Health Institutions Research Articles

Decreased urinary excretion of norepinephrine and dopamine in autonomic synucleinopathies.

Autonomic synucleinopathies feature autonomic failure and intracellular deposition of the protein alpha-synuclein. Three such conditions are the Lewy body diseases (LBDs) Parkinson's disease (PD) and pure autonomic failure (PAF) and the non-LBD synucleinopathy multiple system atrophy (MSA). These diseases all entail catecholaminergic abnormalities in the brain, sympathetically innervated organs, or both; however, little is known about renal catecholaminergic functions in autonomic synucleinopathies. We measured urinary excretion rates of the sympathetic neurotransmitter norepinephrine, the hormone epinephrine, the autocrine-paracrine substance dopamine, the catecholamine precursor 3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylglycol (DHPG, the main neuronal metabolite of norepinephrine), and 3,4-dihydroxyphenylacetic acid (DOPAC, a major dopamine metabolite), in PD, PAF, and MSA groups and controls. Data were reviewed from all research participants who had urine collections (usually 3.5 h) at the National Institutes of Health (NIH) Clinical Center from 1995 to 2024. The control cohort had neither autonomic failure nor a movement disorder. Norepinephrine excretion rates were decreased compared with controls in PD (p = 0.0001), PAF (p < 0.0001), and MSA (p < 0.0001). Dopamine excretion was also decreased in the three groups (PD: p = 0.0136, PAF: p = 0.0027, MSA: p = 0.0344). DHPG excretion was decreased in PD (p = 0.0004) and PAF (p = 0.0004) but not in MSA. DOPA and epinephrine excretion did not differ among the study groups. Autonomic synucleinopathies involve decreased urinary excretion rates of norepinephrine and dopamine. Since virtually all ofurinary dopamine in humans is derived from circulating DOPA, the low rates of urinary norepinephrine and dopamine excretion may reflect dysfunctions in the renal sympathetic noradrenergic system, the DOPA-dopamine autocrine-paracrine system, or both systems.

Social determinants of health as risk factors for keratoconus in the All of Us database

Background/aimsClinical risk factors for keratoconus (KCN) have previously been established. While the impact of the social determinants of health on the epidemiology and pathophysiology of KCN has been explored, further...

Cross-Sectional Survey Analysis of Institutional Research Partnerships in Complementary and Integrative Health: Identifying Barriers and Facilitators.

Objective: Collaboration between complementary and integrative health (CIH) institutions and research-intensive (R1) institutions has been successfully undertaken in the United States, resulting in federally funded research projects, educational programs, and faculty development. The aim of this cross-sectional survey study was to explore the barriers and facilitators to establishing and maintaining such collaborative partnerships. Methods: A 32-question survey was sent to participants recruited through author contacts and resources, literature review, and database searches. Participants were required to be researchers and affiliates who attempted, completed, or had current collaborative endeavors involving CIH and R1 institutions. Data were collected in the research electronic data capture (REDCap) system and descriptive quantitative and qualitative data analysis was undertaken. Results: A total of 26 unique entries were included in the final data analysis; four of which were paired entries (one from an R1 institution and one from a CIH institution) to make up two dyad data collections. Eighty-one percent of the participants had senior leadership roles at CIH institutions representing five CIH disciplines-East Asian medicine (acupuncture and Traditional Chinese Medicine), chiropractic medicine, massage therapy, naturopathy, and yoga. Collaborative research projects were often (>38%) in response to specific project funding mechanisms. Over 60% of the collaborations also included educational activities and faculty development. Collaborations resulted in multiple different types of benefits to both institutions but were not without associated challenges. Conclusion: Collaborations between R1 and CIH institutions can be cooperative, productive, and mutually beneficial. Funding mechanisms supporting R1 and CIH collaboration increase CIH research productivity as well as the development of innovative research methodology to study the real-world practice of CIH therapies, whole systems, and whole person health. CIH researchers would greatly benefit from such funding, allowing access to research infrastructure, professional development, and the provision of protected time to conduct research.

Predictive analysis of lung function in school-age children born with very low birthweight, according to the definition used of bronchopulmonary dysplasia. A retrospective observational analysis.

To determine the predictive value of the definition of bronchopulmonary dysplasia (BPD) on spirometric parameters of very low birthweight (VLBW) children of school age between 1 January 2008 and 31 December 2016. In this longitudinal retrospective observational study, we analyse a cohort of children admitted to a neonatal intensive care unit between 1 January 2008 and 31 December 2016. All newborns weighing <1500 g and born before 32 weeks of gestational age were included in the study (VLBW newborns). The existence of BPD was established retrospectively according to the definitions proposed by the National Institutes of Health (NIH) in 2001 and the National Institute of Child Health and Human Development (NICHD) in 2018. Lung function of the school-age cohort was evaluated prospectively as FEV1, FVC, FEF25-75% and FEV1/FVC by spirometry. The predictive analysis was performed by multivariate linear regression. Of the 145 children included in the study cohort, 60 were diagnosed with BPD according to the NIH definition and 36 according to that of the NICHD. Lung function was reduced by about 20% in patients with BPD, irrespective of the definition applied. However, the predictive regression model only produced a statistically significant fit with the spirometric variables when the NIH definition was adopted. Our findings highlight the value of continuing to consider oxygen requirements at 28 days of chronological age in the definition of BPD, in order to obtain higher quality predictions of lung function parameters assessed later, during school age.

Waning success: a 2013–2022 spatial and temporal trend analysis of malaria in Ethiopia

BackgroundDespite consecutive decades of success in reducing malaria transmission, Ethiopia went off track towards its goal of malaria elimination by 2030, as outlined in the NMCP malaria strategy. Recent malaria outbreaks in Ethiopia are attributed to the emergence and spread of diagnostic and drug-resistant Plasmodium falciparum, increased insecticide resistance in major vectors and the spread of invasive Anopheles stephensi. The effects of the COVID-19 pandemic, environmental anomalies and internal conflicts have also potentially played a role in increasing malaria transmission. This study aimed to evaluate the contribution of environmental factors and An. stephensi to the spatiotemporal trends of recent malaria cases in Ethiopia.MethodsClinical malaria case data reported weekly between January 2013 and January 2023 were obtained from the Ethiopian Public Health Institute (EPHI), Addis Ababa. A negative binomial regression model was used to explain the variability and potential overdispersion in the weekly number of malaria cases reported across Ethiopian administrative zones. This model incorporated fixed effects for selected environmental factors and random effects to capture temporal trends, zone specific seasonal patterns, spatial trends at the zone level, and the presence of An. stephensi and its impact.ResultsOur negative binomial regression model highlighted 56% variability in the data and slightly more than half (55%) was due to environmental factors, while the remainder was captured by random effects. A significant nationwide decline in malaria risk was observed between 2013 and 2018, followed by a sharp increase in early 2022. Malaria risk was higher in western and northwestern zones of Ethiopia compared to other zones. Zone-specific seasonal patterns, not explained by environmental factors, were grouped into four clusters of seasonal behaviours. The presence of An. stephensi was not shown to have any significant impact on malaria risk.ConclusionsUnderstanding the spatial and temporal drivers of malaria transmission and therefore identifying more appropriate malaria control strategies are key to the success of any malaria elimination and eradication programmes in Ethiopia. Our study found that approximately 50% of malaria risk variability could be explained by environmental, temporal, and spatial factors included in the analysis, while the remaining variation was unexplained and may stem from other factors not considered in this study. This highlights the need for a better understanding of underlying factors driving local malaria transmission and outbreaks, to better tailor regional programmatic responses.Graphical

Knowledge, attitude, and practice towards COVID-19 and associated factors among students in Ethiopia: Systematic review and meta-analysis.

The World Health Organization (WHO) has not confirmed the eradication of the COVID-19 pandemic or the development of a cure. Ongoing research is necessary to update public understanding, attitudes, and behaviors. Therefore, this study aims to evaluate the knowledge, attitudes, and practices related to COVID-19 among students in Ethiopia. To estimate the pooled proportions and associated factors of knowledge, positive attitude, and prevention practice toward COVID-19 among students in Ethiopia. The study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and was registered on the PROSPERO database. Data extraction was done using an Excel spreadsheet, and analysis was conducted using STATA. The quality of the articles was assessed using the Joanna Briggs Institute (JBI) grading approach. A narrative summary and random-effects model with a 95% confidence interval were used. Heterogeneity and publication bias were also assessed. The results were presented using a forest plot and tables. Out of 2089 studies reviewed, only 16 met the inclusion criteria. The pooled proportions of COVID-19 good knowledge, positive attitude, and good prevention practice among students in Ethiopia were found to be 62.68% [95% CI 50.96-74.40, I2 = 98.93%], 60.22% [95% CI 51.64-68.80, I2 = 97.68%], 48.47% [95% CI, 44.16-52.78, I2 = 91.45%] respectively. Factors that affected knowledge included marital status, family size, sex, study year, and residency. Knowledge and residency were identified as predictors of attitude. Determinants of practice included knowledge, attitude, sex, study program, and residency. The pooled proportion of students in Ethiopia with good knowledge, positive attitudes, and good practices regarding COVID-19 was low. Policymakers, the Ministry of Health, Public Health Institutions, and other stakeholders should intensify their efforts on COVID-19 and develop interventions aimed at females, rural residents, and extension students. The protocol was registered on the PROSPERO database with ID = CRD42023478234.

Groundbreaking NIMH initiative seeks accessible predictive tools

Precision medicine is revolutionizing some health care disciplines but has had comparatively little impact in mental health. An ambitious research initiative funded by the National Institute of Mental Health (NIMH) will explore whether innovations in the collection of patient data can improve the understanding of mental health disorders, leading to more accurate prediction of whether a patient will respond to a specific treatment.

Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children.

B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes. We conducted a phase 3 trial involving children with newly diagnosed standard-risk B-cell ALL who had an average or high risk of relapse. Patients were randomly assigned to receive chemotherapy alone or chemotherapy plus two nonsequential 28-day cycles of blinatumomab. The primary end point was disease-free survival. The data and safety monitoring committee reviewed the results from the first interim efficacy analysis, which included 1440 patients who had undergone randomization (722 to chemotherapy alone and 718 to blinatumomab and chemotherapy) and recommended early termination of randomization. At a median follow-up of 2.5 years, the estimated 3-year disease-free survival (±SE) was 96.0±1.2% with blinatumomab and chemotherapy and 87.9±2.1% with chemotherapy alone (difference in restricted mean survival time, 72 days; 95% confidence interval, 36 to 108; P<0.001 by stratified log-rank test). The estimated 3-year disease-free survival among patients with an average relapse risk was 97.5±1.3% with blinatumomab and chemotherapy and 90.2±2.3% with chemotherapy alone; among those with a high relapse risk, the corresponding values were 94.1±2.5% and 84.8±3.8%. Cytokine release syndrome, seizures, and sepsis of grade 3 or higher were rare during blinatumomab cycles, but the overall incidence of nonfatal sepsis and catheter-related infections was significantly higher among patients with an average relapse risk who had been assigned to receive blinatumomab and chemotherapy than among those assigned to receive chemotherapy alone. Adding blinatumomab to combination chemotherapy in patients with newly diagnosed childhood standard-risk B-cell ALL of average or high risk of relapse significantly improved disease-free survival. (Funded by the National Institutes of Health and others; AALL1731 ClinicalTrials.gov number, NCT03914625.).

Considerations for the implementation of a non-pharmacological, patient-centered approach to chronic non-oncological pain treatment in the UK and Chile

Non-oncological chronic pain imposes a significant global burden, and its prevalence is increasing. The World Health Organisation and UK National Institute for Health and Care Excellence promote patient-centered care as an effective approach to treating chronic non-oncological pain. This approach improves long term health outcomes by identifying root causes which impact these conditions, within the framework of the biopsychosocial care model. Within Chile and the United Kingdom, patients advocate for pharmacological interventions, however Centres for Disease Control and Prevention emphasise a preference for non-pharmacological management strategies. As the UK healthcare system actively seeks to reduce reliance on pharmacological treatment modalities, using alternative interventions, Chilean healthcare has also begun to regenerate its approaches to treatment. The objective of this paper is to reflect upon the implementation of these strategies to gain insights into their potential for driving change.

Screen time associated with substance use in young adolescents

Researchers have found that screen tie was associated with alcohol, nicotine, and cannabis experimentation in young teens. With each additional hour spent on social media, texting, and video chatting, the odds of any substance experimentation went up. The study, “Prospective association between screen use modalities and substance use experimentation in early adolescents” by Jason M. Nagata M.D. is published in the January 2025 issue of Drug and Alcohol Dependence. The researchers based their information on data from the Adolescent Brain Cognitive Development (ABCD) study of the National Institutes of Health, which funded the study.

Home delivery and associated factors among women who gave birth after antenatal care follow-up in the last 6 months in Jabitehnan District, Northwest Ethiopia: mixed community-based study

IntroductionMaternal mortality is a global issue, with developing countries accounting for over 99% of maternal deaths, with 30% of Ethiopian mothers dying from pregnancy-related causes. This study aimed to assess the magnitude, associated factors, and reasons for home delivery among women who gave birth after antenatal care follow-up in the last 6 months in Jabitehnan District, Northwest Ethiopia.MethodsA mixed community-based study was conducted on women who gave birth after antenatal care follow-up in the last 6 months. Data was collected through face-to-face interviews and structured questionnaires. Bivariate and multivariable logistic regressions were performed to identify factors associated with home delivery. Qualitative data were collected through focus group discussions and in-depth interviews and analyzed using a thematic content analysis method.ResultIn this study, the magnitude of home delivery after ANC follow-up among mothers who gave birth in the last 6 months was 37%, with a 95% CI of 32.5 and 41.5. Pregnancy plan [AOR: 4.56 (2.65, 7.86)], experience of abortion AOR: 3.01 [1.631, (5.55)], ANC follow-up at public hospitals [AOR: 1.89 (1.119, 3.18)], and pregnant mothers visited at home by healthcare providers during their ANC follow-up absent [AOR: 1.61 (1.02, 2.53)] were predictors of home delivery. Poor counseling during ANC, and lack of pregnancy plans, traditions, and beliefs were reasons for home delivery.ConclusionThe study reveals a high magnitude of home delivery as compared to a study done in Bahir Dar (21.2%). Factors include pregnancy plans, health institution type, abortion experience, and absence from antenatal care. Poor counseling during ANC, and lack of pregnancy plans, traditions, and beliefs were reasons for home delivery. Health professionals should receive training in communication and counseling techniques, and they should encourage mothers to plan their pregnancies and visit facility delivery services during ANC follow-up.

Developing a framework for community childcare doctors to support community-based parental health education in preventing unintentional injuries among children aged below 6 years: a grounded theory exploration in eastern China

ObjectiveUnintentional injuries are a major threat to children’s health. Community-based health management services, which include the prevention of unintentional injuries among children aged 0–6 years, are important basic national public...

The projected burden of arthritis among adults and children in Australia to the year 2040: a population-level forecasting study.

Understanding how many people could be living with arthritis in the future is essential for planning health service needs and national health workforce requirements, and for arthritis advocacy and policy development. This study aimed to forecast the size of different populations with arthritis in Australia and associated health system expenditure, up to the year 2040. In this population-level forecasting study for Australia, prevalence data for arthritis, osteoarthritis, and rheumatoid arthritis were obtained from the Australian Bureau of Statistics 2022 National Health Survey. Prevalence rates for juvenile idiopathic arthritis were sourced from 2021 Census data. Overall, age-specific and sex-specific prevalence data were applied to national population projections to forecast arthritis, osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis populations for 2025, 2030, 2035, and 2040. The base case analysis considered medium population growth; sensitivity analyses considered low and high growth scenarios. Health system expenditure data from the Australian Institute of Health and Welfare were extrapolated to base case projections for the years 2025, 2030, 2035, and 2040, and were then inflated to future dollars. To understand the broader context and implications of our projections through the lens of lived experience, an arthritis consumer researcher and members of the Arthritis Australia Consumer Advisory Panel reviewed the arthritis burden estimates. With population growth and ageing, 5·39 million (95% CI 5·19-5·58) people are projected to have arthritis in Australia in 2040, representing an increase of 31% from 4·11 million (3·95-4·27) in 2025. By 2040, 3·11 million (2·99-3·23) people are expected to have osteoarthritis, 749 000 (652 000-846 000) are expected to have rheumatoid arthritis, and about 8500 children and adolescents are expected to have juvenile idiopathic arthritis. The age-standardised rate of osteoarthritis is forecast to increase for males from 6·28% in 2025 to 7·03% in 2040, and for females from 10·82% to 12·18% over this period. The age-standardised rate of rheumatoid arthritis is forecast to increase for males from 1·56% in 2025 to 1·75% in 2040, and for females from 2·62% in 2025 to 2·94% in 2040. Little change is anticipated in the number of children and adolescents with juvenile idiopathic arthritis (estimated at 8500 individuals in 2040). Based on current spending levels of AU$2100 per person with osteoarthritis and $1918 per person with rheumatoid arthritis, annual health system expenditure for osteoarthritis and rheumatoid arthritis is conservatively forecast to exceed AU$11·92 billion by 2040. Using the latest national-level data, this study has generated contemporary projections of the substantial burden of arthritis (both population size and health-care costs) in Australia. These projections underscore the importance of well-resourced health services that can capably deliver timely, high-value care to a growing number of people with arthritis. Arthritis Australia and National Health and Medical Research Council.

Information access and COVID-19 vaccination hesitancy among foreign-born persons in Sweden – a focus group interview-study

BackgroundIn most countries, lower rates of COVID-19 vaccination have been observed in foreign-born individuals, yet little is known about the underlying reasons, especially as reported by these individuals themselves. This exploratory interview study investigated lack of information access and hesitancy towards taking the COVID-19 vaccine among foreign-born individuals in Sweden.MethodsWe used purposive sampling to recruit foreign-born adults who expressed being hesitant towards getting vaccinated, as well as health guides and doulas who were assigned to spread COVID-19 related information in immigrant-dense urban areas. Data were collected using semi-structured focus group interviews, which were transcribed verbatim and analysed according to systematic text condensation.ResultsThree focus group interviews were conducted with altogether eleven participants. One group consisted of health guides/doulas, while the participants in the other groups were gainfully employed in other jobs, or full-time students, or housewives. Four main themes emerged: (1) Language barriers and sociocultural differences, (2) Consequences of not using official Swedish information, (3) Decision-making on COVID-19 vaccination, and (4) Suggestions to improve information dissemination. The lack of information in other languages than Swedish and lack of effective information channels resulted in that most participants barely used information from official Swedish health care and public health institutions. Instead, they relied on social media, social contacts and international media, through which contradictive and negative information about the vaccine was spread. The decision to get vaccinated or not became a process fraught with insecurities about the effectiveness and side effects of the vaccine, which was balanced against wishing to be protected and to contribute to the battle against COVID-19. The participants suggested that information dissemination could be improved by producing a multilingual information outreach and to increase the use of transmission through social interaction with trusted persons and platforms.ConclusionsAn inadequately adapted information strategy prevented some members of the society from making fact-based decisions about getting vaccinated. Several suggestions for improving dissemination were brought forth that can be tested in future communication strategies.

Cybersecurity in Hospitals: A Case Analysis of the University of Ghana Medical Centre

The University of Ghana Medical Centre Ltd is a premier academic health facility that delivers tertiary/quaternary level health services, education and research in Ghana, Africa and the globe. It is Ghana’s premier quasi health institution and is the only quaternary health centre in Ghana. It is a fully digitalised institution vulnerable to cyberattacks because of patient data, hospital systems, availability of health services and also data of prominent people in society. The paper analysed cybersecurity measures implemented at the health facility to reveal its advantages and disadvantages, and further outlook for its development. The research method comprised an assessment of cybersecurity-related activities, reports and documentation to explore cybersecurity measures and regulatory compliance in explaining timely employee awareness and responding to incidents to protect patients’ details with cybersecurity specialists’ cooperation. The study reports the proactive measures taken by the health facility to avert and mitigate potential cybersecurity threats. However, it also identifies the need for the facility to partner with cybersecurity experts in developing comprehensive response plans, and this comes in recognition of some weaknesses in the current implemented system which are institutional, bureaucratic and technology related.

A child opportunity index in Italy: a pilot proposal

BackgroundThe Child Opportunity Index (COI) is a new and innovative tool designed to assess the environment in which children grow up, offering a broad evaluation of the opportunities available to them in different neighborhoods. This initiative aims to ensure improvements in children’s living conditions and future health outcomes.MethodsThe study was performed in the cities of Palermo and Rome. Our Italian COI consists of three main domains: education, health and environment, and economy, each subdivided into specific indicators. We collected information, when available, useful for our indicators from institutional sites and municipal archives. Furthermore, in the city of Rome, we distributed a questionnaire through local pediatricians, collecting data in 2 randomly chosen neighborhoods with questions on children’s health and quality of life, proposing an initial approach that, when implemented using data provided by the government and public and private health institutions, aims to evaluate the correlation between socio-economic opportunities and the psycho-physical health of children, as demonstrated in the literature.ResultsAs a result, many aspects, such as the rate of air pollution or the illegal occupation of houses, were not taken into consideration. We therefore consider our COI proposal only a starting model that will have to be implemented once all the necessary information has been obtained. However, what can be deduced from this first descriptive study is how the opportunities in different neighborhoods are not the same for all children. The number of educational opportunities as well as the number of environmental opportunities differs between the various districts and is not homogeneous between different cities or within the same city.ConclusionsIn conclusion, it is not simple to analyze in a scientific manner the child’s health impact of living in different areas. The COI could be a useful and simple tool that can give us this information. Pediatricians could collaborate with institutions to implement intervention plans and to reduce existing differences, social and health inequalities. Future studies will have to implement this pilot study to create and validate an Italian model of COI to be used as a useful tool in children’s assistance.

Integration of patient-oriented research principles in health institutions: a scoping review protocol

IntroductionIn 2011, the Canadian Institutes of Health Research launched a Strategy for Patient-Oriented Research (POR) for healthcare and academic institutions to increase patient participation in health research. POR considers patients...

Public engagement to refine a whole-school intervention to promote adolescent mental health.

Despite high rates of adolescent mental health problems, there are few effective school-based interventions to address this. Whole-school interventions offer a feasible and sustainable means of promoting mental health, but few have to date been evaluated. Previously we trialled the Learning Together intervention comprising local needs assessment, student and staff participation in decision-making, restorative practice, and a social and emotional skills curriculum. This was effective not only in preventing bullying (primary outcome), but also in promoting mental well-being and psychological functioning (secondary outcomes). We aimed to adapt Learning Together to develop Learning Together for Mental Health, focused on promoting mental health. This paper reports on how we refined and elaborated intervention materials to produce the Learning Together for Mental Health intervention including through patient and public involvement and engagement. We reviewed evidence to inform choice of the curriculum component and the contents of our needs assessment survey. We conducted patient and public involvement and engagement with school staff and students, and children and young people from the National Children's Bureau to adapt the intervention. We also conducted a systematic review of reviews to inform a menu of evidence-based actions, but this is reported separately. Southern England. Patient and public involvement and engagement was conducted with four staff and five students from one secondary school, and a group of two school senior leadership team members from different schools, and about eight children and young people who were members of the Young National Children's Bureau. None. We refined and elaborated our initial plans for Learning Together for Mental Health to generate an intervention supported by full materials, training and external facilitation. We focused needs assessment on mental health, added a menu of evidence-based whole-school mental health actions, and switched to a different social and emotional skills curriculum. We retained restorative practice and staff/student involvement in decisions. No further refinements were made to the intervention theory of change or overall approach. Patient and public involvement and engagement was useful, but not all suggestions were acted on either because some participants suggested dropping pre-determined elements (e.g. needs survey) or because suggestions (e.g. to include aromatherapy) lacked evidence of effectiveness. Not all of our engagements with patient and public involvement and engagement stakeholders were sustained over time. Our patient and public involvement and engagement work was affected by its having occurred within the recovery period from COVID-19 when schools were more stressed than normal. We had planned for the school involved in patient and public involvement and engagement to be above average in student free-school-meals eligibility, but the school initially recruited dropped out at the last minute. Its replacement had a lower-than-average rate of free-school-meal entitlement. This paper reports on the process of adaptation and reflects on the various ways in which engagement and evidence review were useful in this process. We found that it is possible to refine interventions and elaborate them to provide full materials and support via processes drawing on evidence review and patient and public involvement and engagement. The latter proved valuable in informing refinement of Learning Together for Mental Health in terms of ensuring its feasibility, acceptability, and inclusiveness. However, in our opinion, not all suggestions from patient and public involvement and engagement can or should be acted on, especially when they do not align with the evidence base. A feasibility study to optimise the intervention and assess whether progression to a full trial is justified. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR131594.

NLRP3 inflammasome in expressed prostatic secretions as a potential biomarker of chronic prostatitis/chronic pelvic pain syndrome.

Pyroptosis has been implicated in the progression of chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS). The present study was performed to explore the diagnostic value of the levels of the pyroptosis-related protein nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome in the expressed prostatic secretions (EPS) of patients with CP. A total of 167 CP patients, including 85 National Institutes of Health (NIH)-IIIA CP patients and 82 NIH-IIIB CP patients, as well as 80 benign prostatic hyperplasia (BPH) patients and 80 healthy controls, were enrolled. The levels of NLRP3, interleukin 1 beta (IL-1β), and interleukin 18 (IL-18) in EPS were detected using an enzyme-linked immunosorbent assay (ELISA). Disease severity was assessed using the Bergman CP scale. Differences in EPS NLRP3 inflammasome levels between the groups were analyzed, and receiver operating characteristic (ROC) curves were used to investigate the clinical value of the NLRP3 inflammasome in the diagnosis of CP. The numerical rating scale (NRS), the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the Danish Prostatic Symptom Score (DAN-PSS-1) were applied to evaluate symptom severity. The cutoff value of NLRP3 expression was calculated using R language. NLRP3 inflammasome levels in EPS were significantly higher in CP patients of NIH-IIIA and NIH-IIIB compared to the BPH patients and controls. NLRP3 levels in EPS were positively associated with Bergman grade. In addition, NRS levels were in a positive relationship with NIH-CPSI and DAN-PSS-1. The ROC curve analysis demonstrated that NLRP3 in EPS may act as a decent indicator for the diagnosis of CP/CPPS. The cutoff value of EPS NLRP3 expression was ≥55.25 ng/mL. NLRP3 levels in EPS were significantly higher in NIH-IIIA and NIH-IIIB patients compared to BPH patients and healthy controls. NLRP3 inflammasome levels in EPS may be valuable as diagnostic indicators, and targeting chemokines may present a promising approach to treatment for those suffering from CPPS.

Orthopoxvirus Genome Sequencing, Assembly, and Analysis.

Poxviruses have exceptionally large genomes compared to most other viruses, which represent unique challenges to sequencing and assembly due to complex features such as repeat elements and low complexity sequences. The 2022 global mpox outbreak led to an unprecedented level of poxvirus sequencing as public health and research institutions faced with large sample numbers and demand for fast turnaround, merged NGS protocols designed for small RNA viruses with poxvirus expertise. Traditional manual assembly, checking, and editing of genomes was not feasible. Here, we present a protocol for metagenomic sequencing and orthopoxvirus genome assembly directly from DNA extracted from a patient lesion swab with no viral enrichment or host depletion. This sequencing approach is cost effective when using high throughput sequencing instruments and allows for detection of genomic insertions, deletions, and large rearrangement with confidence. We describe usage of two publicly available bioinformatic pipelines for genome assembly, quality control, annotation, and submission to sequence repositories.