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BACKGROUND: The COVID-19 pandemic has caused over 68.7 million infections and 1.35 million deaths in South America. There are limited data on SARS-CoV-2 seropositivity and its determinants from Andean countries prior to mass vaccinations against COVID-19. OBJECTIVE: To estimate SARS-CoV-2 seropositivity and its determinants before vaccination in occupational groups of adults presumed to have different levels of exposure and associations with potential symptomatology. METHODS: We measured seropositivity of anti-SARS-CoV-2 IgG antibodies in a cross-sectional study of vaccine-naïve adults aged 18 years and older, recruited within three occupational risk groups (defined as low [LR], moderate [MR], and high [HR]) between January and September 2021 in two Andean cities in Ecuador. Associations with risk factors were estimated using logistic regression. RESULTS: In a sample of 882 adults, IgG seropositivity for the three different occupational risk groups was 39.9% (CI 95% 35.3-44.6), 74.6% (CI 95% 66.4-81.4), and 39.0% (CI 95% 34.0-44.4) for the HR, MR, and LR groups, respectively. History of an illness with loss of taste and/or smell was significantly associated with seropositivity in all occupational groups, with adjusted ORs of 14.31 (95%CI, 5.83-35.12; p

The rapid advances in Generative AI tools have produced both excitement and worry about how AI will impact academic writing. However, little is known about what norms are emerging around AI use in manuscript preparation or how these norms might be enforced. We address both gaps in the literature by conducting a survey of 271 academics about whether it is necessary to report ChatGPT use in manuscript preparation and by running GPT-modified abstracts from 2,716 published papers through a leading AI detection software to see if these detectors can detect different AI uses in manuscript preparation. We find that most academics do not think that using ChatGPT to fix grammar needs to be reported, but detection software did not always draw this distinction, as abstracts for which GPT was used to fix grammar were often flagged as having a high chance of being written by AI. We also find disagreements among academics on whether more substantial use of ChatGPT to rewrite text needs to be reported, and these differences were related to perceptions of ethics, academic role, and English language background. Finally, we found little difference in their perceptions about reporting ChatGPT and research assistant help, but significant differences in reporting perceptions between these sources of assistance and paid proofreading and other AI assistant tools (Grammarly and Word). Our results suggest that there might be challenges in getting authors to report AI use in manuscript preparation because (i) there is not uniform agreement about what uses of AI should be reported and (ii) journals might have trouble enforcing nuanced reporting requirements using AI detection tools.

Small extracellular vesicles (sEVs) are cell-released vesicles ranging from 30-150nm in size. They have garnered increasing attention because of their potential for both the diagnosis and treatment of disease. The diversity of sEVs derives from their biological composition and cargo content. Currently, the isolation of sEV subpopulations is primarily based on bio-physical and affinity-based approaches. Since a standardized definition for sEV subpopulations is yet to be fully established, it is important to further investigate the correlation between the biomolecular composition of sEVs and their physical properties. In this study, we employed a platform combining single-vesicle surface-enhanced Raman spectroscopy (SERS) and machine learning to examine individual sEVs isolated by size-exclusion chromatography (SEC). The biomolecular composition of each vesicle examined was reflected by its corresponding SERS spectral features (biomolecular "fingerprints"), with their roots in the composition of their collective Raman-active bonds. Origins of the SERS spectral features were validated through a comparative analysis between SERS and mass spectrometry (MS). SERS fingerprinting of individual vesicles was effective in overcoming the challenges posed by EV population averaging, allowing for the possibility of analyzing the variations in biomolecular composition between the vesicles of similar and/or different sizes. Using this approach, we uncovered that each of the size-based fractions of sEVs contained particles with predominantly similar SERS spectral features. Indeed, more than 84% of the vesicles residing within a particular group were clearly distinguishable from that of the other EV sub-populations, despite some spectral variations within each sub-population. Our results suggest the possibility that size-based EV fractionation methods produce samples where similarly eluted sEVs are correlated with their respective biochemical contents, as reflected by their SERS spectra. Our findings therefore highlight the possibility that the biogenesis and respective biological functionalities of the various sEV fractions may be inherently different.

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.

Over the last 30 years, there has been a growing trend in clinical trials towards assessing novel interventions not only against the benchmark of statistical significance, but also with respect to whether they lead to clinically meaningful changes for patients. In the context of Disorders of Consciousness (DOC), despite a growing landscape of experimental interventions, there is no agreed standard as to what counts as a minimal clinically important difference (MCID). In part, this issue springs from the fact that, by definition, DOC patients are either unresponsive (i.e., in a Vegetative State; VS) or non-communicative (i.e., in a Minimally Conscious State; MCS), which renders it impossible to assess any subjective perception of benefit, one of the two core aspects of MCIDs. Here, we develop a novel approach that leverages published, international diagnostic guidelines to establish a probability-based minimal clinically important difference (pMCID), and we apply it to the most validated and frequently used scale in DOC: the Coma Recovery Scale-Revised (CRS-R). This novel method is objective (i.e., based on published criteria for patient diagnosis) and easy to recalculate as the field refines its agreed-upon criteria for diagnosis. We believe this new approach can help clinicians determine whether observed changes in patients behavior are clinically important, even when patients cannot communicate their experiences, and can align the landscape of clinical trials in DOC with the practices in other medical fields.

The container shipping line Maersk undertook a Radical Retrofit to improve the energy efficiency of twelve sister container ships. Noise reduction, identified as a potential added benefit of the retrofitting effort, was investigated in this study. A passive acoustic recording dataset from the Santa Barbara Channel off Southern California was used to compile over 100 opportunistic vessel transits of the twelve G-Class container ships, pre- and post-retrofit. Post-retrofit, the G-Class vessels' capacity was increased from ~9,000 twenty-foot equivalent units (TEUs) to ~11,000 TEUs, which required a draft increase of the vessel by 1.5 m on average. The increased vessel draft resulted in higher radiated noise levels (5 dB) than the pre-retrofit ships in the low-frequency band and the reduction was greatest at low speed. Although multiple design changes occurred during retrofitting, the reduction in the low-frequency band most likely results from a reduction in cavitation due to changes in propeller and bow design.

BackgroundTuberculosis remains a significant global health concern, especially for People Living with HIV, who are at an increased risk of severe TB disease. Despite the availability of TB Preventive Treatment, knowledge gaps persist among People Living with HIV regarding its importance, accessibility, and administration. The study aimed to assess TPT knowledge levels and determinants among People Living with HIV in Tanzania.MethodsA cross-sectional survey was conducted from April to May 2023 in 12 regions of mainland Tanzania. The study included PLHIV aged 18 years and above, receiving HIV care in selected Care and Treatment Centers. Data were collected through face-to-face interviews using a semi-structured questionnaire covering sociodemographic characteristics and Tuberculosis preventive treatment knowledge. Descriptive statistics, chi-square tests, and logistic regression analyses were employed for data analysis.ResultsOut of the 391 People Living with HIV interviewed, 71.4% demonstrated adequate Tuberculosis preventive treatment knowledge. Female participants, those attending urban health facilities, and individuals with longer durations of HIV care exhibited higher Tuberculosis preventive treatment knowledge levels. However, knowledge disparities persisted based on demographic characteristics such as gender and location of health facilities.ConclusionWhile a considerable portion of People Living with HIV demonstrated adequate higher Tuberculosis preventive treatment knowledge, addressing gaps among those with lower understanding is crucial. Targeted education campaigns tailored to the needs of People Living with HIV, especially in rural areas and among male populations, are essential. Collaborative efforts between national health programs and community organizations are vital to integrate Tuberculosis preventive treatment awareness effectively into comprehensive HIV care programs, ultimately reducing the burden of Tuberculosis among People Living with HIV and the general population.

BackgroundThe COVID-19 pandemic revealed a need for better collaboration among research, care, and management in Germany as well as globally. Initially, there was a high demand for broad data collection across Germany, but as the pandemic evolved, localized data became increasingly necessary. Customized dashboards and tools were rapidly developed to provide timely and accurate information. In Saxony, the DISPENSE project was created to predict short-term hospital bed capacity demands, and while it was successful, continuous adjustments and the initial monolithic system architecture of the application made it difficult to customize and scale.MethodsTo analyze the current state of the DISPENSE tool, we conducted an in-depth analysis of the data processing steps and identified data flows underlying users' metrics and dashboards. We also conducted a workshop to understand the different views and constraints of specific user groups, and brought together and clustered the information according to content-related service areas to determine functionality-related service groups. Based on this analysis, we developed a concept for the system architecture, modularized the main services by assigning specialized applications and integrated them into the existing system, allowing for self-service reporting and evaluation of the expert groups' needs.ResultsWe analyzed the applications' dataflow and identified specific user groups. The functionalities of the monolithic application were divided into specific service groups for data processing, data storage, predictions, content visualization, and user management. After composition and implementation, we evaluated the new system architecture against the initial requirements by enabling self-service reporting to the users.DiscussionBy modularizing the monolithic application and creating a more flexible system, the challenges of rapidly changing requirements, growing need for information, and high administrative efforts were addressed.ConclusionWe demonstrated an improved adaptation towards the needs of various user groups, increased efficiency, and reduced burden on administrators, while also enabling self-service functionalities and specialization of single applications on individual service groups.

Recurrent or chronic pain affects 11-38% of children and adolescents. Pediatric pain research typically focuses on risk factors, such as anxiety and parent functional disability, but resilience-building, protective factors also play an important role in the pain experience. New methods to incorporate resilience-enhancing factors into pain research are needed. Photovoice is a highly participatory research method, where participants take photos to address a common question, caption their photos, and discuss the meaning of the photos in a group. The main objective of this study was to determine whether photovoice is an acceptable method to young people living with chronic pain for identifying and sharing sources of joy. Another objective was to explore sources of joy. Sixteen adolescents and young adults participated, which involved meeting in a group to discuss the goal of the study, taking photographs of self-identified sources of joy over a two-week period, and meeting as a group again to discuss the photographs and participate in a focus group about the experience. Results suggest that photovoice is an acceptable method, as all participants took photographs and attended both meetings, and three themes from the focus group data suggested the participants considered photovoice to be appropriate: 1.) Relief associated with meeting peers, 2.) Potential to benefit young people living with pain, and 3.) Potential to raise awareness. Three themes emerged from the discussion of the photographs to describe sources of joy: 1.) Gratitude for everyday pleasures and accomplishments, 2.) Support from pets, and 3.) Journey of acceptance. Results add to the strengths-based literature on pediatric pain by identifying an acceptable method that could be further explored for use as an intervention to enhance protective factors such as positive affect, gratitude, and social support and to compare the experiences of different populations of youth living with pain.

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Despite well-documented health benefits from exercise, a study on national trends in achieving the recommended minutes of physical activity guidelines has not improved since the guidelines were published in 2008. Peer interactions have been identified as a critical factor for increasing a population's physical activity. The objective of this study is for establishing criteria for social influences on physical activity for establishing criteria that lead to exercise persistence. A system of differential equations was developed that projects exercise trends over time. The system includes both social and non-social influences that impact changes in physical activity habits and establishes quantitative conditions that delineate population-wide persistence habits from domination of sedentary behavior. The model was generally designed with parameter values that can be estimated to data. Complete absence of social or peer influences resulted in long-term dominance of sedentary behavior and a decline of physically active populations. Social interactions between sedentary and moderately active populations were the most important social parameter that influenced low active populations to become and remain physically active. On the other hand, social interactions encouraging moderately active individuals to become sedentary drove exercise persistence to extinction. Communities should focus on increasing social interactions between sedentary and moderately active individuals to draw sedentary populations to become more active. Additionally, reducing opportunities for moderately active individuals to engage with sedentary individuals through sedentary social activities should be addressed.

Adaptive radiations offer an excellent opportunity to understand the eco-evolutionary dynamics of gut microbiota and host niche specialization. In a laboratory common garden, we compared the gut microbiota of two novel derived trophic specialist pupfishes, a scale-eater and a molluscivore, to closely related and distant outgroup generalist populations, spanning both rapid trophic evolution within 10 kya and stable generalist diets persisting over 11 Mya. We predicted an adaptive and highly divergent microbiome composition in the trophic specialists reflecting their rapid rates of craniofacial and behavioral diversification. We sequenced 16S rRNA amplicons of gut microbiomes from lab-reared adult pupfishes raised under identical conditions and fed the same high protein diet. In contrast to our predictions, gut microbiota largely reflected phylogenetic distance among species, rather than generalist or specialist life history, in support of phylosymbiosis. However, we did find significant enrichment of Burkholderiaceae bacteria in replicated lab-reared scale-eater populations. These bacteria sometimes digest collagen, the major component of fish scales, supporting an adaptive shift. We also found some enrichment of Rhodobacteraceae and Planctomycetia in lab-reared molluscivore populations, but these bacteria target cellulose. Overall phylogenetic conservation of microbiome composition contrasts with predictions of adaptive radiation theory and observations of rapid diversification in all other trophic traits in these hosts, including craniofacial morphology, foraging behavior, aggression, and gene expression, suggesting that the functional role of these minor shifts in microbiota will be important for understanding the role of the microbiome in trophic diversification.

BackgroundPrior to direct-acting antivirals (DAAs), HCV incidence rose among men who have sex with men (MSM) living with HIV infection in Germany despite high hepatitis C virus (HCV) treatment rates. We establish a HCV elimination modeling framework to evaluate whether existing treatment rates can achieve the World Health Organization (WHO) incidence target among MSM living with HIV in Germany.MethodsTo evaluate progress towards HCV elimination in Germany, we adapted a previously published HCV transmission model among MSM living with diagnosed HIV. We modelled HCV incidence and prevalence until 2030 (relative to 2015) under existing treatment and DAA scale-up and explored potential impacts of disruptions in treatment and behavioral risk reduction due to the COVID-19 pandemic.ResultsContinuing current treatment rates will result in stable HCV incidence among MSM living with HIV in Germany between 2015-2030. The WHO HCV incidence target is achievable under DAA scale-up to 100% treatment combined with treatment of those previously diagnosed and untreated (at a rate of 15%/year) and would result in greater reductions with early treatment (3 vs 6 months) reducing incidence from 4.0/100person-years to 0.8/100person-years by 2030. A 12-month disruption to HCV treatment (20% reduction) and risk behaviors (25%,50%,75% reduction) during the COVID-19 pandemic would result in a 15% relative increase in total HCV incidence in 2030 compared to that expected under the status quo.ConclusionsHCV elimination among MSM living with HIV in Germany requires further DAA scale-up among those newly diagnosed combined with efforts to treat those previously diagnosed but untreated. Prospective monitoring will establish whether Germany is on track for HCV microelimination.

Vaccines are highly effective in minimizing serious cases of COVID-19 and pivotal to managing the COVID-19 pandemic. Despite widespread availability, vaccination rates fall short of levels required to bring about widespread immunity, with low rates attributed to vaccine hesitancy. It is therefore important to identify the beliefs and concerns associated with vaccine intentions and uptake. The present study aimed to develop and validate, using the AMEE Guide, the Vaccination Concerns in COVID-19 Scale (VaCCS), a comprehensive measure of beliefs and concerns with respect to COVID-19 vaccines. In the scale development phase, samples of Australian (N = 53) and USA (N = 48) residents completed an initial open-response survey to elicit beliefs and concerns about COVID-19 vaccines. A concurrent rapid literature review was conducted to identify content from existing scales on vaccination beliefs. An initial pool of items was developed informed by the survey responses and rapid review. The readability and face validity of the item pool was assessed by behavioral science experts (N = 5) and non-experts (N = 10). In the scale validation phase, samples of Australian (N = 522) and USA (N = 499) residents completed scaled versions of the final item pool and measures of socio-political, health beliefs and outcomes, and trait measures. Exploratory factor analysis yielded a scale comprising 35 items with 8 subscales, and subsequent confirmatory factor analyses indicated acceptable fit of the scale structure with the data in each sample and factorial invariance across samples. Concurrent and predictive validity tests indicated a theoretically and conceptually predictable pattern of relations between the VaCCS subscales with the socio-political, health beliefs and outcomes, and trait measures, and key subscales predicted intentions to receive the COVID-19 vaccine. The VaCCS provides a novel measure to assess beliefs and concerns toward COVID-19 vaccination that researchers and practitioners can use in its entirety or select specific sub-scales to use according to their needs.

Although there have been great advancements in the field of HIV treatment and prevention, there is no cure. There are two types of HIV: HIV-1 and HIV-2. In addition to genetic differences between the two types of HIV, HIV-2 infection causes a slower disease progression, and the rate of new HIV-2 infections has dramatically decreased since 2003. Like HIV-1, HIV-2 is capable of establishing latent infection in CD4+ T cells, thereby allowing the virus to evade viral cytopathic effects and detection by the immune system. The mechanisms underlying HIV latency are not fully understood, rendering this a significant barrier to development of a cure. Using RT-ddPCR, we previously demonstrated that latent infection with HIV-1 may be due to blocks to HIV transcriptional elongation, distal transcription/polyadenylation, and multiple splicing. In this study, we describe the development of seven highly-specific RT-ddPCR assays for HIV-2 that can be applied to the study of HIV-2 infections and latency. We designed and validated seven assays targeting different HIV-2 RNA regions along the genome that can be used to measure the degree of progression through different blocks to HIV-2 transcription and splicing. Given that HIV-2 is vastly understudied relative to HIV-1 and that it can be considered a model of a less virulent infection, application of these assays to studies of HIV-2 latency may inform new therapies for HIV-2, HIV-1, and other retroviruses.

ContextMultimorbidity is highly prevalent among older adults and associated with a high mortality. Prediction of mortality in multimorbid people would be clinically useful but there is no mortality risk index designed for this population. Our objective was therefore to develop and internally validate a 1-year mortality prognostic index for older multimorbid adults.MethodsWe analysed data of the OPERAM cohort study in Bern, Switzerland, including 822 adults aged 70 years or more with multimorbidity (3 or more chronic medical conditions) and polypharmacy (use of 5 drugs or more for >30 days). Time to all-cause mortality was assessed up to 1 year of follow-up. We performed a parametric Weibull regression model with backward stepwise selection to identify mortality risk predictors. The model was internally validated and optimism corrected using bootstrapping techniques. We derived a point-based risk score from the regression coefficients. Calibration and discrimination were assessed by the calibration slope and C statistic.Results805 participants were included in the analysis. During 1-year of follow-up, 158 participants (20%) had died. Age, Charlson-Comorbidity-Index, number of drugs, body mass index, number of hospitalizations, Barthel-Index (functional impairment), and nursing home residency were predictors of 1-year mortality in a multivariable model. Using these variables, the 1-year probability of dying could be predicted with an optimism-corrected C statistic of 0.70. The optimism-corrected calibration slope was 0.93. Based on the derived point-based risk score to predict mortality risk, 7% of the patients classified at low-risk of mortality, 19% at moderate-risk, and 37% at high-risk died after one year of follow-up. A simpler mortality score, without the Charlson-Comorbidity-Index and Barthel-Index, showed reduced discriminative power (optimism-corrected C statistic: 0.59) compared to the full score.ConclusionWe developed and internally validated a mortality risk index including for the first-time specific predictors for multimorbid adults. This new 1-year mortality prediction point-based score allowed to classify multimorbid older patients into three categories of increasing risk of mortality. Further validation of the score among various populations of multimorbid patients is needed before its implementation into practice.

Accurate determination of pre-pregnancy weight is essential for optimal pregnancy monitoring and antenatal care. Determining pre-pregnancy weight in limited-resources settings is challenging for both clinical practice and public health research. From a 2014-2017 pre-pregnancy cohort in Benin, we evaluated the agreement between the measured pre-pregnancy weight (MPPW) and two proxies: (i) the first trimester pregnancy weight (FTPW) and (ii) the estimated pre-pregnancy weight (EPPW) using Thomas & al. formula. We analysed data from 302 pregnant women with both pre-pregnancy weight measured within 3 months before conception and weight measured during the first trimester. Using segmented linear regression, we first assessed up to which gestational age the weight measured during the first trimester could reasonably estimate the MPPW. Then the Bland & Altman method was used to assess agreement between MPPW and the two proxies. Additional analyses were performed to assess the sensitivity of results to the timing of measurement of either MPPW or the two proxies. On average, FTPW did not feature significant difference with MPPW up to 13.03 (11.99-14.06) weeks of gestational age. FTPW, measured on average at 7 ± 2.4 weeks of gestation, and the EPPW showed similar Bland & Altman limits of agreement with the MPPW. However, while the FTPW slightly underestimated the MPPW by a mean of-0.16 (-0.08; +0.39) kg, the EPPW overestimated it by a mean of + 0.43 (+0.20; +0.66) kg. Minor differences in these results were observed when the MPPW was assessed earlier or within three months before pregnancy, or according to the gestational age at the time of the proxy's measurement. In conclusion, in Southern Benin and up to 12-14 weeks of pregnancy, the FTPW appeared to be a good proxy of the MPPW while using Thomas' formula did not enhance pre-pregnancy weight estimation.

BackgroundAs cannabis legalization continues to spread across the United States, average Δ9-tetrahydrocannabinol concentrations in recreational products have significantly increased, and no prior study has evaluated effective treatments to reduce cannabis use among high potency cannabis users. Some research has found that the non-intoxicating cannabinoid cannabidiol reduces cannabis use and cannabis use disorder-related symptoms, such as affective disturbance and withdrawal. Results of these studies are promising but limited to synthetic or isolated forms of cannabidiol.ObjectiveConduct a placebo-controlled randomized control trial comparing the effects of hemp-derived cannabidiol on reducing Δ9-tetrahydrocannabinol use in concentrate users with cannabis use disorder.MethodsDesign. Double-blind, three-arm randomized placebo-controlled trial. Setting. University in the Denver-Boulder, CO, USA area. Study population. Community members who are heavy, stable cannabis concentrate users that meet criteria for at least moderate cannabis use disorder and are seeking to decrease or stop cannabis use. Data. Self-report demographics, substance use, and mental health characteristics, blood and urine based biomarkers and anthropometrics. Outcomes. Affective, physiological, and physical withdrawal symptoms, Δ9-tetrahydrocannabinol use. Analysis. Three-group ANOVAs and χ2 tests will be used to compare baseline variables between groups. Characteristics that differ between groups will be evaluated as potential covariates in subsequent analyses. A multilevel modeling framework will be used for primary outcome analysis to account for the repeated observations nested within participants over time. Pairwise post-hoc simple effects tests will be conducted to confirm patterns of differences.Trial registrationClinicalTrials.gov NCT06107062.

High fertility constitutes a challenge to men's health conditions in Nigeria, a low-income country. Religion and ethnicity are central to the current Male Fertility (MF) level in Nigeria. This study determined the relationship between Male Fertility (MF) and Religion Ethnic Interaction (REI) amidst other socio-demographic characteristics in Nigeria. Nigeria Demographic and Health Survey data, 2018 was used. Men aged 15-59 years [n = 8,786] were sampled using a multi-stage approach. Fertility was measured by the number of Children Ever Born (CEB). REI was generated using the combination of religion and ethnic groups; Hausa/Fulani Muslim, Igbo Christian, Yoruba Christian, and Yoruba Muslim. However, Hausa/Fulani Christians and Igbo Muslims were excluded from this study because a few men in these categories were available in the original sample. Weighted data were analyzed using the Negative Binomial (NB) model (α0.05). The mean age and CEB of the men were 32.9±12.0 years and 3.18±4.4 respectively. The mean CEB among men aged 45-59 years was highest among Hausa/Fulani Muslims (x = 11.57±5.98), but least among Yoruba Christians (x = 4.44±2.67). About 33.4% of the Hausa/Fulani Muslims had had ≥5 children, while 13.7% were reported among the Yoruba Christian men (p

BackgroundCOVID-19 infection and its associated consequence, known as long-COVID, lead to a significant burden on the global healthcare system and limitations in people's personal and work lives. This study aims to provide further insight into the impact of acute and ongoing COVID-19 symptoms and investigates the role of patients' gender and vaccination status.Methods416 individuals (73.9% female) between the ages of 16 and 80 years (M = 44.18, SD = 12.90) with self-reported symptoms of long-COVID participated in an online survey conducted between March and May 2022.Results6.0%, 74.3%, and 19.7% of all respondents reported having had an asymptomatic, mild, or severe acute illness, respectively. Out of all participants, 7.8% required hospitalization. The most prevalent symptoms during the acute infection (Mdn = 23.50 symptoms, IQR = 13-39) included fatigue, exhaustion, cough, brain fog, and memory problems. The median long-COVID disease duration was 12.10 months (IQR = 2.8-17.4). Among 64 inquired long-COVID symptoms (Mdn = 17.00 symptoms, IQR = 9-27), participants reported fatigue, exhaustion, memory problems, brain fog, and dyspnea as the most common ongoing symptoms, which were generally experienced as fluctuating and deteriorating after physical or cognitive activity. Common consequences of long-COVID included financial losses (40.5%), changes in the participants' profession (41.0%), stress resistance (87.5%), sexual life (38.1%), and mood (72.1%), as well as breathing difficulties (41.3%), or an increased drug intake (e.g., medicine, alcohol; 44.6%). In addition, vaccinated individuals exhibited a shorter acute illness duration and an earlier onset of long-COVID symptoms. In general, women reported more long-COVID symptoms than men.ConclusionLong-COVID represents a heterogeneous disease and impacts multiple life aspects of those affected. Tailored rehabilitation programs targeting the plurality of physical and mental symptoms are needed.

BackgroundHailey-Hailey disease (HHD) is a rare autosomal dominant skin disease caused by mutations in the ATP2C1 gene, which encodes the secretory Ca2+/Mn2+-ATPase (SPCA1) pump in the Golgi apparatus. Although ATP2C1 is ubiquitously expressed in the body, possible extracutaneous manifestations of HHD are unknown. However, dysfunction of the Golgi apparatus not specifically coupled to ATP2C1 has been associated with heart disease.ObjectiveTo investigate the association between HHD and common heart disease in a Swedish, population-based cohort.MethodsWe conducted a population-based cohort study based on a linkage of Swedish nationwide registers to investigate the relationship between HHD and heart disease. We have been granted ethical approval from the Swedish Ethical Review Authority to conduct this study. The patients in this manuscript have given written informed consent to the publication of their case details. A total of 342 individuals with an ICD-10 diagnosis of HHD (Q82.8E) were identified and matched with randomly selected comparison individuals without HHD on a 1:100 ratio. Furthermore, in a separate clinical cohort we matched 23 HHD patients for age, sex, and BMI with control subjects to examine electrocardiogram parameters, electrolytes, and cardiovascular biomarkers.ResultsCompared with individuals without HHD, individuals with HHD had an excess risk of arrhythmia (RR 1.4, CI 1.0-2.0), whereas no increased risks of myocardial infarction (RR 1.1, CI 0.6-1.7) or heart failure (RR 1.0, CI 0.6-1.6; Table 1) were found. We found no difference in ECG parameters, cardiovascular biomarkers, and electrolytes in the clinical subset.ConclusionThis study reveals that HHD is associated with an increased risk of arrhythmia and represents the first data of any extracutaneous comorbidity in HHD. Thus, HHD may be a systemic disease. Our findings also shed light on the importance of the Golgi apparatus' Ca2+/Mn2+ homeostasis in common heart disease.

IntroductionIn March 2023, a Marburg Virus Disease (MVD) outbreak was declared in Kagera region, Northwestern Tanzania. This was the first MVD outbreak in the country. We describe the epidemiological characteristics of MVD cases and contacts.MethodsThe Ministry of Health activated an outbreak response team. Outbreak investigation methods were applied to cases identified through MVD standard case definitions and confirmed through reverse-transcriptase polymerase chain reaction (RT PCR). All identified case contacts were added into the contact listing form and followed up in-person daily for any signs or symptoms for 21 days. Data collected from various forms was managed and analyzed using Excel and QGIS software for mapping.ResultsA total of nine MVD cases were reported with eight laboratory-confirmed and one probable. Two of the reported cases were frontline healthcare workers and seven were family related members. Cases were children and adults between 1-59 years of age with a median age of 34 years. Six were males. Six cases died equivalent to a case fatality rate (CFR) of 66.7%. A total of 212 individuals were identified as contacts and two (2) became cases. The outbreak was localized in two geo-administrative wards (Maruku and Kanyangereko) of Bukoba District Council.ConclusionTransmission during this outbreak occurred among family members and healthcare workers who provided care to the cases. The delay in detection aggravated the spread and possibly the consequent fatality but once confirmed the swift response stemmed further transmission containing the disease at the epicenter wards. The outbreak lasted for 72 days but as the origin is still unknown, further research is required to explore the source of this outbreak.

BackgroundEndemic African malaria vectors are poorly adapted to typical urban ecologies. However, Anopheles stephensi, an urban malaria vector formerly confined to South Asia and the Persian Gulf, was recently detected in Africa and may change the epidemiology of malaria across the continent. Little is known about the public health implications of An. stephensi in Africa. This study is designed to assess the relative importance of household exposure to An. stephensi and endemic malaria vectors for malaria risk in urban Sudan and Ethiopia.MethodsCase-control studies will be conducted in 3 urban settings (2 in Sudan, 1 in Ethiopia) to assess the association between presence of An. stephensi in and around households and malaria. Cases, defined as individuals positive for Plasmodium falciparum and/or P. vivax by microscopy/rapid diagnostic test (RDT), and controls, defined as age-matched individuals negative for P. falciparum and/or P. vivax by microscopy/RDT, will be recruited from public health facilities. Both household surveys and entomological surveillance for adult and immature mosquitoes will be conducted at participant homes within 48 hours of enrolment. Adult and immature mosquitoes will be identified by polymerase chain reaction (PCR). Conditional logistic regression will be used to estimate the association between presence of An. stephensi and malaria status, adjusted for co-occurrence of other malaria vectors and participant gender.ConclusionsFindings from this study will provide evidence of the relative importance of An. stephensi for malaria burden in urban African settings, shedding light on the need for future intervention planning and policy development.

BackgroundSurveillance of HIV-1 pre-treatment drug resistance (PDR) is essential for ensuring the success of first-line antiretroviral therapy (ART). Beside population-based surveys, sentinel surveillance of PDR and circulating HIV-1 clades in specific populations such as blood donors could efficiently inform decision-making on ART program. We therefore sought to ascertain HIV-1 residual infection, the threshold of PDR and viral diversity among recently-diagnosed blood donors in Gabon.MethodsA sentinel surveillance was conducted among 381 consenting blood donors at the National Blood Transfusion Center (NBTC) in Gabon from August 3,2020 to August, 31, 2021. In order to determine the residual risk of HIV transmission, viral load and HIV-1 Sanger-sequencing were performed at the Chantal BIYA International Reference Center (CIRCB)-Cameroon on HIV samples previously tested seronegative with ELISA in Gabon. Phylogeny was performed using MEGA X, PDR threshold>10% was considered high and data were analysed using p≤0.05 for statistical significance.ResultsFive HIV-negative blood donors had a detectable viral load indicating a high residual risk of HIV transmission. Among the samples successfully sequenced, four participants had major drug resistance mutations (DRMs), giving a threshold of PDR of 25% (4/16). By drug class, major DRMs targeting NNRTI (K103N, E138G), NRTIs (L210W) and PI/r (M46L). The most representative viral clades were CRF02_AG and subtype A1. The genetic diversity of HIV-1 had no significant effect on the residual risk in blood transfusion (CRF02_AG, P = 0.3 and Recombinants, P = 0.5).ConclusionThis sentinel surveillance indicates a high residual risk of HIV-1 transfusion in Gabon, thereby underscoring the need for optimal screening strategy for blood safety. Moreover, HIV-1 transmission goes with high-risk of PDR, suggesting suboptimal efficacy of ART. Nonetheless, the genetic diversity has limited (if any effect) on the residual risk of infection and PDR in blood donors.

Chronic physical illnesses (CPI) are highly prevalent among people with serious mental illnesses (PWSMI) yet people in this population experience significant challenges accessing healthcare. This study utilised a constructivist grounded theory approach to collect and analyse data related to the enablers and barriers to public healthcare access for PWSMI & CPI. Data were collected through semi-structured interviews conducted with fifty-seven participants comprising PWSMI &CPI and their caregivers, health policymakers, primary care physicians, psychiatrists, and mental health nurses. Enablers and barriers to healthcare access were represented using a socio-ecological model consisting of five levels: wider society, health system, clinician, family and community, and individual. Jamaica's free public healthcare system was the most pronounced enabler of healthcare access, while poverty, stigma, and discrimination were the most pronounced barriers. Factors such as social support, time, clinician beliefs, attitudes and training, and individual characteristics were identified as consisting of dimensions that were both enablers and barriers to healthcare access. These findings indicated that factors that influenced healthcare access for PWSMI & CPI were aligned with the social determinants of health. Improved healthcare access for PWSMI & CPI necessitates strategies that incorporate a multi-sectoral approach to address social and environmental factors influencing healthcare access across all levels of the socio-ecological model.

BackgroundTranscutaneous spinal stimulation (TSS) and neuromuscular electrical stimulation (NMES) can facilitate self-assisted standing in individuals with paralysis. However, individual variability in responses to each modality may limit their effectiveness in generating the necessary leg extension force for full body weight standing. To address this challenge, we proposed combining TSS and NMES to enhance leg extensor muscle activation, with optimizing timing adjustment to maximize the interaction between the two modalities.MethodsTo assess the effects of TSS and NMES on knee extension and plantarflexion force, ten neurologically intact participants underwent three conditions: (1) TSS control, (2) NMES control, and (3) TSS + NMES. TSS was delivered between the T10 and L2 vertebrae, while NMES was delivered to the skin over the right knee extensors and plantarflexors. TSS and NMES were administered using a 15 Hz train of three 0.5 ms biphasic pulses. During the TSS + NMES condition, the timing between modalities was adjusted in increments of ¼ the interval within a 15 Hz frequency, i.e., 66, 49.5, 33, 16.5, and 1 ms.ResultsNMES combined with TSS, produced synergistic effects even on non-targeted muscle groups, thereby promoting leg extension across multiple joints in the kinematic chain. The sequence of NMES or TSS trains relative to each other did not significantly impact motor output. Notably, a delay of 16.5 to 49.5 ms between interleaved TSS and NMES pulses, each delivered at 15 Hz, results in more robust and synergistic responses in knee extensors and plantarflexors.ConclusionsBy adjusting the timing between TSS and NMES, we can optimize the combined use of these modalities for functional restoration. Our findings highlight the potential of integrated TSS and NMES protocols to enhance motor function, suggesting promising avenues for therapeutic applications, particularly in the rehabilitation of individuals with SCI.

Valproate is the most effective treatment for idiopathic generalised epilepsy. Currently, its use is restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk to men's offspring, prompting recommendations to restrict use in everybody aged

ObjectivesLimited research exists on COVID-19 associated brain fog, and on the long-term cognitive and psychiatric sequelae in racially and ethnically diverse patients. We characterize the neuropsychological sequelae of post-acute COVID-19 in a diverse cohort and investigate whether COVID-19 clinical severity remains associated with brain fog and cognitive deficits approximately 2 years post infection.MethodsA cross-sectional study of patients with a history of COVID-19 hospitalization (March-September 2020). COVID-19 clinical severity was indexed using the National Early Warning Score 2 and a comprehensive neuropsychological tele-battery was administered 2 years post discharge. Pearson's r correlations assessed association, while independent sample t-tests examined group differences. Significant outcomes were further analyzed using multiple regression and ANCOVAs, adjusting for key covariates.ResultsIn 41 adult patients (19 female, 30 Hispanic, 13 Black, mean age of 65 (SD = 15), COVID-19 level of severity was associated with greater number of endorsed brain fog symptoms (Pearson's r = .34, 95% CI [.04, .59]), worse overall cognitive functioning (global cognition: r = -.36, 95% CI [-.61, -.05]) and reduced performance on an attention and working memory task (digit span backwards: r = -.41, 95% CI [-.66, -.09]) at 2-year follow-up. Brain fog symptoms most associated with COVID-19 severity included difficulty focusing (r = .46, 95% CI [.18, .67]), detached (r = .41, 95% CI [.12, .64]) and feeling sleepy (r = .40, 95% CI [.11, .63]). Patients' cognitive performance was generally below average (global cognition z-score: M = -.96, SD = .66), with group differences based on sex and ethnicity evidenced on individual cognitive tests.DiscussionThis study emphasizes the importance of continued research on the long-term effects of COVID-19 infection on neuropsychological outcomes, particularly among underrepresented, health-disparate groups. Greater understanding of these associations could improve detection and treatment of those at increased risk of cognitive decline or impairment.

BackgroundThe COVID-19 pandemic has caused over 68.7 million infections and 1.35 million deaths in South America. There are limited data on SARS-CoV-2 seropositivity and its determinants from Andean countries prior to mass vaccinations against COVID-19.ObjectiveTo estimate SARS-CoV-2 seropositivity and its determinants before vaccination in occupational groups of adults presumed to have different levels of exposure and associations with potential symptomatology.MethodsWe measured seropositivity of anti-SARS-CoV-2 IgG antibodies in a cross-sectional study of vaccine-naïve adults aged 18 years and older, recruited within three occupational risk groups (defined as low [LR], moderate [MR], and high [HR]) between January and September 2021 in two Andean cities in Ecuador. Associations with risk factors were estimated using logistic regression.ResultsIn a sample of 882 adults, IgG seropositivity for the three different occupational risk groups was 39.9% (CI 95% 35.3-44.6), 74.6% (CI 95% 66.4-81.4), and 39.0% (CI 95% 34.0-44.4) for the HR, MR, and LR groups, respectively. History of an illness with loss of taste and/or smell was significantly associated with seropositivity in all occupational groups, with adjusted ORs of 14.31 (95%CI, 5.83-35.12; pConclusionNotable proportions of seropositivity were seen in all occupational groups between January and September 2021 prior to mass vaccination. Loss of taste and/or smell was strongly associated with presence of anti-SARS-CoV-2 IgG antibodies irrespective of presumed occupational exposure risk.

ObjectivePeople regularly contact emergency medicine services concerned that they have been exposed to drink spiking, i.e., exposure to drugs without their knowledge or permission. We identified drugs in blood and urine samples from patients suspecting exposure to drink spiking, with special consideration for drugs not reported taken by the patient (unreported drugs).MethodsFrom September 2018 to May 2019, we collected blood and urine samples from patients 16 years or older presenting at an emergency clinic in Oslo, Norway, within 48 hours of suspected exposure to drink spiking. We also collected information on ethanol ingestion and drugs taken. Blood samples were analyzed for 20 classical recreational drugs using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and an automated enzymatic method for ethanol. Urine samples were analyzed using immunoassay methods and a specific gas chromatography mass spectrometry (GCMS) method for gammahydroxybutyrate (GHB).ResultsFrom 100 included patients (median age 24 years, 62 females), we collected 100 blood samples and 72 urine samples. Median time since exposure was 5 hours. Unreported drugs were found in 15 patients. Unreported drugs in the blood samples were clonazepam in 3, methylenedioxymethamphetamine (MDMA) in 3, amphetamine in 2, tetrahydrocannabinol (THC) in 2, tramadol in 1, cocaine in 1, and methamphetamine in 1. Unreported drugs in the urine samples were cocaine in 5, amphetamine in 4, ecstasy in 3, and cannabis in 2. Ethanol was found in 69 patients, all reporting ethanol ingestion. Median blood ethanol concentration was higher in patients with no unreported drugs detected, 1.00‰ (interquartile range (IQR) 0-1.52) vs. 0‰ (IQR 0-0.46) (pConclusionUnreported drugs, possibly used for drink spiking, were found in 15% of patients. Blood ethanol concentration was higher when no unreported drugs were found. GHB was not detected in any patient.

BackgroundThe SARS-CoV-2 pandemic presented a challenge for caregiving relatives in the home care setting. Caregivers can transmit SARS-CoV-2 to their relatives who are often at high risk for a severe course of COVID-19. Regular testing of asymptomatic caregivers for SARS-CoV-2 may reduce the risk of transmission. The optimal method and frequency of regular asymptomatic testing is unknown. We conducted a prospective, randomised trial to assess the feasibility, recruitment and acceptance of different testing frequencies. This serves to inform a future definitive randomised controlled trial.MethodsWe carried out a parallel three-armed feasibility trial, enrolling adult participants who provided home-based care for a relative at least twice a week. Participants were randomly assigned using sealed envelopes to either conduct saliva-based antigen self-testing at a frequency of once a week (group I), twice a week (group II), or every two days (group III). The participants completed questionnaires on a weekly basis. Main outcome measures were feasibility of recruitment, adherence to self-tests and distress caused by self-testing. We further collected data on the use of mouth-nose mask.ResultsFrom 25 March to 7 May 2021 we assessed 27 participants and randomised 26 in the study: 8 participants in group I, 8 in group II and 10 in group III. All participants completed the study. In group I 48/48 (100.0%; 95% CI 92.6% to 100.0%), in group II 93/96 (96.9%; 95% CI 91.2% to 98.9%) and in group III 209/210 (99.5%; 95% CI 97.4% to 99.9%) self-tests were carried out at home. Participants did not perceive regular self-testing as burdensome in any of the study arms. We did not observe any infection with SARS-CoV-2. During the study, mask adherence decreased from 35% to 19% in all groups.ConclusionConducting such a study was feasible. The participants tolerated regular self-testing well, which was reflected in a high level of test adherence. However, regular self-testing may have led to decreased protective behaviour. To demonstrate that regular asymptomatic testing reduces infection transmission, a future definitive trial should be performed at a time of a high prevalence of SARS-CoV-2 and be implemented as a multicentre study.Trial registrationThe trial is registered with the German Clinical Trials Register, DRKS00026234.

IntroductionA combination of self-reported questionnaire and administrative data could potentially enhance ascertainment of outcomes and alleviate the limitations of both in follow up studies. However, it is uncertain how access to only one of these data sources to assess outcomes impact study findings. Therefore, this study aimed to determine whether the study findings would be altered if the outcomes were assessed by different data sources alone or in combination.MethodsAt 50-year follow-up of participants in a randomized trial, we assessed the effect of antenatal betamethasone exposure on the diagnosis of diabetes, pre-diabetes, hyperlipidemia, hypertension, mental health disorders, and asthma using a self-reported questionnaire, administrative data, a combination of both, or any data source, with or without adjudication by an expert panel of five clinicians. Differences between relative risks derived from each data source were calculated using the Bland-Altman approach.ResultsThere were 424 participants (46% of those eligible, aged 49 years, SD 1, 50% male). There were no differences in study outcomes between participants exposed to betamethasone and those exposed to placebo when the outcomes were assessed using different data sources. When compared to the study findings determined using adjudicated outcomes, the mean difference (limits of agreement) in relative risks derived from other data sources were: self-reported questionnaires 0.02 (-0.35 to 0.40), administrative data 0.06 (-0.32 to 0.44), both questionnaire and administrative data 0.01 (-0.41 to 0.43), and any data source, 0.01 (-0.08 to 0.10).ConclusionUtilizing a self-reported questionnaire, administrative data, both questionnaire and administrative data, or any of these sources for assessing study outcomes had no impact on the study findings compared with when study outcomes were assessed using adjudicated outcomes.

Medical education is experiencing a paradigm shift towards more interactive and collaborative pedagogical approaches. Barcamps, also known as unconferences, offer an interactive, participant-driven learning approach. This study aims to evaluate the feasibility of using barcamps as an educational model in medical education. Furthermore, the possibility of establishing barcamps in medical education as a pedagogical tool is discussed. The study integrates two evaluations to achieve a multifaceted understanding: a pilot study conducted in 2022 and a subsequent feasibility study in 2023. Participation in the barcamps and their evaluations was voluntary. We combined quantitative data, primarily from post-event evaluations, and qualitative data from open-ended survey questions. These methods were designed to capture a broad range of participant experiences and perceptions. The pilot study in 2022 included 11 participants and produced a response rate for the evaluations. The feasibility study in 2023 had 34 participants but a lower evaluation response rate of 53%. Both barcamps were generally positively evaluated by the participants, indicating a high level of satisfaction and perceived value. Regarding the active participation of participants, the wide range of presented topics highlights the adaptability and flexibility of the barcamp model. Attendees at the pilot mentioned a significantly higher previous experience with barcamps. The study suggests that barcamps are generally well received as an interactive and collaborative educational tool in medical education, reflected by high participant evaluation scores. The wide range of topics presented and discussed indicates that barcamps can accommodate diverse educational needs and interests. However, the study also identified areas for improvement, most notably in the structure of topic plans and the overall learning environment. Finally, the principals for barcamps might adapt to other educational methods by adding more interaction, choice, collaboration, communication, critical thinking, creativity, and caring to the learning process.

IntroductionEpithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease.Study designRegistry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE.ObjectivesTo improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern.MethodsSettings and participantsIt is an hospital-based registry established in centers with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for routine patient follow-up. VariablesFull details on patients and disease features, treatment and outcome will be collected, according to common clinical practice guidelines developed and shared with all the contributing centers. In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will also be collected. Statistical methodsThe data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression.ResultsThe registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual.

This study sought to develop a user-friendly decision-making tool to explore country-specific estimates for costs and economic consequences of different options for scaling screening and psychosocial interventions for women with common perinatal mental health problems in Malawi. We developed a simple simulation model using a structure and parameter estimates that were established iteratively with experts, based on published trials, international databases and resources, statistical data, best practice guidance and intervention manuals. The model projects annual costs and returns to investment from 2022 to 2026. The study perspective is societal, including health expenditure and productivity losses. Outcomes in the form of health-related quality of life are measured in Disability Adjusted Life Years, which were converted into monetary values. Economic consequences include those that occur in the year in which the intervention takes place. Results suggest that the net benefit is relatively small at the beginning but increases over time as learning effects lead to a higher number of women being identified and receiving (cost‑)effective treatment. For a scenario in which screening is first provided by health professionals (such as midwives) and a second screening and the intervention are provided by trained and supervised volunteers to equal proportions in group and individual sessions, as well as in clinic versus community setting, total costs in 2022 amount to US$ 0.66 million and health benefits to US$ 0.36 million. Costs increase to US$ 1.03 million and health benefits to US$ 0.93 million in 2026. Net benefits increase from US$ 35,000 in 2022 to US$ 0.52 million in 2026, and return-on-investment ratios from 1.05 to 1.45. Results from sensitivity analysis suggest that positive net benefit results are highly sensitive to an increase in staff salaries. This study demonstrates the feasibility of developing an economic decision-making tool that can be used by local policy makers and influencers to inform investments in maternal mental health.

BackgroundGammaKnife (GK) and CyberKnife (CK) have been the mainstay stereotactic radiosurgery (SRS) solution for multiple brain metastases (MBM) for several years. Recent technological advancement has seen an increase in single-isocentre C-arm linac-based SRS. This systematic review focuses on dosimetric and geometric insights into contemporary MBM SRS and thereby establish if linac-based SRS has matured to match the mainstay SRS delivery systems.MethodsThe PubMed, Web of Science and Scopus databases were interrogated which yielded 891 relevant articles that narrowed to 20 articles after removing duplicates and applying the inclusion and exclusion criteria. Primary studies which reported the use of SRS for treatment of MBM SRS and reported the technical aspects including dosimetry were included. The review was limited to English language publications from January 2015 to August 2023. Only full-length papers were included in the final analysis. Opinion papers, commentary pieces, letters to the editor, abstracts, conference proceedings and editorials were excluded. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The reporting of conformity indices (CI) and gradient indices, V12Gy, monitor units and the impact of translational and rotational shifts were extracted and analysed.ResultsThe single-isocentre technique for MBM dominated recent SRS studies and the most studied delivery platforms were Varian. The C-arm linac-based SRS plan quality and normal brain tissue sparing was comparable to GK and CK and in some cases better. The most used nominal beam energy was 6FFF, and optimised couch and collimator angles could reduce mean normal brain dose by 11.3%. Reduction in volume of the healthy brain receiving a certain dose was dependent on the number and size of the metastases and the relative geometric location. GK and CK required 4.5-8.4 times treatment time compared with linac-based SRS. Rotational shifts caused larger changes in CI in C-arm linac-based single-isocentre SRS.ConclusionC-arm linac-based SRS produced comparable MBM plan quality and the delivery is notably shorter compared to GK and CK SRS.

ObjectivesThis study aims to investigate the previously reported dependency of intravoxel incoherent motion (IVIM) parameters on simultaneous multislice (SMS) acquisition and repetition time (TR). This includes the influence of slice thickness, slice gaps, and slice order on measured IVIM parameters.Materials and methodsDiffusion-weighted imaging (DWI) of the liver was performed on 10 healthy volunteers (aged 20-30 years) at 3T with a slice thickness of 5 mm, a slice gap of 5 mm, and a linear slice order. Diffusion-weighted images were acquired with 19 b-values (0-800 s/mm2) using both conventional slice excitation with an acceleration factor of one (AF1) and SMS excitation with an acceleration factor of three (AF3). Each of these measurements were carried out with two repetition times (TRs)- 1,300 ms (prefix s) and 4,500 ms (prefix l)-resulting in four different combinations: sAF1, sAF3, lAF1, and lAF3. Five volunteers underwent additional measurements using a 10 mm slice thickness and with AF1. Median signal values in the liver were used to determine the biexponential IVIM parameters. Statistical significances were assessed using the Kruskal-Wallis test, Wilcoxon signed-rank test, and Student's t-test. In-silico investigations were also used to interpret the data.ResultsThere were no significant differences between the biexponential IVIM parameters acquired from sAF1, sAF3, lAF1, and lAF3. Median values of the perfusion fraction f were as follows: 29.9% (sAF1), 26.9% (sAF3), 28.1% (lAF1), and 27.5% (lAF3). In the 10 mm-thick slices, f decreased from 31.3% (lAF1) to 27.4% (sAF1) (p = 0.141).ConclusionThe slice excitation mode did not appear to have any significant influence on the biexponential IVIM parameters. However, our simulations, as well as values reported from previous publications, show that slice thickness, slice gaps, and slice order are relevant and should thus be reported in IVIM studies.

BackgroundCanadian health systems fare poorly in providing timely access to elective surgical care, which is crucial for quality, trust, and satisfaction.MethodsWe conducted a cross-sectional analysis of surgical wait times for adults receiving non-urgent cataract surgery, knee arthroplasty, hip arthroplasty, gallbladder surgery, and non-cancer uterine surgery in Ontario, Canada, between 2013 and 2019. We obtained data from the Wait Times Information System (WTIS) database. Inter- and intra-hospital and surgeon variations in wait time were described graphically with caterpillar plots. We used non-nested 3-level hierarchical random effects models to estimate variation partition coefficients, quantifying the proportion of wait time variance attributable to surgeons and hospitals.ResultsA total of 942,605 procedures at 107 healthcare facilities, conducted by 1,834 surgeons, were included in the analysis. We observed significant intra- and inter-provider variations in wait times across all five surgical procedures. Inter-facility median wait time varied between six-fold for gallbladder surgery and 15-fold for knee arthroplasty. Inter-surgeon variation was more pronounced, ranging from a 17-fold median wait time difference for cataract surgery to a 216-fold difference for non-cancer uterine surgery. The proportion of variation in wait times attributable to facilities ranged from 6.2% for gallbladder surgery to 23.0% for cataract surgery. In comparison, surgeon-related variation ranged from 16.0% for non-cancer uterine surgery to 28.0% for cataract surgery.ImplicationsThere is extreme variability in surgical wait times for five common, high-volume, non-urgent surgical procedures. Strategies to address surgical wait times must address the variation between service providers through better coordination of supply and demand. Approaches such as single-entry models could improve surgical system performance.

BackgroundHuman Papilloma Virus (HPV) vaccination can prevent more than 90% of cancers caused by HPV. Although this vaccination is recommended and provided at no cost to all adolescent girls aged 9 to19 years in Uganda, its uptake remains low. We sought to determine the uptake of, and factors associated with HPV vaccination among adolescent girls living with HIV in Uganda.MethodsWe conducted an explanatory sequential mixed methods study, among adolescent girls living with HIV, attending HIV care at the Mulago ISS HIV clinic in Kampala, Uganda. We administered a structured questionnaire to elicit data on HPV vaccination and its covariates to a systematic random sample of 264 adolescent girls with HIV. A participant who had received all the three recommended HPV vaccine doses was classified as fully vaccinated. We then conducted four focus group discussions among adolescent girls living with HIV (n = 32), eight in-depth interviews among their parents and five Key informant interviews among their healthcare providers. We conducted descriptive statistics and logistic regression analyses for the quantitative data before thematic analysis for the qualitative data.ResultOf 264 adolescent girls, 31% (83/264) had at least one HPV vaccine dose; 22% (59/264) two doses, while 8.0% (21/264) were fully vaccinated (received three doses). While most participants received their first and second doses (48% (40/83)) and 57.6% (34/59), respectively) from school, the largest number of participants (47.1% (12/21)) received their third dose at community outreaches. Participants who received counseling from community members were three times more likely to get fully vaccinated compared to those who did not receive counseling (aOR 3.28, Cl:1.07-10.08, P = 0.038). From the qualitative follow-up, three major themes were identified: (1): Limited information about HPV vaccination, which gave room for misconceptions and doubts about the vaccine; (2) Parental influence on adolescent decisions was strong despite parents having limited knowledge about HPV vaccination and (3) Inadequacy of HPV vaccination services at the hospital and in the schools.ConclusionFull HPV vaccination was low among adolescent girls living with HIV. Counseling of the adolescents by community members, alongside HPV vaccination community outreaches, provided a platform for vaccination. There should be strategies to provide adequate information about HPV vaccine to health workers, parents, and the adolescents. In addition to schools, community-based initiatives, including outreaches and lay-health workers can be utilized to improve HPV vaccine uptake among girls with HIV.

BackgroundKetamine has recently attracted considerable attention for its rapid effects on patients with major depressive disorder, including treatment-resistant depression (TRD). Despite ketamine's promising results in treating depression, a significant number of patients do not respond to the treatment, and predicting who will benefit remains a challenge. Although its antidepressant effects are known to be linked to its action as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, the precise mechanisms that determine why some patients respond and others do not are still unclear.ObjectiveThis study aims to understand the computational mechanisms underlying changes in the auditory mismatch negativity (MMN) response following treatment with intravenous ketamine. Moreover, we aim to link the computational mechanisms to their underlying neural causes and use the parameters of the neurocomputational model to make individual treatment predictions.MethodsThis is a prospective study of 30 patients with TRD who are undergoing intravenous ketamine therapy. Prior to 3 out of 4 ketamine infusions, EEG will be recorded while patients complete the auditory MMN task. Depression, suicidality, and anxiety will be assessed throughout the study and a week after the last ketamine infusion. To translate the effects of ketamine on the MMN to computational mechanisms, we will model changes in the auditory MMN using the hierarchical Gaussian filter, a hierarchical Bayesian model. Furthermore, we will employ a conductance-based neural mass model of the electrophysiological data to link these computational mechanisms to their neural causes.ConclusionThe findings of this study may improve understanding of the mechanisms underlying response and resistance to ketamine treatment in patients with TRD. The parameters obtained from fitting computational models to EEG recordings may facilitate single-patient treatment predictions, which could provide clinically useful prognostic information.Trial registrationClinicaltrials.gov NCT05464264. Registered June 24, 2022.

[This corrects the article DOI: 10.1371/journal.pone.0265724.].

Field studies suggest that changes in the stable isotope ratios of phytoplankton communities can be used to track changes in the utilization of different nitrogen sources, i.e., to detect shifts from dissolved inorganic nitrogen (DIN) uptake to atmospheric nitrogen (N2) fixation by diazotrophic cyanobacteria as an indication of nitrogen limitation. We explored changes in the stable isotope signature of the diazotrophic cyanobacterium Trichormus variabilis in response to increasing nitrate (NO3-) concentrations (0 to 170 mg L-1) under controlled laboratory conditions. In addition, we explored the influence of nitrogen utilization at the primary producer level on trophic fractionation by studying potential changes in isotope ratios in the freshwater model Daphnia magna feeding on the differently grown cyanobacteria. We show that δ 15N values of the cyanobacterium increase asymptotically with DIN availability, from -0.7 ‰ in the absence of DIN (suggesting N2 fixation) to 2.9 ‰ at the highest DIN concentration (exclusive DIN uptake). In contrast, δ 13C values of the cyanobacterium did not show a clear relationship with DIN availability. The stable isotope ratios of the consumer reflected those of the differently grown cyanobacteria but also revealed significant trophic fractionation in response to nitrogen utilization at the primary producer level. Nitrogen isotope turnover rates of Daphnia were highest in the absence of DIN as a consequence of N2 fixation and resulting depletion in 15N at the primary producer level. Our results highlight the potential of stable isotopes to assess nitrogen limitation and to explore diazotrophy in aquatic food webs.

BackgroundPatients with breast cancer (BC) exhibit circadian rhythm disruptions, mainly of rest-activity rhythm (RAR), of which sleep is an essential component, and cortisol rhythm. Sleep complaints such as insomnia and cognitive impairments are prevalent in BC. In general population, sleep is known to contribute greatly to cognition. Thus, improving RAR (and particularly sleep) could help limiting cognitive impairments in BC patients. It has recently been suggested that, in addition to its essential role in spatial memory, the vestibular system contributes to RAR synchronization. Its stimulation could therefore limit both sleep disturbances and spatial memory deficits in BC.ObjectivesThe main aim of the ICANSLEEP-2 study is to assess the effects of galvanic vestibular stimulation (GVS) on circadian rhythms. The secondary aim is to assess whether GVS improves sleep and spatial memory in BC patients.MethodsTwo groups with insomnia complaints (Insomnia Severity Index > 7) will be included: a patients' group with BC (n = 50) and a healthy control group without history of cancer (n = 25). There will be two assessment sessions, before and after 2 weeks of GVS. Patients will be randomly assigned to either a GVS group or a sham group (noneffective stimulation). Controls will receive GVS. GVS effects will be quantified and compared between groups. Assessments will include actigraphy, salivary cortisol, polysomnography, a cognitive test battery (including a computer-based task for spatial memory) and validated questionnaires (for psychological functioning and sleep complaints).DiscussionCurrent methods for improving sleep in BC have had controversial outcomes regarding sleep structure. We expect GVS to offer a new mean of directly targeting RAR disruptions in BC patients, with beneficial effects on sleep structure. Given the crucial impact of sleep on cognitive functioning, notably spatial memory, improving sleep of BC patients should enhance their cognitive functioning.Ethics and disseminationThis study received ethical approval from the Ile de France IV institutional review board on 19 April 2022 (no. ID-RCB: 2022-A00437-36). The findings yielded by this protocol will be presented at various conferences and in peer-reviewed journals.Clinicaltrials.gov registration numberNCT05414357.

Metastasis remains the leading cause of cancer deaths worldwide and lung cancer, known for its highly metastatic progression, remains among the most lethal of malignancies. Lung cancer metastasis can selectively spread to multiple different organs, however the genetic and molecular drivers for this process are still poorly understood. Understanding the heterogeneous genomic profile of lung cancer metastases is considered key in identifying therapeutic targets that prevent its spread. Research has identified the key source for metastasis being clusters of cells rather than individual cancer cells. These clusters, known as metastatic cancer cell clusters (MCCCs) have been shown to be 100-fold more tumorigenic than individual cancer cells. Unfortunately, access to these primary drivers of metastases remains difficult and has limited our understanding of their molecular and genomic profiles. Strong evidence in the literature suggests that differentially regulated biological pathways in MCCCs can provide new therapeutic drug targets to help combat cancer metastases. In order to expand research into MCCCs and their role in metastasis, we demonstrate a novel, proof of principle technology, to capture MCCCs directly from patients' whole blood. Our platform can be readily tuned for different solid tumor types by combining a biomimicry-based margination effect coupled with immunoaffinity to isolate MCCCs. Adopting a selective capture approach based on overexpressed CD44 in MCCCs provides a methodology that preferentially isolates them from whole blood. Furthermore, we demonstrate a high capture efficiency of more than 90% when spiking MCCC-like model cell clusters into whole blood. Characterization of the captured MCCCs from lung cancer patients by immunofluorescence staining and genomic analyses, suggests highly differential morphologies and genomic profiles. This study lays the foundation to identify potential drug targets thus unlocking a new area of anti-metastatic therapeutics.

BackgroundMaximising quality of life is a central goal for all healthcare, especially when dealing with dementing disorders. In this study we aimed to compare health-related quality of life (HRQoL), depressive symptoms and functional impairment between individuals with and without idiopathic normal pressure hydrocephalus (iNPH) from the general population.MethodsA total of 122 individuals, 30 with iNPH (median age 75 years, 67 females) underwent neurological examinations and computed tomography of the brain with standardised rating of imaging findings and clinical symptoms. The participants completed the Geriatric Depression Scale (GDS-15) and the HRQoL instrument EQ5D-5L. In addition, the modified Rankin Scale (mRS) was used to evaluate functional impairment.ResultsCompared with participants without iNPH, those with iNPH reported a higher score on GDS-15 (median 3 vs 1) and mRS (median 2 vs 1) (p < 0.05). Further, those with iNPH rated lower on EQ5D-5L (index 0.79, VAS 70) than those without iNPH (index 0.86, VAS 80) (p < 0.05). In logistic regression models, low HRQoL was associated with more depressive symptoms, a higher degree of iNPH symptoms, and lower functional status.ConclusionsIn this population-based sample, those with iNPH had more depressive symptoms, lower functional status, and worse quality of life compared to those without iNPH. The strongest association with low HRQoL was found for depressive symptoms, functional level, and degree of iNPH symptoms. These results underline the value of shunt surgery because of its potential to reduce symptoms and disability in iNPH and therefore improve HRQoL.

Eps15 (epidermal growth factor receptor pathway substrate 15) homology domain-containing proteins (EHDs) comprise a family of eukaryotic dynamin-related ATPases that participate in various endocytic membrane trafficking pathways. Dysregulation of EHDs function has been implicated in various diseases, including cancer. The lack of small molecule inhibitors which acutely target individual EHD members has hampered progress in dissecting their detailed cellular membrane trafficking pathways and their function during disease. Here, we established a Malachite green-based assay compatible with high throughput screening to monitor the liposome-stimulated ATPase of EHD4. In this way, we identified a drug-like molecule that inhibited EHD4's liposome-stimulated ATPase activity. Structure activity relationship (SAR) studies indicated sites of preferred substitutions for more potent inhibitor synthesis. Moreover, the assay optimization in this work can be applied to other dynamin family members showing a weak and liposome-dependent nucleotide hydrolysis activity.

Although cochlear implants have become a well-established method for patients with sensory neural hearing loss, clinical results indicate that in some cases, corrosion of electrode contacts leads to high impedance that interferes with successful stimulation of the auditory nerve. As it is unclear whether corrosion products induce cell damage, we focused on cell culture models of the organ of Corti cell line (HEI-OC1), rat spiral ganglion cells (SGC) and rat organ of Corti explant (OCex) cultivated from neonatal rat cochleae to characterize the cytotoxicity of sodium hexachloroplatinate (IV) (Na2(PtCl6)). The oxidative activity in HEI-OC1 cells decreased with increasing Na2(PtCl6) concentrations between 8 and 16 ng/μl, and live cell staining with Calcein acetoxymethyl/Ethidium homodimer III revealed an increasing number of cells with disrupted membranes. Ultrastructural evidence of mitophagy followed by necroptosis was detected. Additionally, exposure of the SGC to 15-35 ng/μl Na2(PtCl6) dose-dependently reduced neuronal survival and neuritogenesis, as determined by neurofilament antigen staining. In parallel, staining glial cells and fibroblasts with specific antibodies confirmed the dose-dependent induction of cell death by Na2(PtCl6). Exposure of the OCex to 25-45 ng/μl Na2(PtCl6) resulted in severe concentration-dependent hair cell loss. Our data show for the first time that Na2(PtCl6) induces cell death in a concentration-dependent manner in inner ear cell types and tissues.