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Background: The use of traditional/alternative medicine for health care in Africa has been examined for various conditions. However, there is limited research about traditional/alternative health care for intellectual disability. The present authors explored the explanatory models (EMs) of intellectual disability held by traditional/faith healers in Ghana. Methods: Using a case vignette, the present authors conducted semi-structured interviews with 36 traditional/faith healers in Accra, Ghana. Using the EMs of illness framework as a guide, participants were asked questions to examine their beliefs about the nature, causes, course and recommended treatment of intellectual disability. Results: The healers' causal explanations included maternal negligence during pregnancy and spiritual factors. They also believed that intellectual disability was a congenital, lifelong condition which could not be cured. Conclusions: Unlike other conditions which traditional healers claimed to cure, participants admitted that intellectual disability was not curable. The present authors suggest that the findings highlight opportunities that exist for collaboration between biomedicine and traditional medicine.

Abstract Background The rapid advancement of gerontechnology, technologies for older adults, needs a collaboration that integrates the efforts of researchers, industry and community partners. Multisector collaboration fosters a holistic view of technologies, merging industry expertise, academic rigour, and the lived experiences of older adults and caregivers. This paper explores the role of Equity, Diversity, and Inclusion (EDI) perspectives in Patient and Public Involvement (PPI). Methods We present two case studies from Canada and Australia. Study One involves a dementia television project, and Study Two is an innovative rural dementia care project. Data sources included transcripts of the case studies’ focus groups, research meeting notes, and associated study publications between 2021 and 2023 and 2016–2024, respectively. Utilizing Rolfe’s reflective model, we reflected on lessons learned regarding challenges, strategies, and their implications for future research. Our analysis focused on two questions: (1) What were the common challenges of partnering with industry and PPI in the research process? And (2) How can EDI be applied to help overcome those challenges? Results Thematic analysis identified five common themes of challenges and ten practical strategies. The challenges are (1) experiential bias, (2) underrepresentation, (3) communication gaps, (4) mistrust and (5) power dynamics. Based on the lessons learned, we identified ten practical strategies using EDI principles: (1) seek diverse representation, (2) establish transparent agreements, (3) adopt inclusive language and cultural sensitivity, (4) apply flexibility to learn and adapt, (5) embed team reflection (6) take time to build trust and relationships, (7) facilitate meaningful engagement, (8) provide equitable recognition and opportunity, (9) foster a respectful environment for knowledge transfer, and (10) cultivate a long-term sustained relationship. Conclusion The older population is diverse, and their needs are complex. EDI considerations contribute to fostering research excellence and maximizing the potential of PPI to develop technologies to improve aging experiences that truly meet the diverse needs of older adults for societal impact. Multisector collaboration requires clear communication and intentional efforts to build trust. EDI considerations should be embedded at every stage of the research process. This paper outlines common challenges, strategies, and implications as practical tips for future research and practice.

Abstract Cotton is the most common natural fibre used in textile manufacture, used alone or with other fibres to create a wide range of fashion clothing and household textiles. Most of these textiles are cleaned using detergents and domestic or commercial washing machines using processes that require many chemicals and large quantities of water and energy. Enzymes can reduce this environmental footprint by enabling effective detergency at reduced temperatures, mostly by directly attacking substrates present in the soils. In the present study, we report the contribution of a cleaning cellulase enzyme based on the family 44 glycoside hydrolase (GH) endo-beta-1,4-glucanase from Paenibacillus polymyxa. The action of this enzyme on textile fibres improves laundry detergent performance in several vectors including soil anti-redeposition, dye transfer inhibition and stain removal. Molecular probes are used to study how this enzyme is targeting both amorphous cellulose and xyloglucan on textile fibres and the relationship between textile surface effects and observed performance benefits.

Abstract The objective of this study was to evaluate clinical outcomes for patients undergoing IVF treatment where an artificial intelligence (AI) platform was utilized by clinicians to help determine the optimal starting dose of FSH and timing of trigger injection. This was a prospective clinical trial with historical control arm. Four physicians from two assisted reproductive technology treatment centers in the United States participated in the study. The treatment arm included patients undergoing autologous IVF cycles between December 2022–April 2023 where the physician use AI to help select starting dose of follicle stimulating hormone (FSH) and trigger injection timing (N = 291). The control arm included historical patients treated where the same doctor did not use AI between September 2021 and September 2022. The main outcome measures were total FSH used and average number of mature metaphase II (MII) oocytes. There was a non-significant trend towards improved patient outcomes and a reduction in FSH with physician use of AI. Overall, the average number of MIIs in the treatment vs. control arm was 12.20 vs 11.24 (improvement = 0.96, p = 0.16). The average number of oocytes retrieved in the treatment vs. control arm was 16.01 vs 14.54 (improvement = 1.47, p = 0.08). The average total FSH in the treatment arm was 3671.95 IUs and the average in the control arm was 3846.29 IUs (difference = −174.35 IUs, p = 0.13). These results suggests that AI can safely assist in refining the starting dose of FSH while narrowing down the timing of the trigger injection during ovarian stimulation, benefiting the patient in optimizing the count of MII oocytes retrieved.

Abstract Background Interprofessional education (IPE) has the potential to shape students’ collaboration perception and interprofessional identity but remains understudied. This study aims to understand the effects of the IPE program as a contextual trigger to promote collaboration perception change and interprofessional identity formation among healthcare professional students. Methods Using concurrent triangulation mixed-methods, we examined the relationship between collaboration perception and interprofessional identity change among health profession students (N = 263), and explored their perspectives on how their IPE experiences influenced their perception and identity. Participants completed the Interdisciplinary Education Perception Scale and Extended Professional Identity Scale and responded to open-ended questions before and after the IPE intervention. Pearson’s correlation, t-tests, regression (quantitative), and thematic analysis (qualitative) were conducted. Results Teams with initially lower collaboration perception (M = 3.59) and lower interprofessional identity (M = 3.59) showed a significant increase in collaboration perception (M = 3.76, t = 2.63; p = .02) and interprofessional identity (M = 3.97, t = 4.86; p

Abstract Wolbachia is an obligate intracellular α-proteobacterium, which commonly infects arthropods and filarial nematodes. Different strains of Wolbachia are capable of a wide range of regulatory manipulations in their diverse hosts, including the modulation of host cellular differentiation to influence host reproduction. The genetic basis for the majority of these phenotypes is unknown. The wWil strain from the neotropical fruit fly, Drosophila willistoni, exhibits a remarkably high affinity for host germline-derived cells relative to the somatic cells. This trait could be leveraged for understanding how Wolbachia influences the host germline and for controlling host populations in the field. To further the use of this strain in biological and biomedical research, we sequenced the genome of the wWil strain isolated from host cell culture cells. Here, we present the first high quality Nanopore assembly of wWil, the Wolbachia endosymbiont of D. willistoni. Our assembly resulted in a circular genome of 1.27 Mb with a BUSCO completeness score of 99.7%. Consistent with other insect-associated Wolbachia strains, comparative genomic analysis revealed that wWil has a highly mosaic genome relative to the closely related wMel and wAu strains from Drosophila melanogaster and Drosophila simulans, respectively.

Abstract Background The relationship between lifestyle and migraine is complex, as it remains uncertain which specific lifestyle factors play the most prominent role in the development of migraine, or which modifiable metabolic traits serve as mediators in establishing causality. Methods Independent genetic variants strongly associated with 20 lifestyle factors were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for migraine were obtained from the FinnGen consortium (18,477 cases and 287,837 controls) as a discovery set and the GWAS meta-analysis data (26,052 cases and 487,214 controls) as a replication set. Estimates derived from the two datasets were combined using fixed-effects meta-analysis. Two-step univariable MR (UVMR) and multivariable Mendelian randomization (MVMR) analyses were conducted to evaluate 19 potential mediators of association and determine the proportions of these mediators. Results The combined effect of inverse variance weighted revealed that a one standard deviation (SD) increase in genetically predicted Leisure screen time (LST) was associated with a 27.7% increase (95% CI: 1.14–1.44) in migraine risk, while Moderate or/and vigorous physical activity (MVPA) was associated with a 26.9% decrease (95% CI: 0.61–0.87) in migraine risk. The results of the mediation analysis indicated that out of the 19 modifiable metabolic risk factors examined, hypertension explains 24.81% of the relationship between LST and the risk of experiencing migraine. Furthermore, hypertension and diastolic blood pressure (DBP) partially weaken the association between MVPA and migraines, mediating 4.86% and 4.66% respectively. Conclusion Our research findings indicated that both LST and MVPA in lifestyle have independent causal effects on migraine. Additionally, we have identified that hypertension and DBP play a mediating role in the causal pathway between these two factors and migraine.

Context: Childbirth is a normal physiological process in a woman’s life, yet it is a life-changing experience for the primigravida mothers. Boosting confidence regarding pregnancy and childbirth by enhancing knowledge is an important component of care. Aims: The aim was to assess the effectiveness of the video-assisted childbirth education programme on the knowledge of the primigravida mothers regarding childbirth. Settings and Design: A quantitative research approach with a quasi-experimental non-equivalent control group design was adopted. Non-probability convenient sampling technique was used to select the 60 primigravida mothers who completed 34 weeks of gestation and are attending the Gynaec Outpatient Department (OPD) of a tertiary care hospital in Bhopal. Methods and Material: The self-structured knowledge questionnaire was developed. On the first day of contact with the sample, pretest was taken from both groups. A tailor-made video was administered to the experimental group on the same day. Posttest was taken on the seventh day from both groups. Statistical Analysis Used: Repeated measures analysis of variance (ANOVA) used to determine the effectiveness of video-assisted childbirth education programme revealed a significant interaction between the intervention and time, F (1,58) =29.398, P < .001. Results: The mean difference in knowledge score over time was greater in the experimental group compared to the control group and the difference was statistically significant. Conclusions: The video-assisted childbirth education programme was effective in enhancing the knowledge of primigravida mothers regarding childbirth.

Abstract Safe and effective brain tumor surgery aims to remove tumor tissue, not non-tumoral brain. This is a challenge since tumor cells are often not visually distinguishable from peritumoral brain during surgery. To address this, we conducted a multicenter study testing whether the Sentry System could distinguish the three most common types of brain tumors from brain tissue in a label-free manner. The Sentry System is a new real time, in situ brain tumor detection device that merges Raman spectroscopy with machine learning tissue classifiers. Nine hundred and seventy-six in situ spectroscopy measurements and colocalized tissue specimens were acquired from 67 patients undergoing surgery for glioblastoma, brain metastases, or meningioma to assess tumor classification. The device achieved diagnostic accuracies of 91% for glioblastoma, 97% for brain metastases, and 96% for meningiomas. These data show that the Sentry System discriminated tumor containing tissue from non-tumoral brain in real time and prior to resection.

IntroductionOne emerging technology in long-term care (LTC) is virtual reality (VR), an innovative tool that uses head-mounted devices to provide the viewer with an immersive experience. It has been shown that VR has a positive impact on the well-being of residents living with dementia, and staff are essential in the implementation and sustainable use of technology. Currently, there is a lack of inclusion and focus on direct staff perspectives on VR implementation in LTC. This paper aims to report staff perspectives on VR adoption in a 2-year study on a virtual reality program at three Canadian LTC homes.MethodsOur interdisciplinary team (clinicians, people living with dementia and family partners, trainees, and researchers) explored the facilitators and barriers to implementing VR in LTC, guided by the Consolidated Framework for Implementation Research (CFIR) and intersectionality supplemented CFIR. Twenty-one participants were recruited, including recreation staff, care aides, nurses, screeners, and leadership team members. The team collected data through staff interviews, focus groups, and ethnographic observation field notes. Reflexive thematic analysis was performed to identify themes reporting the facilitators and barriers for VR implementation in LTC from staff perspectives.ResultsThe data analysis resulted in three facilitators and four barriers. Facilitators are (1) perceived VR benefits, (2) integrate VR into workflow and routines, and (3) partner with skillful VR champions. Barriers include (1) staff concerns about VR use, (2) financial burden and competing priorities, (3) lack of infrastructure and physical spaces, and (4) staff workload and limited leadership support.DiscussionThis study contributes to the field with staff perspectives on facilitators and barriers to VR implementation. It underscores the rarely discussed aspects of VR implementation, such as funding prioritization and implementation timing. We offer practical strategies to inform future practices and research. Future studies should further explore long-term VR implementation, the involvement of family members as VR facilitators, and the use of VR in LTC.

DNA damage can be caused by a number of intrinsic and extrinsic factors. A recent study showed that free-living house sparrows (Passer domesticus) have higher DNA damage in the summer than the winter across five different tissues. This result was consistent when house sparrows were brought into captivity and exposed to comparable light cycles, with all other variables held constant. These results generated two hypotheses: (1) seasonal variation in DNA damage is related to circadian regulation and (2) seasonal variation in DNA damage is related to the total number of active hours. To investigate these hypotheses, we first quantified erythrocyte DNA damage in wild-caught house sparrows held in captivity on a 12L:12D light cycle at six points during the day to assess a diel or circadian rhythm but did not find one. We then performed a resonance experiment, in which birds experienced unnatural light cycles, and compared DNA damage in birds held on 6L:6D and 4.5L:7.5D resonance light cycles with their natural counterparts, 12L:12D and 9L:15D, respectively. We assessed corticosterone levels and DNA damage in blood before and after the resonance light cycles and DNA damage in abdominal fat, hippocampus, hypothalamus, and liver after the resonance light cycles. While our second experiment was not able to effectively test our hypotheses, we were able to demonstrate some interesting patterns. Throughout the resonance experiment, baseline corticosterone and testes size increased, consistent with the birds being photostimulated and preparing to breed. Surprisingly, the direction of change of DNA damage throughout the resonance photoperiod differed with tissue, which is not consistent with patterns during the breeding season in the wild. Our data indicate a potential uncoupling of the breeding physiology with the effect on DNA damage due to exposure to a resonance light cycle, which the birds may have interpreted as a skeleton photoperiod. Finally, though we were unable to fully disentangle the dynamics underlying seasonal DNA damage, we show that the previously documented patterns are not simply due to diel changes or the total amount of light exposure within a 24-hour period.

Introduction The ketogenic diet is a very low carbohydrate diet known for its ability to reduce weight and counteract hyperglycaemia. However, ketogenic diets recommend an increased intake of fats, raising concerns about cardiometabolic risk in adults. Due to the higher intake of fats in the ketogenic diet, there is significant variability in outcomes of lipid metabolism in the population. Interventions have reported improvements in lipid profile while other studies did not find changes, and there are reports of increased low density lipoprotein (LDL) and triglyceride values. Hence, this is a protocol for a systematic review of the published literature and a summary of the effect of ketogenic diets on lipid metabolism in adults.Methods and analysis Five databases (PubMed, Embase, Scopus, Cochrane Library and Web of Science) will be searched for studies on ketogenic diets in adult populations. Studies will be included if they report results from ketogenic diet interventions among adults. Exclusion is populations with diagnosed neurological disorders. Two reviewers will independently screen retrieved citations, extract data and appraise the risk of bias. Quantitative estimates (eg, standardised mean difference) measuring the change in the total cholesterol, LDL and triglyceride concentration will be pooled using random effects meta-analysis to produce one summarised weighted estimate. Sources of heterogeneity will be explored using subgroup analysis. This protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols (PRISMA), and the final review will be reported following the PRISMA 2020 guidelines.Ethics and dissemination The present protocol and the systematic review to be carried out do not require ethics clearance. The data source will be published studies. This review will provide estimates to inform the public about the effect of ketogenic diets on lipid metabolism and the possible peril of increasing cardiometabolic risk. The results will be published in a peer-reviewed journal.PROSPERO registration number CRD42022309665.

Objective: The objective was to learn about the characteristics of psychotherapists who use energy meridian techniques (EMTs). Methods: We conducted an Internet-based survey of the practices and attitudes of licensed psychotherapists. Results: Of 149 survey respondents (21.4% social workers), 42.3% reported that they frequently use or are inclined to use EMTs. EMT therapists reported higher use of a number of techniques from different theoretical orientations, reliance on intuition in decision making, positive attitudes toward complementary and alternative treatments, erroneous health beliefs, and importance placed on the intuitive appeal of evidence-based treatments. EMT therapists also had lower scores on a test of critical thinking. Conclusions: Results suggest that a number of characteristics differentiate therapists who are inclined to use EMTs, which can aid in future educational efforts. (Contains 2 tables and 2 figures.)

Background/Objective: Asthma is a common chronic medical condition among children and the most common diagnosis associated with interfacility transports for pediatric patients. As many as 40% of pediatric transfers may be unnecessary, resulting in potential delays in care and unnecessary costs. Our objective was to identify the patient-related factors associated with potentially unnecessary transfers for pediatric patients with asthma. Methods: We used patient care data from the California Department of Health Care Access and Information patient discharge and emergency department (ED) datasets to capture ED visits where a pediatric patient (age 2–17 years) presented with asthma and was transferred to another ED or acute care hospital. The outcome of interest was a potentially unnecessary transfer, defined as a visit where length of stay after transfer was

Abstract Neurodegenerative diseases (NDDs) are characterized by neuronal damage and progressive loss of neuron function. Microbiome-based interventions, such as dietary interventions, biotics, and fecal microbiome transplant, have been proposed as a novel approach to managing symptoms and modulating disease progression. Emerging clinical trials have investigated the efficacy of interventions modulating the GM in alleviating or reversing disease progression, yet no comprehensive synthesis have been done. A systematic review of the literature was therefore conducted to investigate the efficacy of microbiome-modulating methods. The search yielded 4051 articles, with 15 clinical trials included. The overall risk of bias was moderate in most studies. Most microbiome-modulating interventions changed the GM composition. Despite inconsistent changes in GM composition, the meta-analysis showed that microbiome-modulating interventions improved disease burden (SMD, − 0.57; 95% CI − 0.93 to − 0.21; I2 = 42%; P = 0.002) with a qualitative trend of improvement in constipation. However, current studies have high methodological heterogeneity and small sample sizes, requiring more well-designed and controlled studies to elucidate the complex linkage between microbiome, microbiome-modulating interventions, and NDDs.

Abstract Background The use of virtual learning platforms is on the rise internationally, however, successful integration into existing curricula is a complex undertaking fraught with unintended consequences. Looking beyond medical and pedagogic literature can provide insight into factors affecting the user experience. The technology acceptance model, widely used in software evaluation, can be used to identify barriers and enablers of engagement with virtual learning platforms. Here, the technology acceptance model was used to scaffold the exploration of the factors that influenced students' perceptions of the virtual anatomy platform, Anatomage and how these shaped their intention to use it. Methods Focus groups identified factors influencing students use of the Anatomage tables. Interventions were rolled out to address these findings, then further focus groups and the technology acceptance model identified how factors including self-efficacy, enjoyment, and social norms influenced students’ intention to use the Anatomage table in the future. Results Students raised significant concerns about understanding how to use the Anatomage table. Moreover, students who considered themselves to be poor at using technology perceived the Anatomage table as more complicated to use. The subjective norm of the group significantly altered the perceived ease of use and usefulness of the Anatomage. However, enjoyment had the greatest impact in influencing both perceived usefulness and perceived ease of use. Indicating that enjoyment is the largest contributing factor in altering technology engagement in healthcare cohorts and has the biggest potential to be manipulated to promote engagement. Conclusions Focus groups used in tandem with the technology acceptance model provide an effective way to understand student perceptions around technology used in the healthcare curricula. This research determined interventions that promote student engagement with virtual learning platforms, which are important in supporting all healthcare programmes that incorporate technology enhanced learning.

Abstract Background The objective of this analysis was to gain new insights into the patient characteristics and other factors associated with lasmiditan usage and clinical outcomes under conditions resembling the real-world setting. Methods This was a post hoc analysis of data from the 12-month, open-label extension (OLE) of the phase 3, double-blind, randomized, controlled CENTURION trial, which examined the efficacy and safety of lasmiditan as acute treatment across four migraine attacks. Patients completing the main study who treated ≥ 3 attacks could continue in the OLE. The initial lasmiditan dose was 100 mg, with dose adjustments to 50 mg or 200 mg allowed at the investigator’s discretion. Patient and clinical characteristics were summarized by dosing pattern and completion status. Safety was assessed based on adverse event (AE) frequency by number of doses. Results In total, 445 patients treated ≥ 1 migraine attacks with lasmiditan during the OLE, 321 of whom (72.1%) completed the study. Forty-seven percent of patients remained on the 100-mg initial dose during the OLE whereas 20.2% used both 100 mg and 50 mg, 30.6% used both 100 mg and 200 mg, and 6 (1.3%) used multiple dose levels. All dosing patterns were associated with clinical and patient-reported improvement; however, the 100-mg group had the highest proportion of patients reporting improvement in the Patient Global Impression of Change – Migraine Headache Condition (56.5% vs 33.4%–52.2%). In comparison, all three groups that made dose adjustments had higher rates of completion compared to the 100-mg group (72.1%–83.3% vs 68.9%). The frequency of AEs decreased with continued use of lasmiditan. Concomitant triptans and lasmiditan use did not increase AE frequency. Conclusions Based on high persistence and patient satisfaction rates, the 100-mg dose appears optimal for most patients. For those who adjusted dose levels, dose adjustments appeared beneficial to improve efficacy or tolerability, retaining patients on treatment. Collectively, the data suggest that patients who experienced efficacy continued to use lasmiditan regardless of the occurrence or frequency of AEs, and continued use appeared associated with fewer AEs. Trial registration European Union Drug Regulating Authorities Clinical Trials Database (EudraCT): 2018–001661-17; ClinicalTrials.gov: NCT03670810; registration date: September 12, 2018. Graphical Abstract

Abstract The increasing global demand for food, coupled with concerns about the environmental impact of synthetic fertilizers, underscores the urgency of developing sustainable agricultural practices. Nitrogen-fixing bacteria, known as diazotrophs, offer a potential solution by converting atmospheric nitrogen into bioavailable forms, reducing the reliance on synthetic fertilizers. However, a deeper understanding of their interactions with plants and other microbes is needed. In this study, we introduce a recently developed label-free 3D quantitative phase imaging technology called dynamic quantitative oblique back-illumination microscopy (DqOBM) to assess the functional dynamic activity of diazotrophs in vitro and in situ. Our experiments involved three different diazotrophs (Sinorhizobium meliloti, Azotobacter vinelandii, and Rahnella aquatilis) cultured on media with amendments of carbon and nitrogen sources. Over 5 days, we observed increased dynamics in nutrient-amended media. These results suggest that the observed bacterial dynamics correlate with their metabolic activity. Furthermore, we applied qOBM to visualize microbial dynamics within the root cap and elongation zone of Arabidopsis thaliana primary roots. This allowed us to identify distinct areas of microbial infiltration in plant roots without the need for fluorescent markers. Our findings demonstrate that DqOBM can effectively characterize microbial dynamics and provide insights into plant-microbe interactions in situ, offering a valuable tool for advancing our understanding of sustainable agriculture.

Objective: This study aimed to quantify public acceptability and anticipated uptake with risk stratification incorporated at three points on the bowel cancer screening pathway, compared with current screening in England. Methods: We conducted an online population-based survey of 1,203 UK adults in 2024. The main outcome measures were overall acceptability of three strategies where risk stratification is introduced at 1) the point of eligibility, 2) the referral threshold and 3) the screening interval, compared with the current programme (screening as usual), and the acceptability of high- and low-risk screening practices at each point. Other outcomes included anticipated uptake of screening and the acceptability of data collection methods. Results: Acceptability of risk-stratified eligibility and referral thresholds was significantly greater than for screening as usual (p

Diabetic retinopathy is a common yet severe complication of diabetes mellitus and is the leading cause of blindness in middle-aged adults. After years of poorly managed hyperglycemia, complications begin as non-proliferative diabetic retinopathy but can then progress into the proliferative stage marked by neovascularization of the retina. Multiple pathologic mechanisms caused by chronic hyperglycemia damage the retinal vasculature leading to pericyte drop out and the progression of the disease. This review outlines the major pathways of pathogenesis in diabetic retinopathy, highlighting the protective role pericytes play in preserving the blood-retinal barrier. Given the loss of this cell line is a defining feature of the disease, ways in which to prevent pericyte dropout within retinal vasculature is discussed, targeting various pathogenesis pathways of diabetic retinopathy.

Value-based healthcare payment models are an alternative insurance payment system that compensates healthcare providers based on their patients’ outcomes rather than the individual services healthcare workers provide. This shift from the current fee-for-service model that predominates our medical system has received renewed popularity and attention within organized medicine such as the American Medical Association. Advocates believe that this new payment model will address many of the unsolved issues in healthcare such as medical waste and unsustainable healthcare costs. In practice, however, this model is plagued with a myriad of unresolved issues of its own. In this commentary, we outline these issues and suggest that the intentions of those advocating for value-based payment models are either misguided or disingenuous. We then offer solutions that preserve our current fee-for-service model while making necessary changes that will benefit both physicians and patients nationwide.

Introduction Therapeutic exercise has an important role in the population living with cancer as it improves function and quality of life and reduces the symptoms of cancer treatment. There is little clinical evidence on the effects of hypopressive exercise in women with gynecological cancer. Objective Evaluate the effects of 4 weeks of hypopressive exercise associated with muscle strength training and aerobic exercises on fatigue, urinary incontinence symptoms, sexual function, and quality of life in women treated for gynecological cancer compared to a group that will perform conventional training. Methods This randomized, single-blinded clinical trial study is set in the Clinical Research Laboratory, Department of Kinesiotherapy, at a Chilean University. Patients will be randomly assigned to an experimental group of hypopressive exercises associated with muscle strength training and aerobic exercises or a control group of muscle strength training and aerobic exercises. Twelve tele-rehabilitation sessions will be performed. Women over 18 years of age with gynecologic cancer who have been prescribed radiotherapy or chemotherapy will participate. Fatigue, quality of life, urinary incontinence symptoms, and sexual function will be assessed before and after the intervention. Expected results The results of this clinical trial have important implications for specific treatment for the cancer population and generate new techniques in the practice of oncology-specialized kinesiologists. Hypopressive exercise is expected to reduce incontinence symptoms due to neuromuscular activation of the pelvic floor muscles. However, more studies are needed to confirm the beneficial effects of hypopressive exercises in face-to-face or remote rehabilitation.

Introduction Poor communication about serious injury in older adults can lead to treatment that is inconsistent with patient preferences, create conflict and strain healthcare resources. We developed a communication intervention called Best Case/Worst Case-intensive care unit (ICU) that uses daily scenario planning, that is, a narrative description of plausible futures, to support prognostication and facilitate dialogue among patients, their families and the trauma ICU team. This article describes a protocol for a multisite, randomised, stepped-wedge study to test the effectiveness of the intervention on the quality of communication (QOC) in the ICU.Methods and analysis We will follow all patients aged 50 and older admitted to the trauma ICU for 3 or more days after a serious injury at eight high-volume level 1 trauma centres. We aim to survey one family or ‘like family’ member per eligible patient 5–7 days following their loved ones’ admission and clinicians providing care in the trauma ICU. Using a stepped-wedge design, we will use permuted block randomisation to assign the timing for each site to begin implementation of the intervention and routine use of the Best Case/Worst Case-ICU tool. We will use a linear mixed-effects model to test the effect of the tool on family-reported QOC (using the QOC scale) as compared with usual care. Secondary outcomes include the effect of the tool on reducing clinician moral distress (using the Measure of Moral Distress for Healthcare Professionals scale) and patients’ length of stay in the ICU.Ethics and dissemination Institutional review board (IRB) approval was granted at the University of Wisconsin, and all study sites ceded review to the primary IRB. We plan to report results in peer-reviewed publications and national meetings.Trial registration number NCT05780918.

Objectives To understand how health, education and social care services for disabled children changed during the COVID-19 pandemic, what did or did not work well and what the impacts of service changes were on both professionals and families.Design Qualitative study using semistructured interviews.Setting Telephone and video call interviews and focus groups with professionals working in one of five local authority areas in England.Participants 78 health, education and social care professionals working with children in one of five local authority areas in England.Results There was a significant disruption to services and reduced contact with families during the early stages of the pandemic; nevertheless, professionals were able to reflect on innovative ways they interacted with and sought to support and maintain health, education and social care provision to disabled children and their families. As waitlists have substantially increased, this and the longevity of the pandemic were perceived to have had negative consequences for staff health and well-being, the health and psychosocial outcomes of children and young people, and their parent carers.Conclusions Key learning from this study for service recovery and planning for future emergencies is the need to be able to identify disabled children, classify their level of need and risk, assess the impact of loss of services and maintain clear communication across services to meet the needs of disabled children. Finally, services need to work collaboratively with families to develop child-centred care to strengthen resilience during service disruption.

IntroductionResearch involvement of people with lived experiences is increasing. Few tools are designed to evaluate their engagement in research. The Patient Engagement In Research Scale (PEIRS) is one of the few validated tools. Our team employed the PEIRS with patient and family partners with lived experiences of dementia every 6 months in a two-year telepresence robot project. This reflection paper reports our self-study on key learnings and proposes practical tips on using the PEIRS to evaluate patient and family partners' engagement in dementia research. It is the first to document a case using the PEIRS multiple times in a dementia research project.MethodsGuided by Rolfe et al.'s reflective model, we conducted three team reflective sessions to examine the team's experiences using the PEIRS to improve and evaluate patient and family partners' engagement in the research. We also reviewed our meeting notes and fieldnotes documented in the research journal. A reflexive thematic analysis was performed.ResultsThe team identified three key learnings: the values of using the PEIRS survey, the adaptations, and the factors influencing its implementation as an evaluation tool. Using the PEIRS provided significant benefits to the project, although some patient and family partners felt it was burdensome. The evaluation tool was enhanced with emojis and comment boxes based on suggestions from patient partners. The emojis introduced an element of fun, while the comment boxes allowed for personalized responses. Several factors influenced the PEIRS tool's effectiveness: the interviewer's identity, the confidentiality of responses and follow-ups, the timing and frequency of using the tool, and the presentation of the evaluations. These learnings led to the development of six practical tips,—“ENGAGE”: Enjoyable and fun process, Never impose, Get prepared early, Adapt to the team's needs, Give people options, and Engage and reflect.ConclusionWith the emerging trend of including people with lived experiences in dementia research, there is a need for ongoing assessment of engagement from both patient and family partners and the research team strategies. Future research can further explore survey logistics, co-development of evaluation tools, and the use of tools with people living with dementia.

Objectives Workplace stigmatisation and discrimination are significant barriers to accessing employment opportunities, reintegration and promotion in the workforce for people with mental illnesses in comparison to other disabilities. This paper presents qualitative evidence of anticipated and experienced workplace stigma and discrimination among individuals with major depressive disorder (MDD) in 35 countries, and how these experiences differ across countries based on their Human Development Index (HDI) level.Design Mixed-method cross-sectional survey.Participants, setting and measures The qualitative data were gathered as part of the combined European Union Anti-Stigma Programme European Network and global International Study of Discrimination and Stigma Outcomes for Depression studies examining stigma and discrimination among individuals with MDD across 35 countries. Anticipated and experienced stigma and discrimination were assessed using the Discrimination and Stigma Scale version 12 (DISC-12). This study used responses to the open-ended DISC-12 questions related to employment. Data were analysed using the framework analysis method.Results The framework analysis of qualitative data of 141 participants identified 6 key ‘frames’ exploring (1) participants reported experiences of workplace stigma and discrimination; (2) impact of experienced workplace stigma and discrimination; (3) anticipated workplace stigma and discrimination; (4) ways of coping; (5) positive work experiences and (6) contextualisation of workplace stigma and discrimination. In general, participants from very high HDI countries reported higher levels of anticipated and experienced discrimination than other HDI groups (eg, less understanding and support, being more avoided/shunned, stopping themselves from looking for work because of expectation and fear of discrimination). Furthermore, participants from medium/low HDI countries were more likely to report positive workplace experiences.Conclusions This study makes a significant contribution towards workplace stigma and discrimination among individuals with MDD, still an under-researched mental health diagnosis. These findings illuminate important relationships that may exist between countries/contexts and stigma and discrimination, identifying that individuals from very high HDI countries were more likely to report anticipated and experienced workplace discrimination.

Abstract In this literature overview, we share with the reader challenges faced by LGBTQ + individuals pursuing medical education, from undergraduate to postgraduate training. The LGBTQ + acronym has evolved to encompass the diverse spectrum of sexual orientation and gender identities. Recently, the term “Sexual and Gender Minority” (SGM) has emerged as an umbrella term to provide consistency in research advancing SGM health. The unique obstacles LGBTQ + trainees encounter are highlighted throughout this article, including external factors influencing career decisions, a lack of LGBTQ + healthcare curricula, discriminatory social interactions, limited mentorship opportunities, and a higher mental health burden. These challenges have the capacity to affect educational experiences, personal well-being, and professional growth. Additionally, we examine the impact of inclusive institutional climates on LGBTQ + trainees’ selection of medical schools and residency programs, as they may prioritize inclusiveness and diversity when making their choice. In postgraduate training, LGBTQ + trainees continue to face challenges, exemplified by disparities in placement rates and discriminatory experiences based on sexual orientation and gender identity. We describe the gap in current research and its long-term impact of these challenges on career paths. Hostile environments persist in certain specialties, and the lack of LGBTQ + mentorship and support can hinder academic pursuits. We shed light on the unique and pervasive challenges faced by LGBTQ + trainees throughout their medical education journey, while emphasizing the need for inclusive policies, support systems, and research to address these challenges. With increasing research and studies, we hope to create a medical workforce and community that better represents the diverse communities it serves.

Abstract Background Growing demand for student-centered learning (SCL) has been observed in higher education settings including dentistry. However, application of SCL in dental education is limited. Hence, this study aimed to facilitate SCL application in dentistry utilising a decision tree machine learning (ML) technique to map dental students’ preferred learning styles (LS) with suitable instructional strategies (IS) as a promising approach to develop an IS recommender tool for dental students. Methods A total of 255 dental students in Universiti Malaya completed the modified Index of Learning Styles (m-ILS) questionnaire containing 44 items which classified them into their respective LS. The collected data, referred to as dataset, was used in a decision tree supervised learning to automate the mapping of students' learning styles with the most suitable IS. The accuracy of the ML-empowered IS recommender tool was then evaluated. Results The application of a decision tree model in the automation process of the mapping between LS (input) and IS (target output) was able to instantly generate the list of suitable instructional strategies for each dental student. The IS recommender tool demonstrated perfect precision and recall for overall model accuracy, suggesting a good sensitivity and specificity in mapping LS with IS. Conclusion The decision tree ML empowered IS recommender tool was proven to be accurate at matching dental students’ learning styles with the relevant instructional strategies. This tool provides a workable path to planning student-centered lessons or modules that potentially will enhance the learning experience of the students.

AbstractBackground: At the start of the pandemic, relaxation of buprenorphine prescribing regulations created an opportunity to create new models of medications for opioid use disorder (MOUD) delivery and care. To expand and improve access to MOUD, we adapted and implemented the Tele-Harm Reduction (THR) intervention; a multicomponent, telehealth-based and peer-driven intervention to promote HIV viral suppression among people who inject drugs (PWID) accessing a syringe services program (SSP). This study examined buprenorphine initiation and retention among PWID with opioid use disorder who received the adapted THR intervention at the IDEA Miami SSP.Methods: A retrospective chart review of participants who received the THR intervention for MOUD was performed to examine the impact of telehealth on buprenorphine retention. Our primary outcome was three-month retention, defined as three consecutive months of buprenorphine dispensed from the pharmacy.Results: A total of 109 participants received the adapted THR intervention. Three-month retention rate on buprenorphine was 58.7%. Seeing a provider via telehealth at baseline or any follow up visit (aOR = 7.53, 95% CI: [2.36, 23.98]) and participants who had received an escalating dose of buprenorphine after baseline visit (aOR = 8.09, 95% CI: [1.83, 35.87]) had a higher adjusted odds of retention at three months. Participants who self-reported or tested positive for a stimulant (methamphetamine, amphetamine, or cocaine) at baseline had a lower adjusted odds of retention on buprenorphine at three months (aOR = 0.29, 95% CI: [0.09, 0.93]).Conclusions: Harm reduction settings can adapt dynamically to the needs of PWID in provision of critical lifesaving buprenorphine in a truly destigmatising approach. Our pilot suggests that an SSP may be an acceptable and feasible venue for delivery of THR to increase uptake of buprenorphine by PWID and promote retention in care.KEY MESSAGESThe Tele-Harm Reduction intervention can be adapted for initiating and retaining people who inject drugs with opioid use disorder on buprenorphine within a syringe services program settingUsing telehealth was associated with increased three-month buprenorphine retentionBaseline stimulant use was negatively associated with three-month buprenorphine retention

The integration of artificial intelligence (AI) in clinical medicine marks a revolutionary shift, enhancing diagnostic accuracy, therapeutic efficacy, and overall healthcare delivery. This review explores the current uses, benefits, limitations, and future applications of AI in infectious diseases, highlighting its specific applications in diagnostics, clinical decision making, and personalized medicine. The transformative potential of AI in infectious diseases is emphasized, addressing gaps in rapid and accurate disease diagnosis, surveillance, outbreak detection and management, and treatment optimization. Despite these advancements, significant limitations and challenges exist, including data privacy concerns, potential biases, and ethical dilemmas. The article underscores the need for stringent regulatory frameworks and inclusive databases to ensure equitable, ethical, and effective AI utilization in the field of clinical and laboratory infectious diseases.

In the Firmicutes phylum, GpsB is a membrane associated protein that coordinates peptidoglycan synthesis with cell growth and division. Although GpsB has been studied in several bacteria, the structure, function, and interactome of Staphylococcus aureus GpsB is largely uncharacterized. To address this knowledge gap, we solved the crystal structure of the N-terminal domain of S. aureus GpsB, which adopts an atypical, asymmetric dimer, and demonstrates major conformational flexibility that can be mapped to a hinge region formed by a three-residue insertion exclusive to Staphylococci. When this three-residue insertion is excised, its thermal stability increases, and the mutant no longer produces a previously reported lethal phenotype when overexpressed in Bacillus subtilis. In S. aureus, we show that these hinge mutants are less functional and speculate that the conformational flexibility imparted by the hinge region may serve as a dynamic switch to fine-tune the function of the GpsB complex and/or to promote interaction with its various partners. Furthermore, we provide the first biochemical, biophysical, and crystallographic evidence that the N-terminal domain of GpsB binds not only PBP4, but also FtsZ, through a conserved recognition motif located on their C-termini, thus coupling peptidoglycan synthesis to cell division. Taken together, the unique structure of S. aureus GpsB and its direct interaction with FtsZ/PBP4 provide deeper insight into the central role of GpsB in S. aureus cell division.

Purpose: Current guidelines recommend debriefing following medical resuscitations to improve patient outcomes. The goal of this study was to describe national trends in postresuscitation debriefing practices among pediatric critical care medicine (PCCM) fellows to identify potential gaps in fellow education. Methods: A 13-item survey was distributed to fellows in all 76 ACGME-accredited PCCM programs in the United States in the spring of 2021. The online survey addressed frequency and timing of debriefings following medical resuscitations, whether formal training is provided, which medical professionals are present, and providers’ comfort level leading a debriefing. Results were analyzed using descriptive statistics. Results: A total of 102 responses (out of a possible N of 536) were gathered from current PCCM fellows. All fellows (100%) reported participation in a medical resuscitation. Only 21% stated that debriefings occurred after every resuscitation event, and 44% did not follow a structured protocol for debriefing. While 66% reported feeling very or somewhat comfortable leading the debriefing, 19% felt either somewhat uncomfortable or very uncomfortable. A vast majority (92%) of participating fellows believed that debriefing would be helpful in improving team member performance during future resuscitations, and 92% expressed interest in learning more about debriefing. Conclusions: The majority of PCCM fellows do not receive formal training on how to lead a debriefing. Given that 74% of fellows in our study did not feel very comfortable leading a debriefing but almost universally expressed that this practice is useful for provider well-being and performance, there is a clear need for increased incorporation of debriefing training into PCCM curricula across the United States.

Abstract Background Severe forms of depression have been linked to hyperactivity of the subcallosal cingulate cortex. The ability to stimulate the subcallosal cingulate cortex or associated circuits noninvasively and directly would maximize the number of patients who could receive treatment. To this end, we have developed an ultrasound-based device for effective noninvasive modulation of deep brain circuits. Here we describe an application of this tool to an individual with treatment-resistant depression. Case presentation A 30-year-old Caucasian woman with severe treatment-resistant non-psychotic depression was recruited into a clinical study approved by the Institutional Review Board of the University of Utah. The patient had a history of electroconvulsive therapy with full remission but without sustained benefit. Magnetic resonance imaging was used to coregister the ultrasound device to the subject’s brain anatomy and to evaluate neural responses to stimulation. Brief, 30-millisecond pulses of low-intensity ultrasound delivered into the subcallosal cingulate cortex target every 4 seconds caused a robust decrease in functional magnetic resonance imaging blood-oxygen-level-dependent activity within the target. Following repeated stimulation of three anterior cingulate targets, the patient’s depressive symptoms resolved within 24 hours of the stimulation. The patient remained in remission for at least 44 days afterwards. Conclusions This case illustrates the potential for ultrasonic neuromodulation to precisely engage deep neural circuits and to trigger a durable therapeutic reset of those circuits. Trial registration ClinicalTrials.gov, NCT05301036. Registered 29 March 2022, https://clinicaltrials.gov/ct2/show/NCT05301036

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition associated primarily with PKD1 and PKD2 genes. However, ADPKD patients in Latin America have had limited access to comprehensive care. The ProPKD score predicts the likelihood of kidney failure before the age of 60. This study aimed to describe the clinical and genetic characteristics of Chilean ADPKD patients and assess the ProPKD score. Methods We enrolled 40 ADPKD probands and 122 relatives from different centers. Genetic analysis of PKD1 and PKD2 genes was performed by combining direct and next-generation sequencing. Pathogenicity was determined using bioinformatic tools. ProPKD scores were calculated based on clinical and genetic data. Results ADPKD probands were diagnosed at a median age of 35 years. Pathogenic, likely pathogenic, or uncertain significance variants were identified in 38/40 pedigrees, with 89% involving PKD1 and 11% involving PKD2 variants. Among the identified variants, 62% were novel. Patients with PKD1 truncating variants had a more severe disease course, reaching kidney failure by a median age of 48.5 years. ProPKD scores were assessed in 72 individuals, stratifying them into high-, intermediate-, or low-risk categories and the median ages for kidney failure were 45, 49, and 52 years, respectively (log-rank p = 0.001). Conclusion This study provides valuable insights into the clinical and genetic profiles of ADPKD patients in Chile. ADPKD poses a significant public health concern, warranting improvements in diagnosis and treatment. The use of the ProPKD score to predict disease progression should be further explored to enhance patient care and management.

Objective. To report the progress in Peru, since June 2019, in the implementation of the World Health Organization Global Initiative for Childhood Cancer using the CureAll framework, which can be replicated in low- and middle-income countries. Methods. A mixed method was used of participatory and documentary evaluation. The participatory evaluation included stakeholders from various government institutions, nonprofit organizations, and international partners. The documentary aspect consisted of a review of data on the regulatory environment, national projects, and interventions implemented. The Ministry of Health engaged more than 150 participants to form working committees, which have developed policy and regulatory documents to strengthen care services. Results. Achievements include a decrease in the national treatment abandonment rate from 18.6% to 8.5%, the approval of the Childhood Cancer Law, improvements in the management of patients with febrile neutropenia, and a reduction in rates of events of clinical deterioration and mortality of hospitalized patients. The Cure All implementation framework allows local teams to implement specific strategies and monitor early outcomes in pediatric oncology. Conclusions. The results obtained reflect the teamwork, the leadership of the authorities, the technical support of professionals, and the support of involved organizations. Further actions will be needed to guarantee sustainability, and monitoring tools are needed to assure success in the planned activities.

Background: Acute appendicitis (AA) is the most common abdominal surgical emergency in children and adolescents. In the year immediately following the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO), there was a precipitous decline in emergency department (ED) visits especially for surgical conditions and infectious diseases. Fear of exposure to severe acute respiratory coronavirus 2 infection resulted in delay in presentation and time to surgery, and a shift toward more conservative management. Objective: Our goal was to compare the incidence and severity of AA before and during the COVID-19 pandemic. Methods: Patients aged 2–18 years admitted with the diagnosis of AA to Flushing Hospital Medical Center or Jamaica Hospital Medical Center in Queens, New York, were selected for chart review. Data extracted from electronic health records included demographics, clinical findings, imaging studies, and operative and pathological findings. We calculated the Alvarado score (AS) for incidence and the American Association for the Surgery of Trauma (AAST) grade for severity. We compared patients admitted between March 1, 2018–February 29, 2020 (pre-pandemic) to patients admitted between March 1, 2020–February 28, 2021 (pandemic). We then compared pre-pandemic and pandemic groups to determine differences in pediatric AA incidence and severity. Results: Of 239 patients diagnosed with AA, 184 (77%) were in the pre-pandemic group and 55 (23%) in the pandemic group. Incidence (number per year) of AA declined by 40%. The pandemic group had significantly greater overall AS of ≥7, indicating increased likelihood to require surgery, (P = 0.04) and higher AAST grade demonstrating increased severity (P = 0.02). Conclusion: There was a decline in the number of AA cases seen in our pediatric EDs and admitted during the first year of the pandemic. Clinicians need to be aware of increased severity of AA at time of presentation during public health emergencies such as a pandemic, possibly due to modified patient behavior.

Abstract Cancer is a significant healthcare issue, and early screening methods based on biomarker analysis in liquid biopsies are promising avenues to reduce mortality rates. Electrical detection of nucleic acids at the single molecule level could enable these applications. We examine the electrical detection of RNA cancer biomarkers (KRAS mutants G12C and G12V) as a single-molecule proof-of-concept electrical biosensor for cancer screening applications. We show that the electrical conductance is highly sensitive to the sequence, allowing discrimination of the mutants from a wild-type KRAS sequence differing in just one base. In addition to this high specificity, our results also show that these biosensors are sensitive down to an individual molecule with a high signal-to-noise ratio. These results pave the way for future miniaturized single-molecule electrical biosensors that could be groundbreaking for cancer screening and other applications.

Background: Optic atrophy is a clinical presentation in which the optic disc appears pale due to irreversible damage of retinal ganglion cells and axons in the anterior visual pathway. Aims and Objectives: The aim of this study was to determine the profile of optic atrophy cases in the neuro-ophthalmology department of a tertiary eye hospital and to identify the common causes and associated visual impairments. Materials and Methods: This was a cross-sectional study conducted from January 2021 to December 2021, using convenience sampling method for data collection. Demographic data, medical history, and examinations were conducted on all included patients. Optic atrophy secondary to glaucomatous optic nerve damage was excluded. This study included both children and adults with both congenital and acquired patients with optic atrophy. Best-corrected visual acuity (BCVA) was recorded and anterior segment examinations were conducted using a torchlight to assess pupillary reaction and slit lamp to assess other anterior segment details. The posterior segment was evaluated on a dilated pupil with a handheld magnifying 90D lens and a slit lamp. Color vision and contrast sensitivity and visual field assessments were performed whenever possible. Results: Out of 127 patients enrolled, 55.1% were male and 44.9% were female. The median age was 40, with a minimum age of 4 years to a maximum of 85 years old. Twenty-one percent were below 20 years old and they were associated with congenital causes, hydrocephalus and sequelae to bilateral papillitis. The most common age group was 40–50 years, comprising 21.3%. The total of eyes presented with optic atrophy was 214. Unilateral involvement of the eye was 31.5%, the patients with the right eye in 18.9% and the left eye in 12.6%. Both eye optic atrophies were found in 68.5%. The most common cause of optic atrophy was non-arteritic anterior ischemic optic neuropathy (NAION) in 22.8% of cases, the second common cause was papilledema in 16.5%, and then, traumatic optic neuropathy comprised 15.7% of patients. BCVA in the right eye was

Abstract Background Immune checkpoint inhibitor therapy has revolutionized the clinical management of a diverse range of cancer types, including advanced cutaneous melanoma. While immunotherapy targeting the PD-1/PD-L1 system has become standard of care, overall response rates remain unsatisfactory for most patients and there are no approved small molecule inhibitors of the PD-1/PD-L1 system. Flubendazole (FLU) is an anthelmintic that has been used to treat worm infections in humans and animals for decades. Methods Here we tested the anti-cancer activity of systemically delivered FLU with suppression of PD-1 in immunocompetent mice. Results In C57BL/6J mice bearing subcutaneous B16F10 melanoma, FLU reduced both tumor growth and PD-1 protein levels without affecting levels of PD-L1. FLU’s suppression of PD-1 was accompanied by increased CD3+ T cell infiltration. Western blotting with extracts from human Jurkat T cells showed that FLU inhibited PD-1 protein expression, findings confirmed by flow cytometry. To gain mechanistic insights on FLU’s ability to suppress PD-1 protein levels, we performed bulk RNA sequencing on extracts of Jurkat T cells exposed to the benzimidazole for 4 h. From a pool of 14,475 genes there were 1218 differentially-expressed genes; 687 with increased expression and 531 with decreased expression. Among the genes induced by FLU was the AP-1 family member, JUN and surprisingly, pdcd1. KEGG pathway analysis showed FLU up-regulated genes over-represented in multiple pathways (p

Abstract Background Systematic reviews summarize and evaluate relevant studies to contribute to evidence-based practice. Internationally, researchers have reached a consensus that the active involvement of the public leads to better research. Despite this agreement, there are many reviews of research concerning healthcare interventions intended to promote the care of people living with dementia and those from their social network (e.g., close contacts, both family and non-family members) primarily involve only healthcare professionals and other experts. Due to the lack of a dementia-sensitive framework to actively involve people living with dementia and those from their social network, and healthcare professionals as co-researchers in systematic reviews, it is important to develop a framework to inform practice. Methods For this framework development process, we will recruit four people living with dementia and a total of four people from their social network, and three healthcare professionals working in acute or long-term care settings. We will conduct regular meetings with these groups of the public and healthcare professionals to include them in all stages of the systematic review. We will also identify and develop methods necessary to ensure meaningful involvement. The results will be documented and analyzed for the development of a framework. For the planning and preparation for these meetings, as well as the conduct of the meetings themselves, we will be guided by the principles of the INVOLVE approach. In addition, the ACTIVE framework will be used to guide the degree of involvement and the stage in the review process. Discussion We assume that our transparent approach to the development of a framework to support the active involvement of people living with dementia and those from their social network, and healthcare professionals in systematic reviews will serve as an impetus for and provide guidance to other researchers with the goal of increasing researchers’ focus on this topic and facilitating systematic reviews that apply participatory approaches. Trial registration: Trial registration is unnecessary as no intervention study will be conducted.

Abstract Connectivity studies have significantly extended the knowledge on motor network alterations after stroke. Compared to interhemispheric or ipsilesional networks, changes in the contralesional hemisphere are poorly understood. Data obtained in the acute stage after stroke and in severely impaired patients are remarkably limited. This exploratory, preliminary study aimed to investigate early functional connectivity changes of the contralesional parieto-frontal motor network and their relevance for the functional outcome after severe motor stroke. Resting-state functional imaging data were acquired in 19 patients within the first 2 weeks after severe stroke. Nineteen healthy participants served as a control group. Functional connectivity was calculated from five key motor areas of the parieto-frontal network on the contralesional hemisphere as seed regions and compared between the groups. Connections exhibiting stroke-related alterations were correlated with clinical follow-up data obtained after 3–6 months. The main finding was an increase in coupling strength between the contralesional supplementary motor area and the sensorimotor cortex. This increase was linked to persistent clinical deficits at follow-up. Thus, an upregulation in contralesional motor network connectivity might be an early pattern in severely impaired stroke patients. It might carry relevant information regarding the outcome which adds to the current concepts of brain network alterations and recovery processes after severe stroke.

Abstract Background In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. Methods Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. Results Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. Conclusion Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.

Abstract Background Personalised medicine (PM) has been fostered by technological and medical advances, but all stakeholders, including healthcare professionals, citizens and policy makers, should achieve adequate health literacy to promote PM implementation. The “Integrating China in the International Consortium for Personalised Medicine” (IC2PerMed) project, funded by the International Consortium for Personalised Medicine, focuses on this issue by highlighting the need to educate healthcare professionals and empower citizens. Within the aforementioned project, building on a mapping of European and Chinese policies in PM, experts in the field of PM participated in an online workshop and a following two-round Delphi survey, in order to identify the priority areas of intervention for healthcare professionals’ education and curricula, engagement and empowerment of citizens and patients. Results Nine experts completed the survey and reached a consensus on seventeen priorities: seven were related to health professionals’ education and curricula, whereas ten on citizen and patients’ awareness and empowerment. Conclusion These priorities emphasized the importance of education and health literacy, multidisciplinary and international collaboration, public trust, and consideration of ethical, legal, and social issues. The present experience highlights the relevance of the involvement of stakeholders in informing decision-makers, developing appropriate national plans, strategies, and policies, and ensuring the adequate implementation of PM in health systems.

Abstract Coffee wilt disease, caused by the fungus Fusarium xylarioides, is a vascular wilt disease that has affected coffee production in sub-Saharan Africa over the past century. Today, the disease has two host-specific populations specialising on arabica and robusta coffee crops, which grow at high and low altitude, respectively. Here we test whether adaptation to different temperatures contributes to specialisation of the fungi on each crop. Firstly, climate models show that the severity of the arabica and robusta populations of coffee wilt disease correlates with temperature. The robusta population shows higher peak severity than the arabica population overall, but the latter has greater cold tolerance. Secondly, growth assays of thermal performance of fungal strains in vitro show that, while robusta strains grow faster than arabicas at intermediate temperatures, the arabica strains have higher sporulation and spore germination rates at temperatures below 15ºC. The match between environmental patterns of severity in nature with thermal performance of fungal cultures in the laboratory supports a role for temperature adaptation in specialisation on arabica and robusta coffee. Extrapolating our temperature-models to future climate change predicts that disease severity could decline on average due to increased temperature but could increase in some coffee-growing regions.

Abstract Aims Chronic migraine (CM) is a common neurological disorder with complex pathogenesis. Evidence suggests that pituitary adenylate cyclase-activating peptide (PACAP) induces migraine-like attacks and may be potential a new target for migraine treatment, but the therapeutic results of targeting PACAP and its receptors are not uniform. Therefore, the aim of this study was to investigate the regulatory effect of PACAP type I receptor (PAC1R) antagonist, PACAP6-38, on nitroglycerin (NTG)-induced central sensitization in a CM model. Methods Sprague–Dawley (SD) rats received repeated injections of NTG to construct a CM model. Mechanical and thermal thresholds were measured using Von Frey filaments and hot plate tests. C-Fos expression was measured by western blotting and immunofluorescence staining to assess the central sensitization. PACAP6-38 was intracerebrally injected into the trigeminal nucleus caudalis (TNC), and then the changes in c-Fos, the synaptic-associated proteins, phospho-ERK1/2 (p-ERK1/2), phosphorylation of cyclic adenosine monophosphate response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were detected. Transmission electron microscopy (TEM) and Golgi-Cox staining were used to observe the ultrastructure of synapses and dendritic structures of TNC neurons. Results The results showed that PACAP and PAC1R expression were significantly raised in the TNC after repeated NTG injections. Additionally, PACAP6-38 treatment alleviated nociceptive sensitization, inhibited NTG-induced overexpression of c-Fos and synaptic-associated proteins in the TNC of CM rat, restored aberrant synaptic structures. Furthermore, the expression of ERK/CREB/BDNF pathway was depressed by PACAP6-38. Conclusions Our results demonstrated that abnormal synaptic structure in the TNC of CM, which could be reversed by inhibition of PAC1R via down-regulating the ERK/CREB/BDNF signaling pathway. PACAP6-38 improves NTG-induced central sensitization by regulating synaptic plasticity in the TNC of CM rat, which may provide new insights into the treatments targeting PACAP/PAC1R in migraine.

PurposeTo describe and explore variation in 'pandemic-related circumstances' among suicide decedents during the first year of the COVID-19 pandemic.MethodsWe identified pandemic-related circumstances using decedents' text narratives in the 2020 National Violent Death Reporting System. We use time-series analysis to compare other psychosocial characteristics (e.g., mental health history, interpersonal difficulties, financial strain) of decedents pre-pandemic (2017/2018: n = 56,968 suicide and n = 7,551 undetermined deaths) to those in 2020 (n = 31,887 suicide and n = 4,100 undetermined). We characterize common themes in the narratives with pandemic-related circumstances using topic modeling, and explore variation in topics by age and other psychosocial circumstances.ResultsIn 2020, n = 2,502 (6.98%) narratives described pandemic-related circumstances. Compared to other deaths in 2020 and to the pre-pandemic period, decedents with pandemic-related circumstances were older and more highly educated. Common themes of pandemic-related circumstances narratives included: concerns about shutdown restrictions, financial losses, and infection risk. Relative to decedents of the same age that did not have pandemic-related circumstances in 2020, those with pandemic-related circumstances were more likely to also have financial (e.g., for 25-44 years, 43% vs. 12%) and mental health (76% vs. 66%) psychosocial circumstances, but had similar or lower prevalence of substance abuse (47% vs. 49%) and interpersonal (40% vs. 42%) circumstances.ConclusionsWhile descriptive, these findings help contextualize suicide mortality during the acute phase of the COVID-19 pandemic and can inform mental health promotion efforts during similar public health emergencies.