroidism (CH), can be the result of defective thyroid gland development or TH synthesis (primary or thyroidal CH (CH-T)). Primary CH is characterized by low blood TH and elevated thyroi d-stimulating hormone (TSH) concentrations. Less frequently, CH is due to insufficient stimulation of the thyroid gland because of disturbed hypothalamic or pituitary function (central CH). Central CH is characterized by low TH concentrations, while TSH is normal, lo w or slightly elevated. Most newborn screening (NBS) programs for CH are primarily TSH based and thereby do not detect central CH. Only a few NBS programs worldwide aim to detect both forms of CH by different strategies. In the Netherlands, we have a uni que T4–TSH–thyroxine-binding globulin (TBG) NBS algorithm for CH, which enables the detection of primary and central CH. Although the necessity of central CH detection by NBS is still under debate, it has been shown that most central CH patients have moderate-to-severe hyp othyroidism instead of mild and that early detection of central CH by NBS probably improves its clinical outcome and clinical care for central CH patients with multiple pituitary hormone deficiency. We are therefore convinced that detection of central CH by NBS is of utmost importance.

The present study aims to evaluate the prevalence and antimicrobial sensitivity of Staphylococcus aureus associated with bovine mastitis to selected antibiotics and plant extracts. In the current study, 140 milk samples were collected from cows and buffaloes. Among the 140 samples, 93 samples were positive for sub-clinical mastitis based on the California Mastitis Test (CMT). Out of the total positive samples, 45 were confirmed for S. aureus on a Mannitol salt agar media. The antimicrobial susceptibility test revealed that 44.82% of the isolates were resistant to cefoxitin (oxacillin) confirming methicillin-resistant S. aureus (MRSA) with a higher percentage (51.61%) in the buffalo than in the cow samples. Furthermore, the PCR assay confirmed the presence of the mecA gene in all the MRSA isolates. Among the seven tested antibiotics, sulfamethoxazole + trimethoprim showed high efficacy (71.1%) against methicillin-susceptible S. aureus isolates (MSSA). Oxytetracycline and sulfamethoxazole + trimethoprim showed 20% efficacy against MRSA followed by enrofloxacin (10%). On the other hand, the tested samples from Pistacia chinensis revealed that the ethyl acetate extract of bark showed a maximum zone of inhibition of 21.3 mm against MSSA and MRSA isolates at 3 000 µg/disc. Moreover, the methanol extract of Cotoneaster microphyllus formed a 12.3 mm and 9.1 mm zone of inhibition against the MSSA and MRSA isolates, respectively.

Introdução: A doação de sangue consiste em um procedimento seguro, predominantemente sem complicações. De acordo com o Marco Conceitual e Operacional de Hemovigilância da Agência Nacional de Vigilância Sanitária (ANVISA), ocasionalmente algum doador poderá apresentar reações adversas. Por reação adversa entende-se a resposta não intencional do doador, associada à coleta de unidade de sangue, hemocomponente ou células progenitoras hematopoiéticas. É muito raro o doador precisar ser hospitalizado, mas pode ocorrer. Entretanto a doação de sangue não é uma atividade perigosa ou que leve risco à saúde e à vida. É um ato de solidariedade. Conforme orientação da legislação vigente, o volume de sangue total a ser coletado deve ser de 450 ml +-45 ml, aos quais podem ser acrescidos 30 ml, no máximo, para exames laboratoriais. Materiais e métodos: Foi realizado um estudo retrospectivo a partir de outubro de 2019 até junho 2023. 54.903 doações de sangue total foram analisadas com o objetivo de verificar a frequência das reações adversas nos doadores do Banco de Sangue Vita Hemoterapia da Bahia, durante ou após o ato. Resultados: Das 54.903 doações de sangue analisadas no período (63% homens e 37% mulheres), 42.937 (78%) foram doações de 1ªvez e 11.969 (22%) foram de doadores que efetuaram mais de uma doação durante o período de estudo. Dessas doações analisadas, 1.378 eventos adversos foram observados no período, o que representa 2,5%. Do total de eventos adversos, não houve uma diferença relevante entre o sexo feminino e sexo o masculino, sendo 23,37% e 25,76% respectivamente. Foi constatado que houve prevalência de reação sistêmica/vasovagal (37%) seguida de reação local/hematoma (0,9%). Na reação vasovagal foram 513 manifestações clínicas encontradas destacando-se: tontura 88% (453), náuseas 2,14% (11), vômito 2,14% (11), palidez cutânea 1,9 % (10), desmaio 1,75% (9), hipotensão1,56% (8), convulsão 1,17% (6) e sudorese e hipertensão, 0,97% (5). As reações leves (tontura, palidez, náuseas, vômito) predominaram dentre os tipos de reações identificadas, com um total de 485 (94,5%) reações adversas; as reações moderadas (desmaio, hipotensão, hipertensão) vêm em seguida, com um percentual de 1,75%; por fim, a reação grave (convulsão) apresentou 1,17% de ocorrência. Após a doação, o doador recebe hidratação oral e é ofertado também um lanche para recuperação. São dadas orientações de como proceder no decorrer do dia e quais são as restrições exigidas e as atividades permitidas no dia da doação. Conclusão: Constatou-se que tontura, palidez cutânea, náuseas e vômito foram as manifestações clínicas mais recorrentes nas reações adversas analisadas. A equipe de enfermagem deve dar assistência diferenciada e maior atenção a estas reações, para que elas não se agravem e tragam prejuízos aos doadores. Apesar da pequena quantidade da reação local hematoma, a equipe de enfermagem também deve ficar atenta para orientar o doador sobre como proceder na prevenção do surgimento dele, e ao mesmo tempo disponibilizar um ambiente satisfatório para conforto, segurança e acolhimento visando a fidelização do doador e possibilitando a melhoria na qualidade da assistência de enfermagem prestada aos doadores de sangue.

Response of gerbera var. Arka Nesara was studied under different soil-less production systems with the aim to improve quality, productivity and water use efficiency, in completely randomized design with eight treatments viz., deep flow technique (DFT), nutrient film technique (NFT), aggregate wick system (AWS) with pots on NFT bench, AWS with pots on ground, AWS with grow bags on ground, AWS on soil bed, aeroponics and conventional soil-based drip system, which were replicated five times. Results revealed that AWS with pots on ground recorded maximum plant height (31.66 cm), leaf length (21.31 cm), leaf breadth (9.96 cm) and stalk diameter near neck (4.75 mm), minimum stem deviation (1.27 cm) and stem deflection (2.2o), prolonged vase life (9.2 days), greater water use efficiency (92 mL/plant/day) and water saving (83.46%). Hence, cultivation of gerbera var. Arka Nesara under aggregate wick system with pots on ground could be the superior alternative for traditional soil cultivation.