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1.
Immunity ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-39013465

ABSTRACT

Antibiotic use in early life disrupts microbial colonization and increases the risk of developing allergies and asthma. We report that mice given antibiotics in early life (EL-Abx), but not in adulthood, were more susceptible to house dust mite (HDM)-induced allergic airway inflammation. This susceptibility was maintained even after normalization of the gut microbiome. EL-Abx decreased systemic levels of indole-3-propionic acid (IPA), which induced long-term changes to cellular stress, metabolism, and mitochondrial respiration in the lung epithelium. IPA reduced mitochondrial respiration and superoxide production and altered chemokine and cytokine production. Consequently, early-life IPA supplementation protected EL-Abx mice against exacerbated HDM-induced allergic airway inflammation in adulthood. These results reveal a mechanism through which EL-Abx can predispose the lung to allergic airway inflammation and highlight a possible preventative approach to mitigate the detrimental consequences of EL-Abx.

2.
J Dev Behav Pediatr ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38990144

ABSTRACT

OBJECTIVE: Short sleep and evening phase preference associate with impaired self-control, yet few studies have assessed the efficacy of sleep extension for improving this behavioral domain. Thus, this secondary analysis of a behavioral sleep intervention measured whether an intervention that enhanced children's sleep also affected self-control. Differences by chronotype were also explored. METHODS: Sixty-seven children (8-11 yr), who reportedly slept <9.5 hr/d, were randomized to either a control or sleep intervention condition (i.e., 4-session behavioral intervention to enhance sleep by 1-1.5 hr/night). Chronotype was assessed using the Child Chronotype Questionnaire at baseline, and self-control was assessed using the Self-Control Rating Scale (SCRS, a caregiver report) at baseline and 8 weeks postrandomization. Total sleep time (TST) was measured using wrist actigraphy for 1 week at both baseline and 8 weeks postrandomization. Partial correlations and mixed-model ANOVAs were used for statistical analyses, with age as a covariate. RESULTS: At baseline, children with shorter TST (r = -0.29, p = 0.02) and an evening preference (r = 0.26, p = 0.049) were perceived as having lower self-control by their caregivers. Significant condition*time interaction effects were found for TST (p < 0.001) and SCRS score (p = 0.046): From baseline to follow-up, children randomized to the sleep intervention exhibited a significant increase in TST and were perceived as having greater self-control by their caregiver; children randomized to the control condition exhibited no change in TST or in SCRS score. The condition*chronotype*time interaction effect was not significant. CONCLUSION: A brief sleep intervention that enhanced TST also resulted in enhanced caregiver reported self-control in school-age children. Results add to the growing evidence for the importance of sleep health in children.

3.
Child Youth Serv Rev ; 1602024 May.
Article in English | MEDLINE | ID: mdl-38946713

ABSTRACT

American Samoan adolescents experience a high prevalence of mental health problems, including depression, anxiety, substance use, and suicidal thoughts and behaviors. To complement existing health system efforts, family-based interventions may be a feasible, cost-effective, and relevant opportunity to promote mental health. This community-partnered, qualitative study aimed to: (1) identify potential family-related psychosocial protective factors for adolescent mental health and (2) develop a framework for a parenting program to promote adolescent mental health in American Samoa. Applying the fa'afaletui framework developed for research in Samoan communities, which emphasizes the importance of weaving a range of community member perspectives to reach consensus, semi-structured in-depth interviews with adult key informants (n=28) were conducted between October 2020 and February 2021. Results were validated through five focus groups with Samoan adolescents (n=35) between May and June 2022. Adult participants were sampled for diversity in profession, age, gender, education, and region of residence; adolescent participants were sampled for diversity in gender. Participants were recruited using personal networks and snowball sampling; adolescent participants also responded to Facebook advertising. The semi-structured interviews focused on broad topics including common mental health problems, contributors to mental illness, and potential interventions, among others. Transcripts were coded in duplicate and analyzed using deductive thematic analysis. Themes were collaboratively mapped onto an adapted fonofale model, an existing framework for Pacific Island health research. Six themes described key practices: (1) provide emotional safety and security; (2) provide physical safety and security; (3) encourage sense of self; (4) strengthen intergenerational communication skills; (5) prioritize quality time; and (6) cultivate healthy coping strategies. Participants also expressed the importance of a supportive environment grounded in culture, family and community, and caregiver mental health. These results provide an initial step to identify family-focused factors that promote adolescent mental health in American Samoa and categorize them into a framework to inform intervention development. Drawing on a collaborative and community-partnered process, these findings provide the first evidence-based framework to develop a parenting program to promote adolescent mental wellbeing and resilience in Samoan communities.

4.
Methods Enzymol ; 700: 49-76, 2024.
Article in English | MEDLINE | ID: mdl-38971612

ABSTRACT

High pressure is both an environmental challenge to which deep sea biology has to adapt, and a highly sensitive thermodynamic tool that can be used to trigger structural changes in biological molecules and assemblies. Lipid membranes are amongst the most pressure sensitive biological assemblies and pressure can have a large influence on their structure and properties. In this chapter, we will explore the use of high pressure small angle X-ray diffraction and high pressure microscopy to measure and quantify changes in the lateral structure of lipid membranes under both equilibrium high pressure conditions and in response to pressure jumps.


Subject(s)
Hydrostatic Pressure , Lipid Bilayers , X-Ray Diffraction , X-Ray Diffraction/methods , Lipid Bilayers/chemistry , Lipid Bilayers/metabolism , Scattering, Small Angle , Membrane Lipids/chemistry , Membrane Lipids/metabolism , Thermodynamics
5.
Infect Dis Model ; 9(4): 1117-1137, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39022298

ABSTRACT

The recent mpox outbreak (in 2022-2023) has different clinical and epidemiological features compared with previous outbreaks of the disease. During this outbreak, sexual contact was believed to be the primary transmission route of the disease. In addition, the community of men having sex with men (MSM) was disproportionately affected by the outbreak. This population is also disproportionately affected by HIV infection. Given that both diseases can be transmitted sexually, the endemicity of HIV, and the high sexual behavior associated with the MSM community, it is essential to understand the effect of the two diseases spreading simultaneously in an MSM population. Particularly, we aim to understand the potential effects of HIV on an mpox outbreak in the MSM population. We develop a mechanistic mathematical model of HIV and mpox co-infection. Our model incorporates the dynamics of both diseases and considers HIV treatment with anti-retroviral therapy (ART). In addition, we consider a potential scenario where HIV infection increases susceptibility to mpox, and investigate the potential impact of this mechanism on mpox dynamics. Our analysis shows that HIV can facilitate the spread of mpox in an MSM population, and that HIV treatment with ART may not be sufficient to control the spread of mpox in the population. However, we showed that a moderate use of condoms or reduction in sexual contact in the population combined with ART is beneficial in controlling mpox transmission. Based on our analysis, it is evident that effective control of HIV, specifically through substantial ART use, moderate condom compliance, and reduction in sexual contact, is imperative for curtailing the transmission of mpox in an MSM population and mitigating the compounding impact of these intertwined epidemics.

6.
Dalton Trans ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953848

ABSTRACT

Complexes formed between the heaviest and lightest elements in the periodic table yield the f-block hydrides, a unique class of compounds with wide-ranging utility and interest, from catalysis to light-responsive materials and nuclear waste storage. Recent developments in syntheses and analytics, such as exploiting low-oxidation state metal ions and improvements in X-ray diffraction tools, have transformed our ability to understand, access and manipulate these important species. This perspective brings together insights from binary metal hydrides, with molecular solution phase studies on heteroleptic complexes and gas phase investigations. It aims to provide an overview of how the f-element influences hydride formation, structure and reactivity including the sometimes-surprising power of co-ligands to tune their behaviour towards a variety of applications.

7.
Rehabil Psychol ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38913739

ABSTRACT

PURPOSE/OBJECTIVE: To examine the association of changes in homebound status (i.e., never/rarely leaving the home) with life satisfaction in the first 10 years after traumatic brain injury (TBI). RESEARCH METHOD/DESIGN: We analyzed data from 2,294 individuals with moderate-to-severe TBI from the TBI Model Systems National Database using a longitudinal multilevel model with time-varying predictors to account for within-person changes over time as well as between-person differences. We measured homebound status (defined as leaving the home ≤ 2 days/week) and life satisfaction (defined as the total score on the Satisfaction With Life Scale) at 1, 2, 5, and 10 years post-TBI. We adjusted the models for demographic and injury-related covariates and used inverse probability weighting to account for selection bias. RESULTS: Forty-five (2%) individuals were homebound at all follow-up visits, 523 (22.8%) were homebound at least one follow-up visit, and 1,726 (75.2%) were never homebound. Individuals with TBI who were consistently homebound had > 1 SD lower life satisfaction compared to those who were never homebound, ß = -8.07, 95% confidence interval (CI) = [-9.39, -6.76], p < .001. Individuals who became homebound experienced a significant, but modest, decline in life satisfaction (ß = -2.13, 95% CI = [-2.66, -1.61], p < .001). CONCLUSIONS/IMPLICATIONS: Our results indicate that being homebound and becoming homebound are associated with decreased life satisfaction. Homeboundness is a potentially modifiable target to improve life satisfaction, and elucidation of contributing factors to homebound status will help develop interventions to ameliorate post-TBI homeboundness. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

8.
PLoS One ; 19(6): e0302643, 2024.
Article in English | MEDLINE | ID: mdl-38829901

ABSTRACT

BACKGROUND: The A allele of rs373863828 in CREB3 regulatory factor is associated with high Body Mass Index, but lower odds of type 2 diabetes. These associations have been replicated elsewhere, but to date all studies have been cross-sectional. Our aims were (1) to describe the development of type 2 diabetes and change in fasting glucose between 2010 and 2018 among a longitudinal cohort of adult Samoans without type 2 diabetes or who were not using diabetes medications at baseline, and (2) to examine associations between fasting glucose rate-of-change (mmol/L per year) and the A allele of rs373863828. METHODS: We describe and test differences in fasting glucose, the development of type 2 diabetes, body mass index, age, smoking status, physical activity, urbanicity of residence, and household asset scores between 2010 and 2018 among a cohort of n = 401 adult Samoans, selected to have a ~2:2:1 ratio of GG:AG: AA rs373863828 genotypes. Multivariate linear regression was used to test whether fasting glucose rate-of-change was associated with rs373863828 genotype, and other baseline variables. RESULTS: By 2018, fasting glucose and BMI significantly increased among all genotype groups, and a substantial portion of the sample developed type 2 diabetes mellitus. The A allele was associated with a lower fasting glucose rate-of-change (ß = -0.05 mmol/L/year per allele, p = 0.058 among women; ß = -0.004 mmol/L/year per allele, p = 0.863 among men), after accounting for baseline variables. Mean fasting glucose and mean BMI increased over an eight-year period and a substantial number of individuals developed type 2 diabetes by 2018. However, fasting glucose rate-of-change, and type 2 diabetes development was lower among females with AG and AA genotypes. CONCLUSIONS: Further research is needed to understand the effect of the A allele on fasting glucose and type 2 diabetes development. Based on our observations that other risk factors increased over time, we advocate for the continued promotion for diabetes prevention and treatment programming, and the reduction of modifiable risk factors, in this setting.


Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Fasting , Humans , Female , Diabetes Mellitus, Type 2/genetics , Male , Middle Aged , Blood Glucose/metabolism , Adult , Fasting/blood , Mutation, Missense , Polymorphism, Single Nucleotide , Alleles , Samoa , Cohort Studies , Body Mass Index , Genotype , Longitudinal Studies , Cross-Sectional Studies , Aged , Tumor Suppressor Proteins
9.
Ther Adv Med Oncol ; 16: 17588359241253115, 2024.
Article in English | MEDLINE | ID: mdl-38832300

ABSTRACT

Background: The COVID-19 pandemic affected cancer screening, diagnosis and treatments. Many surgeries were substituted with bridging therapies during the initial lockdown, yet consideration of treatment side effects and their management was not a priority. Objectives: To examine how the changing social restrictions imposed by the pandemic affected incidence and trends of endocrine treatment prescriptions in newly diagnosed (incident) breast and prostate cancer patients and, secondarily, endocrine treatment-related outcomes (including bisphosphonate prescriptions, osteopenia and osteoporosis), in UK clinical practice from March 2020 to June 2022. Design: Population-based cohort study using UK primary care Clinical Practice Research Datalink GOLD database. Methods: There were 13,701 newly diagnosed breast cancer patients and 12,221 prostate cancer patients with ⩾1-year data availability since diagnosis between January 2017 and June 2022. Incidence rates (IR) and incidence rate ratios (IRR) were calculated across multiple time periods before and after lockdown to examine the impact of changing social restrictions on endocrine treatments and treatment-related outcomes, including osteopenia, osteoporosis and bisphosphonate prescriptions. Results: In breast cancer patients, aromatase inhibitor (AI) prescriptions increased during lockdown versus pre-pandemic [IRR: 1.22 (95% confidence interval (CI): 1.11-1.34)], followed by a decrease post-first lockdown [IRR: 0.79 (95% CI: 0.69-0.89)]. In prostate cancer patients, first-generation antiandrogen prescriptions increased versus pre-pandemic [IRR: 1.23 (95% CI: 1.08-1.4)]. For breast cancer patients on AIs, diagnoses of osteopenia, osteoporosis and bisphosphonate prescriptions were reduced across all lockdown periods versus pre-pandemic (IRR range: 0.31-0.62). Conclusion: During the first 2 years of the pandemic, newly diagnosed breast and prostate cancer patients were prescribed more endocrine treatments compared to pre-pandemic due to restrictions on hospital procedures replacing surgeries with bridging therapies. But breast cancer patients had fewer diagnoses of osteopenia and osteoporosis and bisphosphonate prescriptions. These patients should be followed up in the coming years for signs of bone thinning. Evidence of poorer management of treatment-related side effects will help assess resource allocation for patients at high risk for bone-related complications.


Effects of the COVID-19 pandemic on hormone treatments for breast and prostate cancer in the UK: implications for bone health The COVID-19 pandemic has had a big impact on health, going beyond just causing illness. One area it has influenced is how patients with breast cancer or prostate cancer are treated. Surgeries and radiotherapies were delayed from the first lockdown as hospitals reduced non-covid related procedures. Some patients with breast or prostate cancer were instead given some medications to help stop their cancers from growing until they were able to have surgery or radiotherapy. These medications (called endocrine treatments) have important side effects, such as conditions that affect the bones. Patients on these medications should be monitored by doctors for signs of bone thinning and should, in some cases, be given other medications to help stop this happening. This study used doctors' records from more than 5 million people to find out whether the pandemic affected the number of endocrine medications being prescribed in patients with breast or prostate cancer, and also looked at the number of these patients that were diagnosed with conditions that affect their bones and whether they were given medications that could protect their bone health. We found that during the first lockdown, patients with breast cancer or prostate cancer had more of some types of endocrine treatments compared to before the lockdown. However, they had fewer diagnoses of conditions related to bone health and fewer medications to protect their bones. It is possible that appointments and tests that are usually carried out to diagnose conditions relating to bone health were not performed in the months after the first lockdown, and so these conditions were underdiagnosed. The use of medications to protect their bones was also reduced, likely because this was not considered a priority during the pandemic. This highlights that such patients should be followed up in the coming years for signs of bone thinning, given the relatively poorer management of these side effects in these people after the pandemic.

10.
PLOS Glob Public Health ; 4(6): e0003315, 2024.
Article in English | MEDLINE | ID: mdl-38861507

ABSTRACT

Pacific Island countries experience a high prevalence of noncommunicable diseases (NCDs), which may be prevented by reducing risk behaviors and strengthening protective factors in childhood and adolescence. To better inform preventative interventions, our objective was to use publicly available data from the Global School-based Student Health Survey (GSHS), to provide cross-sectional and trend estimates for the prevalence of NCD risk and protective factors among school-aged children in 2011 and 2017 in Samoa. Two waves of cross-sectional data included 4,373 children (51.98% female), with a median age of 15 years, who were mainly in school years 9-10 in Samoa. Retrospective analyses were adjusted for the GSHS multistage stratified cluster sample design. Weighted prevalences of overweight/obesity, dietary behaviors, physical activity, and sedentary behavior, oral and hand hygiene, emotional and mental health, and community protective factors were reported by study year. Logistic regressions were fitted to assess differences in the prevalence of risk and protective factors, adjusted for age group, sex, and school year. In 2011 and 2017, the prevalence of overweight/obesity remained consistently high in females (59.12% and 64.29%, p = 0.428) and increased from 44.21% to 53.65% in males (p = 0.039). Time spent sitting for long periods, smoking cigarettes, using other tobacco products, and drinking alcohol were lower in 2017 compared to 2011 (all p<0.05). Many children reported experiencing bullying (33.27% for females and 59.30% for males in 2017), while physical fighting was common among males (73.72% in 2011 and 57.28% in 2017). The high prevalence of obesity and related NCD risk factors require urgent public health action in Samoa. Alongside the continued reduction of tobacco and alcohol use, emotional and mental wellness should be prioritized in interventions and programs to promote healthy behaviors and lifestyle changes starting in childhood.

11.
Musculoskeletal Care ; 22(2): e1898, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38862275

ABSTRACT

BACKGROUND: The use of diagnostic imaging in low back pain (LBP) management is often inappropriate, despite recommendations from clinical practice guidelines. There is a limited understanding of factors that influence the imaging clinical decision-making (CDM) process. AIM: Explore the literature on factors influencing imaging CDM for people with LBP and consider how these findings could be used to reduce inappropriate use of imaging in LBP management. DESIGN: Scoping review. METHOD: This review followed the Preferred Reporting Items for Systematic Review extension for scoping reviews. A digital search was conducted in Medline, the Cumulative Index of Nursing and Allied Health Literature, Scopus, and the Cochrane Central Register of Controlled Trials for eligible studies published between January 2010-2023. Data reporting influences on imaging CDM were extracted. Data were then analysed through an inductive process to group the influencing factors into categories. RESULTS: After screening, 35 studies (5 qualitative and 30 quantitative) were included in the review, which reported factors influencing imaging CDM. Three categories were developed: clinical features (such as red flags, pain, and neurological deficit), non-modifiable factors (such as age, sex, and ethnicity) and modifiable factors (such as beliefs about consequences and clinical practice). Most studies reported non-modifiable factors. CONCLUSIONS: The results of this scoping review challenge the perception that imaging CDM is purely based on clinical history and objective findings. There is a complex interplay between clinical features, patient and clinician characteristics, beliefs, and environment. These findings should be considered when designing strategies to address inappropriate imaging behaviour.


Subject(s)
Clinical Decision-Making , Low Back Pain , Humans , Low Back Pain/diagnostic imaging , Low Back Pain/therapy , Low Back Pain/diagnosis , Diagnostic Imaging
12.
Mucosal Immunol ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38901764

ABSTRACT

Exaggeration of type 2 immune responses promotes lung inflammation and altered lung development; however, eosinophils, despite expansion in the postnatal lung, have not been specifically assessed in the context of neonatal lung disease. Furthermore, early life factors including prematurity and respiratory infection predispose infants to chronic obstructive pulmonary disease later in life. To assess eosinophils in the developing lung and how they may contribute to chronic lung disease, we generated mice harboring eosinophil-specific deletion of the negative regulatory enzyme SH2 domain-containing inositol 5' phosphatase-1. This increased the activity and number of pulmonary eosinophils in the developing lung, which was associated with impaired lung development, expansion of activated alveolar macrophages (AMφ), multinucleated giant cell formation, enlargement of airspaces, and fibrosis. Despite regression of eosinophils following completion of lung development, AMφ-dominated inflammation persisted, alongside lung damage. Bone marrow chimera studies showed that SH2 domain-containing inositol 5' phosphatase-1-deficient eosinophils were not sufficient to drive inflammatory lung disease in adult steady-state mice but once inflammation and damage were present, it could not be resolved. Depletion of eosinophils during alveolarization alleviated pulmonary inflammation and lung pathology, demonstrating an eosinophil-intrinsic effect. These results show that the presence of activated eosinophils during alveolarization aggravates AMφs and promotes sustained inflammation and long-lasting lung pathology.

13.
Neurology ; 102(12): e209417, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38833650

ABSTRACT

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is a concern for US service members and veterans (SMV), leading to heterogeneous psychological and cognitive outcomes. We sought to identify neuropsychological profiles of mild TBI (mTBI) and posttraumatic stress disorder (PTSD) among the largest SMV sample to date. METHODS: We analyzed cross-sectional baseline data from SMV with prior combat deployments enrolled in the ongoing Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium prospective longitudinal study. Latent profile analysis identified symptom profiles using 35 indicators, including physical symptoms, depression, quality of life, sleep quality, postconcussive symptoms, and cognitive performance. It is important to note that the profiles were determined independently of mTBI and probable PTSD status. After profile identification, we examined associations between demographic variables, mTBI characteristics, and PTSD symptoms with symptom profile membership. RESULTS: The analytic sample included 1,659 SMV (mean age 41.1 ± 10.0 years; 87% male); among them 29% (n = 480) had a history of non-deployment-related mTBI only, 14% (n = 239) had deployment-related mTBI only, 36% (n = 602) had both non-deployment and deployment-related mTBI, and 30% (n = 497) met criteria for probable PTSD. A 6-profile model had the best fit, with separation on all indicators (p < 0.001). The model revealed distinct neuropsychological profiles, representing a combination of 3 self-reported functioning patterns: high (HS), moderate (MS), and low (LS), and 2 cognitive performance patterns: high (HC) and low (LC). The profiles were (1) HS/HC: n=301, 18.1%; (2) HS/LC: n=294, 17.7%; (3) MS/HC: n=359, 21.6%; (4) MS/LC: n=316, 19.0%; (5) LS/HC: n=228, 13.7%; and (6) LS/LC: n=161, 9.7%. SMV with deployment-related mTBI tended to be grouped into lower functioning profiles and were more likely to meet criteria for probable PTSD. Conversely, SMV with no mTBI exposure or non-deployment-related mTBI were clustered in higher functioning profiles and had a lower likelihood of meeting criteria for probable PTSD. DISCUSSION: Findings suggest varied symptom and functional profiles in SMV, influenced by injury context and probable PTSD comorbidity. Despite diagnostic challenges, comprehensive assessment of functioning and cognition can detect subtle differences related to mTBI and PTSD, revealing distinct neuropsychological profiles. Prioritizing early treatment based on these profiles may improve prognostication and support efficient recovery.


Subject(s)
Brain Concussion , Military Personnel , Neuropsychological Tests , Stress Disorders, Post-Traumatic , Humans , Male , Adult , Female , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology , Stress Disorders, Post-Traumatic/etiology , Brain Concussion/psychology , Brain Concussion/complications , Brain Concussion/epidemiology , Cross-Sectional Studies , Middle Aged , Military Personnel/psychology , Longitudinal Studies , Veterans/psychology , Prospective Studies , Military Deployment/psychology , Post-Concussion Syndrome/psychology , Post-Concussion Syndrome/epidemiology , Quality of Life
14.
Clin Epidemiol ; 16: 417-429, 2024.
Article in English | MEDLINE | ID: mdl-38882578

ABSTRACT

Purpose: The COVID-19 pandemic profoundly affected healthcare systems and patients. There is a need to comprehend the collateral effects of the pandemic on non-communicable diseases. We examined the impact of the pandemic on short-term survival for common solid tumours, including breast, colorectal, head and neck, liver, lung, oesophageal, pancreatic, prostate, and stomach cancer in the UK. Methods: This was a population-based cohort study of electronic health records from the UK primary care Clinical Practice Research Datalink GOLD database. In sum, 12,259,744 eligible patients aged ≥18 years with ≥1 year's history identified from January 2000 to December 2022 were included. We estimated age-standardised incidence and short-term (one- and two-year) survival for several common cancers from 2000 to 2019 (in five-year strata) and compared these to 2020-2022 using the Kaplan-Meier method. Results: Incidence decreased for most cancers in 2020 and recovered to different extents in 2021-2022. Short-term survival improved for most cancers between 2000 and 2019, but then declined, albeit minimally, for those diagnosed in 2020-2022. This was most pronounced for colorectal cancer, with one-year survival falling from 78.8% (95% CI 78%-79.6%) in 2015-2019 to 77% (95% CI 75.6-78.3%) for those diagnosed in 2020-2022. Conclusion: Short-term survival for many cancers was impacted, albeit minimally, by the pandemic in the UK, with reductions in survivorship from colorectal cancer equivalent to returning to the mortality seen in the first decade of the 2000s. While data on longer-term survival are needed to fully comprehend the impact of COVID-19 on cancer care, our findings illustrate the need for an urgent and substantial commitment from the UK National Health Service to address the existing backlog in cancer screening and diagnostic procedures to improve cancer care and mortality.

15.
BMC Med Educ ; 24(1): 603, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822287

ABSTRACT

BACKGROUND: Videos to support learning of clinical skills are effective; however, little is known about the scope and educational quality of the content of freely available online videos demonstrating task-specific training (TST). This review aimed to determine the extent, characteristics of freely available online videos, and whether the content is suitable to guide skill acquisition of task-specific training for neurological physiotherapists and students. METHODS: A scoping review was conducted. Google video and YouTube were searched in December 2022. Videos that met our eligibility criteria and were explicitly designed for (TST) skill acquisition were included in the report. RESULTS: Ten videos met the inclusion criteria and were difficult to find amongst the range of videos available. Most were presented by physiotherapists or occupational therapists, originated from the USA, featured stroke as the condition of the person being treated, and involved a range of interventions (upper limb, constraint induced movement therapy, balance, bicycling). Most videos were created by universities or private practices and only two used people with a neurological condition as the participant. When the content of videos and their presentation (instruction and/or demonstration), was assessed against each key component of TST (practice structure, specificity, repetition, modification, progression, feedback), five of the videos were rated very suitable and five moderately suitable to guide skill acquisition. Most videos failed to demonstrate and provide instruction on each key component of TST and were missing at least one component, with feedback most frequently omitted. CONCLUSIONS: There are many freely available online videos which could be described as demonstrating TST; very few are suitable to guide skill acquisition. The development of a standardised and validated assessment tool, that is easy to use and assesses the content of TST videos is required to support learners to critically evaluate the educational quality of video content. Guidelines based on sound teaching theory and practice are required to assist creators of online videos to provide suitable resources that meet the learning needs of neurological physiotherapists and students.


Subject(s)
Clinical Competence , Physical Therapists , Video Recording , Humans , Clinical Competence/standards , Physical Therapists/education
16.
J Neurol Phys Ther ; 48(3): 151-158, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38709008

ABSTRACT

BACKGROUND AND PURPOSE: Sport-specific training may improve postural control, while repetitive head acceleration events (RHAEs) may compromise it. Understanding the neural mechanisms underlying postural control may contextualize changes due to training and RHAE. The goal of this study was to determine whether postural sway during the Balance Error Scoring System (BESS) is related to white matter organization (WMO) in collegiate athletes. METHODS: Collegiate soccer ( N = 33) and non-soccer athletes ( N = 44) completed BESS and diffusion tensor imaging. Postural sway during each BESS stance, fractional anisotropy (FA), and mean diffusivity (MD) were extracted for each participant. Partial least squares analyses determined group differences in postural sway and WMO and the relationship between postural sway and WMO in soccer and non-soccer athletes separately. RESULTS: Soccer athletes displayed better performance during BESS 6, with lower FA and higher MD in the medial lemniscus (ML) and inferior cerebellar peduncle (ICP), compared to non-soccer athletes. In soccer athletes, lower sway during BESS 2, 5, and 6 was associated with higher FA and lower MD in the corticospinal tract, ML, and ICP. In non-soccer athletes, lower sway during BESS 2 and 4 was associated with higher FA and lower MD in the ML and ICP. BESS 1 was associated with higher FA, and BESS 3 was associated with lower MD in the same tracts in non-soccer athletes. DISCUSSION AND CONCLUSIONS: Soccer and non-soccer athletes showed unique relationships between sway and WMO, suggesting that sport-specific exposures are partly responsible for changes in neurological structure and accompanying postural control performance and should be considered when evaluating postural control after injury.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content, available at: http://links.lww.com/JNPT/A472 ).


Subject(s)
Athletes , Diffusion Tensor Imaging , Postural Balance , Soccer , Humans , Postural Balance/physiology , Soccer/physiology , Male , Young Adult , White Matter/diagnostic imaging , White Matter/physiology , Female , Adolescent
17.
ACS Med Chem Lett ; 15(5): 646-652, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38746889

ABSTRACT

The potassium (K+) ion channel KCNK13 is specifically expressed in human microglia with elevated expression observed in post-mortem human brain tissue from patients with Alzheimer's disease. Modulation of KCNK13 activity by a small-molecule inhibitor is proposed as a potential treatment for neurodegenerative diseases. Herein, we describe the evolution of a series of KCNK13 inhibitors derived from a high-throughput screening campaign, resulting in CVN293, a potent, selective, and brain permeable clinical candidate molecule. CVN293 demonstrated a concentration-dependent inhibition of the NLRP3-inflammasome mediated production of IL-1ß from LPS-primed murine microglia. Cross-species pharmacokinetic data of CVN293 are also disclosed. These findings support the advancement of CVN293 in clinical trials.

18.
Immunity ; 57(5): 935-937, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38749395

ABSTRACT

The intestinal epithelium interacts with immune cells to support tissue homeostasis and coordinate responses against pathogens. In this issue of Immunity, Yang et al. unveil a central role for mast cell-epithelial cell interactions in orchestrating protective type 2 immune responses following intestinal helminth infection.


Subject(s)
Intestinal Mucosa , Mast Cells , Mast Cells/immunology , Animals , Intestinal Mucosa/immunology , Intestinal Mucosa/parasitology , Humans , Homeostasis/immunology , Helminthiasis/immunology , Helminthiasis/parasitology , Epithelial Cells/immunology , Mice
19.
Pulm Ther ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758409

ABSTRACT

Worldwide, over 2 billion children under the age of 5 experience stunting, wasting, or are underweight. Malnutrition contributes to 45% of all deaths in this age group (approximately 3.1 million deaths) [1]. Poverty, food insecurity, suboptimal feeding practices, climate change, and conflict are all contributing factors. Malnutrition causes significant respiratory problems, including increased risk of respiratory infections, impaired lung function, and increased risk of subsequent adult respiratory disease, including asthma, COPD, and lung cancer. Childhood malnutrition not only has serious consequences for children's health but it also has numerous consequences on wellbeing and educational attainment. Childhood malnutrition is a complex and multifaceted problem. However, by understanding and addressing the underlying causes, and investing in prevention and treatment programs, it is possible to maximize children's health and wellbeing on a global scale. This narrative review will focus on the impact of childhood malnutrition on lung development, the consequent respiratory disease, and what actions can be taken to reduce the burden of malnutrition on lung health.

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