12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction and Microthrombi after Subarachnoid Hemorrhage in Mice.

Background and Purpose: Impaired cerebral circulation, induced by blood vessel constrictions and microthrombi, leads to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). 12/15-Lipooxygenase (12/15-LOX) overexpression has been implicated in worsening early brain injury outcomes following SAH. However, it is unknown if 12/15-LOX is important in delayed pathophysiological events after SAH. Since 12/15-LOX produces metabolites that induce inflammation and vasoconstriction, we hypothesized that 12/15-LOX leads to microvessel constriction and microthrombi formation after SAH, and thus 12/15-LOX is an important target to prevent delayed cerebral ischemia. Methods: SAH was induced in C57BL/6 and 12/15-LOX-/- mice of both sexes by endovascular perforation. Expression of 12/15-LOX was assessed in brain tissue slices and in vitro. C57BL/6 mice were administered either ML351 (12/15-LOX inhibitor) or vehicle. Mice were evaluated for daily neuroscore and euthanized on day five to assess cerebral 12/15-LOX expression, vessel constrictions, platelet activation, microthrombi, neurodegeneration, infarction, cortical perfusion, and for development of delayed deficits. Finally, the effect of 12/15-LOX inhibition on platelet activation was assessed in SAH patient samples using a platelet spreading assay. Results: In SAH mice, 12/15-LOX was upregulated in brain vascular cells and there was an increase in 12-S-HETE. Inhibition of 12/15-LOX improved brain perfusion on days 4-5 and attenuated delayed pathophysiological events, including microvessel constrictions, microthrombi, neuronal degeneration, and infarction. Additionally, 12/15-LOX inhibition reduced platelet activation in human and mouse blood samples. Conclusions: Cerebrovascular 12/15-LOX overexpression plays a major role in brain dysfunction after SAH by triggering microvessel constrictions and microthrombi formation, which reduces brain perfusion. Inhibiting 12/15-LOX may be a therapeutic target to improve outcomes after SAH.

Enhancing brain tumor detection in MRI with a rotation invariant Vision Transformer.

Background: The Rotation Invariant Vision Transformer (RViT) is a novel deep learning model tailored for brain tumor classification using MRI scans. Methods: RViT incorporates rotated patch embeddings to enhance the accuracy of brain tumor identification. Results: Evaluation on the Brain Tumor MRI Dataset from Kaggle demonstrates RViT's superior performance with sensitivity (1.0), specificity (0.975), F1-score (0.984), Matthew's Correlation Coefficient (MCC) (0.972), and an overall accuracy of 0.986. Conclusion: RViT outperforms the standard Vision Transformer model and several existing techniques, highlighting its efficacy in medical imaging. The study confirms that integrating rotational patch embeddings improves the model's capability to handle diverse orientations, a common challenge in tumor imaging. The specialized architecture and rotational invariance approach of RViT have the potential to enhance current methodologies for brain tumor detection and extend to other complex imaging tasks.

Eating Speed Measurement Using Wrist-Worn IMU Sensors Towards Free-Living Environments.

Eating speed is an important indicator that has been widely investigated in nutritional studies. The relationship between eating speed and several intake-related problems such as obesity, diabetes, and oral health has received increased attention from researchers. However, existing studies mainly use self-reported questionnaires to obtain participants' eating speed, where they choose options from slow, medium, and fast. Such a non-quantitative method is highly subjective and coarse at the individual level. This study integrates two classical tasks in automated food intake monitoring domain: bite detection and eating episode detection, to advance eating speed measurement in near-free-living environments automatically and objectively. Specifically, a temporal convolutional network combined with a multi-head attention module (TCN-MHA) is developed to detect bites (including eating and drinking gestures) from IMU data. The predicted bite sequences are then clustered into eating episodes. Eating speed is calculated by using the time taken to finish the eating episode to divide the number of bites. To validate the proposed approach on eating speed measurement, a 7-fold cross validation is applied to the self-collected fine-annotated full-day-I (FD-I) dataset, and a holdout experiment is conducted on the full-day-II (FD-II) dataset. The two datasets are collected from 61 participants with a total duration of 513 h, which are publicly available. Experimental results show that the proposed approach achieves a mean absolute percentage error (MAPE) of 0.110 and 0.146 in the FD-I and FD-II datasets, respectively, showcasing the feasibility of automated eating speed measurement in near-free-living environments.

Lipid Trolling to Optimize A3 Adenosine Receptor-Positive Allosteric Modulators (PAMs).

A3 adenosine receptor (A3AR) positive allosteric modulators (PAMs) (2,4-disubstituted-1H-imidazo[4,5-c]quinolin-4-amines) allosterically increase the Emax of A3AR agonists, but not potency, due to concurrent orthosteric antagonism. Following mutagenesis/homology modeling of the proposed lipid-exposed allosteric binding site on the cytosolic side, we functionalized the scaffold, including heteroatom substitutions and exocyclic phenylamine extensions, to increase allosteric binding. Strategically appended linear alkyl-alkynyl chains with terminal amino/guanidino groups improved allosteric effects at both human and mouse A3ARs. The chain length, functionality, and attachment position were varied to modulate A3AR PAM activity. For example, 26 (MRS8247, p-alkyne-linked 8 methylenes) and homologues increased agonist Cl-IB-MECA's Emax and potency ([35S]GTPγS binding). The putative mechanism involves a flexible, terminally cationic chain penetrating the lipid environment for stable electrostatic anchoring to cytosolic phospholipid head groups, suggesting "lipid trolling", supported by molecular dynamic simulation of the active-state model. Thus, we have improved A3AR PAM activity through rational design based on an extrahelical, lipidic binding site.

Amplification of temperature extremes in Arabian Peninsula under warmer worlds.

The Paris Agreement and the Special Report on Global Warming of 1.5 °C from the Intergovernmental Panel on Climate Change (IPCC) highlighted the potential risks of climate change across different global warming levels (GWLs). The increasing occurrence of extreme high-temperature events is linked to a warmer climate that is particularly prevalent in the Arabian Peninsula (AP). This study investigates future changes in temperatures and related extremes over AP, under four GWLs, such as 1.5 °C, 2.0 °C, 3.0 °C, and 4.0 °C, with three different Shared Socioeconomic Pathways (SSPs: SSP1-2.6, SSP2-4.5, and SSP5-8.5). The study uses high-resolution datasets of 27 models from the NASA Earth Exchange Global Daily Downscaled Projections of the Coupled Model Intercomparison Project Phase 6 (NEX-GDDP-CMIP6). The results showed that the NEX-GDDP-CMIP6 individual models and their multi-model means reasonably captured the extreme temperature events. The summer maximum and winter minimum temperatures are projected to increase by 0.11-0.67 °C and 0.09-0.70 °C per decade under the selected SSPs. Likewise, the projected temperature extremes exhibit significant warming with varying degrees across the GWLs under the selected SSPs. The warm temperature extremes are projected to increase, while the cold extremes are projected to decrease under all GWLs and the selected SSPs. Overall, the findings provide a comprehensive assessment of temperature changes over AP in response to global warming, which can be helpful in the development of climate adaptation and mitigation strategies.

New species of Chalciporus and Tylopilus from India, with keys to the known species.

Two new species, Chalciporus rubrostipitatus and Tylopilus purpureus, are proposed from India based on morphological and molecular data. Chalciporus rubrostipitatus is characterized by basidiomata having purplish red to reddish pileus with subtomentose to rugose surface, whitish pileal context, round to angular pores, and reddish orange to red stipe, which is pruinose toward the apex. Tylopilus purpureus produces basidiomata having a purple to vinaceous purple pileus, whitish pore surface that changes to reddish brown on bruising, and a minutely pubescent purplish stipe. Morphological descriptions and comparisons, taxonomic keys, and results of phylogenetic analyses using sequences of the ITS (internal transcribed spacer), 28S (28S rRNA), and RPB2 (second largest subunit of RNA polymerase II) gene regions are presented.

Effectiveness of Plaque Removal Using Different Toothbrushes in Children - A Comparative Study.

BACKGROUND: Effective plaque control is essential for improved oral health. Advancements in mechanical plaque removal using toothbrushes still continue. One such sophisticated intervention is the app-based toothbrush, a new innovative technology that helps to track the child's brushing habits. AIM: The aim of this study is to evaluate the plaque removal efficacy of three different toothbrushes in children aged 6-8 years. METHODS: A randomized controlled clinical trial was conducted among primary school children with decayed missing filled teeth (dmft) score of ≤2. Baseline plaque score was collected using Turesky modification of the Quigley and Hein Index 1 week after oral prophylaxis. Children were randomly divided into three groups. Group I received conventional toothbrush (n = 25), group II received powered toothbrush (n = 25), and group III received app-based toothbrush (n = 25). Post-intervention plaque score, toothbrush wear and bite mark scores were done at the 15th, 30th, 45th and 90th day. Participant's opinion on their toothbrushes was evaluated using a questionnaire. RESULTS AND CONCLUSION: App-based toothbrush showed maximum plaque reduction followed by powered and conventional toothbrush. Significant reduction in plaque score was seen at 30th-, 45th- and 90th-day follow-up in group II (<0.001) and group III (<0.001). There was no appreciable difference in the toothbrush wear and bite mark score between the three groups. Children preferred app-based toothbrush in spite of the complex nature of using it.

Impact of Social Determinants of Health on Predictive Models for Outcomes After Congenital Heart Surgery.

BACKGROUND: Despite documented associations between social determinants of health and outcomes post-congenital heart surgery, clinical risk models typically exclude these factors. OBJECTIVES: The study sought to characterize associations between social determinants and operative and longitudinal mortality as well as assess impacts on risk model performance. METHODS: Demographic and clinical data were obtained for all congenital heart surgeries (2006-2021) from locally held Congenital Heart Surgery Collaborative for Longitudinal Outcomes and Utilization of Resources Society of Thoracic Surgeons Congenital Heart Surgery Database data. Neighborhood-level American Community Survey and composite sociodemographic measures were linked by zip code. Model prediction, discrimination, and impact on quality assessment were assessed before and after inclusion of social determinants in models based on the 2020 Society of Thoracic Surgeons Congenital Heart Surgery Database Mortality Risk Model. RESULTS: Of 14,173 total index operations across New York State, 12,321 cases, representing 10,271 patients at 8 centers, had zip codes for linkage. A total of 327 (2.7%) patients died in the hospital or before 30 days, and 314 children died by December 31, 2021 (total n = 641; 6.2%). Multiple measures of social determinants of health explained as much or more variability in operative and longitudinal mortality than clinical comorbidities or prior cardiac surgery. Inclusion of social determinants minimally improved models' predictive performance (operative: 0.834-0.844; longitudinal 0.808-0.811), but significantly improved model discrimination; 10.0% more survivors and 4.8% more mortalities were appropriately risk classified with inclusion. Wide variation in reclassification was observed by site, resulting in changes in the center performance classification category for 2 of 8 centers. CONCLUSIONS: Although indiscriminate inclusion of social determinants in clinical risk modeling can conceal inequities, thoughtful consideration can help centers understand their performance across populations and guide efforts to improve health equity.

A pilot study of childhood-onset Takayasu arteritis using whole exome sequencing suggests oligogenic inheritance involving classical complement, collagen, and autoinflammatory pathways.

Takayasu arteritis (TA) is a chronic granulomatous inflammatory disease affecting the aorta and its branches. Paediatric TA (pTA) may present from 6 months after birth till the adolescent age group. Genetics and pathogenesis of pTA are not fully understood. Earlier studies reported monogenic mutation in NOD2, XIAP, and STAT1 genes in patients with pTA. TA, a relatively rare disease, is more common in geographical pockets, including India. We hypothesized that South Asian patients with pTA, namely, those of Indian subcontinent origin, may have clinically relevant and unique pathogenic variants involving one or more genes, especially those linked to genetically driven vasculitic illnesses, including autoinflammatory pathologies. Children with pTA fulfilling EULAR/PRINTO/PReS classification criteria and presenting with clinical symptoms to the Paediatric Rheumatology clinic of Christian Medical College, Vellore, were included. Blood samples were collected after getting informed consent from parents or guardians and assent forms from children. DNA was extracted from whole blood using the Qiagen DNA extraction kit. Initially, the common variant in Indian population, namely, ADA2 c.139G > A; p.Gly47Arg, was screened, followed by whole exome sequencing. Fourteen children were recruited for the study. Median age of patients was 11 years (4 months-14 years) with a male-to-female ratio of 4:10. Distribution of angiographic subsets by Numano's classification of included children were as follows: type 5 (n = 7), type 4 (n = 5), and type 3 (n = 2). We identified novel variants in ten different genes. This include variants in genes of classical complement pathway, namely, C2, C3, C6, C7, and C9, and other genes, namely, CYBA, SH3BP2, GUCY2C, CTC1, COL5A1, and NLPR3. Two of 14 patients have heterozygous pathogenic variants; this implies that combination of heterozygous variants in C3 and COL5A1 might lead to disease development, suggesting digenic inheritance. One patient has a homozygous variant in CYBA. None of the patients were identified to have ADA2 variants. Whole exome sequencing reveals combination of rare variants in genes C3, COL5A1, and CYBA associated with disease development in children with Takayasu Arteritis. Key Points • We identified novel variants in genes of classical complement pathway, namely, C2, C3, C6, C7, and C9, and other genes, namely, CYBA, SH3BP2, GUCY2C, CTC1, COL5A1, and NLPR3. • Two of 14 patients have heterozygous pathogenic variants in C3 and COL5A1; this may have implications in disease development, suggesting digenic inheritance. • One patient has homozygous variant in CYBA. • None of the patients were identified to have ADA2 variants.

Community pharmacists as antimicrobial resistance stewards: a narrative review on their contributions and challenges in low- and middle-income countries.

Antimicrobial resistance (AMR) is a global public health crisis that impedes the therapeutic effectiveness of available antimicrobial agents. Due to the high burden of infectious diseases and limited resources, especially trained healthcare professionals, low- and middle-income countries (LMICs) are particularly susceptible to the detrimental effects of AMR. Sometimes, as the first and last point of contact for patients seeking treatment for infections, community pharmacists can play a pivotal role in the stewardship required for AMR. This review aims to highlight the contributions made by community pharmacists in LMICs as AMR stewards. The review considers the challenges from the perspectives of limited resources, inadequate training, a lack of policies and regulations, and issues related to patient behavior. Community pharmacists in LMICs could optimize their advocacy contributions by focusing on One Health AMR stewardship. Transformational and actionable patient and population-centric antimicrobial stewardship (AMS) is feasible with the synergy of policymakers and other healthcare providers in the implementation of AMS policies and programs that support community pharmacists in their efforts to promote rational antimicrobial use.

Correction: Hybrid optimal-FOPID based UPQC for reducing harmonics and compensate load power in renewable energy sources grid connected system.

[This corrects the article DOI: 10.1371/journal.pone.0300145.].

Photoredox Catalysis by 21-Thiaporphyrins: A Green and Efficient Approach for C-N Borylation and C-H Arylation.

Photoredox catalysis provides a green and sustainable alternative for C-H activation of organic molecules that eludes harsh conditions and use of transition metals. The photocatalytic C-N borylation and C-H arylation mostly depend on the ruthenium and iridium complexes or eosin Y and the use of porphyrin catalysts is still in infancy. A series of novel 21-thiaporphyrins (A2B2 and A3B type) were synthesized having carbazole/phenothiazine moieties at their meso-positions and screened as catalysts for C-N borylation and C-H arylation. This paper demonstrates the 21-thiaporphyrin catalyzed C-N borylation and het-arylation of anilines under visible light. The method utilizes only 0.1 mol % of 21-thiaporphyrin catalyst under blue light for the direct C-N borylation and het-arylation reactions. A variety of substituted anilines were used as source for expensive and unstable aryl diazonium salts in the reactions. The heterobiaryls and aryl boronic esters were obtained in decent yields (up to 88 %). Versatility of the 21-thiaporphyrin catalyst was tested by thiolation and selenylation of anilines under similar conditions. Mechanistic insight was obtained from DFT studies, suggesting that 21-thiaporphyrin undergo an oxidative quenching pathway. The photoredox process catalyzed by 21-thiaporphyrins offers a mild, efficient and metal-free alternative for the formation of C-C, C-S, and C-Se bonds in aryl compounds; it can also be extended to borylation reaction.

Hybrid optimal-FOPID based UPQC for reducing harmonics and compensate load power in renewable energy sources grid connected system.

Integration of renewable energy sources (RES) to the grid in today's electrical system is being encouraged to meet the increase in demand of electrical power and also overcome the environmental related problems by reducing the usage of fossil fuels. Power Quality (PQ) is a critical problem that could have an effect on utilities and consumers. PQ issues in the modern electric power system were turned on by a linkage of RES, smart grid technologies and widespread usage of power electronics equipment. Unified Power Quality Conditioner (UPQC) is widely employed for solving issues with the distribution grid caused by anomalous voltage, current, or frequency. To enhance UPQC performance, Fractional Order Proportional Integral Derivative (FOPID) is developed; nevertheless, a number of tuning parameters restricts its performance. The best solution for the FOPID controller problem is found by using a Coati Optimization Algorithm (COA) and Osprey Optimization Algorithm (OOA) are combined to make a hybrid optimization CO-OA algorithm approach to mitigate these problems. This paper proposes an improved FOPID controller to reduce PQ problems while taking load power into account. In the suggested model, a RES is connected to the grid system to supply the necessary load demand during the PQ problems period. Through the use of an enhanced FOPID controller, both current and voltage PQ concerns are separately modified. The pulse signal of UPQC was done using the optimal controller, which analyzes the error value of reference value and actual value to generate pulses. The integrated design mitigates PQ issues in a system at non-linear load and linear load conditions. The proposed model provides THD of 12.15% and 0.82% at the sag period, 10.18% and 0.48% at the swell period, and 10.07% and 1.01% at the interruption period of non-linear load condition. A comparison between the FOPID controller and the traditional PI controller was additionally taken. The results showed that the recommended improved FOPID controller for UPQC has been successful in reducing the PQ challenges in the grid-connected RESs system.

Evidence of potential impacts of a nutrition-sensitive agroecology program in Andhra Pradesh, India, on dietary diversity, nutritional status, and child development.

INTRODUCTION: While a number of studies have examined the nutritional impacts of agroecological interventions, few have examined impacts on child development, maternal and child anemia, and men's dietary diversity. Moreover, there have been few such evaluations at scale. We evaluated the impact of a large-scale, multi-component food-based nutrition intervention involving homestead food production, nutrition counselling, cooking demonstrations, and crop planning exercises. METHODS: A cross-sectional assessment was conducted in 2021-2022 of 50 intervention villages where the nutrition-sensitive agroecology program had been implemented since 2018 and 79 control villages where only the agroecology program had been implemented. Data on self-reported dietary intake, caregiver-reported early child development, anthropometric measurements, and hemoglobin concentrations were collected using standardized procedures by trained Nutrition Farming Fellows, who were also responsible for implementing the program. RESULTS: A sample of 3,511 households (1,121 intervention and 2,390 control) participated in the survey. Dietary diversity scores (DDS) among women and men were mean (SD) 6.53 (±1.62) and 6.16 (±1.65), respectively, in intervention villages and 5.81 (±1.58) and 5.39 (±1.61), respectively, in control villages (p<0.01). DDS among children 6-24 months of age in intervention and control villages was 2.99 (±1.52) and 2.73 (±1.62), respectively (p<0.01). Children <2 years of age were less likely to be anemic in intervention versus control villages (59% versus 69%, p<0.01). Children 18-35 months age in intervention villages had higher child development scores than children in control villages (all p<0.05). CONCLUSION: Nutrition-sensitive agroecological programs may be effective in improving diets, nutrition, and child development in rural India.

A Long-term Comparison of Outcome of Arthroscopic Anterior Cruciate Ligament Reconstruction Using Bioabsorbable Interference Screw and Endobutton on Femur.

Introduction: Arthroscopic anterior cruciate ligament (ACL) reconstruction is a very commonly done procedure in recent times. There is a need for a long-term outcome study of ACL reconstruction with a comparison between different types of fixation techniques. The graft fixation methods vary from aperture fixation (interference screws) to suspensory fixation methods (endobutton). Failure of graft incorporation and the development of tunnel widening (TW) after ACL reconstruction have been frequently reported in the long term in present literature. TW especially complicates revision ACL surgery. This is a prospective non-randomized clinical study of arthroscopic ACL reconstruction comparing the functional results between aperture fixation and suspensory fixation. Materials and Methods: Two groups of 14 patients who underwent autogenous hamstring ACL reconstruction with a minimum of 2-year follow-up evaluation were included in the study. The first group underwent aperture fixation with bioabsorbable interference screw at tibial and femoral side. The second group underwent suspensory fixation with endobutton fixation on the femoral side and biointerference screw on the tibial side. Both group patients were examined clinically before surgery, and at 3 months, 6 months, 1 year, and at 2 years. They were compared for functional outcome with Tegner Lysholm knee score. Observation and Results: There was a significant improvement in functional outcome in both the groups for base and at 3 months, also for 3 months and 6 months but for 6 months-1 year. Group 2 is almost significant. This improvement in outcome in Group 2 is consistent from 1 year to 2 years. Conclusion: In our prospective study comparing the outcomes of functional outcomes of ACL reconstruction with aperture fixation versus suspensory fixation on the femur, which was evaluated using Tegner Lysholm knee score over a period of 2 years, suspensory fixation was found to be better. However, further studies involving a larger series of cases are required for a better evaluation of the outcome.

Assessing climate change and health provisions among staff in higher education institutions: A preliminary investigation.

Climate change can have direct and indirect effects on human health. Direct effects can include an increase in extreme weather events, such as heatwaves and floods, as well as an increase in the spread of vector-borne and infectious diseases, which may lead to a set of health problems and diseases. Indirect effects can include changes in air quality, water availability, and food production and distribution. These changes can lead to an increase in respiratory problems, malnutrition, and increased food insecurity. There is a perceived need to investigate the extent to which Higher Education Institutions (HEIs) are engaged in efforts to foster a greater understanding of the connections between climate change and health. In this context, this preliminary investigation offers an overview of the relationships between climate change and health. By means of a survey among teaching staff and researchers at HEIs from 42 countries across all continents working on the connection between climate change and health. The study has investigated the extent to which current provisions for education and training on the connection between climate change and health are being considered and how current needs in terms of policy development, research, and training are being met. A series of case studies illustrate how universities worldwide are actively developing strategies and implementing measures to address climate change and health. The study concludes by providing specific recommendations aimed at facilitating the handling of issues related to climate change and health in a higher education context.

Probiotic potential of a novel endophytic Streptomyces griseorubens CIBA-NS1 isolated from Salicornia sp. against Vibrio campbellii infection in shrimp.

A novel endophytic Streptomyces griseorubens CIBA-NS1 was isolated from a salt marsh plant Salicornia sp. The antagonistic effect of S. griseorubens against Vibrio campbellii, was studied both in vitro and in vivo. The strain was validated for its endophytic nature and characterized through scanning electron microscopy, morphological and biochemical studies and 16SrDNA sequencing. The salinity tolerance experiment has shown that highest antibacterial activity was at 40‰ (16 ± 1.4 mm) and lowest was at 10 ‰ salinity (6.94 ± 0.51 mm). In vivo exclusion of Vibrio by S. griseorubens CIBA-NS1 was studied in Penaeus indicus post larvae and evaluated for its ability to improve growth and survival of P. indicus. After 20 days administration of S. griseorubens CIBA-NS1, shrimps were challenged with V. campbellii. The S. griseorubens CIBA-NS1 reduced Vibrio population in test group when compared to control, improved survival (60.5 ± 6.4%) and growth, as indicated by weight gain (1.8 ± 0.05g). In control group survival and growth were 48.4 ± 3.5% and 1.4 ± 0.03 g respectively. On challenge with V. campbellii, the S. griseorubens CIBA-NS1 administered group showed better survival (85.6 ± 10%) than positive control (64.3 ± 10%). The results suggested that S. griseorubens CIBA-NS1 is antagonistic to V. campbellii, reduce Vibrio population in the culture system and improve growth and survival. This is the first report on antagonistic activity of S. griseorubens isolated from salt marsh plant Salicornia sp, as a probiotic candidate to prevent V. campbellii infection in shrimps.