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Adult attention deficit hyperactivity disorder (ADHD), a prevalent psychiatric disorder, significantly impacts social, academic, and occupational functioning. However, it has been relatively less prioritized compared to childhood ADHD. This study employed a functional near-infrared spectroscopy (fNIRS) during verbal fluency tasks in conjunction with machine learning (ML) techniques to differentiate between healthy controls (N =75) and ADHD individuals (N =120). Efficient feature selection in high-dimensional fNIRS datasets is crucial for improving accuracy. To address this, we propose a hybrid feature selection method that combines a wrapper-based and embedded approach, termed Bayesian-Tuned Ridge RFECV (BTR-RFECV). The proposed method facilitated streamlined feature selection and hyperparameter tuning in high-dimensional data, thereby reducing the number of features while enhancing accuracy. HbO features from the combined frontal and temporal regions were key, with the models achieving precision (89.89%), recall (89.74%), F-1 score (89.66%), accuracy (89.74%), MCC (78.36%), and GDR (88.45%). The outcomes of this study highlight the promising potential of combining fNIRS with ML as diagnostic tools in clinical settings, offering a pathway to significantly reduce manual intervention.

Abstract Background Nicotine use and nicotine use disorder (NUD) are the leading causes of preventable death in the United States. Persons with mental disorders (e.g., bipolar disorder) are differentially susceptible to nicotine use. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity and show preliminary evidence of efficacy in addiction-related behaviours. Herein, we synthesize extant preclinical and clinical evidence evaluating the effect of GLP-1RAs on neurobiological systems and behaviours salient to nicotine consumption and cessation. Methods Online databases (MedLine, Embase, AMED, PsychINFO, JBI EBP Database, PubMed, Web of Science, Google Scholar) were searched from inception to May 21, 2024. Relevant studies were also extracted from the reference lists of the obtained articles. All articles were screened against inclusion and exclusion criteria. Results Administration of GLP-1RAs reduced nicotine self-administration and nicotine-seeking behaviour in animal models that, in some cases, is sustained beyond exposure to the agent. GLP-1RAs also mitigated post-nicotine cessation weight gain, craving, withdrawal, and hyperphagia. The preceding effects are attributable to modulation of reward-related brain regions (e.g., mesolimbic dopamine system), resulting in nicotine aversion. GLP-1RAs were also efficacious as adjunctive therapies [e.g., in combination with nicotine replacement therapies (NRTs)]. Conclusion The multi-effect characteristics in NUD paradigms provide a compelling rationale for large, adequately powered, long-term, randomized controlled trials of GLP-1RAs in the treatment and prevention of NUD. The replicated effect on mitigating post-nicotine cessation weight gain is a differentiating feature of GLP-1RAs from extant proven therapies for NUD.

Abstract The smoking cessation drug cytisine exerts neuroprotection in substantia nigra pars compacta (SNc) dopaminergic (DA) neurons of female but not male 6-hydroxydopamine (6-OHDA) lesioned parkinsonian mice. To address the important question of whether circulating 17β−estradiol mediates this effect, we employ two mouse models aimed at depleting systemically circulating 17β-estradiol: (i) bilateral ovariectomy (OVX), and (ii) aromatase inhibition with systemically administered letrozole. In both models, depleting systemically circulating 17β-estradiol in female 6-OHDA lesioned parkinsonian mice results in the loss of cytisine-mediated neuroprotection as measured using apomorphine-induced contralateral rotations and SNc DA neurodegeneration. Our experiments also reveal that OVX alone exerts neuroprotection in SNc DA neurons due to compensatory changes not observed in the letrozole model, which underscores the importance of using independent models of 17β-estradiol depletion to study neuroprotection. Taken together, our findings suggest that the smoking cessation drug cytisine is a viable neuroprotective drug for pre-menopausal women with Parkinson’s disease.

Abstract Extracellular vesicles (EVs)-mediated communication by cancer cells contributes towards the pro-tumoral reprogramming of the tumor microenvironment. Viral infection has been observed to alter the biogenesis and cargo of EVs secreted from host cells in the context of infectious biology. However, the impact of oncolytic viruses on the cargo and function of EVs released by cancer cells remains unknown. Here we show that upon oncolytic virotherapy with Semliki Forest virus-based replicon particles (rSFV), metastatic melanoma cells release EVs with a distinct biochemical profile and do not lead to suppression of immune cells. Specifically, we demonstrate that viral infection causes a differential loading of regulatory microRNAs (miRNAs) in EVs in addition to changes in their physical features. EVs derived from cancer cells potentially suppress splenocyte proliferation and induce regulatory macrophages. In contrast, EVs obtained from rSFV-infected cells did not exhibit such effects. Our results thus show that rSFV infection induces changes in the immunomodulatory properties of melanoma EVs, which may contribute to enhancing the therapeutic efficacy of virotherapy. Finally, our results show that the use of an oncolytic virus capable of a single-round of infection allows the analysis of EVs secreted from infected cells while preventing interference from extracellular virus particles.

Abstract Understanding subsurface temperature variations is crucial for assessing material degradation in underground structures. This study maps subsurface temperatures across the contiguous United States for depths from 50 to 3500 m, comparing linear interpolation, gradient boosting (LightGBM), neural networks, and a novel hybrid approach combining linear interpolation with LightGBM. Results reveal heterogeneous temperature patterns both horizontally and vertically. The hybrid model performed best achieving a root mean square error of 2.61 °C at shallow depths (50–350 m). Model performance generally decreased with depth, highlighting challenges in deep temperature prediction. State-level analyses emphasized the importance of considering local geological factors. This study provides valuable insights for designing efficient underground facilities and infrastructure, underscoring the need for depth-specific and region-specific modeling approaches in subsurface temperature assessment.

Abstract Depression treatment responses vary widely among individuals. Identifying objective biomarkers with predictive accuracy for therapeutic outcomes can enhance treatment efficiency and avoid ineffective therapies. This study investigates whether functional near-infrared spectroscopy (fNIRS) and clinical assessment information can predict treatment response in major depressive disorder (MDD) through machine-learning techniques. Seventy patients with MDD were included in this 6-month longitudinal study, with the primary treatment outcome measured by changes in the Hamilton Depression Rating Scale (HAM-D) scores. fNIRS and clinical information were strictly evaluated using nested cross-validation to predict responders and non-responders based on machine-learning models, including support vector machine, random forest, XGBoost, discriminant analysis, Naïve Bayes, and transformers. The task change of total haemoglobin (HbT), defined as the difference between pre-task and post-task average HbT concentrations, in the dorsolateral prefrontal cortex (dlPFC) is significantly correlated with treatment response (p

Anatomical variations in hepatic arteries are both common and diverse. According to the classic classification systems, a replaced right hepatic artery typically originates from the superior mesenteric artery, supplying blood to the right liver lobe in the absence of the right branch of the proper hepatic artery. This article reports 2 cases of a rare variation, a replaced right hepatic artery arising directly from the celiac trunk. In these cases, the artery courses posterior to the common hepatic artery and then behind the portal vein within the hepatoduodenal ligament. The first case, involving a 62-year-old male with intraductal papillary mucinous neoplasm (IPMN) of the pancreas, was identified intraoperatively during a pancreaticoduodenectomy. The second case, involving a 58-year-old female with chronic sclerosing cholangitis, was detected through contrast-enhanced computed tomography angiography. Identification of such variations is critical in hepatobiliary and pancreatic surgeries to prevent serious postoperative complications. Injury to a replaced right hepatic artery can lead to biliary-enteric anastomosis dehiscence after pancreaticoduodenectomy or ischemic liver complications. While hepatic arteries display numerous anatomical variations, classic classification systems fail to encompass all these anomalies. A more comprehensive classification system, such as CRL and ex-CRL classification, is necessary to ensure safer surgical outcomes.

Abstract Background Upper limb impairment post-stroke often leads to a predominant use of the less affected arm and consequent learned disuse of the affected side, hindering upper limb outcome. Wearable sensors such as accelerometers, combined with smart reminders (i.e., based on the amount of arm activity), offer a potential approach to promote increased use of the affected arm to improve upper limb use during daily life. This study aimed to evaluate the efficacy of wrist vibratory reminders during a six-week home-based intervention in chronic stroke survivors. Methods We evaluated the impact of the home-based intervention on the primary outcome, the Motor Activity Log-14 Item Version scores Amount of Use (MAL-14 AOU), and the secondary outcomes MAL-14 Quality of Movement (QOM) and sensor-derived activity metrics from the affected arm. A randomized controlled trial design was used for the study: the intervention group received personalized reminders based on individualized arm activity goals, while the control group did not receive any feedback. Mixed linear models assessed the influence of the group, week of the intervention period, and initial impairment level on MAL-14 and arm activity metrics. Results Forty-two participants were enrolled in the study. Overall, participants exhibited modest but not clinically relevant increases in MAL-14 AOU (+ 0.2 points) and QOM (+ 0.2 points) after the intervention period, with no statistically significant differences between the intervention and control group. Feasibility challenges were noted, such as adherence to wearing the trackers and sensor data quality. However, in participants with sufficiently available sensor data (n = 23), the affected arm use extracted from the sensor data was significantly higher in the intervention group (p

Abstract Motor abnormalities, including psychomotor slowing, are prevalent in a large proportion of individuals with schizophrenia. While postural control deficits have been observed in this population, the impact of motor abnormalities on postural stability remains unclear. This study aimed to objectively evaluate postural stability in patients with and without psychomotor slowing and healthy controls. Seventy-three schizophrenia patients with psychomotor slowing (PS; Salpêtrière Retardation Rating Scale (SRRS) ≥ 15), 25 schizophrenia patients without psychomotor slowing (non-PS; SRRS

Abstract Background Echinococcosis is an infectious parasitic disease that is extremely harmful to human health. Albendazole is provided free of charge to patients requiring medication under the central government finance transfer payment scheme for echinococcosis control and prevention in China. Our aim is to monitor the state of patient medication and its therapeutic impact, which will help improve medication compliance and the therapeutic effect. Methods Random cluster sampling was used to select 10 echinococcosis-endemic counties in China, and all albendazole-treated patients in these counties were investigated. The chi-square and Kruskal–Wallis tests were used to compare two or more rates or constituent ratios, and multiple logistic regression analysis was used to identify the influencing factors. The records of patients were reviewed to obtain the initial diagnosis results as well as the most recent follow-up results and time, and efficacy was assessed. Results We examined 899 patient files treated with albendazole in 10 endemic counties. Of the 582 evaluable files, 7.9% did not take albendazole, and 69.2% did not take albendazole regularly. Only 22.9% took albendazole regularly. Of the 536 patients who took albendazole, 242 exhibited adverse reactions. Patients who were Tibetan, herdsmen, received no formal education, used emulsion, and exhibited adverse reactions demonstrated poor compliance. A total of 174 patients with cystic echinococcosis received their most recent imaging follow-up results within one year of the investigation date. Among them, 9 patients met the criteria for cure, accounting for 5.2%; 56 patients showed effectiveness, accounting for 32.2%; 105 patients were deemed ineffective, accounting for 59.8%; 5 patients experienced recurrence, accounting for 2.9%. Conclusions Albendazole medication compliance in patients with echinococcosis is not ideal. We must prioritize health education and promotion for Tibetans, herdsmen, and those without formal education. Patients who adhered to their medication regimen achieved higher rates of cure and effectiveness. To improve medication compliance and efficacy, it is particularly important to improve communication and medication guidance for patients receiving emulsions and those with adverse reactions after taking albendazole. Simultaneously strengthen patients' attention to follow-up and re-examination. Graphical Abstract

Abstract Innovative strategies such as HIV self-testing (HIVST) are useful for identifying hard-to-reach people living with HIV/AIDS (PLHIV), especially in developing settings where considerable gaps still exist in reaching the first 95% UNAIDS target. We evaluated the effectiveness of HIVST in Cameroon using several distribution models and investigated the predictors of HIV seropositivity among self-testers. The study was conducted from 2021 to 2022 in three regions in Cameroon. HIVST kits were distributed according to 5 distribution models: antenatal, postnatal, maternal and child clinics (ANC/PNC/MCH); partners of PLHIV; workplace; community and HIV-testing services (HTS). Overall, 42,687 people received oral HIVST kits, among whom 15.6% were HIV first-testers. Approximately 85% reported on the test outcome; 2.3% (n = 825) were reactive, and 75.8% came for test confirmation. After the confirmation test, a concordance of 85% was found with the national algorithm. Overall, the HIV seroprevalence was 1.5% [95% CI: 1.4–1.6]; ANC/PNC/MCHC: 1.9%, partners of PLHIV: 6.9%, workplace: 0.5%, community: 0.1% and HTS: 7.0%, p

Abstract Cephalopods produce dynamic colors and skin patterns for communication and camouflage via stratified networks of neuronally actuated yellow, red, and brown chromatophore organs, each filled with thousands of pigment granules. While compositional analysis of chromatophore granules in Doryteuthis pealeii reveals the pigments as ommochromes, the ultrastructural features of the granules and their effects on bulk coloration have not been explored. To investigate this, we isolated granules from specific colored chromatophores and imaged them using multiple modalities. The brown granules are largest with smooth surface coatings. Red granules are intermediate in size with irregular surface textures, and yellow granules are smallest, with rough, porous surfaces. Many of the granules contain sub-granular features that also vary in presentation with color. Correlated light and electron microscopy reveal that differences in hue of individual granules are similarly associated with size, shape, and texture, suggesting that granules may be structurally adapted to modify the dominant visible colors presented within the chromatophores. These findings suggest that granule ultrastructure, not just chemical composition, may be significant in producing the range of colors presented in cephalopod chromatophores.

Abstract Background The 313-variant polygenic risk score (PRS313) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS313 across different European populations which could influence risk estimation has not been performed. Methods We explored the distribution of PRS313 across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank. The mean PRS was calculated by country in the BCAC dataset and by country of birth in the UK Biobank. We explored different approaches to reduce the observed heterogeneity in the mean PRS across the countries, and investigated the implications of the distribution variability in risk prediction. Results The mean PRS313 differed markedly across European countries, being highest in individuals from Greece and Italy and lowest in individuals from Ireland. Using the overall European PRS313 distribution to define risk categories, leads to overestimation and underestimation of risk in some individuals from these countries. Adjustment for principal components explained most of the observed heterogeneity in the mean PRS. The mean estimates derived when using an empirical Bayes approach were similar to the predicted means after principal component adjustment. Conclusions Our results demonstrate that PRS distribution differs even within European ancestry populations leading to underestimation or overestimation of risk in specific European countries, which could potentially influence clinical management of some individuals if is not appropriately accounted for. Population-specific PRS distributions may be used in breast cancer risk estimation to ensure predicted risks are correctly calibrated across risk categories.

Abstract Playing three-dimensional (3D) video games enhances stereo acuity (i.e., the precision of stereopsis) in young adults with normal vision Here we asked whether the improvement in stereoacuity was the result of a reduced disparity pedestal, as indicated by a decreased subjective depth bias (i.e., the accuracy of stereopsis). Twenty-one healthy young participants with normal vision and limited previous video game experience, none had played 3D video games, played first-person-shooter action stereoscopic 3D video games for a total of 40 h. Depth detection performance was measured using random dot stereograms before and after the video game intervention. We found that playing stereoscopic 3D video games boosts the precision, but not the accuracy of depth perception, suggesting that the enhanced stereoacuity did not result from reducing the effects of a disparity pedestal. These types of video games have potential therapeutic applications for improving stereo vision in patients with binocular vision anomalies.

Abstract Global mean sea-level (GMSL) change can shed light on how the Earth system responds to warming. Glaciological evidence indicates that Earth’s ice sheets retreated inland of early industrial (1850 CE) extents during the Holocene (11.7-0 ka), yet previous work suggests that Holocene GMSL never surpassed early industrial levels. We merge sea-level data with a glacial isostatic adjustment model ensemble and reconstructions of postglacial thermosteric sea-level and mountain glacier evolution to estimate Holocene GMSL and ice volume. We show it is likely (probability P = 0.75) GMSL exceeded early industrial levels after 7.5ka, reaching 0.24 m (−3.3 to 1.0 m, 90% credible interval) above present by 3.2ka; Antarctica was likely (P = 0.78) smaller than present after 7ka; GMSL rise by 2150 will very likely (P = 0.9) be the fastest in the last 5000 years; and by 2060, GMSL will as likely than not (P = 0.5) be the highest in 115,000 years.

Abstract Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events. This prothrombotic state is considered a key factor in the increased risk of stroke, which is observed clinically during both acute infection and long after symptoms clear. Here, we develop a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells (ECs), pericytes (PCs), and smooth muscle cells (SMCs) to recapitulate the vascular pathology associated with SARS-CoV-2 exposure. Our results demonstrate that perivascular cells, particularly SMCs, are a susceptible vascular target for SARS-CoV-2 infection. Utilizing RNA sequencing, we characterize the transcriptomic changes accompanying SARS-CoV-2 infection of SMCs, PCs, and ECs. We observe that infected SMCs shift to a pro-inflammatory state and increase the expression of key mediators of the coagulation cascade. Further, we show human ECs exposed to the secretome of infected SMCs produce hemostatic factors that contribute to vascular dysfunction despite not being susceptible to direct infection. The findings here recapitulate observations from patient sera in human COVID-19 patients and provide mechanistic insight into the unique vascular implications of SARS-CoV-2 infection at a cellular level.

Depression is one of the most common psychiatric disorders and frequently accompanied by other mental disorders. There is therefore a need to develop and document new treatments that could have a beneficial effect in treating depression. A new treatment approach to depression that has produced encouraging results is metacognitive therapy (MCT). This paper provides a general introduction to the theory of MCT and especially of how to use MCT in treating depressive disorders. The treatment is illustrated with the clinical case of Andrew, and in the final part of this paper the current evidence for MCT for depression is presented.

Abstract Background A subdural hematoma is a type of traumatic brain injury that results from the rupture of the bridging veins. It often presents with various neurological deficits. The Kernohan–Woltman notch phenomenon (KWNP) is a rare complication associated with subdural hematomas, characterized by ipsilateral hemiparesis due to compression of the contralateral cerebral peduncle. Case presentation We present a case of a 30-year-old female with a left subdural hematoma who exhibited paradoxical ipsilateral hemiparesis and discuss the appearance of KWNP in the context of alcohol withdrawal. We also report on the appearance of delirium tremens 6 days after evacuation. Conclusion In our report, we effectively rule out other causes of ipsilateral hemiparesis such as cerebrovascular accident or mass effect, and demonstrate a rare presentation of KWNP in an uncommon demographic. Our report also demonstrates an incidental finding of delirium tremens that may have been delayed in presentation due to intubation. The findings contribute to further research on these uncommon neurological and psychiatric manifestations.

Abstract Information encountered in different events, such as people and objects, can be interlinked in memory. Such memory integration supports novel inferences about the world. This study investigates the role of episodic context on memory integration in two experiments using an associative inference task. Participants encoded events with overlapping (AB and BC) and non-overlapping associations (XY) presented in the same or different episodic contexts. Inference performance across events (AC) was tested in the absence (Experiment 1) and in the presence (Experiment 2) of the encoding context. Our data show that inferences across events encoded in the same context were more accurate, faster, and made with greater confidence compared to those encoded in different contexts. However, this effect was observed only when the context was presented during testing, suggesting that context enhances associative inferences by facilitating retrieval of events associated with that context. These findings demonstrate that revisiting the encoding context promotes memory integration by providing privileged access to contextually associated memory traces and facilitating their flexible recombination to form novel inferences.

Abstract Background Immunotherapy has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with immunotherapy naïve and exposed primary ccRCC tumors to better understand immunotherapy resistance. Results Spatial molecular imaging of tumor and adjacent stroma samples from 21 tumors suggests that viable tumors following immunotherapy harbor more stromal CD8 + T cells and neutrophils than immunotherapy naïve tumors. YES1 is significantly upregulated in immunotherapy exposed tumor cells. Spatial GSEA shows that the epithelial-mesenchymal transition pathway is spatially enriched and the associated ligand-receptor transcript pair COL4A1-ITGAV has significantly higher autocorrelation in the stroma after exposure to immunotherapy. More integrin αV + cells are observed in immunotherapy exposed stroma on multiplex immunofluorescence validation. Compared to other cancers in TCGA, ccRCC tumors have the highest expression of both COL4A1 and ITGAV. Assessing bulk RNA expression and proteomic correlates in CPTAC databases reveals that collagen IV protein is more abundant in advanced stages of disease. Conclusions Spatial transcriptomics of samples of 3 patient cohorts with cRCC tumors indicates that COL4A1 and ITGAV are more autocorrelated in immunotherapy-exposed stroma compared to immunotherapy-naïve tumors, with high expression among fibroblasts, tumor cells, and endothelium. Further research is needed to understand changes in the ccRCC tumor immune microenvironment and explore potential therapeutic role of integrin after immunotherapy treatment.

Abstract The physics of spin-orbit entangled magnetic moments of 4d and 5d transition metal ions on a honeycomb lattice has been much explored in the search for unconventional magnetic orders or quantum spin liquids expected for compass spin models, where different bonds in the lattice favour different orientations for the magnetic moments. Realising such physics with rare-earth ions is a promising route to achieve exotic ground states in the extreme spin-orbit limit; however, this regime has remained experimentally largely unexplored due to major challenges in materials synthesis. Here we report the successful synthesis of powders and single crystals of β-Na2PrO3, with 4f 1 Pr4+ j eff = 1/2 magnetic moments arranged on a hyperhoneycomb lattice with the same threefold coordination as the planar honeycomb. We find a strongly non-collinear magnetic order with highly dispersive gapped excitations that we argue arise from frustration between bond-dependent, anisotropic off-diagonal exchanges, a compass quantum spin model not explored experimentally so far. Our results show that rare-earth ions on threefold coordinated lattices offer a platform for the exploration of quantum compass spin models in the extreme spin-orbit regime, with qualitatively distinct physics from that of 4d and 5d Kitaev materials.

Abstract To increase antibody affinity against pathogens, positively selected GC-B cells initiate cell division in the light zone (LZ) of germinal centers (GCs). Among these, higher-affinity clones migrate to the dark zone (DZ) and vigorously proliferate by utilizing energy provided by oxidative phosphorylation (OXPHOS). However, it remains unknown how positively selected GC-B cells adapt their metabolism for cell division in the glycolysis-dominant, cell cycle arrest-inducing, hypoxic LZ microenvironment. Here, we show that microRNA (miR)−155 mediates metabolic reprogramming during positive selection to protect high-affinity clones. Mechanistically, miR-155 regulates H3K36me2 levels in hypoxic conditions by directly repressing the histone lysine demethylase, Kdm2a, whose expression increases in response to hypoxia. The miR-155-Kdm2a interaction is crucial for enhancing OXPHOS through optimizing the expression of vital nuclear mitochondrial genes under hypoxia, thereby preventing excessive production of reactive oxygen species and subsequent apoptosis. Thus, miR-155-mediated epigenetic regulation promotes mitochondrial fitness in high-affinity GC-B cells, ensuring their expansion and consequently affinity maturation.

Abstract The Large Hadron Collider’s high luminosity era presents major computational challenges in the analysis of collision events. Large amounts of Monte Carlo (MC) simulation will be required to constrain the statistical uncertainties of the simulated datasets below these of the experimental data. Modelling of high-energy particles propagating through the calorimeter section of the detector is the most computationally intensive MC simulation task. We introduce a technique combining recent advancements in generative models and quantum annealing for fast and efficient simulation of high-energy particle-calorimeter interactions.

Abstract Background Antenatal iron and folic acid (IFA) supplementation remains an effective strategy in the prevention of maternal anemia and low birthweight and is universally recommended by WHO. However, uptake of IFA has varied globally due to challenges with acceptability, supply and distribution, counselling and knowledge, and access to health services. In Botswana, nearly one-third of pregnant women engaged in antenatal care do not receive IFA, despite it being standard of care. The objectives of this study were to assess knowledge of and barriers and facilitators to IFA supplementation before and during pregnancy. Methods We conducted qualitative interviews with two key stakeholder groups at two different levels—the individual level (pregnant women) and the service delivery level (health care providers). Here, we present results from interviews with pregnant women at two representative antenatal clinic sites in Botswana in 2022. Results Pregnant women were motivated to be healthy and were knowledgeable about the benefits of supplementation during pregnancy to mothers and their infants; however, women knew more about the benefits of iron than folic acid. Most women were in favor of receiving IFA supplementation prior to pregnancy and receiving fortified foods. Several key barriers were identified: lack of supplement availability in the clinics, poverty, side effects, number of tablets, and adherence. Approaches to overcome these barriers included improving supplement availability, improving health education, increasing supply of nutritious and fortified foods, backyard gardens, and increasing family and monetary support. Conclusions Our study identified a need to 1) increase the availability of supplementation at antenatal clinics and 2) improve education regarding supplementation to include information about the benefits of folic acid and other micronutrients. Implementation research is needed to ascertain whether increasing supply and improving education could increase utilization of supplementation during pregnancy, with the ultimate goal of improving maternal and infant outcomes.

Abstract Adeno-associated virus-based gene therapy is a promising avenue in heart failure treatment, but has shown limited cardiac virus uptake in humans, requiring new approaches for clinical translation. Using a Yorkshire swine ischemic heart failure model, we demonstrate significant improvement in gene uptake with temporary coronary occlusions assisted by mechanical circulatory support. We first show that mechanical support during coronary artery occlusions prevents hemodynamic deterioration (n = 5 female). Subsequent experiments show that coronary artery occlusions during gene delivery improve gene transduction, while adding coronary sinus occlusion (Stop-flow) further improves gene expression up to >1 million-fold relative to conventional intracoronary infusion. Complete survival during and after delivery (n = 10 female, n = 10 male) further indicates safety of the approach. Improved cardiac gene expression correlates with virus uptake without an increase in extra-cardiac expression. Stop-flow delivery of virus-sized gold nanoparticles exhibits enhanced endothelial adherence and uptake, suggesting a mechanism independent of virus biology. Together, utilizing mechanical support for cardiac gene delivery offers a clinically-applicable strategy for heart failure-targeted therapies.

Antimicrobial resistance (AMR) is a threat to animal and ecosystem health, agriculture, water, and sanitation systems, posing risks not only to human health, but also to society and the systems upon which it depends. Global health governance draws on the One Health (OH) approach to combat AMR. However, the effective implementation of these approaches faces several constraints, including governance and implementation challenges arising from the interconnected nature of AMR with other global health threats, as well as local and structural socioecological factors that affect policy outcomes, that are often overlooked in governance approaches. This article aims to clarify how scientific literature has situated OH-AMR governance responses in relation to six socioecological dimensions: global health threats, broader concerns, governance frameworks, socioeconomic factors, health equity, and environmental justice. Informed by an Urban Political Ecology (UPE) lens and guided by the Critical Interpretive Synthesis (CIS) methodology of Dixon-Woods et al., our critical interpretive synthesis identified 18 articles situating OH-AMR arrangements within these socioecological dimensions. The role of global governance frameworks in shaping state governance arrangements has rarely been the object of analysis in the selected studies. The synthesis highlights the connections between urbanization, AMR risks, global health threats, and broader ecological challenges, calling for a reassessment of current global and state governance approaches. The study also offers a case for the adoption of a UPE lens to address AMR and related global health challenges.

Background: Recent studies have suggested an increased risk of acute myocardial infarction (AMI) following daylight saving time (DST) transitions in cohorts of American and European patients. We aim to validate this finding in a Canadian population. Methods: We performed a retrospective cohort study of patients admitted to the Hôpital du Sacré-Coeur de Montréal with a diagnosis of AMI requiring a coronary angiogram from 28 February 2016 to 3 December 2022. The transition period was defined as two weeks following DST, while the control periods were two weeks before and two weeks after the transition period. Patients aged 18 years or older were included. The primary endpoint was the incidence rate ratio (IRR) of AMI following DST transitions while the secondary endpoint was infarct size by biomarkers. A subgroup analysis compared the pre-COVID-19 period (2016–2019) to the post-COVID-19 period (2020–2022). Results: A total of 1058 patients were included (362 in the transition group and 696 in the control group). The baseline clinical characteristics were comparable between both groups. The rate of AMI per day following the DST transitions was 1.85 compared to 1.78 during control periods. The DST transitions were not associated with an increase in AMI (IRR = 1.04, 95% CI 0.91–1.18, p = 0.56) nor with infarct size. In the subgroup analysis, DST was associated with a significant increase in the incidence of AMI only in the pre-COVID-19 period, with a rate of 2.04 AMI per day in the transition group compared to 1.71 in the control group (IRR = 1.19, 95% CI 1.01–1.41, p = 0.041). In contrast, there was a significant increase in the size of AMI following DST in the post-COVID-19 period subgroup, with a creatine phosphokinase-MB (CK-MB) concentration of 137 ± 229 µg/L compared to 93 ± 142 µg/L (p = 0.013). Conclusions: In this Canadian cohort, there was a significant increase in the incidence of AMI in the pre-COVID-19 period, and infarct sizes were significantly larger following the DST transitions in the post-COVID-19 period. No significant associations emerged when pre- and post-COVID-19 periods were pooled.

Le mouvement de la Négritude, dont on peut situer la naissance en 1935, très masculin, voire machiste, n’a pas voulu reconnaître sa gestation au salon des sœurs Nardal, à Clamart, fondatrices de La Revue du monde noir. Encore moins les autrices qui l’ont précédé : Drasta Houël, poète (Les Vies légères, 1916) et romancière (Cruautés et tendresses, 1925), et les cousines Suzanne et Renée Lacascade, autrices respectivement des romans Claire-Solange, âme africaine (1924) et L’Île qui meurt (1930). La présente étude saisit l’occasion de la récente réédition de ces œuvres et des feux nouvellement braqués sur l’apport culturel des femmes pour en démontrer l’intérêt tout en suggérant pourquoi elles ont été négligées : elles travaillaient indépendamment l’une de l’autre et ne donnaient pas suite à leurs écrits. Ce manque de visibilité fait contraste avec l’effort concerté des hommes de la Négritude.

The soybean cyst nematode (SCN; Heterodera glycines) facilitates infection by secreting a repertoire of effector proteins into host cells to establish a permanent feeding site composed of a syncytium of root cells. Among the diverse proteins secreted by the nematode, we were specifically interested in identifying proteases to pursue our goal of engineering decoy substrates that elicit an immune response when cleaved by an SCN protease. We identified a cysteine protease that we named Cysteine Protease 1 (CPR1), which was predicted to be a secreted effector based on transcriptomic data obtained from SCN esophageal gland cells, the presence of a signal peptide, and the lack of transmembrane domains. CPR1 is conserved in all isolates of SCN sequenced to date, suggesting it is critical for virulence. Transient expression of CPR1 in Nicotiana benthamiana leaves suppressed cell death induced by a constitutively active nucleotide binding leucine-rich repeat protein, RPS5, indicating that CPR1 inhibits effector-triggered immunity. CPR1 localizes in part to the mitochondria when expressed in planta. Proximity-based labeling in transgenic soybean roots, co-immunoprecipitation, and cleavage assays identified a branched-chain amino acid aminotransferase from soybean (GmBCAT1) as a substrate of CPR1. Consistent with this, GmBCAT1 also localizes to mitochondria. Silencing of the CPR1 transcript in the nematode reduced penetration frequency in soybean roots, while the expression of CPR1 in soybean roots enhanced susceptibility. Our data demonstrates that CPR1 is a conserved effector protease with a direct target in soybean roots, highlighting it as a promising candidate for decoy engineering. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Healthy aging often entails a decline in cognitive and motor functions, affecting independence and quality of life in older adults. Brain stimulation shows potential to enhance these functions, but studies show variable effects. Previous studies have tried to identify responders and non-responders through correlations between behavioral change and baseline parameters, but results lack generalization to independent cohorts. We propose a method to predict an individual’s likelihood of benefiting from stimulation, based on baseline performance of a sequential motor task. Our results show that individuals with less efficient learning mechanisms benefit from stimulation, while those with optimal learning strategies experience none or even detrimental effects. This differential effect, first identified in a public dataset and replicated here in an independent cohort, was linked to one’s ability to integrate task-relevant information and not age. This study constitutes a further step towards personalized clinical-translational interventions based on brain stimulation.

Abstract Background The elevated incidence of tuberculosis (TB) outbreaks in schools poses a significant challenge to prevention and control efforts in China. The commonality among most outbreaks is the failure to isolate patients at an early stage. Early isolation of TB cases is crucial for reducing the spread of TB within schools. This study aims to quantify the impact of different isolation proportions and durations on the attack rate of TB in schools. It explored the intervention effects of isolation measures in preventing and controlling TB in school settings. The goal is to provide insights that can serve as a reference for reducing the occurrence of TB outbreaks in schools. Methods We collected data from 4 school TB outbreaks. Susceptible-Exposed-Infected-Recovered (SEIR) model was used to fit the collected data and calculate transmissibility. Susceptible-Exposed-Infected-Quarantined-Recovered (SEIQR) model was employed to evaluate the effect of isolation. Effective reproduction numbers and cumulative incidence were used to quantify the transmissibility of TB. Results In the 4 outbreaks, the majority of student cases were distributed in high grades of high school and universities, with a widespread occurrence of significant intervention delays. The median ascending reproduction value for the 4 outbreaks was 18.44 [interquartile range: 15.40-20.11]. Isolating 100% of the patients at the first month could reduce the number of cases by 99.47%, 87.99%, 96.48%, and 99.16%, respectively. Conclusions This study suggests that high schools and universities may represent significant high-risk environments for TB outbreaks. Early detection and isolation of cases are important strategies that can help reduce the risk of TB outbreaks, with observed case reductions of up to 99.47% when implemented promptly.

Abstract The current cholesterol guidelines recommend maintaining low levels of low-density lipoprotein cholesterol (LDL-C) in patients with coronary artery disease (CAD). However, recent studies have suggested that both very low and very high LDL-C levels may be associated with increased mortality in the general population. We utilized data from TriNetX, a global health research network, to investigate the association between LDL-C levels and all-cause mortality in patients with CAD. CAD patients were identified using the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code and stratified into six LDL-C categories:

Abstract Infectious disease is the result of interactions between host and pathogen and can depend on genetic variations in both. We conduct a genome-to-genome study of paired human and Mycobacterium tuberculosis genomes from a cohort of 1556 tuberculosis patients in Lima, Peru. We identify an association between a human intronic variant (rs3130660, OR = 10.06, 95%CI: 4.87 − 20.77, P = 7.92 × 10−8) in the FLOT1 gene and a subclavaluee of Mtb Lineage 2. In a human macrophage infection model, we observe hosts with the rs3130660-A allele exhibited stronger interferon gene signatures. The interacting strains have altered redox states due to a thioredoxin reductase mutation. We investigate this association in a 2020 cohort of 699 patients recruited during the COVID-19 pandemic. While the prevalence of the interacting strain almost doubled between 2010 and 2020, its infection is not associated with rs3130660 in this recent cohort. These findings suggest a complex interplay among host, pathogen, and environmental factors in tuberculosis dynamics.

Abstract Integrating diverse types of biological data is essential for a holistic understanding of cancer biology, yet it remains challenging due to data heterogeneity, complexity, and sparsity. Addressing this, our study introduces an unsupervised deep learning model, MOSA (Multi-Omic Synthetic Augmentation), specifically designed to integrate and augment the Cancer Dependency Map (DepMap). Harnessing orthogonal multi-omic information, this model successfully generates molecular and phenotypic profiles, resulting in an increase of 32.7% in the number of multi-omic profiles and thereby generating a complete DepMap for 1523 cancer cell lines. The synthetically enhanced data increases statistical power, uncovering less studied mechanisms associated with drug resistance, and refines the identification of genetic associations and clustering of cancer cell lines. By applying SHapley Additive exPlanations (SHAP) for model interpretation, MOSA reveals multi-omic features essential for cell clustering and biomarker identification related to drug and gene dependencies. This understanding is crucial for developing much-needed effective strategies to prioritize cancer targets.

Abstract Background The rapid establishment and persistence of latent HIV-1 reservoirs is one of the main obstacles towards an HIV cure. While antiretroviral therapy supresses viral replication, it does not eradicate the latent reservoir of HIV-1-infected cells. Recent evidence suggests that the human microbiome, particularly the gut microbiome, may have the potential to modulate the HIV-1 reservoir. However, literature is limited and the exact mechanisms underlying the role of the microbiome in HIV immunity and potential regulation of the viral reservoir remain poorly understood. Results Here, we review updated knowledge on the associations between the human microbiome and HIV reservoir across different anatomical sites, including the gut, the lungs and blood. We provide an overview of the predominant taxa associated with prominent microbiome changes in the context of HIV infection. Based on the current evidence, we summarize the main study findings, with specific focus on consistent bacterial and related byproduct associations. Specifically, we address the contribution of immune activation and inflammatory signatures on HIV-1 persistence. Furthermore, we discuss possible scenarios by which bacterial-associated inflammatory mediators, related metabolites and host immune signatures may modulate the HIV reservoir size. Finally, we speculate on potential implications of microbiome-based therapeutics for future HIV-1 cure strategies, highlighting challenges and limitations inherent in this research field. Conclusions Despite recent advances, this review underscores the need for further research to deepen the understanding of the complex interplay between the human microbiome and HIV reservoir. Further integrative multi-omics assessments and functional studies are crucial to test the outlined hypothesis and to identify potential therapeutic targets ultimately able to achieve an effective cure for HIV.

Abstract Background Prolactin, a hormone produced by the pituitary gland, regulates breast development and may contribute to breast cancer etiology. However, most epidemiologic studies of prolactin and breast cancer have been restricted to single, often small, study samples with limited exploration of effect modification. Methods The Biomarkers in Breast Cancer Risk Prediction consortium includes 8,279 postmenopausal women sampled from four prospective cohort studies, of whom 3,441 were diagnosed with invasive breast cancer after enrollment. Prolactin concentrations were measured for all study participants on plasma samples collected when all women were postmenopausal and before any breast cancer diagnosis using ELISA assays. Pooled, unconditional logistic regression models, adjusted for confounders, estimated odd ratios (OR) for associations of prolactin and postmenopausal breast cancer risk overall and stratified by breast cancer risk factors. Results Higher plasma prolactin concentrations were positively associated with postmenopausal breast cancer risk (> 13.2 ng/mL vs. 13.2 ng/mL vs.

Objective: Poorly differentiated thyroid carcinomas (PDTCs) are rare and aggressive head and neck malignancies with a poor prognosis. Systemic treatment for incurable PDTC consists of multi-kinase inhibitors (MKIs) based on extrapolation from the experience with radioiodine refractory differentiated thyroid cancer (DTC). Cabozantinib is an approved second-line MKI therapy for DTC, but there are limited data regarding the safety and efficacy of cabozantinib for PDTC. Methods: We conducted a single-institution, retrospective analysis of patients with PDTC who received cabozantinib in any line of therapy. Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record. Median progression-free survival (PFS) and overall survival (OS) were primary endpoints and estimated using Kaplan–Meier methodology. Results: Seven patients with PDTC who received cabozantinib were included. 4/7 (57%) patients had a partial response to cabozantinib, while 2/7 (29%) had stable disease (SD) as their best response. The median time on treatment for cabozantinib was 10.53 months. The median PFS from the start of cabozantinib was 12.9 months, and median OS was 14.21 months. Most adverse events to treatment (5/6) were low grade. Two (29%) patients were alive at the date of the last follow-up. Conclusion: Cabozantinib is an effective and reasonably well-tolerated treatment option for patients with PDTC. Prospective studies are needed to further investigate the role of cabozantinib in the treatment of PDTC, alone and in combination with other agents, including checkpoint inhibitors.

Abstract Background Crimean-Congo haemorrhagic fever (CCHF) is a lethal acute viral zoonosis with a case fatality rate of 5–50%. Due to the potential of human-to human transmission of the disease, healthcare workers (HCWs) are at risk of occupational exposure to CCHF virus. Little is known about CCHF virus route of transmission and risks in Iranian HCWs. Therefore this study was designed to identify the routes of exposure to the CCHF virus among Iranian HCWs. Methods From Oct 2000 to Feb 2023, 96 CCHF suspected healthcare workers referred to national reference laboratory were tested for CCHF virus infection by the use of RT-PCR and IgM Capture Enzyme-Linked Immunosorbent Assay (MAC-ELISA) and exposure history of cases were investigated to determine the CCHF virus routes of transmission in nosocomial settings. Results Twelve CCHF confirmed cases were identified including seven nurses and five physicians, with the median age of 32.5 years (range 23–53 years) and the median incubation period of 6.8 days (range from 1 to 22 days). None of the cases reported a history of tick bite or close contact with tissues or animal blood. The cases were from Razavi Khorasan (seven cases), Sistan and Baluchistan (two cases), Isfahan (one case), South Khorasan (one case) and Fars (one case). Percutaneous exposure (needle stick) (three cases), mucosal exposure (blood splash in to face) (three cases) and skin contact with blood (three cases) constituted the most prevalent routes of transmission. Since 2013, no CCHF cases have been identified among Iranian HCWs. Conclusions In healthcare settings, physicians and nurses are at risk of nosocomial CCHF virus infection. The routes of transmission mainly include direct exposures via needle-stick, mucosal or direct contact with the skin to infected blood. Continuous education and implementation of infection prevention and control measures are key factors to minimize the incidence of healthcare related CCHF.

Abstract The Arenaviridae family of segmented RNA viruses contains nearly 70 species with several associated with fatal haemorrhagic fevers, including Lassa, Lujo and Junin viruses. Lymphocytic choriomeningitis arenavirus (LCMV) is associated with fatal neurologic disease in humans and additionally represents a tractable model for studying arenavirus biology. Within cultured cells, a high proportion of LCMV spread is between directly neighbouring cells, suggesting infectivity may pass through intercellular connections, bypassing the canonical extracellular route involving egress from the plasma membrane. Consistent with this, we visualized abundant actin- and tubulin-rich connections conjoining LCMV-infected and uninfected cells within cultures, resembling tunnelling nanotubes (TNTs). Within these TNT-like connections, confocal and STED microscopy identified puncta containing the major structural components of LCMV virions alongside genomic RNA, consistent with intercellular transit of assembled virions or ribonucleoprotein genome segments. Blocking the extracellular route of infection by adding potent LCMV neutralising antibody M28 to supernatants during infection revealed around 50% of LCMV transmission was via intercellular connections. These results show arenaviruses transmission is more complex than previously thought involving both extracellular and intercellular routes.

Abstract A combination of multiple genetic and environmental factors appear to be required to trigger the onset of amyotrophic lateral sclerosis (ALS). Early life environmental exposures have been reported to be risk factors for a variety of adult-onset diseases, so we used data from an online international ALS case–control questionnaire to estimate whether any of these could be risk factors for the clinical onset of ALS. Responses were obtained from 1,049 people aged 40 years or more, 568 with ALS and 481 controls. People with ALS were more likely to have been born and lived longer in a country area than in a city area, to have younger parents, and to have lower educational attainment and fewer years of education. No ALS-control differences were found in sibling numbers, birth order, adult height, birth weight, parent smoking, Cesarean delivery, or age of starting smoking. In conclusion, early life events and conditions may be part of a group of polyenvironmental risk factors that act together with polygenetic variants to trigger the onset of ALS. Reducing exposure to adverse environmental factors in early life could help to lower the risk of later developing ALS.

Abstract Altered hepatic glucose fluxes are critical during the pathogenesis of type 2 diabetes. G protein-coupled receptors represent important regulators of hepatic glucose production. Recent studies have shown that hepatocytes express GPCRs that can couple to G12/13, a subfamily of heterotrimeric G proteins that has attracted relatively little attention in the past. Here we show, by analyzing several mutant mouse strains, that selective activation of hepatocyte G12/13 signaling leads to pronounced hyperglycemia and that this effect involves the stimulation of the ROCK1-JNK signaling cascade. Using both mouse and human hepatocytes, we also show that activation of endogenous sphingosine-1-phosphate type 1 receptors strongly promotes glucose release in a G12/13-dependent fashion. Studies with human liver samples indicate that hepatic GNA12 (encoding Gα12) expression levels positively correlate with indices of insulin resistance and impaired glucose homeostasis, consistent with a potential pathophysiological role of enhanced hepatic G12/13 signaling.

Abstract Positional coding along the anterior-posterior axis is regulated by HOX genes, whose 3’ to 5’ expression correlates with location along this axis. The precise utilisation of HOX genes in different human cell types is not fully understood. Here, we use single-cell and spatial-transcriptomics, along with in-situ sequencing, to create a developmental atlas of the human fetal spine. We analyse HOX gene expression across cell types during development, finding that neural-crest derivatives unexpectedly retain the anatomical HOX code of their origin while also adopting the code of their destination. This trend is confirmed across multiple organs. In the axial plane of the spinal cord, we find distinct patterns in the ventral and dorsal domains, providing insights into motor pool organisation and loss of collinearity in HOXB genes. Our findings shed new light on HOX gene expression in the developing spine, highlighting a HOX gene ‘source code’ in neural-crest cell derivatives.

Abstract Harnessing quantum correlations can enable sensing beyond classical precision limits, with the realization of such sensors poised for transformative impacts across science and engineering. Real devices, however, face the accumulated impacts of noise and architecture constraints, making the design and success of practical quantum sensors challenging. Numerical and theoretical frameworks to optimize and analyze sensing protocols in their entirety are thus crucial for translating quantum advantage into widespread practice. Here, we present an end-to-end variational framework for quantum sensing protocols, where parameterized quantum circuits and neural networks form trainable, adaptive models for quantum sensor dynamics and estimation, respectively. The framework is general and can be adapted towards arbitrary qubit architectures, as we demonstrate with experimentally-relevant ansätze for trapped-ion and photonic systems, and enables to directly quantify the impacts that noise and finite data sampling. End-to-end variational approaches can thus underpin powerful design and analysis tools for practical quantum sensing advantage.

Daily vitamin B12 (VB12) requirements of humans can naturally be fulfilled by animal product consumption, especially products from ruminants because of bacteria dwelling in their rumen. Indeed, only bacteria can synthesize this vitamin. Milk is hence an excellent source of VB12. This cross-sectional study was undertaken to unravel factors, such as genetic variation, diet and cow characteristics, and milk production, explaining the large variation in milk VB12 concentration among cows by using an integrative approach. Milk samples from 2 consecutive milkings were collected from 3,533 Canadian Holstein cows (1,239 first, 932 second, and 1,362 third and more lactations) located in 99 herds with various feeding management. For the purpose of genetic variation analysis, pedigrees were traced back for 3 complete generations for each sire and dam. A total of 10,021 identities were used in the subsequent genetic analyses. Milk VB12 averaged 4.2 ng/mL with a range between 0.7 and 9.0 ng/mL. Dietary fiber (NDF from forage, dietary NDF, ADF, and lignin) increased and dietary components related to energy (NFC, starch, NEL, and percentage of concentrate) decreased VB12 in milk. Milk VB12 varied with DIM, with a similar pattern as milk fat and protein concentration lactation curves. Milk VB12 increased as age at calving increased. When disregarding the herd variance, the heritability value was 0.37, meaning that milk VB12 can be modified by genetic selection. The final model including factors related to the diet, animal characteristics and milk productivity, and genetic variation explained 79% (pseudo-R2) of the milk VB12 variation. When excluding the random effect of the cow (i.e., excluding the animal and genetic relationships), the pseudo-R2 dropped to 43%, reinforcing the importance of genetic variation in explaining milk VB12 variation. To our knowledge, the present study is the most comprehensive evaluation of factors affecting milk VB12 variation including the greatest number of cows from various lactation stages.

Abstract Background Essential oils of Cymbopogon citratus and Hyptis suaveolens are known for their insecticidal properties, but remain ineffective against mosquitoes resistant to synthetic insecticides. In order to improve insecticidal properties of these plants, this study aimed to investigate the chemical composition and insecticidal activity against Anopheles gambiae mosquitoes of essential oil obtained by co-distillation of dry leaves of C. citratus and H. suaveolens. Methods Essential oils were extracted by hydrodistillation from dry leaves of C. citratus and H. suaveolens, separately, then from the mixture of the dry leaves of the two plants in mass ratio 50/50. Each pure essential oil and the mixture obtained either by co-distillation or by combining pure essential oils in volume ratio 50/50 were then analysed by GC/MS. All essential oils and Deltamethrin 0.05% (positive control) were tested on two species of mosquitoes of the genus Anopheles gambiae according to the World Health Organization standard methods. Results Essential oil obtained by co-distillation mainly contained piperitone (40.80%), 1,8-cineole (24.64%), p-menth-4(8)-ene (13.20%), limonene (6.09%) and α-pinene (4.73%). However, the mixture of pure essential oils of these two plants mostly contained geranial (20.74%), neral (16.42%), 1,8-cineole (19.79%), sabinene (6.03%) and β-pinene (3.87%). The essential oil of C. citratus mainly contained geranial (41.49%), neral (32.83%), β-myrcene (13.66%) and geraniol (3.49%) while the major constituents of essential oil of H. suaveolens were 1,8-cineole (39.58%), sabinene (12.06%), β-pinene (7.73%), α-terpinolene (6.72%) and (E)-caryophyllene (7.49%). At the dose of 1%, all essential oils, except that of H. suaveolens, induced about 100% of mortality on the sensitive species of An. gambiae. However, on the resistant species at the same dose, the essential oil obtained by co-distillation induced the highest mortality (53.44%). The essential oils of C. citratus, H. suaveolens and the mixture of the two pure essential oils caused respectively 2.47, 15.28 and 18.33% of mortality. The synthetic insecticide caused 100 and 14.84% of mortality respectively on the sensitive and resistant species of An. gambiae. Conclusion Essential oil obtained by co-distillation showed good insecticidal efficacy against a resistant species of An. gambiae and might constitute a new solution to fight against mosquitoes resistant to synthetic insecticides.

Abstract The present investigation aimed to assess the safety of photobiomodulation (PBM) on the oral carcinogenesis process induced by 4NQO, focusing on cell proliferation and apoptosis. Sixty-six Wistar rats received systemic 4NQO for 12 (n = 33) and 20 weeks (n = 33), divided into Control group, PBM 0.3 J, and PBM 1 J. Applications for PBM occurred three times a week. At weeks 12 and 20, the animals were euthanized. The immunoreactivity for anti-ROS1 and anti-p53 antibodies was also assessed. Statistical analysis was assessed by multiple t-tests, Kruskal-Wallis, and Spearman’s correlation. At 12 weeks, PBM 1 J group had nodular lesions, distinct from control and PBM 0.3 J groups (p = 0.005). At 20 weeks, nodular lesions were common in control and PBM 0.3 J groups. Histopathological characteristics did not significantly differ between groups at 12 (p = 0.30) and 20 weeks (p = 0.58). Epithelial dysplasia (n = 21) was common at 12 weeks. After 20 weeks, most of the cases revealed squamous cell carcinoma (n = 24). No differences were observed in the immunostaining of p53 and ROS1 among the control and experimental groups and there was no correlation of these proteins with clinicopathological data. During the carcinogenesis process, the PBM did not modify the development of oral lesions and the expression of proliferative and apoptosis proteins.

Magnesium (Mg) – based alloys are becoming attractive materials for medical applications as temporary bone implants for support of fracture healing, e.g. as a suture anchor. Due to their mechanical properties and biocompatibility, they may replace titanium or stainless-steel implants, commonly used in orthopedic field. Nevertheless, patient safety has to be assured by finding a long-term balance between metal degradation, osseointegration, bone ultrastructure adaptation and element distribution in organs. In order to determine the implant behavior and its influence on bone and tissues, we investigated two Mg alloys with gadolinium contents of 5 and 10 wt percent in comparison to permanent materials titanium and polyether ether ketone. The implants were present in rat tibia for 10, 20 and 32 weeks before sacrifice of the animal. Synchrotron radiation-based micro computed tomography enables the distinction of features like residual metal, degradation layer and bone structure. Additionally, X-ray diffraction and X-ray fluorescence yield information on parameters describing the bone ultrastructure and elemental composition at the bone-to-implant interface. Finally, with element specific mass spectrometry, the elements and their accumulation in the main organs and tissues are traced. The results show that Mg-xGd implants degrade in vivo under the formation of a stable degradation layer with bone remodeling similar to that of Ti after 10 weeks. No accumulation of Mg and Gd was observed in selected organs, except for the interfacial bone after 8 months of healing. Thus, we confirm that Mg-5Gd and Mg-10Gd are suitable material choices for bone implants.

Abstract Objective Lower socioeconomic status (SES) is a risk factor for poorer pain-related outcomes. Further, the neighborhood environments of disadvantaged communities can create a milieu of increased stress and deprivation that adversely affects pain-related and other health outcomes. Socioenvironmental variables such as the Area Deprivation Index, which ranks neighborhoods based on socioeconomic factors could be used to capture environmental aspects associated with poor pain outcomes. However, it is unclear whether the ADI could be used as a risk assessment tool in addition to individual-level SES. Methods The current study investigated whether neighborhood-level disadvantage impacts knee pain-related outcomes above sociodemographic measures. Participants were 188 community-dwelling adults who self-identified as non-Hispanic Black or non-Hispanic White and reported knee pain. Area Deprivation Index (ADI; measure of neighborhood-level disadvantage) state deciles were derived for each participant. Participants reported educational attainment and annual household income as measures of SES, and completed several measures of pain and function: Short-form McGill Pain Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index, and Graded Chronic Pain Scale were completed, and movement-evoked pain was assessed following the Short Physical Performance Battery. Hierarchical linear regression analyses were used to assess whether environmental and sociodemographic measures (i.e., ADI 80/20 [80% least disadvantaged and 20% most disadvantaged]; education/income, race) were associated with pain-related clinical outcomes. Results Living in the most deprived neighborhood was associated with poorer clinical knee pain-related outcomes compared to living in less deprived neighborhoods (ps

Abstract Background Research highlights the intense physiological demands of thoroughbred racing on jockeys, with elevated heart rates and substantial oxygen uptake, confirming the rigorous physical nature of the sport, however, the cardiovascular changes resulting from the physical demands of thoroughbred racing remain unexplored in Australian jockeys. Therefore, the objective of this study was to compare measures of cardiac structure and function of professional Australian jockeys to that of the general population and to determine if there are differences in heart structure and function detected using echocardiography. Methods Forty-six jockeys and thirty-three participants from the general population underwent two-dimensional echocardiography, which included all standard views and measurements. Each measurement was compared between groups using a Mann-Whitney U test. Results Groups were matched for age (jockeys (35 ± 12 years) and controls (36 ± 13 years)). Jockeys were shorter (1.64 ± 0.07 m vs. 1.75 ± 0.09 m, p