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Abstract Abuse of the highly toxic compound fentanyl and its analogues is increasing, raising serious public health concerns due to their potency and availability. Therefore, there is a need for decontamination methodologies to safely remove fentanyl to avoid harmful exposure. In this study, the efficacy of commercial and in-house synthesized decontamination agents (Dahlgren Decon, RSDL (Reactive Skin Decontamination Lotion), FAST-ACT (First applied sorbent treatment against chemical threats), GDS2000, alldecont MED, bleach, Domestos Spray Bleach, Effekt Klor, MgO, TiO2-nanodiamond, and CeO2) were evaluated for the degradation of fentanyl and carfentanil under controlled laboratory conditions and on wooden floor surfaces. Liquid chromatography/mass spectrometry analysis showed that oxidative decontamination agents were the most effective, with N-oxides identified as major degradation products. The physiological effects of these N-oxides were also investigated regarding their ability to activate the µ-opioid receptor and their metabolism in human liver microsomes. The results provide empirical evidence that complements prior research findings on the degradation of fentanyl and carfentanil using a variety of decontamination agents.

Introduction: Maternal urinary iodine concentration and blood neonatal thyroid-stimulating hormone (TSH) concentration reflect iodine status in pregnancy and serve as markers of iodine deficiency. As dietary measures in gestational diabetes mellitus (GDM) could affect iodine intake, our study aimed to investigate iodine supply in women with GDM compared to healthy pregnant women and to evaluate its relationship to maternal and neonatal thyroid function. Methods: Urinary iodine concentration (UIC) and serum TSH, free thyroxine (FT4), and autoantibodies against thyroid peroxidase (TPOAb) were analyzed in 195 women with GDM and 88 healthy pregnant women in the second trimester. Subsequently, neonatal TSH concentrations measured 72 h after delivery in a subgroup of 154 newborns (115 of mothers with GDM and 39 controls) from the national register were analyzed. Results: Median UIC was significantly lower in women with GDM compared to controls (89.50 μg/L vs. 150.05 μg/L; P < 0.001). Optimal iodine intake was found only in nine women with GDM (4.6%) and 33 healthy pregnant women (37.5%) (P < 0.001). Most pregnant women with GDM (88.7%) compared to one half of controls (50%) had iodine deficiency (P < 0.001). Although serum TSH and the prevalence of hypothyroidism (TSH > 4.0 mIU/L) were not different in both groups, hypothyroxinaemia was more prevalent in GDM compared to controls (12.3% vs 3.4%, P = 0.032). Consistently, neonatal TSH > 5.0 mIU/L indicating iodine deficiency, was found in 6 (5.2%) newborns of women with GDM as compared to none in controls. In women with GDM, the prevalence of perinatal complications was significantly lower in those who were taking dietary iodine supplements compared to those who were not (3/39 (7.69%) vs 46/156 (28.85%), P

Abstract. Along with the surge of unearthed medical literature and cultural relics in recent years, a network of channels in the system of medical conduit vessels (meridians) during the early Western Han dynasty has become much clearer gradually. In it, the increasing number of channel branches, network vessels and needle insertion holes (acupoints) is an important feature of the development of channel medicine during the Western Han dynasty. This is not only a reflection of the expanding requirements of the theoretical system of the main trunk channels and other vessels, but also an inevitable result of the continuous enrichment and accumulation of clinical experience. This article integrates the information about channel branches, network vessels, inscriptions, dots and further relics on the Tianhui (天回) Lacquered Meridian Figurine to compare the unearthed literature of the channel genre with the transmitted classical literature about acupuncture. The “Heart-Regulated Channel” in Medical Manuscripts on Bamboo Slips from Tianhui (《天回医简》) serves as an example to explain the occurrence, development and changes of the channel branches and network vessels in the early system of medical channels.

Abstract Background The aim of the randomized controlled clinical trial study was to evaluate the effectiveness in reducing pathologically increased pocket probing depths (PPD > 3 mm) using the Guided Biofilm Therapy (GBT) protocol (adapted to the clinical conditions in non-surgical periodontal therapy (NSPT): staining, air-polishing, ultrasonic scaler, air-polishing) compared to conventional instrumentation (staining, hand curettes/sonic scaler, polishing with rotary instruments) both by less experienced practitioners (dental students). Methods All patients were treated according to a split-mouth design under supervision as diseased teeth of quadrants I/III and II/IV randomly assigned to GBT or conventional treatment. In addition to the treatment time, periodontal parameters such as PPD and bleeding on probing (BOP) before NSPT (T0) and after NSPT (T1: 5 ± 2 months after T0) were documented by two calibrated and blinded examiners (Ethics vote/ Trial-register: Kiel-D509-18/ DRKS00026041). Results Data of 60 patients were analyzed (stage III/IV: n = 36/ n = 24; grade A/ B/ C: n = 1/ n = 31/ n = 28). At T1, a PPD reduction of all diseased tooth surfaces was observed in 57.0% of the GBT group and 58.7% of the control group (p = 0.067). The target endpoint (PPD ≤ 4 mm without BOP) was achieved in 11.5% for GBT (conventional treatment: 11.2%; p = 0.714). With the exception for number of sites with BOP, which was at T1 15.9% in the GBT group and 14.3% in the control group (p

Yearling rough-stock bulls (n = 38) were utilized in a randomized complete block design to evaluate dietary hempseed meal (HSM) inclusion on growth (ADG), intake (DMI), and efficiency (F:G). Bulls were blocked by body weight (BW), grouped into 10 pens (n = 3–4 bulls/pen), and randomly assigned to an HSM or control supplement treatment (CON; 72.5% cottonseed meal, 14.5% soy hulls, 13% fat). Treatments were offered at 10%, while 90% was fed as a mixed ration [50% Bermuda grass hay, 40% textured commercial feed (10% CP)]. Diet samples were dried and DMI was calculated. F:G was evaluated using DMI and ADG. Blood for plasma analysis and BW were obtained on sample days, prior to feed delivery. Data were analyzed using the GLIMMIX procedure in SAS version 9.4. The results were considered significant when p ≤ 0.050. There was no treatment × time interaction, or treatment effect for interim BW, ADG, or F:G (p ≥ 0.100). A treatment × time interaction occurred for DMI (p < 0.01), and BW (p = 0.01) increased in all bulls over time, while ADG decreased (p = 0.005), suggesting that interim live performance was not affected by HSM. Plasma urea nitrogen increased over time (p < 0.001) in all bulls, with greater concentrations observed in HSM bulls (p = 0.043).

Abstract Background Quality of life (QoL) provides a comprehensive concept underpinning veterinary decision-making that encompasses factors beyond physical health. It becomes particularly pertinent when seeking responsible choices for chronically ill or old horses that emphasise their well-being and a good QoL over the extension of life. How different stakeholders use the concept of QoL is highly relevant when considering the complexity of these decisions in real-life situations. Methods Seven focus group discussions (N = 39) were conducted to gain insights into how stakeholders assess and use equine QoL in veterinary care decisions for chronically ill and/or old horses. The discussions included horse owners (n = 17), equine veterinarians (n = 7), veterinary officers (n = 6), farriers (n = 4), and horse caregivers (n = 5). The combination of deductive and inductive qualitative content analysis of the group discussions focused on identifying both similarities and differences in the views of these groups regarding QoL for old and/or chronically ill horses. Results Findings show agreement about two issues: the importance of the individuality of the horse for assessing QoL and the relevance of QoL in making decisions about veterinary interventions. We identified differences between the groups with respect to three issues: the time required to assess QoL, stakeholders’ contributions to QoL assessments, and challenges resulting from those contributions. While owners and caregivers of horses emphasised their knowledge of a horse and the relevance of the time they spend with their horse, the veterinarians in the study focused on the differences between their own QoL assessments and those of horse owners. In response to challenges regarding QoL assessments and decision-making, stakeholders described different strategies such as drawing comparisons to human experiences. Conclusions Differences between stakeholders regarding equine QoL assessments contribute to challenges when making decisions about the care of chronically ill or old horses. The results of this study suggest that individual and collaborative reflection about a horse’s QoL should be encouraged, for example by developing practicable QoL assessment tools that support relevant stakeholders in this process.

BackgroundOlder patients with cancer already represent the largest proportion of cancer survivors which will further increase in the upcoming years. However, older patients are highly underrepresented in clinical research, leading to a detrimental knowledge gap. Research on important aspects of quality of life (QoL) and associated factors for older patients with cancer is insufficient to date.AimThe objective of this scoping review therefore is to investigate the dimensions of QoL including functional health, life-relevant values and preferences in older adults with cancer across all tumor entities and health care settings. It will further identify medical, sociodemographic, psychosocial and geriatric aspects associated with QoL in the elderly and compare these with younger cancer patients and older non-cancer cases.MethodsPublished articles investigating QoL dimensions and associated factors in older patients with cancer, i.e., exclusively patients ≥65 years or mean/median age ≥ 70 years for age-mixed samples, or that compare results of older with younger cancer patients or with older non-cancer cases will be considered for this scoping review. Older patients with cancer across all tumor entities, disease stages and health care setting will be included. PubMed and PsychINFO databases will be searched for relevant articles. Abstracts and titles will be screened for basic inclusion, and two independent reviewers will conduct a full text screening to evaluate the age criteria and decide on the final inclusion of the study. Data on study and participant characteristics, QoL dimensions and geriatric factors will be extracted using a data extraction sheet. Results will be summarized descriptively to address the objectives of this review.DiscussionThe findings of this scoping review will provide valuable insights into central dimensions of QoL, including values, preferences and functional health in older adults with cancer, and help to improve targeted interventions and healthcare planning.

ABSTRACT In spring 2022, an increase in metallo-β-lactamase-producing Pseudomonas aeruginosa (MBL-Pa) infections was detected in a hospital in Upper Austria. To identify the source of infection and to stop further transmissions, an epidemiological outbreak investigation including whole-genome sequencing (WGS)-based typing was conducted. The final case definition included cases admitted to the hospital between 2020 and 2023 with an MBL-Pa in one of the three genomic clusters identified. In addition, the investigation was extended to include historical cases from 2017. Core genome multilocus sequence typing was performed to assess the genetic relatedness between the isolates. Fifty-four clinical P. aeruginosa isolates and eight P. aeruginosa isolates from the hospital environment were obtained. All but nine isolates grouped into one of three genomic clusters (ST235/blaVIM-1, ST111/blaVIM-2, or ST621/blaIMP-13), which were considered to be distinct, prolonged outbreaks involving 47 out of 52 cases. The most likely source of infection for cluster 1 (ST111/blaVIM-2) and cluster 2 (ST235/blaVIM-1) was sinks in the intensive care unit (ICU) washroom. Cluster 3 clone (ST621/blaIMP-13) could have originated in the urology ward in 2020 and then spread to the ICU years later. However, the nosocomial origin of this clone could not be proven. In March 2023, following the implementation of control measures (gowning, patient isolation, screening, and daily disinfection), no further MLB-Pa was detected, and the outbreaks were considered to be over. As ICUs play an important role in the transmission of P. aeruginosa, emphasis should be placed on genomic surveillance, infection prevention, and control in such wards.IMPORTANCEThe significance of our work lies in the successful resolution of three prolonged outbreaks of MBL-Pa infections in a hospital in Upper Austria. Through a comprehensive epidemiological investigation coupled with WGS-based typing of P. aeruginosa isolates, the study identified three distinct genomic clusters responsible for prolonged outbreaks involving 47 cases. The investigation pinpointed sinks in the ICU washroom as the likely source of infection for two of the clusters. The study demonstrates the effectiveness of control measures such as hand hygiene, gowning, patient isolation, screening, and disinfection in stopping further transmission and bringing the outbreaks to a close. This underscores the critical role of genomic surveillance and control measures, particularly in high-risk settings like ICUs, in reducing nosocomial transmission of MBL-Pa infections.

IntroductionInfections with Fasciola hepatica and Ostertagia ostertagi impinge upon dairy cow health and welfare and represent a major economic factor in livestock industry. Control measures largely rely on the use of anthelminthic drugs. However, reports of anthelmintic resistance necessitate sustainable approaches. Farmer characteristics such as attitude and personality are crucial for the implementation of control strategies and on-farm practices.MethodsIn the present study, the HEXACO (Honesty-Humility, Emotionality, eXtraversion, Agreeableness, Conscientiousness, Openness to experience) model of personality structure, which conceptualizes human personality, was used to evaluate the relationship of farmer aspects with on-farm bulk tank milk seropositivity for F. hepatica and O. ostertagi. Moreover, information on farm structure, housing, management, and farmers’ attitude was collected in a face-to-face interview. Farm-level seropositivity for F. hepatica and O. ostertagi was predicted via elastic net regression.ResultsOut of 193 farms housing 8,774 cows in the German Federal State of Bavaria, 47 farms (24.4%) were seropositive for F. hepatica, 77 farms (39.9%) for O. ostertagi, and 42 farms (21.8%) for both endoparasites. The model for F. hepatica seropositivity selected the covariates pasture access, O. ostertagi seropositivity, higher farmer conscientiousness, and organic farming as relevant predictors. Seropositivity for O. ostertagi was predicted by F. hepatica seropositivity, pasture access, organic farming, and farmers being neutral regarding their satisfaction with animal health on their farm. Higher values for the HEXACO factors extraversion and emotionality were inversely associated with O. ostertagi seropositivity.DiscussionThe present work emphasizes the importance of farmer traits in regard to animal health and parasite occurrence. For the effective acceptance and implementation of sustainable control strategies for livestock helminth infections, it is crucial to consider these aspects to holistically address the challenges of managing parasitic diseases. Moreover, tailored communication strategies can be developed incorporating the understanding of individual stockman characteristics and subsequently ensuring encouragement of stakeholders.

Background: Prenatal exposure to phthalates, a group of synthetic chemicals widely used in consumer products, has previously been associated with adverse infant and child development. Studies also suggest that maternal depression and anxiety, may amplify the harmful effects of phthalates on infant and child neurodevelopment. Study design: Our analysis included a subset of dyads enrolled in the Atlanta African American Maternal-Child Cohort (N = 81). We measured eight phthalate metabolites in first and second trimester (8–14 weeks and 24–32 weeks gestation) maternal urine samples to estimate prenatal exposures. Phthalate metabolite concentrations were averaged across visits and natural log-transformed for analysis. Maternal symptoms of depression and anxiety were assessed using validated questionnaires (Edinberg Postnatal Depression Scale and State Trait Anxiety Inventory, respectively) and the total score on each scale was averaged across study visits. The NICU Network Neurobehavioral Scale (NNNS) was administered at two weeks of age. Our primary outcomes included two composite NNNS scores reflecting newborn attention and arousal. Linear regression was used to estimate associations between individual phthalate exposures and newborn attention and arousal. We assessed effect modification by maternal depression and anxiety. Results: Higher levels of urinary phthalate metabolites were not associated with higher levels of infant attention and arousal, but true associations may still exist given the limited power of this analysis. In models examining effect modification by maternal depression, we observed that an interquartile range increase in mono (2-ethlyhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was associated with a significant increase in newborn arousal only among those with high depressive symptoms (MEHP: β = 0.71, 95% confidence interval [CI] = 0.10, 1.32 for high, β = −0.30, 95% CI = −0.73, 0.12 for low; MEOHP: β = 0.60, 95% CI = −0.03, 1.23 for high, β = −0.12, 95% CI = −0.58, 0.33 for low; MEHHP: β = 0.54, 95% CI = −0.04, 1.11 for high, β = −0.11, 95% CI = −0.54, 0.32 for low). Similar patterns were observed in models stratified by maternal anxiety, although CIs were wide. Conclusion: Our results suggest maternal anxiety and depression symptoms may exacerbate the effect of phthalates on infant neurodevelopment. Future studies are needed to determine the optimal levels of attention and arousal in early infancy.

Measures of physical growth, such as weight and height have long been the predominant outcomes for monitoring child health and evaluating interventional outcomes in public health studies, including those that may impact neurodevelopment. While physical growth generally reflects overall health and nutritional status, it lacks sensitivity and specificity to brain growth and developing cognitive skills and abilities. Psychometric tools, e.g., the Bayley Scales of Infant and Toddler Development, may afford more direct assessment of cognitive development but they require language translation, cultural adaptation, and population norming. Further, they are not always reliable predictors of future outcomes when assessed within the first 12–18 months of a child’s life. Neuroimaging may provide more objective, sensitive, and predictive measures of neurodevelopment but tools such as magnetic resonance (MR) imaging are not readily available in many low and middle-income countries (LMICs). MRI systems that operate at lower magnetic fields (< 100mT) may offer increased accessibility, but their use for global health studies remains nascent. The UNITY project is envisaged as a global partnership to advance neuroimaging in global health studies. Here we describe the UNITY project, its goals, methods, operating procedures, and expected outcomes in characterizing neurodevelopment in sub-Saharan Africa and South Asia.

Abstract Introduction Early childhood development is a strong predictor of long‐term health outcomes, potentially mediated via epigenetics (DNA methylation). The aim of the current study was to examine how childhood experiences, punitive parenting, and an intergenerational psychotherapeutic intervention may impact DNA methylation in young children and their mothers. Methods Mothers and their infants/toddlers between 0 and 24 months were recruited at baseline (n = 146, 73 pairs) to participate in a randomized control trial evaluating the effectiveness of The Michigan Model of Infant Mental Health Home Visiting (IMH‐HV) parent–infant psychotherapy compared to treatment as usual. Baseline and 12‐month post‐enrollment data were collected in the family's home and included self‐report questionnaires, biological saliva samples, home environment observation, video‐taped parent–child interaction, and audio‐recorded interviews. Saliva DNA methylation was measured at the genes, nuclear receptor subfamily 3 group C member 1 (NR3C1), solute carrier family 6 member 4 (SLC6A4), brain‐derived neurotrophic factor (BDNF), and the genetic element, long interspersed nuclear element‐1 (LINE1). Results For mothers, baseline methylation of BDNF, SLC6A4, NR3C1, or LINE1 was largely not associated with baseline measures of their childhood adversity, adverse life experiences, demographic characteristics related to structurally driven inequities, or to IMH‐HV treatment effect. In infants, there were suggestions that methylation in SLC6A4 and LINE1 was associated with parenting attitudes. Infant BDNF methylation suggested an overall decrease in response to IMH‐HV psychotherapy over 12 months. Conclusions Overall, our findings suggest that the epigenome in infants and young children may be sensitive to both early life experiences and parent–infant psychotherapy.

In the wake of recent medical developments in small animal practice, curing animals of their illnesses and restoring their health can be realized better than ever before. However, the growing medical possibilities are also leading to an increase in demand for better care for patients suffering from terminal illnesses. Consequently, the field of animal hospice and palliative care has become increasingly available, enabling veterinarians to optimize the quality of life of patients, such as dogs and cats, who no longer have a prospect of full recovery. Using qualitative, semi-structured interviews with 20 small animal veterinarians involved in hospice and palliative care, we investigated the factors that motivate veterinarians to become involved in hospice and palliative care and explored the importance of relationships, communication, time and infrastructure in this area. Findings show that personal experiences with their own pets or during training or work life motivated veterinarians to provide this service. Although veterinarians highlighted the importance of empathetic-driven relationships, they were aware that keeping an emotional distance from the patient and caregiver is significant to provide successful care. Further, veterinarians emphasized their high investment of time that resulted primarily from the increased frequency and provided opportunities to communicate with caregivers. The overall conclusion is that having time for patients and the patients’ caregivers is one of the most important aspects of work in this field. However, as it will be also shown, veterinarians must consider aspects of self-care management by reflecting on their own time and energy resources while caring for animals and their caregivers.

Social support from family and friends, albeit associated with beneficial health effects, does not always help to cope with pain. This may be because humans elicit mixed expectations of social support and evaluative judgment. The present studies aimed to test whether pet dogs are a more beneficial source of support in a painful situation than human companions because they are not evaluative. For this, 74 (Study 1) and 50 (Study 2) women completed a cold-pressor task in the presence of either their own (S1) or an unfamiliar (S2) dog, a friend (S1), or an unknown human companion (S2), or alone. In both studies, participants reported less pain and exhibited less pain behavior in the presence of dogs compared to human companions. Reactions to pain were moderated by attitudes towards dogs in S2. This suggests that pet dogs may help individuals to cope with painful situations, especially if the individual in pain generally feels affectionate towards dogs.

Adolescence is a period of increased risk taking, including increased alcohol and drug use. Multiple clinical studies report a positive relationship between adolescent alcohol consumption and risk of developing an alcohol use disorder (AUD) in adulthood. However, few preclinical studies have attempted to tease apart the biological contributions of adolescent alcohol exposure, independent of other social, environmental, and stress factors, and studies that have been conducted show mixed results. Here we use several adolescent voluntary consumption of alcohol models, conducted across four labs in three institutes and with two rodent species, to investigate the ramifications of adolescent alcohol consumption on adulthood alcohol consumption in controlled, pre-clinical environments. We consistently demonstrate a lack of robust increases in adulthood alcohol consumption. This work highlights that risks seen in both human datasets and other murine drinking models may be due to unique social and environmental factors – some of which may be unique to humans.

Recently, β-alanine (BA) supplementation was shown to improve cognitive function in older adults with decreased cognitive function. Mechanisms supporting these improvements have not been well defined. This study examined the effects of 10-weeks of BA supplementation on changes in circulating brain inflammatory markers, brain derived neurotrophic factor (BDNF), and brain morphology. Twenty participants were initially randomized into BA (2.4 g·d−1) or placebo (PL) groups. At each testing session, participants provided a resting blood sample and completed the Montreal cognitive assessment (MoCA) test and magnetic resonance imaging, which included diffusion tensor imaging to assess brain tissue integrity. Only participants that scored at or below normal for the MoCA assessment were analyzed (6 BA and 4 PL). The Mann-Whitney U test was used to examine Δ (POST–PRE) differences between the groups. No differences in Δ scores were noted in any blood marker (BDNF, CRP, TNF-α and GFAP). Changes in fractional anisotropy scores were significantly greater for BA than PL in the right hippocampus (p = 0.033) and the left amygdala (p = 0.05). No other differences were noted. The results provide a potential mechanism of how BA supplementation may improve cognitive function as reflected by improved tissue integrity within the hippocampus and amygdala.

Abstract Detecting recurrent weather patterns and understanding the transitions between such regimes are key to advancing our knowledge of the low-frequency variability of the atmosphere and have important implications in terms of weather and climate-related risks. We adopt an analysis pipeline inspired by Markov State Modelling and detect in an unsupervised manner the dominant winter mid-latitude Northern Hemisphere weather patterns in the Atlantic and Pacific sectors. The daily 500 hPa geopotential height fields are first classified in about 200 microstates. The weather dynamics are then represented on the basis of these microstates and the slowest decaying modes are identified from the spectral properties of the transition probability matrix. These modes are defined on the basis of the nonlinear dynamical processes of the system and not as tentative metastable states, as often done in Markov state analysis. When focusing on a shifting longitudinal window of 60∘, we find that the longitude-dependent estimate of the longest relaxation time is smaller where stronger baroclinic activity is found. In the Atlantic and Pacific sectors slow relaxation processes are mainly related to transitions between blocked regimes and zonal flow. We also find strong evidence of a dynamical regime associated with the simultaneous Atlantic-Pacific blocking. When the analysis is performed on a broader geographical region of the Atlantic sector, we discover that the slowest relaxation modes of the system are associated with transitions between dynamical regimes that resemble teleconnection patterns like the North Atlantic Oscillation and weather regimes like the Scandinavian and Greenland blocking, yet have a much stronger dynamical foundation than classical methods based e.g. on EOF analysis. Our method clarifies that, as a result of the lack of a time-scale separation in the atmospheric variability of the mid-latitudes, there is no clear-cut way to represent the atmospheric dynamics in terms of few, well-defined modes of variability. The approach proposed here can be seamlessly applied across different regions of the globe for detecting regional modes of variability, and has a great potential for intercomparing climate models and for assessing the impact of climate change on the low-frequency variability of the atmosphere.

Ambadasu Bharatha,1 Nkemcho Ojeh,1 Ahbab Mohammad Fazle Rabbi,2 Michael H Campbell,1 Kandamaran Krishnamurthy,1 Rhaheem NA Layne-Yarde,1 Alok Kumar,1 Dale CR Springer,1 Kenneth L Connell,1 Md Anwarul Azim Majumder1 1Faculty of Medical Sciences, The University of the West Indies, Bridgetown, Barbados; 2Department of Population Sciences, University of Dhaka, Dhaka, BangladeshCorrespondence: Md Anwarul Azim Majumder, Director of Medical Education, Faculty of Medical Sciences, The University of the West Indies, Cave Hill Campus, Barbados, Email azim.majumder@cavehill.uwi.edu Ambadasu Bharatha, Lecturer in Pharmacology, Faculty of Medical Sciences, The University of the West Indies, Cave Hill Campus, Barbados, Email ambadasu.bharatha@cavehill.uwi.eduIntroduction: This research investigated the capabilities of ChatGPT-4 compared to medical students in answering MCQs using the revised Bloom’s Taxonomy as a benchmark.Methods: A cross-sectional study was conducted at The University of the West Indies, Barbados. ChatGPT-4 and medical students were assessed on MCQs from various medical courses using computer-based testing.Results: The study included 304 MCQs. Students demonstrated good knowledge, with 78% correctly answering at least 90% of the questions. However, ChatGPT-4 achieved a higher overall score (73.7%) compared to students (66.7%). Course type significantly affected ChatGPT-4’s performance, but revised Bloom’s Taxonomy levels did not. A detailed association check between program levels and Bloom’s taxonomy levels for correct answers by ChatGPT-4 showed a highly significant correlation (p< 0.001), reflecting a concentration of “remember-level” questions in preclinical and “evaluate-level” questions in clinical courses.Discussion: The study highlights ChatGPT-4’s proficiency in standardized tests but indicates limitations in clinical reasoning and practical skills. This performance discrepancy suggests that the effectiveness of artificial intelligence (AI) varies based on course content.Conclusion: While ChatGPT-4 shows promise as an educational tool, its role should be supplementary, with strategic integration into medical education to leverage its strengths and address limitations. Further research is needed to explore AI’s impact on medical education and student performance across educational levels and courses.Keywords: artificial intelligence, ChatGPT-4’s, medical students, knowledge, interpretation abilities, multiple choice questions

Extended X-ray absorption fine structure (EXAFS) conducted on an equiatomic MoNbTaW bcc medium-entropy alloy that was annealed at 2273 K reveals unexpectedly small 1st and 2nd shell element-specific lattice distortions. An experimental size-mismatch parameter, [Formula: see text], is determined to be ca. 50% lower than the corresponding calculated value. Around W, short-range order (SRO) preferring 4d elements in the 1st and 2nd shells persists. A Nb-W ordering is found, which is reminiscent of ordering emerging at lower temperatures in the B2(Mo,W;Ta,Nb)- and B32(Nb,W)-phases. With high-temperature ordering preferences in fcc also foreshadowing low-temperature phase, these findings suggest a general feature of high-temperature SRO.

Abstract Disease-causing variants have been identified for less than 20% of suspected equine genetic diseases. Whole genome sequencing (WGS) allows rapid identification of rare disease causal variants. However, interpreting the clinical variant consequence is confounded by the number of predicted deleterious variants that healthy individuals carry (predicted genetic burden). Estimation of the predicted genetic burden and baseline frequencies of known deleterious or phenotype associated variants within and across the major horse breeds have not been performed. We used WGS of 605 horses across 48 breeds to identify 32,818,945 variants, demonstrate a high predicted genetic burden (median 730 variants/horse, interquartile range: 613–829), show breed differences in predicted genetic burden across 12 target breeds, and estimate the high frequencies of some previously reported disease variants. This large-scale variant catalog for a major and highly athletic domestic animal species will enhance its ability to serve as a model for human phenotypes and improves our ability to discover the bases for important equine phenotypes.

Abstract Despite recent advances in cancer immunotherapy, pancreatic ductal adenocarcinoma (PDAC) remains unresponsive due to an immunosuppressive tumor microenvironment, which is characterized by the abundance of cancer-associated fibroblasts (CAFs). Once identified, CAF-mediated immune inhibitory mechanisms could be exploited for cancer immunotherapy. Siglec receptors are increasingly recognized as immune checkpoints, and their ligands, sialic acids, are known to be overexpressed by cancer cells. Here, we unveil a previously unrecognized role of sialic acid-containing glycans on PDAC CAFs as crucial modulators of myeloid cells. Using multiplex immunohistochemistry and transcriptomics, we show that PDAC stroma is enriched in sialic acid-containing glycans compared to tumor cells and normal fibroblasts, and characterized by ST3GAL4 expression. We demonstrate that sialic acids on CAF cell lines serve as ligands for Siglec-7, -9, -10 and -15, distinct from the ligands on tumor cells, and that these receptors are found on myeloid cells in the stroma of PDAC biopsies. Furthermore, we show that CAFs drive the differentiation of monocytes to immunosuppressive tumor-associated macrophages in vitro, and that CAF sialylation plays a dominant role in this process compared to tumor cell sialylation. Collectively, our findings unravel sialic acids as a mechanism of CAF-mediated immunomodulation, which may provide targets for immunotherapy in PDAC.

Abstract Mutations in PINK1 and Parkin cause early-onset Parkinson’s Disease (PD). PINK1 is a kinase which functions as a mitochondrial damage sensor and initiates mitochondrial quality control by accumulating on the damaged organelle. There, it phosphorylates ubiquitin, which in turn recruits and activates Parkin, an E3 ubiquitin ligase. Ubiquitylation of mitochondrial proteins leads to the autophagic degradation of the damaged organelle. Pharmacological modulation of PINK1 constitutes an appealing avenue to study its physiological function and develop therapeutics. In this study, we used a thermal shift assay with insect PINK1 to identify small molecules that inhibit ATP hydrolysis and ubiquitin phosphorylation. PRT062607, an SYK inhibitor, is the most potent inhibitor in our screen and inhibits both insect and human PINK1, with an IC50 in the 0.5–3 µM range in HeLa cells and dopaminergic neurons. The crystal structures of insect PINK1 bound to PRT062607 or CYC116 reveal how the compounds interact with the ATP-binding pocket. PRT062607 notably engages with the catalytic aspartate and causes a destabilization of insert-2 at the autophosphorylation dimer interface. While PRT062607 is not selective for PINK1, it provides a scaffold for the development of more selective and potent inhibitors of PINK1 that could be used as chemical probes.

Abstract Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1. Analysis shows that including these three corrections alone accounts for the measured fusion performance variability in the two highest performing experimental campaigns on the NIF to within error. Here we quantify the performance sensitivity to mode-2 symmetry in the burning plasma regime and apply the results, in the form of an empirical correction to a 1D performance model. Furthermore, we find the sensitivity to mode-2 determined through a series of integrated 2D radiation hydrodynamic simulations to be consistent with the experimentally determined sensitivity only when including alpha-heating.

Preexposure prophylaxis (PrEP) is underused in persons who use drugs and justice-involved persons. In an ongoing randomized controlled trial in 4 US locations comparing patient navigation versus mobile health unit on time to initiation of HIV medication or PrEP for justice-involved persons who use stimulants or opioids and who are at risk for or living with HIV, we assessed HIV risk factors, perceived HIV risk, and interest in PrEP. Participants without HIV (n = 195) were 77% men, 65% White, 23% Black, and 26% Hispanic; 73% reported a recent history of condomless sex, mainly with partners of unknown HIV status. Of 34% (67/195) reporting injection drug use, 43% reported sharing equipment. Despite risk factors, many persons reported their risk for acquiring HIV as low (47%) or no (43%) risk, although 51/93 (55%) with PrEP indications reported interest in PrEP. Justice-involved persons who use drugs underestimated their HIV risk and might benefit from increased PrEP education efforts.

Abstract Background Gestational weight gain (GWG) is a routinely monitored aspect of pregnancy health, yet critical gaps remain about optimal GWG in pregnant people from socially marginalized groups, or with pre-pregnancy body mass index (BMI) in the lower or upper extremes. The PROMISE study aims to determine overall and trimester-specific GWG associated with the lowest risk of adverse birth outcomes and detrimental infant and child growth in these underrepresented subgroups. This paper presents methods used to construct the PROMISE cohort using electronic health record data from a network of community-based healthcare organizations and characterize the cohort with respect to baseline characteristics, longitudinal data availability, and GWG. Methods We developed an algorithm to identify and date pregnancies based on outpatient clinical data for patients 15 years or older. The cohort included pregnancies delivered in 2005–2020 with gestational age between 20 weeks, 0 days and 42 weeks, 6 days; and with known height and adequate weight measures needed to examine GWG patterns. We linked offspring data from birth records and clinical records. We defined study variables with attention to timing relative to pregnancy and clinical data collection processes. Descriptive analyses characterize the sociodemographic, baseline, and longitudinal data characteristics of the cohort, overall and within BMI categories. Results The cohort includes 77,599 pregnancies: 53% had incomes below the federal poverty level, 82% had public insurance, and the largest race and ethnicity groups were Hispanic (56%), non-Hispanic White (23%) and non-Hispanic Black (12%). Pre-pregnancy BMI groups included 2% underweight, 34% normal weight, 31% overweight, and 19%, 8%, and 5% Class I, II, and III obesity. Longitudinal data enable the calculation of trimester-specific GWG; e.g., a median of 2, 4, and 6 valid weight measures were available in the first, second, and third trimesters, respectively. Weekly rate of GWG was 0.00, 0.46, and 0.51 kg per week in the first, second, and third trimesters; differences in GWG between BMI groups were greatest in the second trimester. Conclusions The PROMISE cohort enables characterization of GWG patterns and estimation of effects on child growth in underrepresented subgroups, ultimately improving the representativeness of GWG evidence and corresponding guidelines.

Background: Clinical trial participation can improve overall survival and mitigate healthcare disparities for gynecologic cancer patients in low-volume community centers. This study aimed to assess the effectiveness of a centrally regulated but administratively decentralized electronic screening log system to identify eligible patients across a large catchment area for a National Cancer Institute (NCI)-designated cancer center's open clinical trials. Methods: Electronic screening log data collected between 2014 and 2021 from ten community partner sites in a single NCI-designated cancer center's catchment area were reviewed retrospectively. Clinical factors assessed included cancer site, primary versus recurrent disease status, and histology. Identification efficiency (the ratio of patients screened identified with an available trial) was calculated. Identification inefficiencies (failures to identify patients with a potentially relevant trial) were assessed, and etiologies were characterized. Results: Across ten community partner sites, 492 gynecologic cancer patients were screened for seven open clinical trials during the study period. This included 170 (34.5 %) ovarian cancer patients, 156 (31.7 %) endometrial cancer patients, and 119 (24.2 %) cervical cancer patients. Over 40 % had advanced stage disease, and 10.6 % had recurrent disease. Only three patients were identified as having a relevant open trial; none ultimately enrolled due to not meeting trial eligibility criteria. An additional 2–52 patients were retrospectively found to have a relevant trial available despite not being identified as such within the electronic screening log system. Up to 14.4 % of patients had one or more missing minimum data elements that hindered full evaluation of clinical trial availability. Re-screening patients when new trials open may identify 12-15 additional patients per recurrent disease trial. Conclusions: An electronic screening log system can increase awareness of gynecologic oncology clinical trials at a NCI-designated cancer center's community partner sites. However, it is inadequate as a single intervention to increase clinical trial enrollment. Providing adequate support staff, documenting clinical factors consistently, re-screening patients at relevant intervals, and coordinating with central study personnel may increase its utility.

Understanding the impact of parasites on wildlife populations is an important aspect of conservation management. However, research on ectoparasites in wildlife can be difficult, as examinations of live animals which are not habituated to human handling are often impossible. The European wildcat (Felis silvestris) is a strictly protected wildlife species whose population has been recovering in Germany in recent decades. Several studies from different European countries have investigated the parasitological status of European wildcat populations. However, most of these studies assessed endoparasite infections, whereas ectoparasite infestations have often been neglected. To fill this knowledge gap for wildcats in Germany, 131 dead found specimens were examined for ectoparasites by macroscopic and microscopic examination of the fur and the ear canals. Infestation with ectoparasites was present in 84.0% (110/131) of the wildcats. Ticks showed the highest prevalence with 72.5% (95/131) of wildcats infested, with 49.6% (65/131) infested with Ixodes ricinus and 36.6% (48/131) with Ixodes hexagonus/canisuga. A total of 27.5% (36/131) of the wildcats were positive for at least one flea species. Of the nine different flea species identified by morphology and/or molecular analyses, Ceratophyllidae were most common (16.8% [22/131]), with Ceratophyllus sciurorum confirmed on 12.2% (16/131) and Nosopsyllus fasciatus on 1.5% (2/131) animals, followed by Pulex irritans (5.3% [7/131]), Spilopsyllus cuniculi (3.8% [5/131]), Chaetopsylla spp. (3.1% [4/131]) (2/131 Chaetopsylla trichosa and 1/131 Chaetopsylla globiceps), Ctenocephalides felis (1.5% [2/131]), Archaeopsylla erinacei (1.5% [2/131]) and Ctenophthalmus baeticus (0.8% [1/131]). Further, 23.7% (31/131) of the wildcats harboured mites, identified as Trombicula autumnalis in 12.2% (16/131) and Otodectes cynotis in 4.8% (6/124) of cases. The only louse species detected was Felicola hercynianus with a prevalence of 2.3% (3/131). Infestation intensities ranged from 1 to 86 ticks, 1–49 fleas, 1–1896 mites, and 1–92 F. hercynianus per wildcat. This study demonstrates that a variety of ectoparasites infests wildcats in Germany, but they do not seem to have a serious impact on the general health of wildcats, as judged by the hosts' mostly good or very good nutritional condition. In addition, the potential risk to domestic cats (Felis catus) and humans posed by the wildcats’ ectoparasites, appears to be low but present.

Blood parasites of the genus Leucocytozoon commonly infect many bird species worldwide and are particularly prevalent in birds of prey. As a vector-borne parasitic disease, the infection occurrence overlaps with that of the dominant vectors: blackflies (Diptera, Simuliidae). These blood-sucking insects are dependent on habitats with flowing freshwaters for the development of their larval stages. We investigated the correlation between the proximity to flowing waters and Leucocytozoon infection probability in common buzzard (Buteo buteo) broods, as well as the occurrence of adult blackflies directly at the nests. In addition, we investigated the survival of captured simuliids in relation to host infection intensity. In total in 2019, we examined 112 different nests, including 297 common buzzard nestlings, with a Leucocytozoon prevalence of 56.6% among the nestlings and of 80.3% at brood level. We found no significant association of Leucocytozoon infection probability with nestling age, the distance to the nearest stream and the sum of the length of streams within a radius of 200 and 1000 m around each nest. The number of blackflies caught around the nest showed a tentative correlation with the probability of Leucocyozoon infection of the nestlings. Among the subsample of 218 blackfly individuals that survived day one after capture, survival averaged 6.2 days. Our results suggest that Leucocytozoon transmission is complex and requires consideration of many factors, related to habitat and vector prevalence, especially given their temporal variation.

Madagascar's lemur populations are declining in dwindling habitats due to anthropogenic expansion and changing climatic conditions. Gastrointestinal parasites can be important indicators to assess the health status of threatened species. However, parasites, hosts and the environment are connected in complex interactions. The present study aimed to disentangle the impact of seasonal and several host-specific factors (sex, species, age, reproductive status, and body mass) on endoparasitism in two small-bodied, co-occurring lemur species (Microcebus murinus and Microcebus ravelobensis) in the Ankarafantsika National Park. Helminth prevalence and egg shedding intensity was investigated via copromicroscopic examination of 810 fecal samples that were obtained from 178 individuals across an 11-month period with a longitudinal approach via repeated captures in a 30.6 ha forest area. Both mouse lemur hosts shed seven morphologically distinct egg types (assigned to Subulura baeri, unidentified Enterobiinae, Spirura sp., Lemuricola sp., two Hymenolepididae spp., one unidentified ascarid). Postmortem examination of two deceased individuals enabled assignment of adult worms to egg morphotypes of S. baeri, Spirura sp. and one Hymenolepididae sp., supported by molecular analysis. A significant seasonal variation was observed in the occurrence of the three most common helminth species S. baeri (total prevalence 71%), unidentified Enterobiinae (46%) and Spirura sp. (38%), with a higher likelihood of infection with advancing dry season. Neither host species, sex nor reproductive status had a significant effect on gastrointestinal helminth infections. Host body mass showed pronounced seasonal changes but did not differ significantly between infected and non-infected individuals. The pathogenic effects of gastrointestinal helminths therefore likely remained within compensable limits in the studied mouse lemur populations. Our findings highlight the prominent influence of seasonal changes on helminth communities. The results of combined morphologic and genetic approaches can furthermore help to overcome limitations of parasite identification via copromicroscopy by linking egg morphology to DNA sequences.

Integrins are cell surface receptors that mediate the interactions of cells with their surroundings and play essential roles in cell adhesion, migration, and homeostasis. Eight of the 24 integrins bind to the tripeptide Arg-Gly-Asp (RGD) motif in their extracellular ligands, comprising the RGD-binding integrin subfamily. Despite similarity in recognizing the RGD motif and some redundancy, these integrins can selectively recognize RGD-containing ligands to fulfill specific functions in cellular processes. Antibodies against individual RGD-binding integrins are desirable for investigating their specific functions, and were selected here from a synthetic yeast-displayed Fab library. We discovered 11 antibodies that exhibit high specificity and affinity toward their target integrins, i.e. αVβ3, αVβ5, αVβ6, αVβ8, and α5β1. Of these, six are function-blocking antibodies and contain a ligand-mimetic R(G/L/T)D motif in their CDR3 sequences. We report antibody-binding specificity, kinetics, and binding affinity for purified integrin ectodomains, as well as intact integrins on the cell surface. We further used these antibodies to reveal binding preferences of the αV subunit for its 5 β-subunit partners: β6 = β8 > β3 > β1 = β5.

Background High blood pressure (BP) increases recurrent stroke risk. Methods and Results We assessed hypertension prevalence, treatment, control, medication adherence, and predictors of uncontrolled BP 90 days after ischemic or hemorrhagic stroke among 561 Mexican American and non‐Hispanic White (NHW) survivors of stroke from the BASIC (Brain Attack Surveillance in Corpus Christi) cohort from 2011 to 2014. Uncontrolled BP was defined as average BP ≥140/90 mm Hg at 90 days poststroke. Hypertension was uncontrolled BP or antihypertensive medication prescribed or hypertension history. Treatment was antihypertensive use. Adherence was missing zero antihypertensive doses per week. We investigated predictors of uncontrolled BP using logistic regression adjusting for patient factors. Median (interquartile range) age was 68 (59–78) years, 64% were Mexican American, and 90% of strokes were ischemic. Overall, 94.3% of survivors of stroke had hypertension (95.6% Mexican American versus 92.0% non‐Hispanic White; P=0.09). Of these, 87.9% were treated (87.3% Mexican American versus 89.1% non‐Hispanic White; P=0.54). Among the total population, 38.3% (95% CI, 34.4%–42.4%) had uncontrolled BP. Among those with uncontrolled BP prescribed an antihypertensive, 84.5% reported treatment adherence (95% CI, 78.8%–89.3%). Uncontrolled BP 90 days poststroke was less likely in patients with stroke who had a primary care physician (adjusted odds ratio [aOR], 0.45 [95% CI, 0.24–0.83]; P=0.01), greater stroke severity (aOR per‐1‐point‐higher National Institutes of Health Stroke Scale score, 0.96 [95% CI, 0.93–0.99]; P=0.02), or more depressive symptoms (aOR per‐1‐point‐higher Personal Health Questionnaire Depression Scale‐8 score, 0.95 [95% CI, 0.92–0.99] among those with a history of hypertension at baseline; P=0.009). Conclusions Greater than one third of survivors of stroke have uncontrolled BP at 90 days poststroke in this population‐based study. Interventions are needed to improve BP control after stroke.

Abstract Background Monoallelic germline pathogenic variants (GPVs) in five Fanconi anemia (FA) genes (BRCA1/FANCS, BRCA2/FANCD1, PALB2/FANCN, BRIP1/FANCJ, and RAD51C/FANCO) confer an increased risk of breast (BC) and/or ovarian (OC) cancer, but the role of GPVs in 17 other FA genes remains unclear. Methods Here, we investigated the association of germline variants in FANCG/XRCC9 with BC and OC risk. Results The frequency of truncating GPVs in FANCG did not differ between BC (20/10,204; 0.20%) and OC (8/2966; 0.27%) patients compared to controls (6/3250; 0.18%). In addition, only one out of five tumor samples showed loss‐of‐heterozygosity of the wild‐type FANCG allele. Finally, none of the nine functionally tested rare recurrent missense FANCG variants impaired DNA repair activities (FANCD2 monoubiquitination and FANCD2 foci formation) upon DNA damage, in contrast to all tested FANCG truncations. Conclusion Our study suggests that heterozygous germline FANCG variants are unlikely to contribute to the development of BC or OC.

The Colorado River is a vital water source for the western United States, yet the river is governed by disjointed and outdated policies that have left water management fragmented and water quantities overallocated. Groundwater is an overlooked component of Colorado River Basin (CRB) water supplies, making it vulnerable to overuse from disparities in uncoordinated protective management strategies. In this study, we analyzed state level groundwater policies to reveal the diversity and efficacy of groundwater governance mechanisms. The existing groundwater management plans for each state throughout the basin are fragmented and limited in scope. We found that with policies only covering 22% of the basin, they do not provide adequate protection at the basin scale for the sustainable use of groundwater resources in the face of increasing demands, creating a positive feedback loop that reinforces the scarcity issue. We conclude that a comprehensive management plan that can fully address resource use throughout the CRB is necessary for the sustainable use of groundwater and its contribution to base flow in the Colorado River. We suggest that such a plan could be derived through an interstate compact like the Colorado River Compact that is used for surface water management.

Background: The immunomodulatory imide drugs (IMiDs) thalidomide, lenalidomide and pomalidomide may exhibit therapeutic efficacy in the prostate. In lower urinary tract symptoms (LUTS), voiding and storage disorders may arise from benign prostate hyperplasia, or overactive bladder. While current therapeutic options target smooth muscle contraction or cell proliferation, side effects are mostly cardiovascular. Therefore, we investigated effects of IMiDs on human detrusor and porcine artery smooth muscle contraction, and growth-related functions in detrusor smooth muscle cells (HBdSMC). Methods: Cell viability was assessed by CCK8, and apoptosis and cell death by flow cytometry in cultured HBdSMC. Contractions of human detrusor tissues and porcine interlobar and coronary arteries were induced by contractile agonists, or electric field stimulation (EFS) in the presence or absence of an IMID using an organ bath. Proliferation was assessed by EdU assay and colony formation, cytoskeletal organization by phalloidin staining, Results: Depending on tissue type, IMiDs inhibited cholinergic contractions with varying degree, up to 50 %, while non-cholinergic contractions were inhibited up to 80 % and 60 % for U46619 and endothelin-1, respectively, and EFS-induced contractions up to 75 %. IMiDs reduced viable HBdSM cells in a time-dependent manner. Correspondingly, proliferation was reduced, without showing pro-apoptotic effects. In parallel, IMiDs induced cytoskeletal disorganization. Conclusions: IMiDs exhibit regulatory functions in various smooth muscle-rich tissues, and of cell proliferation in the lower urinary tract. This points to a novel drug class effect for IMiDs, in which the molecular mechanisms of action of IMiDs merit further consideration for the application in LUTS.

Abstract Introduction Depression and its components significantly impact dementia prediction and severity, necessitating reliable objective measures for quantification. Methods We investigated associations between emotion‐based speech measures (valence, arousal, and dominance) during picture descriptions and depression dimensions derived from the geriatric depression scale (GDS, dysphoria, withdrawal‐apathy‐vigor (WAV), anxiety, hopelessness, and subjective memory complaint). Results Higher WAV was associated with more negative valence (estimate = ‐0.133, p = 0.030). While interactions of apolipoprotein E (APOE) 4 status with depression dimensions on emotional valence did not reach significance, there was a trend for more negative valence with higher dysphoria in those with at least one APOE4 allele (estimate = –0.404, p = 0.0846). Associations were similar irrespective of dementia severity. Discussion Our study underscores the potential utility of speech biomarkers in characterizing depression dimensions. In future research, using emotionally charged stimuli may enhance emotional measure elicitation. The role of APOE on the interaction of speech markers and depression dimensions warrants further exploration with greater sample sizes. Highlights Participants reporting higher apathy used more negative words to describe a neutral picture. Those with higher dysphoria and at least one APOE4 allele also tended to use more negative words. Our results suggest the potential use of speech biomarkers in characterizing depression dimensions.

Background Stroke survivors believe neighborhood resources such as community centers are beneficial; however, little is known about the influence of these resources on stroke outcomes. We evaluated whether residing in neighborhoods with greater resource density is associated with favorable post‐stroke outcomes. Methods and Results We included Mexican American and non‐Hispanic White stroke survivors from the Brain Attack Surveillance in Corpus Christi project (2009–2019). The exposure was density of neighborhood resources (eg, community centers, restaurants, stores) within a residential census tract at stroke onset. Outcomes included time to death and recurrence, and at 3 months following stroke: disability (activities of daily living/instrumental activities of daily living), cognition (Modified Mini‐Mental State Exam), depression (Patient Health Questionnaire‐8), and quality of life (abbreviated Stroke‐Specific Quality of Life scale). We fit multivariable Cox regression and mixed linear models. We considered interactions with stroke severity, ethnicity, and sex. Among 1786 stroke survivors, median age was 64 years (interquartile range, 56–73), 55% men, and 62% Mexican American. Resource density was not associated with death, recurrence, or depression. Greater resource density (75th versus 25th percentile) was associated with more favorable cognition (Modified Mini‐Mental State Exam mean difference=0.838, 95% CI=0.092, 1.584) and among moderate–severe stroke survivors, with more favorable functioning (activities of daily living/instrumental activities of daily living=−0.156 [95% CI, −0.284 to 0.027]) and quality of life (abbreviated Stroke‐Specific Quality of Life scale=0.194 [95% CI, 0.029–0.359]). Conclusions We observed associations between greater resource density and cognition overall and with functioning and quality of life among moderate–severe stroke survivors. Further research is needed to confirm these findings and determine if neighborhood resources may be a tool for recovery.

Background: Maternal depression is considered a major contributor to morbidity and mortality in pregnancy. A population at risk are U.S. born or immigrant Hispanic women, and few prenatal depression or immune studies have focused on this population. Objective: The research questions for the study were 1) What are the occurrences, risk factors and outcomes associated with depression in Hispanic pregnant women in the United States and 2) What are the associations of plasma immune cytokines and prenatal depression in this population. Study design: Women of self-reported Hispanic ethnicity were born in the continental United States or foreign-born. Screening of potential participants (n = 690) at a first prenatal clinic visit consisted of antibody testing for Toxoplasma gondii antibodies in a larger grant, and only the women with antibody levels below the cutoff for T. gondii positivity (N = 536) were included in the present study. All participants completed a health and demographic questionnaire, the Edinburgh Postpartum Depression (EPDS) scale, the Perceived Stress Scale (PSS), and the Medical Outcomes Study Social Support (MOS) scale. We surveyed electronic health records (EHR) for risk factors and adverse pregnancy outcomes in the sample. We further measured physical and mental health and seven plasma immune cytokines at four study visits during pregnancy in a longitudinal subsample (N = 128). Results: The frequency of EPDS scores of 10 (depression risk) or above was 18.6 % at the time of enrollment. Socioeconomic factors such as less education, greater unemployment, and U.S. born nativity were associated with greater depression risk, but these relationships became insignificant when we corrected for false discovery rate. Depression scores were not associated with adverse birth and pregnancy outcomes. The inflammatory cytokine TNF-α was significantly higher across pregnancy in women with depression risk (p

Pensar em novas maneiras e novos recursos didáticos para facilitar e qualificar o processo de ensino-aprendizagem da geografia na Educação Básica e em tornar a geografia atraente e divertida, para que o/a estudante participe ativamente da construção do seu conhecimento são desafios atuais. Utilizaram-se as mídias e seus artefatos culturais em processos educativos para contribuir na resolução desta problemática. Desta forma, o presente trabalho teve como objetivo refletir sobre a utilização de desenhos animados como recurso didático-pedagógico para o ensino de geografia na Educação Básica. O presente texto trata-se de uma investigação teórica, na qual foi utilizada como metodologia a revisão bibliográfica e nesta foi considerado o gênero dos/as autores/as, para que o trabalho contemplasse ambos de forma equitativa. Como produtos resultantes foram gerados 9 planejamentos didáticos para o Ensino Fundamental – Anos Iniciais e Anos Finais alicerçados na Base Nacional Comum Curricular (Brasil, 2018) e no Currículo Base do Território Catarinense (Santa Catarina, 2019). Estes planejamentos apresentam temas transversais inovadores, e a diversidade em suas mais distintas facetas. Vislumbra-se que é uma alternativa tornar a geografia atraente e significativa para o/a estudante com artefatos culturais do seu dia-a-dia.

Modern dog and cat owners increasingly use internet resources to obtain information on pet health issues. While access to online information can improve owners’ knowledge of patient care and inform conversations with their veterinarian during consultations, there is also a risk that owners will misinterpret online information or gain a false impression of current standards in veterinary medicine. This in turn can cause problems or tensions, for example if the owner delays consulting their veterinarian about necessary treatment, or questions the veterinarian’s medical advice. Based on an online questionnaire aimed at dog and cat owners in Austria, Denmark and the United Kingdom (N = 2117) we investigated the use of internet resources to find veterinary medical information, the type of internet resources that were used, and whether owner beliefs explain how often they used the internet to find medical information about their pet. Approximately one in three owners reported that they never used internet resources prior to (31.7%) or after (37.0%) a consultation with their veterinarian. However, when owners do make use of the internet, our results show that they were more likely to use it before than after the consultation. The most common internet resources used by owners were practice websites (35.0%), veterinary association websites (24.0%), or ‘other’ websites providing veterinary information (55.2%). Owners who believe that the use of internet resources enables them to have a more informed discussion with their veterinarians more often use internet resources prior to a consultation, whereas owners who believed that internet resources help them to make the right decision for their animal more often use internet resources after a consultation. The results suggest that veterinarians should actively ask pet owners if they use internet resources, and what resources they use, in order to facilitate open discussion about information obtained from the internet. Given that more than a third of pet owners use practice websites, the findings also suggest that veterinarians should actively curate their own websites where they can post information that they consider accurate and trustworthy.

BackgroundThe current research concept of mentalization is used in the study to clearly identify affective and cognitive abilities of the caregiver-child dyad with the aim of compensating deficits on both sides with psychological-psychotherapeutic strategies.MethodsThe objective of this explorative, longitudinal intervention study is to provide an in-depth understanding of the psycho-social background of 30 children aged 6–12 years living in institutional or family-centered foster care. Data will be collected at three time points: before, after and 12 months after participating in the newly developed group intervention, which intends to address the particular needs of children of drug abusing parents living in foster care in the latency period. The study is conducted at the Faculty of Psychology of the University of Vienna in collaboration with the Association “Dialogue” (Verein Dialog). The treatment duration spans 5 months, during which two specifically trained psychotherapists conduct 10 group sessions for children and three group sessions for foster caregivers. All statistical analyses will consider the type of data available. Therefore, the primary outcome of the study will be assessed via the Friedman test due to the ordinal dependent variable as it is the non-parametric alternative to the one-way ANOVA for repeated measures. In addition, the Mann–Whitney U test is used to compare differences between two independent groups (children living in institutional foster care vs. family foster care). To assess potential correlations regarding the child and caregivers’ capacity to mentalize, Spearman correlations (ρ) are conducted. To examine the secondary outcome, apart from the methods previously outlined, we will also utilize qualitative thematic analysis.DiscussionThe present study uses the current research concept of mentalization to identify affective and cognitive abilities of the caregiver-child dyad with the aim of compensating deficits on both sides with psychological-psychotherapeutic strategies. There are some limitations of the study to mention: the small sample size does not allow to generalize the results. Due to the lack of a comparison group, a randomized control study (RCT) was not conducted. The authors are aware of these limitations. However, the studies’ findings, will help to deduce research questions for further studies.

Vector-borne diseases (VBDs) are considered as (re-)emerging, but information on the transmission cycles and wildlife reservoirs is often incomplete, particularly with regard to urban areas. The present study investigated blood samples from European hedgehogs (Erinaceus europaeus) presented at wildlife rehabilitation centres in the region of Hanover. Past exposure to B. burgdorferi sensu lato (s.l.) and tick-borne encephalitis virus (TBEV) was assessed by serological detection of antibodies, while current infections with Borrelia spp., Anaplasma phagocytophilum, Rickettsia spp., Neoehrlichia mikurensis, Bartonella spp., Babesia spp. and Spiroplasma ixodetis were investigated by (q)PCR. Of 539 hedgehogs tested for anti-Borrelia antibodies, 84.8% (457/539) were seropositive, with a higher seropositivity rate in adult than subadult animals, while anti-TBEV antibodies were detected in one animal only (0.2%; 1/526). By qPCR, 31.2% (168/539) of hedgehog blood samples were positive for Borrelia spp., 49.7% (261/525) for A. phagocytophilum, 13.0% (68/525) for Bartonella spp., 8.2% for S. ixodetis (43/525), 8.0% (42/525) for Rickettsia spp. and 1.3% (7/525) for Babesia spp., while N. mikurensis was not detected. While further differentiation of Borrelia spp. infections was not successful, 63.2% of the A. phagocytophilum infections were assigned to the zoonotic ecotype I and among Rickettsia spp. infections, 50.0% to R. helvetica by ecotype- or species-specific qPCR, respectively. Sequencing revealed the presence of a Rickettsia sp. closely related to Rickettsia felis in addition to a Bartonella sp. previously described from hedgehogs, as well as Babesia microti and Babesia venatorum. These findings show that hedgehogs from rehabilitation centres are valuable sources to identify One Health pathogens in urban areas. The hedgehogs are not only exposed to pathogens from fleas and ticks in urban areas, but they also act as potent amplifiers for these vectors and their pathogens, relevant for citizens and their pets.

Heat stress (HS) negatively impacts a variety of production parameters in growing pigs; however, the impact of biological sex on the HS response is largely unknown. To address this, 48 crossbred barrows and gilts (36.8 ± 3.7 kg BW) were individually housed and assigned to one of three constant environmental conditions: (1) thermoneutral (TN) (20.8 ± 1.6 °C; 62.0 ± 4.7% relative humidity; n = 8/sex), (2) HS (39.4 ± 0.6 °C; 33.7 ± 6.3% relative humidity) for 1 d (HS1; n = 8/sex), or (3) or for 7 d (HS7; n = 8/sex). As expected, HS increased rectal temperature (Tr) following 1 d of HS (1.0 °C; P

Germline CHEK2 pathogenic variants confer an increased risk of female breast cancer (FBC). Here we describe a recurrent germline intronic variant c.1009-118_1009-87delinsC, which showed a splice acceptor shift in RNA analysis, introducing a premature stop codon (p.Tyr337PhefsTer37).The variant was found in 21/10,204 (0.21%) Czech FBC patients compared to 1/3250 (0.03%) controls (p = 0.04) and in 4/3639 (0.11%) FBC patients from an independent German dataset. In addition, we found this variant in 5/2966 (0.17%) Czech (but none of the 443 German) ovarian cancer patients, three of whom developed early-onset tumors.Based on these observations, we classified this variant as likely pathogenic.

Abstract Background Changing geographical and seasonal activity patterns of ticks may increase the risk of tick infestation and tick-borne pathogen (TBP) transmission for both humans and animals. Methods To estimate TBP exposure of dogs and cats, 3000 female I. ricinus from these hosts were investigated for Anaplasma phagocytophilum and Borrelia species. Results qPCR inhibition, which was observed for ticks of all engorgement stages but not questing ticks, was eliminated at a template volume of 2 µl. In ticks from dogs, A. phagocytophilum and Borrelia spp. prevalence amounted to 19.0% (285/1500) and 28.5% (427/1500), respectively, while ticks from cats showed significantly higher values of 30.9% (464/1500) and 55.1% (827/1500). Accordingly, the coinfection rate with both A. phagocytophilum and Borrelia spp. was significantly higher in ticks from cats (17.5%, 262/1500) than dogs (6.9%, 104/1500). Borrelia prevalence significantly decreased with increasing engorgement duration in ticks from both host species, whereas A. phagocytophilum prevalence decreased only in ticks from dogs. While A. phagocytophilum copy numbers in positive ticks did not change significantly over the time of engorgement, those of Borrelia decreased initially in dog ticks. In ticks from cats, copy numbers of neither A. phagocytophilum nor Borrelia spp. were affected by engorgement. Borrelia species differentiation was successful in 29.1% (365/1254) of qPCR-positive ticks. The most frequently detected species in ticks from dogs were B. afzelii (39.3% of successfully differentiated infections; 70/178), B. miyamotoi (16.3%; 29/178), and B. valaisiana (15.7%; 28/178), while B. afzelii (40.1%; 91/227), B. spielmanii (21.6%; 49/227), and B. miyamotoi (14.1%; 32/227) occurred most frequently in ticks from cats. Conclusions The differences in pathogen prevalence and Borrelia species distribution between ticks collected from dogs and cats may result from differences in habitat overlap with TBP reservoir hosts. The declining prevalence of A. phagocytophilum with increasing engorgement duration, without a decrease in copy numbers, could indicate transmission to dogs over the time of attachment. The fact that this was not observed in ticks from cats may indicate less efficient transmission. In conclusion, the high prevalence of A. phagocytophilum and Borrelia spp. in ticks collected from dogs and cats underlines the need for effective acaricide tick control to protect both animals and humans from associated health risks. Graphical Abstract

Abstract Background Hyalomma marginatum and H. rufipes are two-host tick species, which are mainly distributed in southern Europe, Africa to central Asia but may also be found in Central and Northern Europe through introduction by migratory birds. Methods Ticks were collected while feeding or crawling on animals and humans, or from the environment, in different regions in Germany, between 2019 and 2021 in a citizen science study and from 2022 to 2023 in the wake of this study. Results From 2019 to 2023, a total of 212 Hyalomma adult ticks were detected in Germany. This included 132 H. marginatum and 43 H. rufipes ticks sent to research institutions and 37 photographic records that were only identified to genus level. The number of detected ticks varied over the years, with the highest number of 119 specimens recorded in 2019, followed by 57 in 2020. Most of the specimens were collected from horses, while some were collected from other animals, humans or found crawling on human clothes or other objects inside or outside houses. The screening of 175 specimens for Crimean-Congo hemorrhagic fever virus and of 132 specimens for Babesia/Theileria spp. by PCR gave negative results, while human-pathogenic Rickettsia were detected in 44% (77/175) of the total samples. Subsequent amplicon sequencing and phylogenetic analysis of representative samples determined the species of 41 Rickettsia aeschlimannii and one R. slovaca sequences. Conclusions Analysis of climatic factors indicated a significantly higher probability of Hyalomma occurrence at locations with higher average spring temperature during the years 2019 and 2020 compared to randomly generated pseudo-absence locations. Dry and hot conditions probably facilitated Hyalomma nymphs’ survival and molting into adults during these years. Graphical Abstract

Abstract Diabetes is associated with cognitive decline, but the underlying mechanisms are complex and their relationship with Alzheimer’s Disease biomarkers is not fully understood. We assessed the association of small vessel disease (SVD) and amyloid burden with cognitive functioning in 47 non-demented older adults with type-2 diabetes from the Israel Diabetes and Cognitive Decline Study (mean age 78Y, 64% females). FLAIR-MRI, Vizamyl amyloid-PET, and T1W-MRI quantified white matter hyperintensities as a measure of SVD, amyloid burden, and gray matter (GM) volume, respectively. Mean hemoglobin A1c levels and duration of type-2 diabetes were used as measures of diabetic control. Cholesterol level and blood pressure were used as measures of cardiovascular risk. A broad neuropsychological battery assessed cognition. Linear regression models revealed that both higher SVD and amyloid burden were associated with lower cognitive functioning. Additional adjustments for type-2 diabetes-related characteristics, GM volume, and cardiovascular risk did not alter the results. The association of amyloid with cognition remained unchanged after further adjustment for SVD, and the association of SVD with cognition remained unchanged after further adjustment for amyloid burden. Our findings suggest that SVD and amyloid pathology may independently contribute to lower cognitive functioning in non-demented older adults with type-2 diabetes, supporting a multimodal approach for diagnosing, preventing, and treating cognitive decline in this population.

Abstract Objective Guidelines suggest considering antiseizure medication (ASM) discontinuation in seizure‐free patients with epilepsy. Past work has poorly explored how discontinuation effects vary between patients. We evaluated (1) what factors modify the influence of discontinuation on seizure risk; and (2) the range of seizure risk increase due to discontinuation across low‐ versus high‐risk patients. Methods We pooled three datasets including seizure‐free patients who did and did not discontinue ASMs. We conducted time‐to‐first‐seizure analyses. First, we evaluated what individual patient factors modified the relative effect of ASM discontinuation on seizure risk via interaction terms. Then, we assessed the distribution of 2‐year risk increase as predicted by our adjusted logistic regressions. Results We included 1626 patients, of whom 678 (42%) planned to discontinue all ASMs. The mean predicted 2‐year seizure risk was 43% [95% confidence interval (CI) 39%–46%] for discontinuation versus 21% (95% CI 19%–24%) for continuation. The mean 2‐year absolute seizure risk increase was 21% (95% CI 18%–26%). No individual interaction term was significant after correcting for multiple comparisons. The median [interquartile range (IQR)] risk increase across patients was 19% (IQR 14%–24%; range 7%–37%). Results were unchanged when restricting analyses to only the two RCTs. Significance No single patient factor significantly modified the influence of discontinuation on seizure risk, although we captured how absolute risk increases change for patients that are at low versus high risk. Patients should likely continue ASMs if even a 7% 2‐year increase in the chance of any more seizures would be too much and should likely discontinue ASMs if even a 37% risk increase would be too little. In between these extremes, individualized risk calculation and a careful understanding of patient preferences are critical. Future work will further develop a two‐armed individualized seizure risk calculator and contextualize seizure risk thresholds below which to consider discontinuation. Plain Language Summary Understanding how much antiseizure medications (ASMs) decrease seizure risk is an important part of determining which patients with epilepsy should be treated, especially for patients who have not had a seizure in a while. We found that there was a wide range in the amount that ASM discontinuation increases seizure risk—between 7% and 37%. We found that no single patient factor modified that amount. Understanding what a patient's seizure risk might be if they discontinued versus continued ASM treatment is critical to making informed decisions about whether the benefit of treatment outweighs the downsides.

Abstract Background The European hedgehog (Erinaceus europaeus) is known for high levels of ectoparasitism that not only represents a health risk for the animals themselves, but also for pet animals and humans as hedgehogs are frequently taken into human care. In the present study, patterns of ectoparasite infestation were assessed in hedgehogs taken into care at northern German animal rehabilitation centres. Methods Ectoparasites (ticks, fleas and mites) of 498 hedgehogs were collected over a period of 3 years from July 2018 to May 2021. Species were identified based on morphological characteristics and also via amplification and sequencing of the partial cytochrome c oxidase subunit 2 (COX-2) gene for fleas of the family Ceratophyllidae. Seasonal changes in infestation patterns as well as correlations with animal age, body weight and health status were assessed using generalised linear models. Results Infestation with ticks, fleas and mites occurred throughout the year. Overall, 86.5% (431/498) of the examined hedgehogs were infested with ticks, 91.4% (455/498) with fleas and 17.7% (88/498) with mites. Ixodes ricinus and Ixodes hexagonus/Ixodes canisuga were the most common tick species detected, with the additional occurrence of one Ixodes frontalis. Significant seasonal changes were observed for I. ricinus, but not for I. hexagonus/I. canisuga. Additionally, I. ricinus nymph prevalence declined significantly as of 2020, probably as a consequence of the climate change-related drought as of 2018. In hedgehogs with flea infestations, Archaeopsylla erinacei, Ceratophyllus sciurorum, Nosopsyllus fasciatus and Ctenocephalides felis were identified. In all cases of mite infestation, Caparinia tripilis was detected, in addition to specimens of the family Macronyssidae and free-living mites of the family Acaridae. Statistical analyses showed correlations regarding the factors month, year, body weight and age, but no correlation was evident regarding the health status of the animals. Conclusions With a detected infestation rate of 98.6%, almost all of the examined hedgehogs were infested with at least one ectoparasite species. The seasonal activity patterns of the different ectoparasite species together with the complex annual cycle of hedgehogs lead to different seasonal patterns in ectoparasite prevalence and infestation intensities. Due to the risk of transmission of zoonotic pathogens as well as the possible negative impact on the host itself, hedgehogs should be treated against ectoparasites when taken into care facilities. Graphical Abstract

For patients with chronic spinal cord injury, the conventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection, pressure sores, osteoporosis, and deep vein thrombosis. Surgery is rarely performed on spinal cord injury in the chronic phase, and few treatments have been proven effective in chronic spinal cord injury patients. Development of effective therapies for chronic spinal cord injury patients is needed. We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal cord injury to compare intensive rehabilitation (weight-bearing walking training) alone with surgical intervention plus intensive rehabilitation. This clinical trial was registered at ClinicalTrials.gov (NCT02663310). The goal of surgical intervention was spinal cord detethering, restoration of cerebrospinal fluid flow, and elimination of residual spinal cord compression. We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement, reduced spasticity, and more rapid bowel and bladder functional recovery than weight-bearing walking training alone. Overall, the surgical procedures and intensive rehabilitation were safe. American Spinal Injury Association Impairment Scale improvement was more common in T7–T11 injuries than in T2–T6 injuries. Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.