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Abstract This paper addresses the pressing issue of diabetes, which is a widespread condition affecting a huge population worldwide. As cells become less responsive to insulin or fail to produce it adequately, blood sugar levels rise. This has the potential to cause severe health complications including kidney disease, vision impairment and heart conditions. Early diagnosis is paramount in mitigating the risk and severity of diabetes-related complications. To tackle this, we proposed a robust framework for diabetes prediction using Synthetic Minority Over-sampling Technique (SMOTE) with ensemble machine learning techniques. Our approach incorporates strategies such as imputation of missing values, outlier rejection, feature selection using correlation analysis and class distribution balancing using SMOTE. The extensive experimentation shows that the proposed combination of AdaBoost and XGBoost shows exceptional performance, with an impressive AUC of 0.968+/-0.015. This outperforms not only alternative methodologies presented in our study but also surpasses current state-of-the-art results. We anticipate that our model will significantly improve diabetes prediction, offering a promising avenue for improved healthcare outcomes in diabetes management.

Dual inhibition of the angiopoietin (Ang)/Tie and vascular endothelial growth factor (VEGF) signalling pathways in patients with retinal diseases, such as neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DME), may induce greater vascular stability and contribute to increased treatment efficacy and durability compared with treatments that only target the VEGF pathway. Faricimab, a bispecific intravitreal agent that inhibits both VEGF and Ang-2, is the first injectable ophthalmic drug to achieve treatment intervals of up to 16 weeks in Phase 3 studies for nAMD and DME while exhibiting improvements in visual acuity and retinal thickness. Data from real-world studies have supported the safety, visual and anatomic benefits and durability of faricimab, even in patients who were previously treated with other intravitreal agents. These evidence-based expert recommendations from a panel of retina specialists consolidate current evidence with clinical experience for the optimal use of faricimab in patients with nAMD or DME, with a focus on switching from an anti-VEGF agent to faricimab.

Background/objectives: Cognitive decline and loss of physical function are common concerns in older adults, with limited effective interventions available. This study aimed to assess the impact of pomegranate extract (PE) supplementation on cognitive and physical function in older adults aged 55–70 years. Methods: A randomised, double-blind placebo-controlled trial was conducted with 86 participants, who were assigned to receive either PE (740 mg) or a placebo (maltodextrin) daily for 12 weeks. Cognitive function was assessed using computerised tests (Corsi, digit span, Wisconsin Card Sorting Test (WCST), Tower of Hanoi, Stroop test and Rey auditory verbal learning test). Physical function was measured through assessments of standing balance, gait speed, chair sit to stand and grip strength. Results: There was a significant effect of treatment and time on WCST performance (F (1,2) = 2.718, p = 0.05), while trends towards better outcomes in the PE group were noted for digit span, Tower of Hanoi and Stroop tests. Physical function did not seem to be affected by the intervention, but results may have been limited by the high baseline physical activity levels and full mobility of the older adults. Conclusions: This was the first study to examine the effect of PE on cognitive and physical function over a duration of 12 weeks. Findings suggest that PE supplementation has potential in improving cognitive function and may offer a promising approach to preventing cognitive decline in ageing adults. Further controlled and well-designed long-term studies are needed to establish the long-term effects of PE on cognitive and physical health, along with the mechanisms of action involved.

Purtscher’s retinopathy is an occlusive micro-vasculopathy causing sudden onset visual loss in trauma. Similar retinal appearance is observed as a rare complication of acute pancreatitis which is identified as Purtscher-like retinopathy (PulR). We report the case of a 15-year-old girl diagnosed to have acute on chronic pancreatitis who noticed a sudden onset loss of vision in the left eye and was found to have significantly diminished visual acuity. A dilated fundoscopic examination demonstrated pathognomonic Purtscher flecken, multiple retinal haemorrhages, cotton wool spots and macular oedema. A clinical diagnosis of PulR was made in the setting of acute on chronic pancreatitis. Optical coherence tomography was used to support the diagnosis and to monitor response to therapy. Given the variable prognosis with no evidence-based therapies available, she had a subjective improvement in visual acuity with administration of intravitreal steroids and observation with management of the acute episode of pancreatitis. Knowledge and awareness of this rare condition will enable its early detection and the search for newer therapies.

Over the last two decades, there have been numerous initiatives to improve undergraduate student outcomes in STEM. One model for scalable reform is the inclusive Research Education Community (iREC). In an iREC, STEM faculty from colleges and universities across the nation are supported to adopt and sustainably implement course-based research – a form of science pedagogy that enhances student learning and persistence in science. In this study, we used pathway modeling to develop a qualitative description that explicates the HHMI Science Education Alliance (SEA) iREC as a model for facilitating the successful adoption and continued advancement of new curricular content and pedagogy. In particular, outcomes that faculty realize through their participation in the SEA iREC were identified, organized by time, and functionally linked. The resulting pathway model was then revised and refined based on several rounds of feedback from over 100 faculty members in the SEA iREC who participated in the study. Our results show that in an iREC, STEM faculty organized as a long-standing community of practice leverage one another, outside expertise, and data to adopt, implement, and iteratively advance their pedagogy. The opportunity to collaborate in this manner and, additionally, to be recognized for pedagogical contributions sustainably engages STEM faculty in the advancement of their pedagogy. Here, we present a detailed pathway model of SEA that, together with underpinning features of an iREC identified in this study, offers a framework to facilitate transformations in undergraduate science education.

Abstract Despite being treatable and preventable, tuberculosis (TB) affected one-fourth of the world population in 2019, and it took the lives of 1.4 million people in 2019. It affected 1.2 million children around the world in the same year. As it is an infectious bacterial disease, the early diagnosis of TB prevents further transmission and increases the survival rate of the affected person. One of the standard diagnosis methods is the sputum culture test. Diagnosing and rapid sputum test results usually take one to eight weeks in 24 h. Using posterior-anterior chest radiographs (CXR) facilitates a rapid and more cost-effective early diagnosis of tuberculosis. Due to intraclass variations and interclass similarities in the images, TB prognosis from CXR is difficult. We proposed an early TB diagnosis system (tbXpert) based on deep learning methods. Deep Fused Linear Triangulation (FLT) is considered for CXR images to reconcile intraclass variation and interclass similarities. To improve the robustness of the prognosis approach, deep information must be obtained from the minimal radiation and uneven quality CXR images. The advanced FLT method accurately visualizes the infected region in the CXR without segmentation. Deep fused images are trained by the Deep learning network (DLN) with residual connections. The largest standard database, comprised of 3500 TB CXR images and 3500 normal CXR images, is utilized for training and validating the recommended model. Specificity, sensitivity, Accuracy, and AUC are estimated to determine the performance of the proposed systems. The proposed system demonstrates a maximum testing accuracy of 99.2%, a sensitivity of 98.9%, a specificity of 99.6%, a precision of 99.6%, and an AUC of 99.4%, all of which are pretty high when compared to current state-of-the-art deep learning approaches for the prognosis of tuberculosis. To lessen the radiologist’s time, effort, and reliance on the level of competence of the specialist, the suggested system named tbXpert can be deployed as a computer-aided diagnosis technique for tuberculosis.

Background Social media is used extensively to disseminate major public health communications. Hashtags (#) are used in social media to share content and can enable content to reach millions. The health sector uses popular hashtags as a medium for promulgating health?related campaigns. As non-communicable diseases (NCDs) are increasing, this study analyzed the use of hashtags including #diabetes_mellitus, #hypertension and #Coronary_artery_disease in the dissemination of health communication messages, in order to assess hashtag campaigns related to non-communicable diseases in social media. The study compared three different campaigns across three different platforms: Twitter, Instagram and Facebook.

Despite a few attempts in exploring genetic variability, management systems, and morphometric descriptions, Thamankaduwa White cattle in Sri Lanka has not been subjected to any evaluation of their endocrinological distinctiveness, especially related to reproduction. The main aims of the present study were to: (1) investigate the dynamics of circulating insulin-like peptide 3 (INSL3) and testosterone in Thamankaduwa bulls during development, and (2) assess the association among INSL3, testosterone and selected morphometric parameters, namely, body weight, height at withers, body length, chest girth of Thamankaduwa White cattle in Sri Lanka. The blood samples were collected from male animals (n = 41) under three age categories; 3-6 months (Group Ⅰ; n = 12), 6-12 months (Group Ⅱ; n = 14) and > 12 months (Group Ⅲ; n = 15), along with their morphometric measurements. Serum INSL3 and extracted testosterone concentrations were measured by using a competitive ELISA. The detection ranges of INSL3 and testosterone assay were 0.078-80 ng/mL and 0.04-40 ng/mL, respectively. Intra- and inter-assay coefficient of variations of INSL3 and testosterone assays were 6.9% (n = 6) and 16.4% (n = 6), and 12.5% (n = 3) and 11.9% (n = 4), respectively. Serum INSL3 and testosterone concentrations ranged between 1.44 - 19.85 ng/mL, and 0.003 ng/mL - 2.81 ng/mL, respectively. The mean serum INSL3 concentrations did not differ between Gr. Ⅰ and Ⅱ (p > 0.05) but were significantly high (p < 0.05) in Gr. Ⅲ. There was a significant association (R2 = 0. 65; p < 0.05) between serum INSL3 and testosterone concentrations in Thmankaduwa White males. No strong associations were observed among hormones and the morphometric parameters tested. In conclusion, the dynamics of INSL3 and testosterone concentrations were compatible and correlated with each other in Thamankaduwa White male cattle.

Abstract Background Miscanthus, a C4 member of Poaceae, is a promising perennial crop for bioenergy, renewable bioproducts, and carbon sequestration. Species of interest include nothospecies M. x giganteus and its parental species M. sacchariflorus and M. sinensis. Use of biotechnology-based procedures to genetically improve Miscanthus, to date, have only included plant transformation procedures for introduction of exogenous genes into the host genome at random, non-targeted sites. Results We developed gene editing procedures for Miscanthus using CRISPR/Cas9 that enabled the mutation of a specific (targeted) endogenous gene to knock out its function. Classified as paleo-allopolyploids (duplicated ancient Sorghum-like DNA plus chromosome fusion event), design of guide RNAs (gRNAs) for Miscanthus needed to target both homeologs and their alleles to account for functional redundancy. Prior research in Zea mays demonstrated that editing the lemon white1 (lw1) gene, involved in chlorophyll and carotenoid biosynthesis, via CRISPR/Cas9 yielded pale green/yellow, striped or white leaf phenotypes making lw1 a promising target for visual confirmation of editing in other species. Using sequence information from both Miscanthus and sorghum, orthologs of maize lw1 were identified; a multi-step screening approach was used to select three gRNAs that could target homeologs of lw1. Embryogenic calli of M. sacchariflorus, M. sinensis and M. x giganteus were transformed via particle bombardment (biolistics) or Agrobacterium tumefaciens introducing the Cas9 gene and three gRNAs to edit lw1. Leaves on edited Miscanthus plants displayed the same phenotypes noted in maize. Sanger sequencing confirmed editing; deletions in lw1 ranged from 1 to 26 bp in length, and one deletion (433 bp) encompassed two target sites. Confocal microscopy verified lack of autofluorescence (chlorophyll) in edited leaves/sectors. Conclusions We developed procedures for gene editing via CRISPR/Cas9 in Miscanthus and, to the best of our knowledge, are the first to do so. This included five genotypes representing three Miscanthus species. Designed gRNAs targeted all copies of lw1 (homeologous copies and their alleles); results also confirmed lw1 made a good editing target in species other than Z. mays. The ability to target specific loci to enable endogenous gene editing presents a new avenue for genetic improvement of this important biomass crop. Graphical Abstract

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education.

Background: Knee osteoarthritis (OA) is a musculoskeletal disorder that causes pain and increasing loss of function, resulting in reduced proprioceptive accuracy and balance. Therefore, the goal of this systematic review and meta-analysis is to evaluate the effectiveness of balance training on pain and functional outcomes in knee OA. Methods: “PubMed”, “Scopus”, “Web of Science”, “Cochrane”, and “Physiotherapy Evidence Database” were searched for studies conducted between January 2000 and December 2021. Randomized controlled trials (RCTs) that investigated the effectiveness of balance training in knee OA, as well as its effects on pain and functional outcome measures, were included. Conference abstracts, case reports, observational studies, and clinical commentaries were not included. Meta-analysis was conducted for the common outcomes, i.e., Visual Analog Scale (VAS), The Timed Up and Go (TUG), Western Ontario and McMaster Universities Arthritis Index (WOMAC). The PEDro scale was used to determine the quality of the included studies. Results: This review includes 22 RCTs of which 17 articles were included for meta-analysis. The included articles had 1456 participants. The meta-analysis showed improvement in the VAS scores in the experimental group compared to the control group [I 2= 92%; mean difference= -0.79; 95% CI= -1.59 to 0.01; p

This study was conducted to assess the variations of milk coagulation properties (MCP) among two native cattle types, e.g., Thamankaduwa White (TW), Lankan cattle (LC) and two improved cattle breeds, e.g., Friesian (FR) and Jersey (JS), in relation to distinctive milk protein compositions. MCP traits, including rennet coagulation time (RCT), curd firmness, meltability and yield, were measured. The milk protein profile of each breed/type was analyzed using capillary zone electrophoresis. Significant differences (p < 0.05) were observed among two native and improved cattle breeds/types in relation to RCT. Friesian and TW milk had the longest and shortest (p < 0.05) RCT, respectively. There was no significant difference in firmness among the four breeds/types. The highest (p < 0.05) coagulum yield was recorded for TW milk, followed by LC, JS and FR. TW milk had the highest (p < 0.05) meltability values. As revealed by the protein profiles, κ-casein concentration was significantly higher in TW milk compared to the other three breeds/types. None of the other milk protein fractions showed significant differences among the four breeds/types. The overall results indicate the superior MCP of TW milk, emphasizing the value of native breeds which could be exploited in the development of niche dairy products while supporting the conservation effort of the native cattle gene pool.

ABSTRACT: Objectives: Over the past decade, daptomycin treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections has led to the emergence of daptomycin nonsusceptible (DAP-NS) MRSA strains and a subsequent interest in combinatorial antibiotic therapies. We investigated the phenotypic and genetic changes associated with the seesaw effect, which describes the correlation between daptomycin resistance and increased β-lactam susceptibility in DAP-NS MRSA and the reverse phenomenon of DAP-NS strains acquiring renewed susceptibility to daptomycin after β-lactam exposure. Methods: A continuous bioreactor model was used to study the effects of incremental doses of daptomycin followed by oxacillin on MRSA strain N315. Minimum inhibitory concentrations for daptomycin and oxacillin were determined for the bioreactor-derived samples. Transmission electron microscopy and cytochrome C binding assays were used to measure cell wall thickness and cell membrane charge, respectively, in the bioreactor-derived samples. Whole-genome sequencing was used to identify mutations associated with the seesaw effect. Results: Although daptomycin resistance conferred enhanced susceptibility to oxacillin, oxacillin treatment of DAP-NS strains was accompanied by a lowered minimum inhibitory concentration for daptomycin. Additionally, there was a reduction in relative positive cell surface charge and cell wall thickness. However, the mutations acquired in our DAP-NS populations were not accompanied by additional genomic changes after treatment with oxacillin, implicating alternative mechanisms for the seesaw effect. Conclusion: In this study, we successfully produced and characterized the seesaw effect in MRSA strain N315 in a unique bioreactor model.

The antibody response to SARS-CoV-2 shows biased immunoglobulin heavy chain variable (IGHV) gene usage, allowing definition of genetic signatures for some classes of neutralizing antibodies. We investigated IGHV gene usage frequencies by sorting spike-specific single memory B cells from individuals infected with SARS-CoV-2 early in the pandemic. From two study participants and 703 spike-specific B cells, the most used genes were IGHV1-69, IGHV3-30-3, and IGHV3-30. Here, we focused on the IGHV3-30 group of genes and an IGHV3-30-3-using ultrapotent neutralizing monoclonal antibody, CAB-F52, which displayed broad neutralizing activity also in its germline-reverted form. IGHV3-30-3 is encoded by a region of the IGH locus that is highly variable at both the allelic and structural levels. Using personalized IG genotyping, we found that 4 of 14 study participants lacked the IGHV3-30-3 gene on both chromosomes, raising the question if other, highly similar IGHV genes could substitute for IGHV3-30-3 in persons lacking this gene. In the context of CAB-F52, we found that none of the tested IGHV3-33 alleles, but several IGHV3-30 alleles could substitute for IGHV3-30-3, suggesting functional redundancy between the highly homologous IGHV3-30 and IGHV3-30-3 genes for this antibody.

Internet of things (IoT) applications in smart agricultural systems vary from monitoring climate conditions, automating irrigation systems, greenhouse automation, crop monitoring and management, and crop prediction, up to end-to-end autonomous farm management systems. One of the main challenges to the advancement of IoT systems for the agricultural domain is the lack of training data under operational environmental conditions. Most of the current designs are based on simulations and artificially generated data. Therefore, the essential first step is studying and understanding the finely tuned and highly sensitive mechanism plants have developed to sense, respond, and adapt to changes in their environment, and their behavior under field and controlled systems. Therefore, this study was designed to achieve two specific objectives; to develop low-cost IoT components from basic building blocks, and to study the performance of the developed systems, and generate real-time experimental data, with and without plants. Low-cost IoT devices developed locally were used to convert existing basic polytunnels to semi-controlled and monitoring-only polytunnels. Their performances were analyzed and compared with each other based on several matrices while maintaining the planted tomato variety and agronomic practices similar. The developed system performed as expected suggesting the possibility of commercial applications and research purposes.

Due to the modern power system’s rapid development, more scattered smart grid components are securely linked into the power system by encircling a wide electrical power network with the underpinning communication system. By enabling a wide range of applications, such as distributed energy management, system state forecasting, and cyberattack security, these components generate vast amounts of data that automate and improve the efficiency of the smart grid. Due to traditional computer technologies’ inability to handle the massive amount of data that smart grid systems generate, AI-based alternatives have received a lot of interest. Long Short-Term Memory (LSTM) and recurrent Neural Networks (RNN) will be specifically developed in this study to address this issue by incorporating the adaptively time-developing energy system’s attributes to enhance the model of the dynamic properties of contemporary Smart Grid (SG) that are impacted by Revised Encoding Scheme (RES) or system reconfiguration to differentiate LSTM changes & real-time threats. More specifically, we provide a federated instructional strategy for consumer sharing of power data to Power Grid (PG) that is supported by edge clouds, protects consumer privacy, and is communication-efficient. They then design two optimization problems for Energy Data Owners (EDO) and energy service operations, as well as a local information assessment method in Federated Learning (FL) by taking non-independent and identically distributed (IID) effects into consideration. The test results revealed that LSTM had a longer training duration, four hidden levels, and higher training loss than other models. The provided method works incredibly well in several situations to identify FDIA. The suggested approach may successfully induce EDOs to employ high-quality local models, increase the payout of the ESP, and decrease task latencies, according to extensive simulations, which are the last points. According to the verification results, every assault sample could be effectively recognized utilizing the current detection methods and the LSTM RNN-based structure created by Smart.

Societal Impact Statement Cinnamomum zeylanicum (“Ceylon cinnamon/true cinnamon”) is native to Sri Lanka. In addition to generating significant foreign income, over 350,000 families are involved in the cinnamon industry, demonstrating its long‐established role in the Sri Lankan society. The spice constitutes many bioactive compounds with antioxidant, antimicrobial, and insecticidal properties, in addition to therapeutic and preventive effects against many diseases and disorders. New uses of cinnamon continue to emerge, and in this review, we discuss the opportunities for crop and product improvement, which will likely impact positively on the lives and livelihood of the population in Sri Lanka. Summary Cinnamomum zeylanicum Blume, known as Ceylon cinnamon, is native to Sri Lanka, whereas Cinnamomum cassia J. Presl (Cassia cinnamon) and other types of Cinnamomum spp. are grown in China and many other parts of Asia. Ceylon cinnamon is relatively expensive due to its chemical composition, high quality, proven health benefits, and ultra‐low levels of the toxic chemical compound, coumarin, which is reported in comparatively high concentrations in Cassia cinnamon. In Sri Lanka, more than 350,000 families are involved in the cinnamon industry. Among the total agricultural produce of Sri Lanka, cinnamon exports provide the second highest in terms of income (second only to tea). In addition to the use of cinnamon as a spice, leaf and bark extracts are used in the food industry to (a) improve the postharvest life of perishable foods through antimicrobial activity and (b) control pests in postharvest storage (insecticidal activity). The human health benefits include antioxidant activity and therapeutic and preventative properties against diseases and disorders. The potential uses of Ceylon cinnamon in the global food industry, health, and cosmetics sectors are abundant. However, to ensure maximum benefits to producers and consumers, accredited laboratory testing and legislative procedures need to be developed and strengthened to detect and reduce malpractice and product adulteration in the global marketplace. There are also considerable opportunities for crop improvement. The application of contemporary genomic and genetic approaches coupled to plant breeding will be needed to improve yields and disease resistance and to safeguard production in the face of the threats posed by global environmental change.

In this work, untreated/treated sisal fibre (SF)-reinforced sodium alginate composites for three different concentrations (1.5%, 2%, and 2.5%) are fabricated by the hand lay-up method, and the variations in mechanical properties such as tensile strength, flexural strength, and impact strength are studied. The treated and untreated composites are analysed and compared using scanning electron microscope to study the surface morphology. Energy-dispersive spectroscopic analysis is carried out to evaluate the elemental compositions. Fourier transform infrared spectroscopic analysis is conducted to determine the interaction between fibres and matrix material. The thermal observations such as differential scanning calorimetry and thermogravimetric analysis showed only slight variations between the untreated and treated SF composites. The results of this work indicate that untreated sample with the maximum sodium alginate gum concentration had significantly enhanced mechanical properties and low moisture absorption rate. Biodegradation test inferred that it was superior for the treated fibre rather than the untreated fibre composites. The primary objective of this work is to assess the suitability of these composites for non-structural engineering applications.

Background: Sublingual temperature measurement is a quick and accurate representation of oral temperature and corresponds closely with core temperature. Sub-lingual temperature measurement using non-contact infrared thermometers has not been studied for this purpose and if accurate they would be a reliable and convenient way of recording temperature of a patient very quickly. The aim of the study was to evaluate the utility of recording sublingual temperature using an infrared non-contact thermometer and establish its accuracy by comparing the readings with tympanic thermometer recordings. Methods: This cross-sectional study was carried out in 29 patients (328 paired recordings from sublingual and tympanic sites simultaneously). Subjects were requested to keep their mouth closed for five minutes before recording the temperature. Sublingual recordings were performed for each patient at different times of the day using an infrared thermometer. The infrared thermometer was quickly brought 1cm away from the sublingual part of the tongue and the recordings were then done immediately. Readings were compared with the corresponding tympanic temperature. Results: The non-contact sublingual temperature correlated very closely with tympanic temperature (r=0.86, p38°C. Conclusions: This innovative modification of using the forehead infrared thermometer to measure the sublingual temperature offers an accurate, rapid and non-contact estimation of core temperature.

Abstract Background Though case reports and limited case series of Sickle cell disease in Sri Lanka have been reported previously, no attempt has been made hitherto to undertake a comprehensive genotypic-phenotypic analysis of this “rare” group of patients. Results All accessible Sickle cell disease patients, totaling 60, including, 51 Sickle β-thalassaemia and 9 homozygous sickle patients were enrolled from seven thalassaemia treatment centres between December 2016–March 2019. The majority of patients were of Sinhalese ethnicity (n = 52, 86.67%). Geographically, two prominent clusters were identified and the distribution of Sickle haemoglobin in the island contrasted markedly with the other haemoglobinopathies. 3/ 9 homozygous sickle patients and 3/ 51 Sickle β-thalassaemia patients were receiving regular transfusion. Joint pain was the commonest clinical symptom among all sickle cell disease patients (n = 39, 65.0%). Dactylitis was significantly more common in homozygous sickle patients compared with the Sickle β-thalassaemia groups (p 0.027). Two genetic backgrounds sickle mutation were identified namely, Arab Indian and Benin. Among the regulators of Foetal hemoglobin in Sickle patients of the present study rs1427407 G > T seemed to be the most prominent modifier, with a significant association with Foetal haemoglobin levels (p 0.04). Conclusions Overall, the clinical course of the Asian version of Sickle cell disease in Sri Lanka appears to be milder than that described in India.

Background: Sublingual temperature measurement is a quick and accurate representation of oral temperature and corresponds closely with core temperature. Sub-lingual temperature measurement using non-contact infrared thermometers has not been studied for this purpose and if accurate they would be a reliable and convenient way of recording temperature of a patient very quickly. The aim of the study was to evaluate the utility of recording sublingual temperature using an infrared non-contact thermometer and establish its accuracy by comparing the readings with tympanic thermometer recordings. Methods: This cross-sectional study was carried out in 29 patients (328 paired recordings from sublingual and tympanic sites simultaneously). Subjects were requested to keep their mouth closed for five minutes before recording the temperature. Sublingual recordings were performed for each patient at different times of the day using an infrared thermometer. The infrared thermometer was quickly brought 1cm away from the sublingual part of the tongue and the recordings were then done immediately. Readings were compared with the corresponding tympanic temperature. Results: The non-contact sublingual temperature correlated very closely with tympanic temperature (r=0.86, p38°C. Conclusions: This innovative modification of using the forehead infrared thermometer to measure the sublingual temperature offers an accurate, rapid and non-contact estimation of core temperature.

We report a case of chest X-ray finding of mitral annular calcification. Mitral annular calcification is a degenerative process involving the fibrous annulus of the mitral valve. It is generally an incidental finding associated with aging and atherosclerosis. It may lead to significant mitral regurgitation and can rarely cause symptomatic mitral stenosis. In addition, mitral annulus calcification may be associated with atrial fibrillation and cardiac arrhythmia. Calcification of mitral annulus in the chest X-ray generally follows the C-shape of the mitral annulus. Confirmation is by echocardiography. Symptomatic cases require repair by surgery.

Introduction: Atopic disorders are showing a consistent trend of increasing prevalence. Kasaragod was an endosulfan aerial spray region that caused multiple health issues in the population. The aim of this paper was to a) determine the prevalence of, b) identify socio-environmental determinants (SED) of atopic disorders amongst school children of age 10–15 years in Kasaragod district. Methodology: The study is a cross-sectional survey of students of class 8 to 10 in 20 schools of Kasaragod educational district. International Study of Asthma and Allergies in Childhood (ISAAC) core questionnaire identified atopic students. A validated, closed-ended 30 questions elicited exposure to SEDs. Results: In 20 schools, 5914 students filled questionnaires. ISAAC questionnaire identified 2310 (41.8%) atopic students; 716 (13%) chronic wheezers, 543 (9.8%) eczema and 1813 (32.8%) rhinitis. The study showed a significant relationship between rhinitis mode of going to school, solid biomass fuel, rodents and reptiles infestation in living places. Rhinitis is prevalent in students who lived near the coastal region, tarred roads and footpaths. The chance of getting asthma, when a student had eczema and vice-versa (odds ratio = 2.388, x2 = 66.450, p = 0.000), between asthma to rhinitis (odds ratio = 3.671, x2 = 270.829, p = 0.000) and eczema and rhinitis (odds ratio = 2.852, x2 = 139.485, p = 0.000) showed significant relation. Discussion: Atopy prevalence is higher in Kasaragod and association with other allergic disorders suggestive of atopic march. Further studies required to identify reasons; mainly on environmental pollution, epigenetic changes in students.

This study assessed the climate resilience and characterized the existing farming systems in steep terrain in the hilly regions in South Asia. The farming systems considered were at an elevation ≥300 m in the mountain regions of two sites from Sri Lanka (Hatton and Welimada) and one site each from Bangladesh (Chittagong) and Nepal (Jhikhu Khola). A Climate Resilience Index (CRIi) score, varying from 0 (negligible resilience) and 1 (very high resilience), was calculated for each household using 31 parameters under Adaptive Capacity (ADC), Absorptive Capacity (ABC) and Transformative Capacity (TC). To spatially represent the CRIi, the four study locations were mapped using Inverse Distance Weighted (IDW) interpolation technique of GIS. All 424 households in the study sites scored a CRIi between 0.36 and 0.76, while the average CRI was the highest in Hatton (0.67), followed by Welimada (0.60), Jhikhu Khola (0.59) and Chittagong (0.48). Different demographic, socioeconomic and environmental parameters have contributed to the level of climate resilience of farming system units. Identification of good management practices of the climate-resilient farming systems and implementing those practices in vulnerable systems would increase the resilience and well-being of farming communities in steep terrain of mountain regions in South Asia.

Local chicken populations belonging to five villages in two geographically separated provinces of Sri Lanka were analyzed using 20 microsatellite markers to determine the genetic diversity of local chickens. Population genetic parameters were estimated separately for five populations based on geographic locations and for eight populations based on phenotypes, such as naked neck, long legged, crested or crown, frizzle feathered, Giriraj, commercial layer, crossbreds, and non-descript chicken. The analysis revealed that there was a high genetic diversity among local chickens with high number of unique alleles, mean number of alleles per locus (MNA), and total number of alleles per locus per population. A total of 185 microsatellite alleles were detected in 192 samples, indicating a high allelic diversity. The MNA ranged from 8.10 (non-descript village chicken) to 3.50 (Giriraj) among phenotypes and from 7.30 (Tabbowa) to 6.50 (Labunoruwa) among village populations. In phenotypic groups, positive inbreeding coefficient (FIS) values indicated the existence of population substructure with evidence of inbreeding. In commercial layers, a high expected heterozygosity He = 0.640 ± 0.042) and a negative FIS were observed. The positive FIS and high He estimates observed in village populations were due to the heterogeneity of samples, owing to free mating facilitated by communal feeding patterns. Highly admixed nature of phenotypes was explained as a result of rearing many phenotypes by households (58%) and interactions of chickens among neighboring households (53%). A weak substructure was evident due to the mating system, which disregarded the phenotypes. Based on genetic distances, crown chickens had the highest distance to other phenotypes, while the highest similarity was observed between non-descript village chickens and naked neck birds. The finding confirms the genetic wealth conserved within the populations as a result of the breeding system commonly practiced by chicken owners. Thus, the existing local chicken populations should be considered as a harbor of gene pool, which can be readily utilized in developing locally adapted and improved chicken breeds in the future.

Understanding the molecular mechanisms by which antibodies target and neutralize the HIV-1 envelope glycoprotein (Env) is critical in guiding immunogen design and vaccine development aimed at eliciting cross-reactive neutralizing antibodies (NAbs). Here, we analyzed monoclonal antibodies (mAbs) isolated from non-human primates (NHPs) immunized with variants of a native flexibly linked (NFL) HIV-1 Env stabilized trimer derived from the tier 2 clade C 16055 strain. The antibodies displayed neutralizing activity against the autologous virus with potencies ranging from 0.005 to 3.68 μg/ml (IC50). Structural characterization using negative-stain EM and X-ray crystallography identified the variable region 2 (V2) of the 16055 NFL trimer to be the common epitope for these antibodies. The crystal structures revealed that the V2 segment adopts a β-hairpin motif identical to that observed in the 16055 NFL crystal structure. These results depict how vaccine-induced antibodies derived from different clonal lineages penetrate through the glycan shield to recognize a hypervariable region within V2 (residues 184-186) that is unique to the 16055 strain. They also provide potential explanations for the potent autologous neutralization of these antibodies, confirming the immunodominance of this site and revealing that multiple angles of approach are permissible for affinity/avidity that results in potent neutralizing capacity. The structural analysis reveals that the most negatively charged paratope correlated with the potency of the mAbs. The atomic level information is of interest to both define the means of autologous neutralization elicited by different tier 2-based immunogens and facilitate trimer redesign to better target more conserved regions of V2 to potentially elicit cross-neutralizing HIV-1 antibodies.

Abstract Background Hybridisation and introgression play key roles in the evolutionary history of animal species. They are commonly observed within several orders in wild birds. The domestic chicken Gallus gallus domesticus is the most common livestock species. More than 65 billion chickens are raised annually to produce meat and 80 million metric tons of egg for global human consumption by the commercial sector. Unravelling the origin of its genetic diversity has major application for sustainable breeding improvement programmes. Results In this study, we report genome-wide analyses for signatures of introgression between indigenous domestic village chicken and the four wild Gallus species. We first assess the genome-wide phylogeny and divergence time across the genus Gallus. Genome-wide sequence divergence analysis supports a sister relationship between the Grey junglefowl G. sonneratii and Ceylon junglefowl G. lafayettii. Both species form a clade that is sister to the Red junglefowl G. gallus, with the Green junglefowl G. varius the most ancient lineage within the genus. We reveal extensive bidirectional introgression between the Grey junglefowl and the domestic chicken and to a much lesser extent with the Ceylon junglefowl. We identify a single case of Green junglefowl introgression. These introgressed regions include genes with biological functions related to development and immune system. Conclusions Our study shows that while the Red junglefowl is the main ancestral species, introgressive hybridisation episodes have impacted the genome and contributed to the diversity of the domestic chicken, although likely at different levels across its geographic range.

Fever is a common symptom of many diseases. Fever temporal patterns can be different depending on the specific pathology. Differentiation of diseases based on multiple mathematical features and visual observations has been recently studied in the scientific literature. However, the classification of diseases using a single mathematical feature has not been tried yet. The aim of the present study is to assess the feasibility of classifying diseases based on fever patterns using a single mathematical feature, specifically an entropy measure, Sample Entropy. This was an observational study. Analysis was carried out using 103 patients, 24 hour continuous tympanic temperature data. Sample Entropy feature was extracted from temperature data of patients. Grouping of diseases (infectious, tuberculosis, non-tuberculosis, and dengue fever) was made based on physicians diagnosis and laboratory findings. The quantitative results confirm the feasibility of the approach proposed, with an overall classification accuracy close to 70%, and the capability of finding significant differences for all the classes studied. %An abstract is a brief of the paper; the abstract should not contain references, the text of the abstract section should be in 12 point normal Times New Roman.

BACKGROUND: Understanding environmental correlates of sedentary behaviour (SB) among young people is important as such data can identify approaches to limit sedentary time. This paper estimates associations of parent-reported neighbourhood and adolescent-reported home environments with SB among adolescents aged 11-19 years from 14 countries. METHODS: In the International Physical activity and the Environment Network (IPEN) Adolescent Study (an observational, cross-sectional multi-country study), adolescents wore a triaxial accelerometer for seven days that assessed sedentary time (ST). Adolescents completed survey measures of sedentary behaviour (SB) related to recreational screen time and sitting time in motor vehicles. Parents and adolescents completed surveys assessing neighbourhood and home environments. Accelerometer based ST was available in 3,982 adolescents while survey data were available for 6,302 dyads. We estimated the total and direct effects of each environmental attribute on ST and SB. Sex of the adolescent and city/country were examined as moderators. RESULTS: The average ST in adolescents from 14 countries ranged from 7.8 to 10.5 h/day. Personal social media was the only significant correlate of total ST across both sexes. With respect to self-reported SB, adolescents accumulated an average of 3.8 h of non-school screen time per day and nearly 40 min of transport-related sitting time. Screen time was associated with all home environment variables, including social media account, as well as land use mix-diversity, traffic safety, and crime safety. Transport-related sitting time was related to land use mix-diversity, recreation facilities, walking facilities, and pedestrian infrastructure, but no home environment variables. City/country and sex were significant moderators of several associations. CONCLUSIONS: Both home and neighbourhood environment features were related to ST and SB. Having social media accounts emerged as a major contributor towards sedentarism in adolescents.

Background Injury is a leading health burden in children yet relatively little is reported about the contemporary risks they face. Current national registry data may under-represent the true burden of injury to children. We aim to analyse contemporary patterns of paediatric trauma and identify current factors putting children at risk of injury.Methods A 3-month prospective multicentre cohort evaluation of injured children across the London Major Trauma System was performed. All children receiving a trauma team activation; meeting National Institute for Health and Care Excellence CT head criteria; or admitted/transferred out due to trauma were included. Data were collected on demographics, mechanism and location of injury, and body region injured. The primary outcome was in-hospital mortality and secondary outcome was safeguarding concerns.Results 659 children were included. Young children were more likely to be injured at home (0–5 years old: 70.8%, n=167 vs adolescents: 15.6%, n=31). Adolescents were more likely to be injured in the street (42.7%, n=85). Head trauma caused over half of injuries in 0–5 years old (51.9%, n=121). Falls were common and increasingly prevalent in younger children, causing 56.6% (n=372) of injuries. In adolescents, penetrating violence caused more than one in five injuries (21.9%, n=50). Most injured children survived (99.8%, n=658), however, one in four (26.1%, n=172) had safeguarding concerns and a quarter of adolescents had police, third sector or external agency involvement (23.2%, n=53).Conclusions This study describes modern-day paediatric trauma and highlights the variance in injury patterns in young children and adolescents. Importantly, it highlights differences in actual rates of injuries compared with those reported from current national registry data. We must understand real risks facing 21st century children to effectively safeguard future generations. The results provide an opportunity to reassess the current approach to injury prevention, child and adolescent safeguarding, and public health campaigns for child safety.

Disproportionate, maladapted, and generalized fear are essential hallmarks of posttraumatic stress disorder (PTSD), which develops upon severe trauma in a subset of exposed individuals. Among the brain areas that are processing fear memories, the hippocampal formation exerts a central role linking emotional-affective with cognitive aspects. In the hippocampus, neuronal excitability is constrained by multiple GABAergic interneurons with highly specialized functions and an extensive repertoire of co-released neuromodulators. Neuropeptide Y (NPY) is one of these co-transmitters that significantly affects hippocampal signaling, with ample evidence supporting its fundamental role in emotional, cognitive, and metabolic circuitries. Here we investigated the role of NPY in relation to GABA, both released from the same interneurons of the dorsal dentate gyrus (DG), in different aspects of fear conditioning. We demonstrated that activation of dentate GABA neurons specifically during fear recall reduced cue-related as well as trace-related freezing behavior, whereas inhibition of the same neurons had no significant effects. Interestingly, concomitant overexpression of NPY in these neurons did not further modify fear recall, neither under baseline conditions nor upon chemogenetic stimulation. However, potentially increased co-release of NPY substantially reduced contextual fear, promoted extinction learning, and long-term suppression of fear in a foreground context–conditioning paradigm. Importantly, NPY in the dorsal DG was not only expressed in somatostatin neurons, but also in parvalbumin-positive basket cells and axoaxonic cells, indicating intense feedback and feedforward modulation of hippocampal signaling and precise curtailing of neuronal engrams. Thus, these findings suggest that co-release of NPY from specific interneuron populations of the dorsal DG modifies dedicated aspects of hippocampal processing by sharpening the activation of neural engrams and the consecutive fear response. Since inappropriate and generalized fear is the major impediment in the treatment of PTSD patients, the dentate NPY system may be a suitable access point to ameliorate PTSD symptoms and improve the inherent disease course.

Summary: The outbreak and spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is the target of neutralizing antibodies. Here, we show that adjuvanted protein immunization with soluble SARS-CoV-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques, with neutralizing antibody titers exceeding those typically measured in SARS-CoV-2 seropositive humans by more than one order of magnitude. Neutralizing antibody responses were observed after a single dose, with exceptionally high titers achieved after boosting. A follow-up to monitor the waning of the neutralizing antibody responses in rhesus macaques demonstrated durable responses that were maintained at high and stable levels at least 4 months after boosting. These data support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines.

The pandemic of Coronavirus disease 2019 (COVID-19) has brought significant pressure on nurses globally as they are the frontline of care. This study aimed to explore the experiences and challenges of nurses who worked with hospitalised patients with COVID-19. In this qualitative study, a purposive sample of 14 nurses participated in in-depth telephone interviews. Data were analysed using Colaizzi's phenomenological method. Five key themes emerged: (1) physical and psychological distress of nurses, (2) willingness to work, (3) the essential role of support mechanisms, (4) educational and informational needs of nurses and (5) the role of modern technology in COVID-19 care. Although the provision of care led to physical and psychological distress among nurses, with their commitment and professional obligation, it is a new experience that leads to personal satisfaction. Guilty feeling related to inefficiency of care, witnessing the suffering of patients, discomfort associated with wearing personal protective equipment (PPE), work-related issues (e.g., long hour shifts), negative impact to the family and rejection by others are the leading distress factors. Religious beliefs, including keeping trust in good and bad merits, have become a strong coping mechanism. Addressing distress among nurses is essential. The reported learning needs of nurses included skills related to donning and doffing PPE, skills in performing nursing procedures and breaking bad news. Nurse managers need to pay special attention to expanding training opportunities as well as support mechanisms, for example, welfare, appreciations and counselling services for nurses. Modern technology, particularly robots and telecommunication, can perform an essential role in COVID-19 care. The establishment of timely policies and strategies to protect health workers during a national disaster like COVID-19 is needed.

The genus Cinnamomum consists of about 250 species spread globally. Out of these, C. verum (C. zeylanicum), also known as true cinnamon or Ceylon cinnamon, has gained worldwide attention due to its culinary uses and medicinal values. Sri Lanka is the largest true cinnamon producer in the world and accounts for about 80-90% of global production. Other than the cultivated species, Sri Lankan natural vegetation is home to seven endemic wild species of the genus Cinnamomum. While these are underutilized, proper identification and characterization are essential steps in any sustainable conservation and utilization strategies. Currently, species identification is purely based on morphological traits, and intraspecific diversity has made it more challenging. In this study, all the eight Cinnamomum species found in Sri Lanka, C. capparu-coronde, C. citriodorum C. dubium, C. litseifolium, C. ovalifolium, C. rivulorum, C. sinharajaense, and C. verum were collected in triplicates and identified using typical morphological traits. DNA extracted with the same collection was assessed with universal barcoding regions, rbcL, matK, and trnH-psbA. While no intraspecific sequence differences were observed in C. citriodorum, C. rivulorum, and C. verum, the others had polymorphic sites in one, two, or all regions assessed. Interestingly, two individuals of C. sinharajaense had identical barcodes to the cultivated species C. verum, while the other one had one variable cite in matK region and three cites in trnH-psbA reigon. Further, one C. dubium and one C. capparu-coronde accession each had identical, rbcL, and trnH-psbA sequences while those had only a single nucleotide variation observed in matK region. Overall, the phylogeny of Cinnamomum species found in Sri Lanka could not be completely resolved with DNA barcoding regions studied.

Summary: Although intramuscular (i.m.) administration is the most commonly used route for licensed vaccines, subcutaneous (s.c.) delivery is being explored for several new vaccines under development. Here, we use rhesus macaques, physiologically relevant to humans, to identify the anatomical compartments and early immune processes engaged in the response to immunization via the two routes. Administration of fluorescently labeled HIV-1 envelope glycoprotein trimers displayed on liposomes enables visualization of targeted cells and tissues. Both s.c. and i.m. routes induce efficient immune cell infiltration, activation, and antigen uptake, functions that are tightly restricted to the skin and muscle, respectively. Antigen is also transported to different lymph nodes depending on route. However, these early differences do not translate into significant differences in the magnitude or quality of antigen-specific cellular and humoral responses over time. Thus, although some distinct immunological differences are noted, the choice of route may instead be motivated by clinical practicality. : Route of immunization, especially intramuscular versus subcutaneous administration, is often debated. Ols et al. use a rhesus macaque model to determine the tissues targeted by a nanoparticle vaccine administered by either route. The authors demonstrate that tissue dissemination is route dependent, but innate and adaptive immune responses develop comparably. Keywords: vaccination, intramuscular, subcutaneous, antigen transport, HIV envelope glycoprotein, dendritic cell, follicular dendritic cell, monocytes, lymph node, B cell follicle

The current diagnostic aids for acute vision loss are static flowcharts that do not provide dynamic, stepwise workups. We tested the diagnostic accuracy of a novel dynamic Bayesian algorithm for acute vision loss. Seventy-nine “participants” with acute vision loss in Windsor, Canada were assessed by an emergency medicine or primary care provider who completed a questionnaire about ocular symptoms/findings (without requiring fundoscopy). An ophthalmologist then attributed an independent “gold-standard diagnosis”. The algorithm employed questionnaire data to produce a differential diagnosis. The referrer diagnostic accuracy was 30.4%, while the algorithm’s accuracy was 70.9%, increasing to 86.1% with the algorithm’s top two diagnoses included and 88.6% with the top three included. In urgent cases of vision loss (n = 54), the referrer diagnostic accuracy was 38.9%, while the algorithm’s top diagnosis was correct in 72.2% of cases, increasing to 85.2% (top two included) and 87.0% (top three included). The algorithm’s sensitivity for urgent cases using the top diagnosis was 94.4% (95% CI: 85–99%), with a specificity of 76.0% (95% CI: 55–91%). This novel algorithm adjusts its workup at each step using clinical symptoms. In doing so, it successfully improves diagnostic accuracy for vision loss using clinical data collected by non-ophthalmologists.