Conectar
by Bushra Sabri, Chakra Budhathoki, Allison M. McFall, Shruti H. Mehta, David D. Celentano, Sunil S. Solomon, Aylur K. Srikrishnan, Santhanam Anand, Canjeevaram K. Vasudevan, Gregory M. Lucas
Lifetime exposures to violence among men who have sex with men (MSM) are associated with multiple psychosocial health risks and can affect engagement and outcomes of HIV treatment. This study a) explored relationships between levels of exposures to violence and HIV care continuum outcomes among MSM living with HIV in India, and b) identified psychosocial correlates of HIV care continuum outcomes among MSM living with HIV and those with lifetime cumulative exposures to violence (CVE). CVE referred to exposures to violence in both childhood and adulthood. This cross-sectional analysis used survey data collected between August 2016 and May 2017 from 1763 men who have sex with men living with HIV across 10 cities in India, using respondent-driven sampling. We found that higher levels of violence exposure were significantly associated with lower awareness of HIV positive status, and lower likelihood of initiating antiretroviral therapy. Compared with MSM living with HIV that had no CVE, those with CVE were more likely to report perpetration of interpersonal violence, alcohol misuse, depressive symptoms, and HIV transmission risk behaviors and to have two to four co-occurring psychosocial problems. In multivariable analysis with the subset of MSM with CVE, psychosocial correlates significantly associated with at least one HIV care continuum outcome were HIV transmission risk behaviors, perpetration of interpersonal violence, depression, and alcohol misuse. The findings highlight the need for integrating care for lifetime violence exposures and associated behavioral problems in HIV care settings for men who have sex with men living with HIV in India.by Nora Tabea Sibert, Tobias Kurth, Clara Breidenbach, Simone Wesselmann, Günther Feick, Ernst-Günter Carl, Sebastian Dieng, Mohamad Hatem Albarghouth, Atiqullah Aziz, Stefan Baltes, Elisabeth Bartolf, Jens Bedke, Andreas Blana, Marko Brock, Stefan Conrad, Christopher Darr, Florian Distler, Konstantinos Drosos, Gregor Duwe, Amr Gaber, Markus Giessing, Nina Natascha Harke, Axel Heidenreich, Sameh Hijazi, Andreas Hinkel, Björn Theodor Kaftan, Shatlyk Kheiderov, Thomas Knoll, Gerd Lümmen, Inga Peters, Bülent Polat, Valentin Schrodi, Jens-Uwe Stolzenburg, Zoltan Varga, Julius von Süßkind-Schwendi, Vahudin Zugor, Christoph Kowalski
BackgroundIncontinence and sexual dysfunction are long-lasting side effects after surgical treatment (radical prostatectomy, RP) of prostate cancer (PC). For an informed treatment decision, physicians and patients should discuss expected impairments. Therefore, this paper firstly aims to develop and validate prognostic models that predict incontinence and sexual function of PC patients one year after RP and secondly to provide an online decision making tool.
MethodsObservational cohorts of PC patients treated between July 2016 and March 2021 in Germany were used. Models to predict functional outcomes one year after RP measured by the EPIC-26 questionnaire were developed using lasso regression, 80–20 splitting of the data set and 10-fold cross validation. To assess performance, R2, RMSE, analysis of residuals and calibration-in-the-large were applied. Final models were externally temporally validated. Additionally, percentages of functional impairment (pad use for incontinence and firmness of erection for sexual score) per score decile were calculated to be used together with the prediction models.
ResultsFor model development and internal as well as external validation, samples of 11 355 and 8 809 patients were analysed. Results from the internal validation (incontinence: R2 = 0.12, RMSE = 25.40, sexual function: R2 = 0.23, RMSE = 21.44) were comparable with those of the external validation. Residual analysis and calibration-in-the-large showed good results. The prediction tool is freely accessible: https://nora-tabea.shinyapps.io/EPIC-26-Prediction/.
ConclusionThe final models showed appropriate predictive properties and can be used together with the calculated risks for specific functional impairments. Main strengths are the large study sample (> 20 000) and the inclusion of an external validation. The models incorporate meaningful and clinically available predictors ensuring an easy implementation. All predictions are displayed together with risks of frequent impairments such as pad use or erectile dysfunction such that the developed online tool provides a detailed and informative overview for clinicians as well as patients.
by Ana Carolina Cavalcante Rodrigues, Caroline Vitória de Lima Moreira, Camila Carlos Prado, Luan Silvestro Bianchini Silva, Rafael Fernandes Costa, Adesina Paul Arikawe, Gustavo Rodrigues Pedrino, Elson Alves Costa, Osmar Nascimento Silva, Hamilton Barbosa Napolitano, Iranse Oliveira-Silva, James Oluwagbamigbe Fajemiroye
Profiling the variability related to the estrous cycle is essential for assessing depressive-like behavior and screening drugs. This study compares circulating plasma corticosterone levels [CORT] and behavioral alterations in mice exposed to sucrose preference, forced swimming, and tail suspension tests (SPT, FST, and TST, respectively). While SPT exposure did not significantly alter [CORT], FST and TST showed notable changes. Mice in the TST exhibited increased movement and decreased immobility time compared to FST, suggesting a lower likelihood of depressive-like behavior in male mice. Notably, during the proestrus phase, female mice displayed the highest tendency for depressive-like behavior and elevated [CORT], but similar response to antidepressants (imipramine and fluoxetine). The inherent stress of the FST and TST tasks appears to influence [CORT] as well as depressant and antidepressant effects. These comparisons provide valuable insights for further behavioral phenotyping, model sensitivity assessment, and deepen our neurobiological understanding of depression in the context of drug screening.by Weiyi Huang, Robin L. Page, Theresa Morris, Susan Ayres, Alva O. Ferdinand, Samiran Sinha
BackgroundThe association of maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with the risk of system-specific congenital malformations in offspring remains unclear. We conducted a meta-analysis to examine this association and the risk difference between these two types of inhibitors.
MethodsA literature search was performed from January 2000 to May 2023 using PubMed and Web of Science databases. Cohort and case-control studies that assess the association of maternal exposure to SSRIs or SNRIs with the risk of congenital abnormalities were eligible for the study.
ResultsTwenty-one cohort studies and seven case-control studies were included in the meta-analysis. Compared to non-exposure, maternal exposure to SNRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.64 with 95% CI: 1.36, 1.97), anomalies of the kidney and urinary tract (pooled OR: 1.63 with 95% CI: 1.21, 2.20), malformations of nervous system (pooled OR: 2.28 with 95% CI: 1.50, 3.45), anomalies of digestive system (pooled OR: 2.05 with 95% CI: 1.60, 2.64) and abdominal birth defects (pooled OR: 2.91 with 95%CI: 1.98, 4.28), while maternal exposure to SSRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.25 with 95%CI: 1.20, 1.30), anomalies of the kidney and urinary tract (pooled OR: 1.14 with 95%CI: 1.02, 1.27), anomalies of digestive system (pooled OR: 1.11 with 95%CI: 1.01, 1.21), abdominal birth defects (pooled OR: 1.33 with 95%CI: 1.16, 1.53) and musculoskeletal malformations (pooled OR: 1.44 with 95%CI: 1.32, 1.56).
ConclusionsSSRIs and SNRIs have various teratogenic risks. Clinicians must consider risk-benefit ratios and patient history when prescribing medicines.
by Chao Li, Zhong Liu, Justin Anderson, Zhongyu Liu, Liping Tang, Yao Li, Ning Peng, Jianguo Chen, Xueming Liu, Lianwu Fu, Tim M. Townes, Steven M. Rowe, David M. Bedwell, Jennifer Guimbellot, Rui Zhao
A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.by Rafaella Rabelo Polato, Cristino Carneiro Oliveira, Yuri Augusto de Sousa Miranda, Leandro Ferracini Cabral, Carla Malaguti, Anderson José
IntroductionSeveral individuals with post-COVID-19 syndrome referred for pulmonary rehabilitation did not participate. This study aimed to explore individuals’ barriers to participating in posthospitalization COVID-19 rehabilitation.
Materials and methodsThis was a qualitative, multicenter study performed using semistructured interviews. This study included 20 individuals hospitalized for COVID-19 who refused to participate in a pulmonary rehabilitation program at a university hospital.
ResultsIndividuals reported difficulties accessing the rehabilitation center, mainly due to distance, transport costs and conditions, and lack of companions. Health problems (e.g., surgeries, pain, and mobility difficulties) and lack of time due to work, commuting, and household work were also reported. Another reported theme was not perceiving the need for rehabilitation due to feeling well. Minor themes included the need for more information about rehabilitation and a lack of interest, motivation, and medical encouragement.
ConclusionIndividuals hospitalized for COVID-19 faced several barriers to participating in a pulmonary rehabilitation program. These barriers included difficulties in accessing the rehabilitation center, health problems, lack of time, and the perception that rehabilitation was unnecessary. There is a need for actions to overcome these barriers to make the program available to a larger number of individuals.
by Andrea D. Tyler, Jane McAllister, Helen Stapleton, Penny Gauci, Kym Antonation, David Thirkettle-Watts, Cindi R. Corbett
From pathogen detection to genome or plasmid closure, the utility of the Oxford Nanopore Technologies (ONT) MinION for microbiological analysis has been well documented. The MinION’s small footprint, portability, and real-time analytic capability situates it well to address challenges in the field of unbiased pathogen detection, as a component of a security investigation. To this end, a multicenter evaluation of the effect of alternative analytical approaches on the outcome of MinION-based sequencing, using a set of well-characterized samples, was explored in a field-based scenario. Three expert scientific response groups evaluated known bacterial DNA extracts as part of an international first responder (Chemical, Biological, Radiological) training exercise. Samples were prepared independently for analysis using the Rapid and/or Rapid PCR sequencing kits as per the best practices of each of the participating groups. Analyses of sequence data were in turn conducted using varied approaches including ONTs What’s in my pot (WIMP) architecture and in-house computational pipelines. Microbial community composition and the ability of each approach to detect pathogens was compared. Each group demonstrated the ability to detect all species present in samples, although several organisms were detected at levels much lower than expected with some organisms even falling below 1% abundance. Several ‘contaminant’ near neighbor species were also detected, at low abundance. Regardless of the sequencing approach chosen, the observed composition of the bacterial communities diverged from the input composition in each of the analyses, although sequencing conducted using the rapid kit produced the least distortion when compared to PCR-based library preparation methods. One of the participating groups generated drastically lower sequencing output than the other groups, likely attributed to the limited computer hard drive capacity, and occasional disruption of the internet connection. These results provide further consideration for conducting unbiased pathogen identification within a field setting using MinION sequencing. However, the benefits of this approach in providing rapid results and unbiased detection must be considered along with the complexity of sample preparation and data analytics, when compared to more traditional methods. When utilized by trained scientific experts, with appropriate computational resources, the MinION sequencing device is a useful tool for field-based pathogen detection in mixed samples.by Irene Boateng, Beth Stuart, Taeko Becque, Bruce Barrett, Jennifer Bostock, Robin Bruyndonckx, Lucy Carr-Knox, Emily J. Ciccone, Samuel Coenen, Mark Ebell, David Gillespie, Gail Hayward, Katarina Hedin, Kerenza Hood, Tin Man Mandy Lau, Paul Little, Dan Merenstein, Edgar Mulogo, Jose Ordóñez-Mena, Peter Muir, Kirsty Samuel, Nader Shaikh, Sharon Tonner, Alike W. van der Velden, Theo Verheij, Kay Wang, Alastair D. Hay, Nick Francis
BackgroundResistance to antibiotics is rising and threatens future antibiotic effectiveness. ‘Antibiotic targeting’ ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence.
AimTo undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs.
MethodsA systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs.
Trial registrationPROSPERO Registration number: CRD42023376769.
by Amy Huang, Ellen Wang, Stephanie Sanger, Alexandra Papaioannou, Isabel B. Rodrigues
Most older adults 65 years and older accumulate over 8.5 hours/day of sedentary time, which is associated with increased risk of metabolic syndromes and falls. The impact of increased sedentary time in older adults has prompted development of sedentary behaviour guidelines. The purpose of our review was to compare national and international sedentary behaviour and physical activity guidelines for older adults and appraise the quality of guidelines using AGREE II. We conducted our search in Medline, Embase, Global Health, Web of Science, CINAHL, and relevant grey literature. We included the most recent guidelines for older adults written in English. We identified 18 national and international guidelines; ten of the 18 guidelines included sedentary behaviour recommendations while all 18 included physical activity recommendations for older adults. The ten sedentary behaviour guidelines were developed using cohort studies, knowledge users’ opinions, systematic reviews, or other guidelines while the physical activity guidelines were developed using randomized controlled trials, systematic reviews, meta-analysis, and overview of reviews. The definition of sedentary behaviour and the recommendations were inconsistent between the guidelines and were based on very low to low quality and certainty of evidence. All guidelines provided consistent recommendations for aerobic and resistance training; the recommendations were developed using moderate to high quality and certainty of evidence. Only eight physical activity guidelines provided recommendations for balance training and six on flexibility training; the balance training recommendations were consistent between guidelines and based on moderate quality evidence. Further work is needed to develop evidenced-based sedentary behaviour recommendations and flexibility training recommendations for older adults.by Elizabeth Dufourcq Sekatcheff, Christian Godon, Aymeric Bailly, Loïc Quevarec, Virginie Camilleri, Simon Galas, Sandrine Frelon
Wildlife is subject to various sources of pollution, including ionizing radiation. Adverse effects can impact the survival, growth, or reproduction of organisms, later affecting population dynamics. In invertebrates, reproduction, which directly impacts population dynamics, has been found to be the most radiosensitive endpoint. Understanding the underlying molecular pathways inducing this reproduction decrease can help to comprehend species-specific differences in radiosensitivity. From our previous studies, we found that decrease in reproduction is life stage dependent in the roundworm Caenorhabditis elegans, possibly resulting from an accumulation of damages during germ cell development and gamete differentiation. To go further, we used the same experimental design to assess more precisely the molecular determinants of reproductive toxicity, primarily decreases in gamete number. As before, worms were chronically exposed to 50 mGy·h−1 external gamma ionizing radiation throughout different developmental periods (namely embryogenesis, gametogenesis, and full development). To enable cross species extrapolation, conserved molecular pathways across invertebrates and vertebrates were analysed: apoptosis and MAP kinase Ras/ERK (MPK-1), both involved in reproduction and stress responses. Our results showed that these pathways are life-stage dependent, resulting from an accumulation of damages upon chronic exposure to IR throughout the life development. The Ras/ERK pathway was activated in our conditions in the pachytene region of the gonad where it regulates cell fate including apoptosis, but not in the ovulation zone, where it controls oocyte maturation and ovulation. Additionally, assessment of germ cell proliferation via Ras/ERK pathway showed no effect. Finally, a functional analysis of apoptosis revealed that while the decrease of the ovulation rate is caused by DNA-damaged induced apoptosis, this process does not occur in spermatocytes. Thus, sperm decrease seems to be mediated via another mechanism, probably a decrease in germ cell proliferation speed that needs further investigation to better characterize sex-specific responses to IR exposure. These results are of main importance to describe radio-induced reprotoxic effects and contribute as weight of evidence for the AOP #396 “Deposition of ionizing energy leads to population decline via impaired meiosis”.by Omar Al Omari, Gerald Amandu, Samir Al-Adawi, Zubaida Shebani, Ibtisam Al Harthy, Arwa Obeidat, Khloud Al Dameery, Mohammad Al Qadire, Iman Al Hashmi, Abduallh Al Khawldeh, Mohammed ALBashtawy, Maen Aljezawi
There is currently limited knowledge about the firsthand experiences of adolescents and young adults with mental health problems and the meanings they ascribe to these experiences, particularly within Arab countries. This study, therefore, aimed to explore the lived experience of Omani adolescents and young adults with a mental health problem. A sample of 15 participants aged 13–22 diagnosed with a range of mental health problems took part in the study. A qualitative interview guide consisting of open-ended questions was used to allow participants to speak in-depth about their experiences. Using the thematic analysis approach to uncover patterns in the data, three major themes emerged: “living in darkness”, “perilous journey” and “uncertain future”. Results show that the progress of adolescents and young adults with mental health problems is characterized by several challenges; the most significant of which is having insufficient knowledge about their illness, leading to unnecessary delays in their treatment. These findings shed light on the breadth and depth of the experience of adolescents and young adults with mental health problems and lay the groundwork for further examinations. Implications lie in the development of approaches for preventing or mitigating difficulties faced by adolescents and young adults with mental health problems.by Julia Reddy, Kristel Black, Keia Bazemore, Kiva Jordan, Jamie B. Jackson, Andrea K. Knittel
BackgroundResearch ethics guidelines and emphasis on representation in research guide the inclusion of marginalized groups, including people with perinatal opioid use disorders (OUD) and people experiencing incarceration in the United States. However, insights from participants regarding the risks and benefits of participation are not adequately considered. The aim of this study was to examine the risks and benefits of research participation from the perspective of pregnant/postpartum people with OUD who have experienced incarceration.
DesignWe recruited people who had experience with perinatal incarceration and were either currently pregnant or postpartum, and at least 18 years old. All participants met the clinical criteria for OUD. Our study did not have exclusion criteria based on gender, race, or ethnicity.
SettingParticipants were either currently incarcerated at the North Carolina Correctional Institute for Women in Raleigh, North Carolina, United States or had previously experienced perinatal incarceration and were recruited from a perinatal substance use disorder treatment program located in North Carolina.
ParticipantsBetween 9/2021-4/2022, we completed 12 interviews with pregnant/postpartum people with OUD, approximately half who were currently incarcerated and half with a recent history of perinatal incarceration.
Intervention/measurementInterviews were conducted via Webex phone or video. The interviews followed a scripted interview guide and lasted one hour on average. Interview transcripts were analyzed using the Rigorous and Accelerated Data Reduction technique to produce an overarching thematic framework.
FindingsOur analysis identified benefits, including the personal advantage of self-expression, helping others and contributing to change, and financial incentives. Risks included stigma and breach of confidentiality, misunderstanding of the distinction between research and advocacy, and limited ability to share their whole experience.
ConclusionsParticipant-identified benefits of research mirrored those from other marginalized populations, though participant-identified risks were novel and nuanced. Recruitment and consent should move beyond normative research ethics committees protocol language to consider the perspectives of participants.
by Laura Capitán-Moyano, Nerea Cañellas-Iniesta, María Arias-Fernández, Miquel Bennasar-Veny, Aina M. Yáñez, Enrique Castro-Sánchez
Food insecurity in recent years has increased worldwide due to many planetary events such as the COVID-19 pandemic, geopolitical conflicts, the climate crisis, and globalization of markets. Adolescents are a particularly vulnerable group to food insecurity, as they enter adulthood with less parental supervision and greater personal autonomy, but less legislative or institutional protection. The experience of food insecurity in adolescents is influenced by several environmental factors at different levels (interpersonal, organizational, community, and societal), although they are not usually addressed in the design of interventions, prioritizing the individual behavioural factors. We present a scoping review protocol for assessing and identifying the environmental factors that could influence adolescents’ food insecurity. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the PRISMA guidelines for Scoping Reviews (PRISMA-ScR) to prepare the protocol. The search strategy will be performed in the following databases: Pubmed/Medline, EMBASE, Biblioteca Virtual de Salud, EBSCOHost, Scopus, Web of Science, and Cochrane Library Plus. The reference list of the included studies will also be hand-searched. Grey literature will be search through the electronic database Grey Literature Report, and local, provincial, national, and international organisations’ websites. Assessment of eligibility after screening of titles, abstract and full text, and the resolution of discrepancies will be performed by three independent reviewers. This scoping review will contribute to refine the “logic model of the problem” which constitutes the first step in the intervention mapping protocol. The “logic model of the problem” from the intervention mapping protocol will serve to classify and analyse the environmental factors. The findings from this review will be presented to relevant stakeholders that have a role in shaping the environmental factors.by Gerben A. van Kleef, Florian Wanders, Annelies E. M. van Vianen, Rohan L. Dunham, Xinkai Du, Astrid C. Homan
Norms play an important role in upholding orderly and well-functioning societies. Indeed, violations of norms can undermine social coordination and stability. Much is known about the antecedents of norm violations, but their social consequences are poorly understood. In particular, it remains unclear when and how norm violators gain or lose influence in groups. Some studies found that norm violators elicit negative responses that curtail their influence in groups, whereas other studies documented positive consequences that enhance violators’ influence. We propose that the complex relationship between norm violation and influence can be understood by considering that norm violations differentially shape perceptions of dominance and prestige, which tend to have opposite effects on voluntary influence granting, depending on the type of norm that is violated. We first provide correlational (Study 1) and causal (Study 2) evidence that norm violations are associated with dominance, and norm abidance with prestige. We then examine how dominance, prestige, and resultant influence granting are shaped by whether local group norms and/or global community norms are violated. In Study 3, protagonists who violated global (university) norms but followed local (sorority/fraternity) norms were more strongly endorsed as leaders than protagonists who followed global norms but violated local norms, because the former were perceived not only as high on dominance but also on prestige. In Study 4, popular high-school students were remembered as violating global (school) norms while abiding by local (peer) norms. In Study 5, individuals who violated global (organizational) norms while abiding by local (team) norms were assigned more leadership tasks when global and local norms conflicted (making violators “rebels with a cause”) than when norms did not conflict, because the former situation inspired greater prestige. We discuss implications for the social dynamics of norms, hierarchy development, and leader emergence.by Kelsey McOwat, Snehal M. Pinto Pereira, Manjula D. Nugawela, Shamez N. Ladhani, Fiona Newlands, Terence Stephenson, Ruth Simmons, Malcolm G. Semple, Terry Segal, Marta Buszewicz, Isobel Heyman, Trudie Chalder, Tamsin Ford, Emma Dalrymple, Consortium , Roz Shafran
BackgroundDuring the COVID-19 pandemic children and young people (CYP) were socially restricted during a stage of life crucial to development, potentially putting an already vulnerable population at higher risk of loneliness, social isolation, and poorer wellbeing. The objectives of this study are to conduct an exploratory analysis into loneliness before and during the pandemic, and determine which self-reported factors are associated with loneliness.
Methods and findingsParticipants from The Children with Long COVID (CLoCk) national study were invited to take part via an online survey, with a total of 31,017 participants taking part, 31,016 of which reported on their experience of loneliness. Participants retrospectively answered questions on demographics, lifestyle, physical health and mental health and loneliness before the pandemic and at the time of answering the survey. Before the pandemic 6.5% (2,006/31,016) of participants reported experiencing loneliness “Often/Always” and at the time of survey completion 17.4% (5,395/31,016) reported feeling lonelier. There was an association between meeting the research definition of long COVID and loneliness [3.49 OR, 95%CI 3.28–3.72]. CYP who reported feeling lonelier at the time of the survey than before the pandemic were assigned female at birth, older CYP, those from Black/African/Caribbean/Black British or other ethnicity groups, those that had 3–4 siblings and lived in more deprived areas.
ConclusionsWe demonstrate associations between multiple factors and experiences of loneliness during the pandemic. There is a need for a multi-faceted integrated approach when developing interventions targeted at loneliness. It is important to follow up the CYP involved at regular intervals to investigate the progression of their experience of loneliness over time.
by Victoria Anne Archer, Samira Samiee-Zafarghandy, Forough Farrokyhar, Daniel Briatico, Luis H. Braga, J. Mark Walton
BackgroundIn neonates, uncontrolled pain and opioid exposure are both correlated with short- and long-term adverse events. Therefore, managing pain using opioid-sparing approaches is critical in neonatal populations. Multimodal pain control offers the opportunity to manage pain while reducing short- and long-term opioid-related adverse events. Intravenous (IV) acetaminophen may represent an appropriate adjunct to opioid-based postoperative pain control regimes. However, no trials assess this drug in patients less than 36 weeks post-conceptual age or weighing less than 1500 g.
ObjectiveThe proposed study aims to determine the feasibility of conducting a randomized control trial to compare IV acetaminophen and fentanyl to a saline placebo and fentanyl for patients admitted to the neonatal intensive care unit (NICU) undergoing major abdominal or thoracic surgery.
Methods and designThis protocol is for a single-centre, external pilot randomized controlled trial (RCT). Infants in the NICU who have undergone major thoracic or abdominal surgery will be enrolled. Sixty participants will undergo 1:1 randomization to receive intravenous acetaminophen and fentanyl or saline placebo and fentanyl. After surgery, IV acetaminophen or placebo will be given routinely for eight days (192 hours). Appropriate dosing will be determined based on the participant’s gestational age. Patients will be followed for eight days after surgery and will undergo a chart review at 90 days. Primarily feasibility outcomes include recruitment rate, follow-up rate, compliance, and blinding index. Secondary clinical outcomes will be collected as well.
ConclusionThis external pilot RCT will assess the feasibility of performing a multicenter RCT comparing IV acetaminophen and fentanyl to a saline placebo and fentanyl in NICU patients following major abdominal and thoracic surgery. The results will inform the design of a multicenter RCT, which will have the appropriate power to determine the efficacy of this treatment.
Trial registrationClinicalTrials.gov NCT05678244, Registered December 6, 2022.
by Katayi Mwila-Kazimbaya, Samuel Bosomprah, Obvious Nchimunya Chilyabanyama, Caroline Cleopatra Chisenga, Mwelwa Chibuye, Natasha Makabilo Laban, Michelo Simuyandi, Bert Huffer Jr, Miren Iturriza-Gomara, Robert K. M. Choy, Roma Chilengi
BackgroundRotavirus gastroenteritis remains a leading cause of morbidity and mortality despite the introduction of vaccines. Research shows there are several factors contributing to the reduced efficacy of rotavirus vaccines in low- and middle-income settings. Proposed factors include environmental enteric dysfunction (EED), malnutrition, and immune dysfunction. This study aimed to assess the effect of these factors on vaccine responses using a machine learning lasso approach.
MethodsSerum samples from two rotavirus clinical trials (CVIA 066 n = 99 and CVIA 061 n = 124) were assessed for 11 analytes using the novel Micronutrient and EED Assessment Tool (MEEDAT) multiplex ELISA. Immune responses to oral rotavirus vaccines (Rotarix, Rotavac, and Rotavac 5D) as well as a parenteral rotavirus vaccine (trivalent P2-VP8) were also measured and machine learning using the lasso approach was then applied to investigate any associations between immune responses and environmental enteric dysfunction, systemic inflammation, and growth hormone resistance biomarkers.
ResultsBoth oral and parenteral rotavirus vaccine responses were negatively associated with retinol binding protein 4 (RBP4), albeit only weakly for oral vaccines. The parenteral vaccine responses were positively associated with thyroglobulin (Tg) and histidine-rich protein 2 (HRP2) for all three serotypes (P8, P6 and P4), whilst intestinal fatty acid binding protein (I-FABP) was negatively associated with P6 and P4, but not P8, and soluble transferrin receptor (sTfR) was positively associated with P6 only.
ConclusionMEEDAT successfully measured biomarkers of growth, systemic inflammation, and EED in infants undergoing vaccination, with RBP4 being the only analyte associated with both oral and parenteral rotavirus vaccine responses. Tg and HRP2 were associated with responses to all three serotypes in the parenteral vaccine, while I-FABP and sTfR results indicated possible strain specific immune responses to parenteral immunization.
by Jonathan Jin, Huda Al-Shamali, Lorraine Smith-MacDonald, Matthew Reeson, Wanda Polzin, Yifeng Wei, Hannah Pazderka, Peter H. Silverstone, Andrew J. Greenshaw
BackgroundDifficulties in access to therapy were highlighted by COVID-19 measures restricting in-person gatherings. Additional challenges arise when focusing on caregivers of child sexual abuse (CSA) survivors in particular, which are a population that has been historically difficult to engage with due to issues of stigma and confidentiality.
ObjectivesTo present preliminary qualitative results from caregivers of CSA survivors.
MethodsThis study was conducted with caregivers of CSA survivors. Two hybrid webinar/focus groups were conducted using a video conferencing platform in fall of 2021 with two groups of stakeholders (11 caregivers and 5 moderators/clinical staff at Little Warriors, an intensive episodic treatment facility). Sessions were recorded, transcribed, and thematically-analyzed using standard qualitative methodology.
ResultsA total of 11 caregivers contributed to the data. Themes include: (1) Challenges of starting and maintaining treatment (i.e., emotional impact of intake day, challenges of enrolling), (2) Therapeutic benefits of specialized treatment (i.e., feeling safe and supported and the importance of trauma-informed care), and (3) Barriers and facilitators of treatment (i.e., avenues to scale-up and self-care).
ConclusionThe importance of a strong therapeutic alliance was highlighted by both caregivers/clinical staff and further support is needed for families post-treatment. The present hybrid webinar/focus group also achieved engagement goals in a population that is typically difficult to reach. Overall, the response rate (12%) was equivalent to reported registrant attendance rates for general business to consumer webinars and the recommended focus group size. This preliminary approach warrants replication in other populations outside our clinical context.
by Jaclyn Schess, Lydia Bennett-Li, Richard Velleman, Urvita Bhatia, Alexander Catalano, Abhijeet Jambhale, Abhijit Nadkarni
Globally, alcohol consumption causes significant societal harm and is a leading risk factor for death and disability in adults. In India, 3.7% of all deaths and 3.1% disability adjusted life years (DALYs) can be attributed to alcohol. In the context of rapid economic development and emphasized by the COVID-19 pandemic, India’s lack of a consolidated and comprehensive alcohol policy has posed significant challenges to addressing this harm. In this context, the aim of our review was to undertake a comprehensive mapping of the State and national policy environment surrounding alcohol and its use in India, based on an analysis of policy documents. We did this though a scoping review of academic and grey literature, which helped to iteratively identify the websites of 15 international organizations, 21 Indian non-governmental organizations, and eight Indian Federal governmental organizations as well as State/Union Territory government sites, to search for relevant policy documents. We identified 19 Federal policy documents and 36 State level policy documents within which we have identified the specific policy measures which address the 10 categories of the World Health Organization’s Global Action Plan to Reduce the Harmful Use of Alcohol. We found that there are major gaps in regulation of marketing and price controls, with much of this controlled by the States. In addition, regulation of availability of alcohol varies widely throughout the country, which is also a policy area controlled locally by States. Through the clear elucidation of the current policy environment surrounding alcohol in India, policy makers, researchers and advocates can create a clearer roadmap for future reform.by Silvia A. Purro, Michael Farmer, Elizabeth Noble, Claire J. Sarell, Megan Powell, Daniel Yip, Lauren Giggins, Leila Zakka, David X. Thomas, Mark Farrow, Andrew J. Nicoll, Dominic Walsh, John Collinge
Oligomers formed from monomers of the amyloid β-protein (Aβ) are thought to be central to the pathogenesis of Alzheimer’s disease (AD). Unsurprisingly for a complex disease, current mouse models of AD fail to fully mimic the clinical disease in humans. Moreover, results obtained in a given mouse model are not always reproduced in a different model. Cellular prion protein (PrPC) is now an established receptor for Aβ oligomers. However, studies of the Aβ-PrPC interaction in different mouse models have yielded contradictory results. Here we performed a longitudinal study assessing a range of biochemical and histological features in the commonly used J20 and APP-PS1 mouse models. Our analysis demonstrated that PrPC ablation had no effect on amyloid accumulation or oligomer production. However, we found that APP-PS1 mice had higher levels of oligomers, that these could bind to recombinant PrPC, and were recognised by the OC antibody which distinguishes parallel, in register fibrils. On the other hand, J20 mice had a lower level of Aβ oligomers, which did not interact with PrPC when tested in vitro and were OC-negative. These results suggest the two mouse models produce diverse Aβ assemblies that could interact with different targets, highlighting the necessity to characterise the conformation of the Aβ oligomers concomitantly with the toxic cascade elicited by them. Our results provide an explanation for the apparent contradictory results found in APP-PS1 mice and the J20 mouse line in regards to Aβ toxicity mediated by PrPC.
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