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Abstract Family members of Asian Americans (AAs) hold enormous potential as health changemakers to help combat the growing non-communicable disease burden in the community. To inform the development of impactful family-based interventions, there is a need to disentangle the mechanisms behind family influences on health. This study aims to deconstruct how interactivity and closeness mediate the association of age and acculturation with how much AA young adults perceive themselves to influence the health behaviors of family members. 502 AA young adults (48.0% East Asian, 20.9% South Asian, 23.1% Southeast Asian) were recruited in March 2021 to participate in an online survey on family interaction patterns, providing data on 944 unique dyadic family relationships. Associations between age, acculturation, interactivity (shared family activities, living proximity, and interaction frequency), closeness (family connectedness and interaction quality), and family health influence (reflecting influence on diet, exercise, sleep, stress, substance use, and relationship building) were evaluated through structural equation modeling. The final model displayed strong fit (CFI:0.956, RMSEA:0.081, SRMR:0.041), and revealed that an increase in closeness compared to interactivity corresponded with a greater increase in family health influence, with both completely mediating the association between age and family health influence. Acculturation was not associated with closeness, and its effect on family health influence was only partially mediated through interactivity. In subgroup analyses, neither interactivity nor closeness mediated the relationship between age and family health influence among South Asians (unlike East and Southeast Asians). Findings suggest the importance of targeting interactivity and closeness separately when developing AA family-based health interventions, and considering how the age and acculturation profile of AA young adults may shape these dynamics.

Abstract Proteins containing both intrinsically disordered regions (IDRs) and RNA binding domains (RBDs) can phase separate in vitro, forming bodies similar to cellular biomolecular condensates. However, how IDR and RBD domains contribute to in vivo recruitment of proteins to biomolecular condensates remains poorly understood. Here, we analyzed the roles of IDRs and RBDs in L-bodies, biomolecular condensates present in Xenopus oocytes. We show that a cytoplasmic isoform of hnRNPAB, which contains two RBDs and an IDR, is highly enriched in L-bodies. While both of these domains contribute to hnRNPAB self-association and phase separation in vitro and mediate enrichment into L-bodies in oocytes, neither the RBDs nor the IDR replicate the localization of full-length hnRNPAB. Our results suggest a model where the combined effects of the IDR and RBDs regulate hnRNPAB partitioning into L-bodies. This model likely has widespread applications as proteins containing RBD and IDR domains are common biomolecular condensate residents.

Abstract Congenital heart disease (CHD) is the most common birth defect in newborns, often requiring cardiac surgery with concomitant thymectomy that is known to increase disease susceptibility later in life. Studies of γδ T cells, which are one of the dominant T cells in the early fetal human thymus, are rare. Here, we provide a comprehensive analysis of the γδ T cell compartment via flow cytometry and next-generation sequencing in children and infants with CHD, who underwent cardiac surgery shortly after birth. A perturbation of the γδ T cell repertoire is evident, and Vδ1 T cell numbers are reduced. However, those cells that are present, do retain cytotoxicity. In contrast, GZMA+CD28+CD161hi innate effector Vγ9Vδ2 T cells are found in higher proportions. TCR-seq identifies an increase in TRDJ3+ γδ T cell clones in children with CHD, but not in a confirmatory group of neonates prior to CHD surgery, which overall points to a persistence of fetal-derived effector γδ T cells in children with CHD.

Abstract Background Immune cell metabolism governs the outcome of immune responses and contributes to the development of autoimmunity by controlling lymphocyte pathogenic potential. In this study, we evaluated the metabolic profile of myelin-specific murine encephalitogenic T cells, to identify novel therapeutic targets for autoimmune neuroinflammation. Methods We performed metabolomics analysis on actively-proliferating encephalitogenic T cells to study their overall metabolic profile in comparison to resting T cells. Metabolomics, phosphoproteomics, in vitro functional assays, and in vivo studies in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), were then implemented to evaluate the effect of metabolic targeting on autoreactive T cell pathogenicity. Finally, we confirmed the translational potential of our targeting approach in human pro-inflammatory T helper cell subsets and in T cells from MS patients. Results We found that autoreactive encephalitogenic T cells display an altered coenzyme A (CoA) synthesis pathway, compared to resting T cells. CoA fueling with the CoA precursor pantethine (PTTH) affected essential immune-related processes of myelin-specific T cells, such as cell proliferation, cytokine production, and cell adhesion, both in vitro and in vivo. Accordingly, pre-clinical treatment with PTTH before disease onset inhibited the development of EAE by limiting T cell pro-inflammatory potential in vivo. Importantly, PTTH also significantly ameliorated the disease course when administered after disease onset in a therapeutic setting. Finally, PTTH reduced pro-inflammatory cytokine production by human T helper 1 (Th1) and Th17 cells and by T cells from MS patients, confirming its translational potential. Conclusion Our data demonstrate that CoA fueling with PTTH in pro-inflammatory and autoreactive T cells may represent a novel therapeutic approach for the treatment of autoimmune neuroinflammation.

Abstract Background The purpose of the present study was to evaluate the use of a free online continuing education (CE) course that sought to address barriers of capability by training dental team members in the specific recommendations of the American Dental Association (ADA)-endorsed adult guideline for the pharmacologic management of acute dental pain, shared decision-making, and the adoption of the guideline into practice. Methods In 2022 and 2023, dentists completed an online, asynchronous CE course on the guideline-concordant pharmacologic management of acute dental pain. They completed 11-item knowledge tests before and after completing the course. Total scores on the pre- and post-tests were compared using a t-test. Results The mean score increased from 7.68 (SD = 1.08) on the pretest to 8.79 (SD = 1.35) on the post-test (t (4468) = -27.34, p

Abstract Alzheimer’s disease (AD) poses a major challenge due to its impact on the elderly population and the lack of effective early diagnosis and treatment options. In an effort to address this issue, a study focused on identifying potential biomarkers and therapeutic agents for AD was carried out. Using RNA-Seq data from AD patients and healthy individuals, 12 differentially expressed genes (DEGs) were identified, with 9 expressing upregulation (ISG15, HRNR, MTATP8P1, MTCO3P12, DTHD1, DCX, ST8SIA2, NNAT, and PCDH11Y) and 3 expressing downregulation (LTF, XIST, and TTR). Among them, TTR exhibited the lowest gene expression profile. Interestingly, functional analysis tied TTR to amyloid fiber formation and neutrophil degranulation through enrichment analysis. These findings suggested the potential of TTR as a diagnostic biomarker for AD. Additionally, druggability analysis revealed that the FDA-approved drug Levothyroxine might be effective against the Transthyretin protein encoded by the TTR gene. Molecular docking and dynamics simulation studies of Levothyroxine and Transthyretin suggested that this drug could be repurposed to treat AD. However, additional studies using in vitro and in vivo models are necessary before these findings can be applied in clinical applications.

The civic mobilisation welcoming Ukrainian refugees after Russia’s invasion in February 2022 has shown how housing is a social infrastructure based on care and solidarity. But it has also shown its discriminatory face. By drawing on our recent collaborative research in Leipzig and Riga and conceptual reflections from previous research, this paper elaborates on how practices of welcoming and housing refugees intertwine with state racism and everyday discrimination. It is grounded in two intersecting lines of inquiry. The first one focuses on migrant housing struggles in the context of increased financialisation, privatisation and austerity urbanism. The second expands on the intersection of race and discrimination with housing, asking how race and racial discrimination intersect and affect migrants, refugees, and asylum seekers’ access to and experiences with housing. The underlying argument is that while housing is the site where this type of discrimination becomes spatialised and visible (and thus can be challenged), there is still a missing discourse around discrimination in migration and housing policy.

Abstract Background Neurovascular deficits and blood-brain barrier (BBB) dysfunction are major hallmarks of brain trauma and neurodegenerative diseases. Oxidative stress is a prominent contributor to neurovascular unit (NVU) dysfunction and can propagate BBB disruption. Oxidative damage results in an imbalance of mitochondrial homeostasis, which can further drive functional impairment of brain capillaries. To this end, we developed a method to track mitochondrial-related changes after oxidative stress in the context of neurovascular pathophysiology as a critical endophenotype of neurodegenerative diseases. Methods To study brain capillary-specific mitochondrial function and dynamics in response to oxidative stress, we developed an ex vivo model in which we used isolated brain capillaries from transgenic mice that express dendra2 green specifically in mitochondria (mtD2g). Isolated brain capillaries were incubated with 2,2’-azobis-2-methyl-propanimidamide dihydrochloride (AAPH) or hydrogen peroxide (H2O2) to induce oxidative stress through lipid peroxidation. Following the oxidative insult, mitochondrial bioenergetics were measured using the Seahorse XFe96 flux analyzer, and mitochondrial dynamics were measured using confocal microscopy with Imaris software. Results We optimized brain capillary isolation with intact endothelial cell tight-junction and pericyte integrity. Further, we demonstrate consistency of the capillary isolation process and cellular enrichment of the isolated capillaries. Mitochondrial bioenergetics and morphology assessments were optimized in isolated brain capillaries. Finally, we found that oxidative stress significantly decreased mitochondrial respiration and altered mitochondrial morphology in brain capillaries, including mitochondrial volume and count. Conclusions Following ex vivo isolation of brain capillaries, we confirmed the stability of mitochondrial parameters, demonstrating the feasibility of this newly developed platform. We also demonstrated that oxidative stress has profound effects on mitochondrial homeostasis in isolated brain capillaries. This novel method can be used to evaluate pharmacological interventions to target oxidative stress or mitochondrial dysfunction in cerebral small vessel disease and neurovascular pathophysiology as major players in neurodegenerative disease.

Abstract Background Systematic counseling on behavioral health risk factors (HRFs) may be suitable to promote health among general hospital patients. This study aimed to investigate the openness of patients towards systematic screening and intervention of HRFs, its relation to actual participation in a multi-behavioral intervention, and whether socio-economic characteristics, HRFs and health indicators are related to approval. Methods All 18- to 64-year-old patients hospitalized in five medical departments at the University Medicine Hospital Greifswald in Germany were asked between May and July 2022 to participate in a survey and in a subsequent pre-post intervention study. Among all eligible patients, 225 (78.9%) participated in the survey. Patients’ approval of systematic screening and intervention of HRFs was assessed using five statements with a total sum score of 0–20 (i.e., scores of 0–6, 7–13, 14–20 referring to low, medium and high approval). Associations with intervention participation, socio-economic, behavioral and health-related patient characteristics were analyzed using logistic and multivariable linear regression analyses. Results The mean total approval of screening and intervention was 13.8 (SD = 4.8). Of the 125/ 73/ 16 patients with high/ medium/ low approval, 88.0%/ 78.1%/ 50.0% participated in the subsequent intervention, respectively. Approval was independent of socio-demographic and -economic characteristics and self-rated general health. Current tobacco smoking was the only HRF negatively (p = 0.02) and diabetes mellitus was the only disease positively (p = 0.01) associated with approval. Conclusion High approval of HRF screening, which was rather independent of socio-economic characteristics and worse self-rated general health, speaks in favor of proactively approaching and motivating all general hospital patients to participate in health behavior change intervention. Tobacco smokers might need higher efforts to motivate participation than non-smokers. Trial registration ClinicalTrials.gov Identifier NCT05365269 on May 9, 2022.

The study was made to explore the implications of plant growth promoting rhizobacterium in French bean while acclimating to drought stress. Among the bacterial strains used in this study, Bacillus amyloliquefaciens (PPB6) was selected as the suitable candidate for having better growth performances in French bean. Plants provided with drought and PPB6 showed better performances in morpho-physiological attributes as compared to drought-stressed plants only. While facing drought, PPB6 reduced Reactive Oxygen Species (ROS); hydrogen peroxide (H2O2), and lipid peroxidation product; malondialdehyde (MDA), and electrolyte leakage as compared to drought-stressed plants only. Consistently, PPB6 reduced proline, total phenolics and flavonoid contents under drought stress than drought-stressed plants only. Besides, significant reduction of the activity of ascorbate peroxidase, glutathione S-transferase and peroxidase by PPB6 suggesting the lowering of drought-induced oxidative damage by this bacterium. Although, control plants showed best performance in the induction of morpho-physiological parameters and reduction of antioxidative properties, the better permeances in this regard by the plants treated with drought and PPB6 than drought-stressed only, suggesting that PPB6 has the ability to reduce the drought impacts and could partially complements the features of non-stressed control plants. We suggest PPB6 as the potential mitigator of the drought stress in French bean.

Introduction: The proximal end of the femur is an important anatomical modification in humans, widely explored to acquire detailed knowledge that aids in determining the exact size of hip prosthesis and minimising postoperative complications. However, thorough analysis of the various parameters of the Fovea Capitis Femoris (FCF) is frequently overlooked, yet it is also important during reconstructive surgery of the ligamentum teres femoris, radiographic evaluation of hip dysplasia, or as an anatomical landmark in hip arthroscopy. Detailed morphological and morphometric measurements of the FCF in the West Bengal population would help bridge this gap, as there are few Indian studies regarding the fovea. Aim: To determine the morphological and morphometric measurements of the FCF in the West Bengal population. Materials and Methods: A cross-sectional study was conducted among 297 dry femora from the Department of Anatomy at Kolkata Medical College, Kolkata, West Bengal, India from October 2023 to February 2024. The position and shape of the fovea were recorded. Morphometric measurements of the fovea (depth, transverse diameter, and vertical diameter) and the head of the femur (transverse and vertical diameters) were taken using a vernier caliper. The collected data were compiled in a Microsoft Excel sheet and analysed using Jamovi software (free version). The Pearson’s correlation formula was used to determine the correlation between various parameters of the fovea and femoral head. A p-value of

Abstract Background The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer’s disease (EOAD). Yet, detailed examination of MTL subfields and drivers of atrophy in amnestic EOAD is lacking. Methods BioFINDER-2 participants with memory impairment, abnormal amyloid-β and tau-PET were included. Forty-one amnestic EOAD individuals ≤65 years and, as comparison, late-onset AD (aLOAD, ≥70 years, n = 154) and amyloid-β-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured. Results AD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups: aLOAD showed thinner entorhinal cortices than aEOAD; aEOAD showed thinner parietal regions than aLOAD. aEOAD showed lower white matter hyperintensities than aLOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity were found. Conclusions We found evidence for MTL atrophy in amnestic EOAD and overall similar levels to aLOAD of MTL tau pathology and co-pathologies.

Abstract The central amygdala (CeA) is a crucial hub in the processing of affective itch, containing a diverse array of neuronal populations. Among these components, Neuropeptide Y (NPY) and its receptors, such as NPY2R, affect various physiological and psychological processes. Despite this broad impact, the precise role of NPY2R+ CeA neurons in itch modulation remains unknown, particularly concerning any potential lateralization effects. To address this, we employed optogenetics to selectively stimulate NPY2R+ CeA neurons in mice, investigating their impact on itch modulation. Optogenetic activation of NPY2R+ CeA neurons reduced scratching behavior elicited by pruritogens without exhibiting any lateralization effects. Electrophysiological recordings confirmed increased neuronal activity upon stimulation. However, this modulation did not affect thermal sensitivity, mechanical sensitivity, or formalin-induced hyperalgesia. Additionally, no alterations in anxiety-like behaviors or locomotion were observed upon stimulation. Projection tracing revealed connections of NPY2R+ CeA neurons to brain regions implicated in itch processing. Overall, this comprehensive study highlights the role of NPY2R+ CeA neurons in itch regulation without any lateralization effects.

Abstract Members of the leucine rich repeat (LRR) and PDZ domain (LAP) protein family are essential for animal development and histogenesis. Densin-180, encoded by LRRC7, is the only LAP protein selectively expressed in neurons. Densin-180 is a postsynaptic scaffold at glutamatergic synapses, linking cytoskeletal elements with signalling proteins such as the α-subunit of Ca2+/calmodulin-dependent protein kinase II. We have previously observed an association between high impact variants in LRRC7 and Intellectual Disability; also three individual cases with variants in LRRC7 had been described. We identify here 33 individuals (one of them previously described) with a dominant neurodevelopmental disorder due to heterozygous missense or loss-of-function variants in LRRC7. The clinical spectrum involves intellectual disability, autism, ADHD, aggression and, in several cases, hyperphagia-associated obesity. A PDZ domain variant interferes with synaptic targeting of Densin-180 in primary cultured neurons. Using in vitro systems (two hybrid, BioID, coimmunoprecipitation of tagged proteins from 293T cells) we identified new candidate interaction partners for the LRR domain, including protein phosphatase 1 (PP1), and observed that variants in the LRR reduced binding to these proteins. We conclude that LRRC7 encodes a major determinant of intellectual development and behaviour.

Abstract The circadian clock of cyanobacteria, which predicts daily environmental changes, typically includes a standard oscillator consisting of proteins KaiA, KaiB, and KaiC. However, several cyanobacteria have diverse Kai protein homologs of unclear function. In particular, Synechocystis sp. PCC 6803 harbours, in addition to a canonical kaiABC gene cluster (named kaiAB1C1), two further kaiB and kaiC homologs (kaiB2, kaiB3, kaiC2, kaiC3). Here, we identify a chimeric KaiA homolog, named KaiA3, encoded by a gene located upstream of kaiB3. At the N-terminus, KaiA3 is similar to response-regulator receiver domains, whereas its C-terminal domain resembles that of KaiA. Homology analysis shows that a KaiA3-KaiB3-KaiC3 system exists in several cyanobacteria and other bacteria. Using the Synechocystis sp. PCC 6803 homologs, we observe circadian oscillations in KaiC3 phosphorylation in vitro in the presence of KaiA3 and KaiB3. Mutations of kaiA3 affect KaiC3 phosphorylation, leading to growth defects under both mixotrophic and chemoheterotrophic conditions. KaiC1 and KaiC3 exhibit phase-locked free-running phosphorylation rhythms. Deletion of either system (∆kaiAB1C1 or ∆kaiA3B3C3) alters the period of the cellular backscattering rhythm. Furthermore, both oscillators are required to maintain high-amplitude, self-sustained backscatter oscillations with a period of approximately 24 h, indicating their interconnected nature.

Abstract Background Microglial activation is one hallmark of Alzheimer disease (AD) neuropathology but the impact of the regional interplay of microglia cells in the brain is poorly understood. We hypothesized that microglial activation is regionally synchronized in the healthy brain but experiences regional desynchronization with ongoing neurodegenerative disease. We addressed the existence of a microglia connectome and investigated microglial desynchronization as an AD biomarker. Methods To validate the concept, we performed microglia depletion in mice to test whether interregional correlation coefficients (ICCs) of 18 kDa translocator protein (TSPO)-PET change when microglia are cleared. Next, we evaluated the influence of dysfunctional microglia and AD pathophysiology on TSPO-PET ICCs in the mouse brain, followed by translation to a human AD-continuum dataset. We correlated a personalized microglia desynchronization index with cognitive performance. Finally, we performed single-cell radiotracing (scRadiotracing) in mice to ensure the microglial source of the measured desynchronization. Results Microglia-depleted mice showed a strong ICC reduction in all brain compartments, indicating microglia-specific desynchronization. AD mouse models demonstrated significant reductions of microglial synchronicity, associated with increasing variability of cellular radiotracer uptake in pathologically altered brain regions. Humans within the AD-continuum indicated a stage-depended reduction of microglia synchronicity associated with cognitive decline. scRadiotracing in mice showed that the increased TSPO signal was attributed to microglia. Conclusion Using TSPO-PET imaging of mice with depleted microglia and scRadiotracing in an amyloid model, we provide first evidence that a microglia connectome can be assessed in the mouse brain. Microglia synchronicity is closely associated with cognitive decline in AD and could serve as an independent personalized biomarker for disease progression.

There is a considerable interest in supplementing fish diets with bio-functional substances such as polyunsaturated fatty acids (PUFAs), and research is being conducted to evaluate their effects on fish physiology, particularly on breeding performances. The objective of this study was to find out how squid-derived lipids (PUFAs) influence the Rohu carp, Labeo rohita, in terms of reproduction, and embryonic and larval growth. The experimental fish were provided with formulated diet for a duration of 90 days, containing 1 % squid-extracted lipids as a primary source of polyunsaturated fatty acids (PUFAs). To determine the accuracy of the formulation, a proximate analysis of the feed ingredients and the formulated feeds were conducted. The results demonstrated remarkable reproductive outcomes during the spawning trial. Observations in fish treated with PUFAs revealed a significant improvement (p

Wastewater treatment plants (WWTPs) have been identified as important point sources for microplastics (MPs) in the environment; monitoring MP emissions in the WWTP effluent is therefore essential for contamination control. The aim of this study is to acquire a large number of samples (320) over a period of two years and three months to determine the temporal variations in microplastic contamination in the outlet of the municipal WWTP Landau-Mörlheim. The effluent of the third cleaning stage is sampled with a 10 µm filter cartridge, processed in the laboratory using a hydrogen peroxide treatment, and MPs are then detected by fluorescence staining. The results show high temporal variations in the microplastic concentrations in the effluent of the WWTP. This indicates that high numbers of samples are necessary to obtain a representative assessment of the microplastic emissions; single samples are not representative. The average microplastic concentration in the effluent was 27.8 ± 29.8 MP/L, ranging from 0.6 MP/L to 194.0 MP/L. This leads to a yearly emission of 1.5 × 1011 MP for the WWTP Landau-Mörlheim, corresponding to an emission of 2.8 × 106 MP/inhabitant and year. Statistically significant seasonal variations could not be observed, although there is a trend towards lower MP concentrations in summer. Further, no correlations with other wastewater or weather parameters could be found.

Background: The World Health Organization (WHO) recommends exclusive breastfeeding for six months. Many intervention programs to increase the coverage of exclusive breastfeeding have been carried out, but the coverage of exclusive breastfeeding has not increased significantly. A systematic review analyzed several factors that influence exclusive breastfeeding in developing countries. Mother's occupation was found to be the most frequently mentioned obstacle. Objective: These studies show that the working status of the mother is something that greatly influences the success of exclusive breastfeeding. Methods: This research is a qualitative phenomenological study to see the support and barriers to exclusive breastfeeding for mothers who work in Sukoharjo. Results: The theme found in this study is the support and inhibition of exclusive breastfeeding for working mothers as seen from the Theory of Planned Behavior and Social Cognitive Theory. The obstacles are: 1) incorrect knowledge about exclusive breastfeeding, 2) barriers from some health workers/institutions, 3) families do not support exclusive breastfeeding, 4) there is no regulation on exclusive breastfeeding in the workplace, 5) the workplace does not yet have a special place for pumping and storing breast milk, 6) does not have a role model, 7) breast milk is reduced by working, 8) already has the intention to mix with formula milk, 9) low self-efficacy, and 10) barriers from the baby's internal factors. The supports are: 1) support from health workers/institutions, 2) the workplace provides a special room for pumping and/or storing breast milk, 3) there is an opportunity for pumping breast milk in the workplace, 4) peer support, 5) there is a high expectation of health. good, 6) intention to exclusively breastfeed, 7) good self-efficacy, 8) family support, 9) leave from work and light workload, 10) skills in breastfeeding, 11) no obstacles from the leadership, and 12) smooth mother's milk. Conclusion: This shows that SCT and TPB can be used as a theory to see the variables that influence the practice of exclusive breastfeeding. There is one finding that cannot be directly included in the SCT and/or TPB constructs, namely: skills in providing breast milk.

To validate three different Active Surveillance Care Pathways for men with prostate cancer, Low-Intensity, Intermediate-Intensity, and High-Intensity schedules were evaluated. Three factors related to the appropriateness and quality of care were considered: patient adherence to the schedule, negative biopsy incidence, and time to detection of significant cancer. The intermediate- intensity schedule had the best adherence as 40.9% adhered to their schedule at the confirma- tory biopsy and 15.9% adhered to the 36-month surveillance biopsy, showing that it was the least burdensome. In terms of negative biopsy rate, the Low-Frequency and High-Frequency Schedules were shown to be most effective in their patient populations. Finally, the High-Frequency Schedule had the earliest time to detection of significant cancer (n= 691 days) showing the best clinical outcomes. Ultimately, further investigation is needed to determine how to increase adherence to the biopsy schedules that lead to the best clinical outcomes.

Abstract Determining movement parameters for pest insects such as tephritid fruit flies is critical to developing models which can be used to increase the effectiveness of surveillance and control strategies. In this study, harmonic radar was used to track wild-caught male Queensland fruit flies (Qflies), Bactrocera tryoni, in papaya fields. Experiment 1 continuously tracked single flies which were prodded to induce movement. Qfly movements from this experiment showed greater mean squared displacement than predicted by both a simple random walk (RW) or a correlated random walk (CRW) model, suggesting that movement parameters derived from the entire data set do not adequately describe the movement of individual Qfly at all spatial scales or for all behavioral states. This conclusion is supported by both fractal and hidden Markov model (HMM) analysis. Lower fractal dimensions (straighter movement paths) were observed at larger spatial scales (> 2.5 m) suggesting that Qflies have qualitatively distinct movement at different scales. Further, a two-state HMM fit the observed movement data better than the CRW or RW models. Experiment 2 identified individual landing locations, twice a day, for groups of released Qflies, demonstrating that flies could be tracked over longer periods of time.

Abstract Despite therapeutic advancements, cervical cancer caused by high-risk subtypes of the human papillomavirus (HPV) remains a leading cause of cancer-related deaths among women worldwide. This study aimed to discover potential drug candidates from the Asian medicinal plant Andrographis paniculata, demonstrating efficacy against the E6 protein of high-risk HPV-16 subtype through an in-silico computational approach. The 3D structures of 32 compounds (selected from 42) derived from A. paniculata, exhibiting higher binding affinity, were obtained from the PubChem database. These structures underwent subsequent analysis and screening based on criteria including binding energy, molecular docking, drug likeness and toxicity prediction using computational techniques. Considering the spectrometry, pharmacokinetic properties, docking results, drug likeliness, and toxicological effects, five compounds—stigmasterol, 1H-Indole-3-carboxylic acid, 5-methoxy-, methyl ester (AP7), andrographolide, apigenin and wogonin—were selected as the potential inhibitors against the E6 protein of HPV-16. We also performed 200 ns molecular dynamics simulations of the compounds to analyze their stability and interactions as protein–ligand complexes using imiquimod (CID-57469) as a control. Screened compounds showed favorable characteristics, including stable root mean square deviation values, minimal root mean square fluctuations and consistent radius of gyration values. Intermolecular interactions, such as hydrogen bonds and hydrophobic contacts, were sustained throughout the simulations. The compounds displayed potential affinity, as indicated by negative binding free energy values. Overall, findings of this study suggest that the selected compounds have the potential to act as inhibitors against the E6 protein of HPV-16, offering promising prospects for the treatment and management of CC.

Abstract Background Scientific evidence highlights the influence of biological sex on the relationship between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress concurrently contribute to metabolic dysregulation in both males and females. Our study aimed to investigate the combined effects of high-fat diet (HFD) induced obesity and repeated stress on fear-related behaviors, metabolic, immune, and hypothalamic outcomes in male and female mice. Methods To investigate this, we used a highly reliable rodent behavioral model that faithfully recapitulates key aspects of post-traumatic stress disorder (PTSD)-like fear. We subjected mice to footshock stressor followed by a weekly singular footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. At weeks 10 and 14 we conducted glucose tolerance and insulin sensitivity measurements. Additionally, we placed the mice in metabolic chambers to perform indirect calorimetric measurements. Finally, we collected brain and peripheral tissues for cellular analysis. Results We observed that HFD-induced obesity disrupted fear memory extinction, increased glucose intolerance, and affected energy expenditure specifically in male mice. Conversely, female mice on HFD exhibited reduced respiratory exchange ratio (RER), and a significant defect in glucose tolerance only when subjected to repeated stress. Furthermore, the combination of repeated stress and HFD led to sex-specific alterations in proinflammatory markers and hematopoietic stem cells across various peripheral metabolic tissues. Single-nuclei RNA sequencing (snRNAseq) analysis of the ventromedial hypothalamus (VMH) revealed microglial activation in female mice on HFD, while male mice on HFD exhibited astrocytic activation under repeated stress. Conclusions Overall, our findings provide insights into complex interplay between repeated stress, high-fat diet regimen, and their cumulative effects on health, including their potential contribution to the development of PTSD-like stress and metabolic dysfunctions, emphasizing the need for further research to fully understand these interconnected pathways and their implications for health.

Abstract Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts. However, the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely understood. Here we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion. Single cell RNA sequencing-based analyses suggested that activation of parts of the apoptotic machinery accompanied the differentiation of osteoclast precursors into mature multinucleated osteoclasts. A subsequent characterization of osteoclast precursors confirmed that RANKL-mediated activation of caspase-8 promoted the non-apoptotic cleavage and activation of downstream effector caspases that translocated to the plasma membrane where they triggered activation of the phospholipid scramblase Xkr8. Xkr8-mediated exposure of phosphatidylserine, in turn, aided cellular fusion of osteoclast precursors and thereby allowed generation of functional multinucleated osteoclast syncytia and initiation of bone resorption. Pharmacological blockage or genetic deletion of caspase-8 accordingly interfered with fusion of osteoclasts and bone resorption resulting in increased bone mass in mice carrying a conditional deletion of caspase-8 in mononuclear osteoclast precursors. These data identify a novel pathway controlling osteoclast biology and bone turnover with the potential to serve as target for therapeutic intervention during diseases characterized by pathologic osteoclast-mediated bone loss. Proposed model of osteoclast fusion regulated by caspase-8 activation and PS exposure. RANK/RANK-L interaction. Activation of procaspase-8 into caspase-8. Caspase-8 activates caspase-3. Active capase-3 cleaves Xkr8. Local PS exposure is induced. Exposed PS is recognized by the fusion partner. FUSION. PS is re-internalized.

Abstract Background Cleft lip and palate (CLP) are among the most common congenital anomaly that affects up to 33,000 newborns in India every year. Nasoalveolar moulding (NAM) is a non-surgical treatment performed between 0 and 6 months of age to reduce the cleft and improve nasal aesthetics prior to lip surgery. The NAM treatment has been a controversial treatment option with 51% of the cleft teams in Europe, 37% of teams in the USA and 25 of cleft teams in India adopting this methodology. This treatment adds to the already existing high burden of care for these patients. Furthermore, the supporting evidence for this technique is limited with no high-quality long-term clinical trials available on the effectiveness of this treatment. Method The NAMUC study is an investigator-initiated, multi-centre, single-blinded randomized controlled trial with a parallel group design. The study will compare the effectiveness of NAM treatment provided prior to lip surgery against the no-treatment control group in 274 patients with non-syndromic unilateral complete cleft lip and palate. The primary endpoint of the trial is the nasolabial aesthetics measured using the Asher McDade index at 5 years of age. The secondary outcomes include dentofacial development, speech, hearing, cost-effectiveness, quality of life, patient perception, feeding and intangible benefits. Randomization will be carried out via central online system and stratified based on cleft width, birth weight and clinical trial site. Discussion We expect the results from this study on the effectiveness of treatment with NAM appliance in the long term along with the cost-effectiveness evaluation can eliminate the dilemma and differences in clinical care across the globe. Trial registration ClinicalTrials.gov CTRI/2022/11/047426 (Clinical Trials Registry India). Registered on 18 November 2022. The first patient was recruited on 11 December 2022. CTR India does not pick up on Google search with just the trial number. The following steps have to be carried out to pick up. How to search: ( https://ctri.nic.in/Clinicaltrials/advsearch.php —use the search boxes by entering the following details: Interventional trial > November 2022 > NAMUC).

Abstract Background Mild cognitive impairment (MCI) involves cognitive decline beyond typical age-related changes, but without significant daily activity disruption. It can encompass various cognitive domains as the causes of MCI are diverse. MCI as well as frequent comorbid neuropsychiatric conditions like depression and anxiety affect individuals’ quality of life. Early interventions are essential, and computerized cognitive training (cCT) is an established treatment method. This paper presents the protocol for the NeuroNation MED Effectiveness Study, evaluating the self-administered mobile cCT intervention (“NeuroNation MED”) in individuals with MCI to assess training effects on cognitive domains, health competence, neuropsychiatric symptoms, psychological well-being, and the general application usability. Methods This study protocol presents a single-blinded multicenter randomized controlled trial that will be carried out in six study centers in Germany and Luxembourg. We included adults with MCI (existing F06.7 ICD-10-GM diagnosis and TICS ≥ 21 and ≤ 32). The intervention group will use a mobile, multi-domain cCT (“NeuroNation MED”) for 12 weeks. Meanwhile, the wait list control group will receive standard medical care or no care. The eligibility of volunteers will be determined through a telephone screening. After completion of the baseline examination, patients will be randomly assigned to one of the experimental conditions in a 2:1 ratio. In total, 286 participants will be included in this study. The primary outcome is the change of cognitive performance measured by the index score of the screening module of the Neuropsychological Assessment Battery. Secondary outcomes are changes in the Cognitive Failures Questionnaire, Hospital Anxiety and Depression Scale, Health-49, Health Literacy Questionnaire, among others. All of the primary and secondary outcomes will be assessed at baseline and after the 12-week post-allocation period. Furthermore, the intervention group will undergo an assessment of the System Usability Scale, and the training data of the NeuroNation MED application will be analyzed. Discussion This study aims to assess the effectiveness of a mobile self-administered cCT in enhancing cognitive abilities among individuals diagnosed with MCI. Should the findings confirm the effectiveness of the NeuroNation MED app, it may confer possible benefits for the care management of patients with MCI, owing to the accessibility, cost-effectiveness, and home-based setting it provides. Specifically, the cCT program could provide patients with personalized cognitive training, educational resources, and relaxation techniques, enabling participants to independently engage in cognitive training sessions at home without further supervision. Trial registration German Clinical Trials Register DRKS00025133. Registered on November 5, 2021.

Summary: During development, Shh attracts axons of spinal cord commissural neurons to the floor plate. Shh-mediated attraction of commissural axons requires the receptor Boc. How Boc regulates cytoskeletal changes in growth cones in response to Shh is not fully understood. To identify effectors of Boc in Shh-mediated axon guidance, we used BioID to screen for proteins in proximity to Boc. Top hits included members of the WAVE regulatory complex (WRC), which acts downstream of Rac1 to promote actin cytoskeleton assembly. Therefore, we hypothesized that the WRC is important for Shh-mediated growth cone turning. Using biochemical and cellular assays, we found that Boc directly interacts with the WRC and that this interaction can occur in live cells. Moreover, we found that knockdown of Nckap1 and Cyfip1/2, two subunits of the WRC, in commissural neurons, impairs axon attraction toward a Shh gradient. Our results demonstrate that the WRC is required for Shh-mediated axon attraction.

Background Nepal implemented a pilot of the Supervision, Performance Assessment, and Recognition Strategy (SPARS) program aimed to increase health workers’ ability to manage medicines through on- the-job training and support from a new cadre of Medicines Management Supervisors (MMS). This study aims to assess the implementation costs.Methods Data from the SPARS central database and facilities was analysed to assess the total cost of the SPARS pilot including 293 public health facilities from 12 districts of 3 provinces, from May 2022 until July 2023. We estimated the number of health facilities to achieve a successful performance status, defined as a SPARS score ≥ 18.75 out of 25 (75%) and estimated the cost per facility to reach a successful score.Results In total, 293 facilities received 838 visits, performed by 48 MMS for an estimated total cost of $226,531. 124 facilities (44.3%) reached a score of 18.75 points after two or more visits. On average, it costs $1827 USD per facility to reach a successful SPARS score.Conclusion This study assesses the costs of implementing SPARS in 12 districts in Nepal. These findings can provide insights into further scaling up SPARS in Nepal or in other countries.

Bidirectional charging, such as Vehicle-to-Grid, is increasingly seen as a way to integrate the growing number of battery electric vehicles into the energy system. The electrical storage capacity in the system can be enhanced by using electric vehicles as flexible storage units. However, large-scale applications of Vehicle-to-Grid may require significant expansion of distribution grids. Previous studies lack a comprehensive environmental assessment of related impacts. Contributing to this research gap, this article combines techno-economic grid simulations with scenario-based Life Cycle Assessments. The case study focuses on rural distribution grids in Southern Germany, projecting the repercussions of different charging scenarios by 2040. Besides a Vehicle-to-Grid scenario, a mixed scenario of Vehicle-to-Home, Vehicle-to-Grid, and direct charging is investigated. Results indicate that Vehicle-to-Grid charging increases grid impacts due to higher charging simultaneities and power losses, especially when following spot market prices. Despite these challenges, the secondary use of battery electric vehicles as storage units can offset adverse environmental effects. Bidirectional charging allows for higher use of volatile renewable energies and can accelerate their integration into the power system. When considering these diverse environmental effects, bidirectional charging scenarios show overall lower impacts on climate change per battery electric vehicle compared to direct charging. The insights provided are valuable for researchers, industry, utilities, and policymakers to understand the potential positive and negative impacts of large-scale battery electric vehicle integration. The article highlights the most influential parameters that should be considered before large-scale penetration.

M. oleifera (Moringa) is a multipurpose tree with the potential to contribute nutrients to people's diets as well as pharmacological benefits. It is widely distributed in low- and middle-income countries, yet it remains underutilized. Here, we examine the potential of M. oleifera to improve rural people's food security and dietary diversity. We focus on Malawi, where 35 % of children under the age of five suffer from stunting and 51 % of the population is classified as severely food insecure. We draw on a survey with 60 women in rural Malawi detailing food security, dietary diversity, and consumption of different M. oleifera parts and products. Using Poisson regressions, we found that M. oleifera tree ownership is associated with a 28 % decrease in food insecurity levels. Moreover, people with awareness of the benefits of M. oleifera consumption were more likely to consume leaf powder compared to people without the same awareness. Specifically, each additional benefit mentioned by women increased the odds of powder consumption by a factor of 4.6. As such, our findings highlight 1) the underutilized potential of M. oleifera in local people's food security, and 2) how awareness can be key to increased consumption. Policies should be designed to raise awareness and educate rural communities about the benefits of M. oleifera, targeting communities, schools, and healthcare facilities. Finally, M. oleifera products could provide rural women with opportunities to increase household income, contingent on establishing contracts with exporters and collectors.

Pumpkin is an imperious vegetable and a large part of the pumpkin flesh goes unused resulting from pumpkin processing, so it needs to be processed properly to be used. The current study's goal was to prepare a drink powder enriched with pumpkin report the impact of storage on bioactive compounds and physicochemical characteristics of drink powder, and also evaluate the sensory properties of beverages prepared from drink powder. The powders were formulated and evaluated based on their physical properties, proximal compositions, minerals, phenolic compounds, and antioxidant ability as measured by DPPH (2,2-Diphenyl-1-picrylhydrazyl), FRAP (Ferric Reducing Antioxidant Power), and ABTS (2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid). Drink powder was made with a mixture of ingredients that were substituted with pumpkin pulp and seed powder in the proportions of 50:50 (S1), 20:30 (S2), 30:20 (S3), and 40:10 (S4). A sensory evaluation was carried out to select the most accepted combination. The most accepted product was subjected to nutritional analysis and storage studies, which were taken as criteria for good quality. Sample S3 had the highest protein, fat, fiber, and ash content while sample S1 had the highest carbohydrate content. It was also observed that enrichment with pumpkin powder enhanced the Mg, P, and Fe content of the drink powder. However, sample S1 had the highest DPPH radical scavenging ability, total phenolic content, and FRAP ability. During storage, a significant increase in moisture content, total sugar, and reducing sugar while a significant decrease in protein, fat, ash, fiber, and titratable acidity was observed. In addition, carotenoids, vitamin C, and antioxidant properties showed significant decreases during long-term storage at ambient temperature. Furthermore, sensory analysis was performed on pumpkin powder beverages, and based on results the color and texture of the drinks were not affected as the pumpkin powder content was increased. The drinks with 20 % pumpkin pulp and 30 % seed powder (S2) obtained the highest score for texture, taste, and overall acceptability assessed. However, the S1 and S3 are the best instances due to their better nutritional content. Hence, the drink powder that utilizes pumpkin may be an efficient means to preserve pumpkin and conserve its bioactive ingredients. In conclusion, pumpkin powder can be successfully incorporated into powdered drinks or other traditional products and also it is recognized as an excellent food source to meet daily nutritional needs.

High-pressure processing (HPP) has been employed in the food and pharmaceutical industries for multiple applications, such as microbial inactivation, shelf life extension, homogenizing/stabilizing emulsions, suspensions, gels, and other colloidal systems, cold extraction of meat in crustaceans, the opening of mollusks, etc. However, high pressure is known to affect the stability and the quality of barosensitive (i.e., sensitivity because of the level of pressure) components of the bioproducts, such as proteins. In general, Le Chatelier's principle dictates the fate of high molecular weight polymeric compounds like proteins under high pressure, suggesting a tendency to degrade into simpler monomers. From a structural analysis point of view, this generally results in increased tendencies for the protein to denature from its native state and possibly affect its ability to renature. Protein crystallization is also affected favorably or unfavorably by pressure, depending on the effect of pressure on nucleation and crystal growth steps for the particular type of protein. Protein refolding is another effect whose kinetics can be optimized by pressure. This work discusses the mechanisms of the impact of pressure on protein structure, crystallization refolding, and unfolding, with examples of the application of these processes in recent literature.

In Germany, the debate on preimplantation and prenatal testing is heavily influenced by the idea of an antagonism between prospective parents and their potential children. Underlying this antagonism is the assumption that prospective parents follow an ableist logic and do not regard the lives of children with a chronic illness as “worth living”. Taking the example of two rare genetic illnesses, Marfan Syndrome and Cystic Fibrosis, we investigate how persons who themselves are affected by these conditions view preimplantation or prenatal testing for their condition in the context of reproductive decision-making. Our empirical research shows that chronically ill patients’ appreciation of their own life as a “life worth living” does not always translate into an unequivocal wish and readiness to give birth to a child that is affected by their condition as well and argue that taking their views into consideration adds an additional level of complexity to the debate.

AbstractVerifyNow (VN) test is a less laborious method to assess pharmacodynamics (PD) compared to light transmittance aggregometry (LTA). VN assay has not been used to study the immediate PD effects of acetylsalicylic acid (ASA). Ten healthy volunteers were randomly assigned to a single 162 or 650 mg dose of chewed and swallowed ASA. Pharmacodynamic and pharmacokinetic measurements were performed at baseline and serially up to 60 min after ASA administration. Onset by VN was 20 ± 7 min with 162 mg and 13 ± 7 min with 650 mg ASA (p = .07). Onset by 1 mM AA-induced PA was 13 ± 12 min with 162 mg and 7 ± 3 min with 650 mg ASA (p=NS). VN correlated with AA-induced PA (r = 0.80, p

IntroductionDepletion of Lactobacillus species and an overgrowth of anaerobes in the vaginal tract bacterial vaginosis (BV)], is associated with non-optimal reproductive health outcomes, and increased susceptibility to sexually transmitted infections (STIs). BV is currently treated with antibiotics, although these provide suboptimal cure levels and high recurrence rates. Vaginal microbiota transplantation (VMT), the transfer of vaginal fluid from healthy donors with an optimal vaginal microbiota to a recipient with BV, has been proposed as an alternative treatment strategy.MethodsHere, we investigated knowledge and perceptions of blood donors to the concept of an optimal vaginal microbiome and VMT via the Western Cape Blood Service (WCBS) clinics in Cape Town, South Africa, by a self-administered questionnaire.Results & discussionAnalysis of responses from 106 eligible women showed that 86% (91/106) would consider donating samples. Responses significantly associated with willingness to donate vaginal samples included: (1) belief that helping others outweighs the inconvenience of donating vaginal sample (p = 1.093e−05) and (2) prior knowledge of the concept of a healthy vaginal microbiome (p = 0.001). Most potential donors (59/91; 65%) were willing to receive a VMT themselves if needed. Participants who were unwilling to donate vaginal samples (15/106; 14%) indicated that vaginal sample collection would be unpleasant and/or embarrassing. The benefits of a collaboration with WCBS for this project include the naturally altruistic nature of blood donors, the constant in-flow of donors to WCBS clinics, and the infrastructure and logistical aspects in place. Data from this observational study highlight factors affecting the willingness of blood donors to become vaginal sample donors.

In recent decades, there has been a growing recognition that mixotrophy, the ability to utilize both phototrophy and phagotrophy, is more common among plankton than previously assumed. Even though mixotrophs can become highly abundant, especially under nutrient limitation, and significantly alter nutrient cycling and food-web dynamics due to their dual nutritional modes, a comprehensive synthesis from a stoichiometric perspective is still lacking. We conducted a systematic literature review in which we identified over 130 studies that directly relate nutrient ratios to mixotrophic protists at the organism to community scale. By conceptually linking mixotrophy with the concept of ecological stoichiometry, we provide insights into (1) the role of mixotrophic metabolism and nutrient limitation in regulating cellular homeostasis, (2) mixotroph abundance and community scale responses to nutrient limitation, and (3) the specific case of harmful algal bloom forming mixotrophs. On the organism scale, the existing literature points towards a stabilizing effect of mixotrophic metabolism on elemental composition, and the use of grazing as a compensation mechanism under stoichiometric imbalances in the water and prey. At the community scale, mixotrophs were found to increase in abundance relative to strict autotrophs and heterotrophs in nutrient-limited communities, and provide beneficial food for zooplankton grazers by maintaining relatively low and stable stoichiometry. Furthermore, global-scale models and studies of harmful algal blooms reveal the increasing importance of mixotrophs under climate change – highlighting the need for continued research addressing the interactions between mixotrophs and dynamic stoichiometry to understand the impacts of mixotrophs on global nutrient cycles.

BackgroundA specific phobia is an anxiety disorder that is characterised by persistent and excessive fear in the presence of the object of the phobia. Animal phobias are the most prevalent forms of specific phobia among humans. Fear of snakes (snake phobia) is present in non-human primates which suggests its evolutionary origins as the ability to detect the threat of snakes was critical for survival. Snake phobia is a critical factor in protecting snakes and mitigating snakebite burden. To date, only one standardised psychometric test [the Snake Questionnaire (SNAQ) developed in 1974] has been used to quantify snake phobia although this was not performed in snakebite-endemic countries. In this study, we aimed to determine snake phobia in India, where snakebites and resulting deaths, disabilities and socioeconomic impacts are high.Methodology/principal findingsA modified version of the SNAQ (i.e. SNAQ12), which has previously demonstrated internal consistency, excellent reliability, and good discrimination between phobics and non-phobics in Europe was used in this study. SNAQ12 was developed both in English and Tamil and validated by testing on several individuals. Then, the final questionnaire was disseminated to members of the public through various methods including social media and in person through academic and clinical organisations. We received a total of 2032 responses, comprising 1086 [53.4%] males and 946 [46.6%] females, and these data were analysed to determine various aspects of snake phobia in the study population.Conclusions/significanceThe results demonstrated good internal consistency in using SNAQ12 to determine the phobia amongst the tested population. The data suggests that males are more snake-phobic in all age groups than females in India, in contrast to previous research that suggested that females are usually more snake-phobic. No other critical factors contribute to snake phobia in this study population. The use of the SNAQ12 allowed us to easily discriminate between individuals with phobia and non-clinical controls. This tool can be used as part of the One Health approach to better understand the relationships between snake phobia and snakebites and their impact on the mental health and well-being of vulnerable populations.

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset disease marked by a progressive degeneration of motor neurons (MNs) present in the spinal cord, brain stem and motor cortex. Death in most patients usually occurs within 2–4 years after symptoms onset. Despite promising progress in delineating underlying mechanisms, such as disturbed proteostasis, DNA/RNA metabolism, splicing or proper nucleocytoplasmic shuttling, there are no effective therapies for the vast majority of cases. A reason for this might be the disease heterogeneity and lack of substantial clinical and molecular biomarkers. The identification and validation of such pathophysiology driven biomarkers could be useful for early diagnosis and treatment stratification. Recent advances in next generation RNA-sequencing approaches have provided important insights to identify key changes of non-coding RNAs (ncRNAs) implicated with ALS disease. Especially, microRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression to target several genes/pathways by degrading messenger RNAs (mRNAs) or repressing levels of gene expression. In this study, we expand our previous work to identify top-regulated differentially expressed (DE)-miRNAs by combining different normalizations to search for important and generalisable pathomechanistic dysregulations in ALS as putative novel biomarkers of the disease. For this we performed a consensus pipeline of existing datasets to investigate the transcriptomic profile (mRNAs and miRNAs) of MN cell lines from iPSC-derived SOD1- and TARDBP (TDP-43 protein)-mutant-ALS patients and healthy controls to identify potential signatures and their related pathways associated with neurodegeneration. Transcriptional profiling of miRNA–mRNA interactions from MN cell lines in ALS patients revealed differential expression of genes showed greater vulnerability to KEAP1-NRF2 stress response pathway, sharing a common molecular denominator linked to both disease conditions. We also reported that mutations in above genes led to significant upregulation of the top candidate miR-10b-5p, which we could validate in immortalized lymphoblast cell lines (LCLs) derived from sporadic and familial ALS patients and postmortem tissues of familial ALS patients. Collectively, our findings suggest that miRNA analysis simultaneously performed in various human biological samples may reveal shared miRNA profiles potentially useful as a biomarker of the disease.

North-Western section of Bangladesh is experiencing a protracted decrease in precipitation, irregular rainfall, and the depletion of ground water, which results in water scarcity and extreme dry weather that impedes the production of agricultural commodities and threatens the people's way of life. Analyzing the precipitation deficit and ground water deficit, along with vegetation cover, temperature condition, and the condition of the vegetation is a crucial component of drought vulnerability assessment. Rajshahi Zilla, a region of Bangladesh located in the middle of the Barind tract, is experiencing a severe water shortage. The irregular rainfall, decrease in rainfall, prolonged absence of rainfall and ground water depletion results in drought. This study aims to access the vulnerability of drought by analyzing precipitation rates, ground water depletion levels, temperature condition, vegetation condition and the vegetative droughts to find out the severe condition of droughts and the severe effects of this in the livelihoods of the farmers and their crop production practices. In this case the study focuses on determining NDVI, NDWI, NDMI, VCI, TCI, and VHI. The VHI results show a significant increase in extreme drought conditions from 2013 (4 %) to 2021 (7 %). By conducting a few questionnaire surveys and Focus Group Discussion the present situation of crop production and the livelihoods of people has been analyzed. Almost 18.3 % of farmers have made a permanent move away from agriculture, and 80 % of permanently relocated farmers report an improvement in their quality of life. Nearly 60 % of farmers believe that the construction of deep ditches has enhanced their crop yield. Once again, more than 20 % are in the same predicament as previously, with over 19 % reporting that deep irrigation has lowered agricultural yield. Comprehending the potential consequences of drought will enable planners and decision-makers to implement mitigation measures aimed at improving the communities' ability to manage drought risk. After analyzing data, it has been found that Rajshahi is facing a critical drought problem, which has led to water scarcity, severely affecting agricultural production and livelihoods.

Background:. Unfortunately, current beauty trends greatly advertised by social media are trespassing recognized cannons of beauty. Of particular interest are patients’ expectations of soft tissue volume augmentation of the face, specifically of the lips. Methods:. An artificial intelligence picture of a White female face was generated. With the fixed standard golden upper-to-lower (U/L) lip ratio, a first set of pictures was generated with varying lip fullness. A second set of pictures was generated with various U/L ratios and lip fullness. In a survey format, the 2 sets of pictures were rated for attractiveness from the most to the least attractive by adult men and women. Results:. Rating the first set of pictures clearly demonstrates that overinflation of lips with upper lip height in excess of 30% of hemi-lip width is highly regarded as unaesthetic and unattractive, with a net preference of 20%–25%. For the second set, U/L ratios between 0.618:1 and 1:1 are still regarded to be most aesthetic. Conclusions:. Though social media have an influence on perception of beauty, data provided by the survey confirm that golden standards of aesthetics remain constant and that exaggerated requests of some patients may not be attributed solely to social media influence but probably to social media in combination with additional personal predisposing factors. Patients must be made aware that how they are perceived by others is essential for them to be satisfied with their appearance.

Background: The complexity of contexts and varied purposes for which biome donation are requested are unknown in South Africa. Objectives: The aim of this study was to provide strategic data towards actualisation of whether a stool donor bank may be established as a collaborative between Western Cape Blood Services (WCBS) and the University of Cape Town (UCT). Method: We designed a cross-sectional, questionnaire-based survey to determine willingness of WCBS blood donors to donate stool specimens for microbiome biobanking. The study was conducted between 01 June 2022 and 01 July 2022 at three WCBS donation centres in Cape Town, South Africa. Anonymous blood donors who met the inclusion criteria were enrolled. Anonymised demographic and interview data were analysed statistically. Results: Analysis of responses from 209/231 blood donors demonstrated in a logistic regression model that compensation (p 0.001) and ‘societal benefit outweighs inconvenience’ beliefs (p = 7.751e-05) were covariates significantly associated with willingness to donate stool. Age was borderline significant at a 5% level (p = 0.0556). Most willing stool donors indicated that donating stool samples would not affect blood donations (140/157, 90%). Factors decreasing willingness to donate were stool collection being unpleasant or embarrassing. Conclusion: The survey provides strategic data for the establishment of a stool bank and provided an understanding of the underlying determinants regarding becoming potential donors. Contribution: This is the first report on the perspectives of potential participants in donating samples towards a stool microbiome biobank in South Africa, a necessity for faecal microbiota transplantation (FMT).

BackgroundDaily dietary intake of macronutrients and energy is closely associated with long-term metabolic health outcomes, but whether 24-h nutritional intervention under isocaloric conditions leads to changes in metabolism remains unclear. Moreover, the short-term effect of diets with different macronutrient composition on hedonic appetite regulation is less clear.MethodsThis study examined the impact of an acute high-fat (F+) and high-carbohydrate (C+) diet on glucose metabolism and hedonic regulation of food intake in young healthy men under controlled conditions. Using a cross-over design, 19 male participants received a one-day isocaloric diet with different macronutrient composition (F+ = 11% carbohydrates, 74% fat; C+ = 79% carbohydrates, 6% fat) compared to a control diet (CON = 55% carbohydrates, 30% fat). Protein content was set at 15% of energy in all diets. The feeling of hunger, as well as “liking” and “wanting” for foods, was assessed through visual analog scales, and blood samples for glucose, insulin, and cortisol levels were assessed repeatedly during the experimental day. An intravenous glucose tolerance test was conducted the next morning.ResultsPostprandial glucose and insulin levels were lowest in F+ over the 24 h. Except for dinner, the CON diet showed the highest mean values in glucose. F+ diet improved insulin resistance, lowering Homeostatis Model Assessment Insulin Resistance (HOMA-IR) values. Changes in hedonic regulation of food intake were not observed during the intervention between the diets, except for higher feelings of satiety under the CON diet.ConclusionAn acute, isocaloric, high-fat diet improved insulin resistance even in healthy individuals but did not affect hedonic food intake regulation. Macronutrient composition modulate glucose metabolism even under short-term (24-h) and isocaloric diets, which should be considered for personalized preventive dietary treatments.

Background and objective: The primary cilium is a small protrusion found on most mammalian cells. It acts as a cellular antenna, being involved in various cell signaling pathways. The length of the primary cilium affects its function. To study the impact of physical or chemical stimuli on cilia, their lengths must be determined easily and reproducibly. Methods: We have developed and evaluated an open-source R package called detectCilia to detect and measure primary cilia automatically. As a case study to demonstrate the capability of our tool, we compared the influence of 4 different cell culture media compositions on the lengths of primary cilia in human chondrocytes. These media compositions include (1) insulin-transferrin-selenium (ITS); (2) ITS and dexamethasone (Dexa); (3) ITS, Dexa, insulin-like growth factor 1 (IGF-1), and transforming growth factor beta 1 (TGF-β1); and (4) fetal bovine serum (FBS). Results: The assessment of detectCilia included a comparison with 2 similar tools: ACDC (Automated Cilia Detection in Cells) and CiliaQ. Several differences and advantages of our package make it a valuable addition to these tools. In the case study, we have observed variations in the ciliary lengths associated with using different media compositions. Conclusions: We conclude that detectCilia can automatically and reproducibly detect and measure primary cilia in confocal microscopy images with low false-positive rates without requiring extensive user interaction.

BackgroundDengue virus (DENV) infection, spread by Aedes aegypti mosquitoes, is a significant public health concern in tropical and subtropical regions. Among the four distinct serotypes of DENV (DENV-1 to DENV-4), DENV-2 is associated with the highest number of fatalities worldwide. However, there is no specific treatment available for dengue patients caused by DENV-2.ObjectiveThis study aimed to identify inhibitory phytocompounds in silico in Vernonia cinerea (V. cinerea), a widely used traditional medicinal plant, for treating DENV-2 associated illnesses.MethodsThe chemical structures of 17 compounds from V. cinerea were sourced from the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) database. These compounds underwent geometry optimization, were screened against nonstructural protein 1 (NSP1) of DENV-2, and further validated through molecular dynamics simulations (MDS). Baicalein, an established drug against DENV-2, was used for validation in molecular screening, MDS, and MM-GBSA analyses.ResultsAmong these compounds, Beta-amyrin, Beta-amyrin acetate, Chrysoeriol, Isoorientin, and Luteolin showed promising potential as inhibitors of the NSP1 of DENV-2, supported by the results of thermodynamic properties, molecular orbitals, electrostatic potentials, spectral data and molecular screening. Besides, these compounds adhered to the Lipinski’s “rule of 5”, showing no hepatotoxicity/cytotoxicity, with mixed mutagenicity, immunotoxicity, and carcinogenicity. Furthermore, final validation through MDS confirmed their potential, demonstrating stable tendencies with significant inhibitory activities against NSP1 of DENV-2 over the control drug Baicalein. Among the screened compounds, Chrysoeriol emerged as the most promising inhibitor of NSP1 of DENV-2, followed by Luteolin and Isoorientin.ConclusionTaken together, our results suggest that Chrysoeriol is the best inhibitor of NSP1 of DENV-2, which could be evaluated as a therapeutic agent or a lead compound to treat and manage DENV-2 infections.

The enzyme, insulin regulated aminopeptidase (IRAP), is expressed in multiple immune cells such as macrophages, dendritic cells and T cells, where it plays a role in regulating the innate and adaptive immune response. There is a genetic association between IRAP and survival outcomes in patients with septic shock where a variant of its gene was found to be associated with increased 28-day mortality. This study investigated the role for IRAP in a lipopolysaccharide (LPS)-induced inflammatory response which is thought to model facets of the systemic inflammation observed in the early stages of human gram-negative sepsis. The frequencies and activation of splenic immune cell populations were investigated in the IRAP knockout (KO) mice compared to the wildtype controls over a period of 4-, 24-, or 48-hours following LPS stimulation. Dendritic cells isolated from the spleen of female IRAP KO mice, displayed significant increases in the activation markers CD40, CD86 and MHCII at 24 hours after LPS induction. A modest heightened pro-inflammatory response to LPS was observed with increased expression of activation marker CD40 in M1 macrophages from male IRAP knockout mice. Observations in vitro in bone marrow-derived macrophages (BMDM) revealed a heightened pro-inflammatory response to LPS with significant increases in the expression of CD40 in IRAP deficient cells compared with BMDM from WT mice. The heightened LPS-induced response was associated with increased pro-inflammatory cytokine secretion in these BMDM cells. A genotype difference was also detected in the BMDM from female mice displaying suppression of the LPS-induced increases in the activation markers CD40, CD86, CD80 and MHCII in IRAP deficient cells. Thus, this study suggests that IRAP plays specific time- and sex-dependent roles in the LPS-induced inflammatory response in dendritic cells and macrophages.

Polymerase chain reaction (PCR)-based assays were widely deployed during the SARS-CoV-2 pandemic for population-scale testing. High-throughput molecular diagnostic laboratories required a high degree of process automation to cope with huge testing demands, fast turnaround times, and quality requirements. However, process developers and optimizers often neglected the critical step of preparing a PCR Master Mix. The construction of PCR Master Mix depends on operator skill during the manual pipetting of reagents. Manual procedures introduce variation, inconsistency, wastage, and potentially risks data integrity. To address this, we developed a liquid-handler-based solution for automated, traceable, and compliant PCR Master Mix preparation. Here, we show that a fully automated PCR Master Mix protocol can replace manual pipetting, even in a diagnostic environment, without affecting accuracy or precision. Ultimately, this method eliminated operator-induced wastage and improved the consistency of the quality of results.

Background: Minimally invasive injectable aesthetic treatments have seen a surge in popularity, particularly in the post-COVID era. However, our understanding of the psychological and social factors that influence patients’ choices when seeking these treatments is still lacking. Objective: This study explored whether the COVID-19 pandemic influenced patients’ motivations and perceptions regarding the above-mentioned treatments. Methods: A comprehensive survey was conducted among 147 patients who had received injectable aesthetic interventions at Acquisition Aesthetics, a leading UK training academy in aesthetic medicine. The survey included questions regarding motivation for treatment initiation, ongoing drivers for continuing treatment, desired outcomes, main concerns about treatment, post-treatment feelings, and the psychological impact of skin aging. Descriptive analysis was performed to explore the patterns of patient responses. Results: This findings revealed that the primary motivation for seeking aesthetic treatment was to improve confidence and address concerns about aging. Patients expressed a strong desire for natural-looking results and reported the significant psychological effects of skin aging, including feelings of self-consciousness and anxiety. After treatment, patients reported increased confidence and satisfaction with their appearance, and reduced self-consciousness. Conclusion: This study revealed that although the core motivations for improving confidence and addressing aging remain central to patients seeking aesthetic treatments, the post-COVID era saw a subtle shift toward heightened concerns about social acceptance and maintaining appearances. Understanding these subtle shifts can allow aesthetic practitioners to tailor their approaches to meet patients’ holistic needs. Level of Evidence: Level V, descriptive study