Stromal cell and B cell dialogue potentiates IL-33-enriched lymphoid niches to support eosinophil recruitment and function during type 2 immunity.

Eosinophils are involved in host protection against multicellular organisms. However, their recruitment to the mesenteric lymph node (mLN) during type 2 immunity is understudied. Our results demonstrate that eosinophil association with lymphoid stromal niches constructed by fibroblastic reticular cells (FRCs) and lymphatic endothelial cells is diminished in mice selectively lacking interleukin (IL)-4Rα or lymphotoxin-ß (LTß) expression on B cells. Furthermore, eosinophil survival, activation, and enhanced Il1rl1 receptor expression are driven by stromal cell and B cell dialogue. The ligation of lymphotoxin-ß receptor (LTßR) on FRCs improves eosinophil survival and significantly augments IL-33 expression and eosinophil homing to the mLN, thus confirming the significance of lymphotoxin signaling for granulocyte recruitment. Eosinophil-deficient ΔdblGATA-1 mice show diminished mLN expansion, reduced interfollicular region (IFR) alarmin expression, and delayed helminth clearance, elucidating their importance in type 2 immunity. These findings provide insight into dialogue between stromal cells and B cells, which govern mLN eosinophilia, and the relevance of these mechanisms during type 2 immunity.

Helminth infection driven gastrointestinal hypermotility is independent of eosinophils and mediated by alterations in smooth muscle instead of enteric neurons.

Intestinal helminth infection triggers a type 2 immune response that promotes a 'weep-and sweep' response characterised by increased mucus secretion and intestinal hypermotility, which function to dislodge the worm from its intestinal habitat. Recent studies have discovered that several other pathogens cause intestinal dysmotility through major alterations to the immune and enteric nervous systems (ENS), and their interactions, within the gastrointestinal tract. However, the involvement of these systems has not been investigated for helminth infections. Eosinophils represent a key cell type recruited by the type 2 immune response and alter intestinal motility under steady-state conditions. Our study aimed to investigate whether altered intestinal motility driven by the murine hookworm, Nippostrongylus brasiliensis, infection involves eosinophils and how the ENS and smooth muscles of the gut are impacted. Eosinophil deficiency did not influence helminth-induced intestinal hypermotility and hypermotility did not involve gross structural or functional changes to the ENS. Hypermotility was instead associated with a dramatic increase in smooth muscle thickness and contractility, an observation that extended to another rodent nematode, Heligmosomoides polygyrus. In summary our data indicate that, in contrast to other pathogens, helminth-induced intestinal hypermotility is driven by largely by myogenic, rather than neurogenic, alterations with such changes occurring independently of eosinophils. (<300 words).

Trends in incidence, prevalence, and survival of breast cancer in the United Kingdom from 2000 to 2021.

Breast cancer is the most frequently diagnosed cancer in females globally. However, we know relatively little about trends in males. This study describes United Kingdom (UK) secular trends in breast cancer from 2000 to 2021 for both sexes. We describe a population-based cohort study using UK primary care Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases. There were 5,848,436 eligible females and 5,539,681 males aged 18+ years, with ≥ one year of prior data availability in the study period. We estimated crude breast cancer incidence rates (IR), prevalence and survival probability at one-, five- and 10-years after diagnosis using the Kaplan-Meier method. Analyses were further stratified by age. Crude IR of breast cancer from 2000 to 2021 was 194.4 per 100,000 person-years for females and 1.16 for males. Crude prevalence in 2021 was 2.1% for females and 0.009% for males. Both sexes have seen around a 2.5-fold increase in prevalence across time. Incidence increased with age for both sexes, peaking in females aged 60-69 years and males 90+ . There was a drop in incidence for females aged 70-79 years. From 2003-2019, incidence increased > twofold in younger females (aged 18-29: IR 2.12 in 2003 vs. 4.58 in 2018); decreased in females aged 50-69 years; and further declined from 2015 onwards in females aged 70-89 years. Survival probability for females after one-, five-, and ten-years after diagnosis was 95.1%, 80.2%, and 68.4%, and for males 92.9%, 69.0%, and 51.3%. Survival probability at one-year increased by 2.08% points, and survival at five years increased by 5.39% from 2000-2004 to 2015-2019 for females, particularly those aged 50-70 years. For males, there were no clear time-trends for short-term and long-term survival probability. Changes in incidence of breast cancer in females largely reflect the success of screening programmes, as rates rise and fall in synchronicity with ages of eligibility for such programmes. Overall survival from breast cancer for females has improved from 2000 to 2021, again reflecting the success of screening programmes, early diagnosis, and improvements in treatments. Male breast cancer patients have worse survival outcomes compared to females, highlighting the need to develop male-specific diagnosis and treatment strategies to improve long-term survival in line with females.

Updated joint ESPGHAN/NASPGHAN guidelines for management of Helicobacter pylori infection in children and adolescents (2023).

BACKGROUND: Evolving epidemiological data and increasing antibiotic resistance mandate an update of the European and North American Societies of Pediatric Gastroenterology, Hepatology and Nutrition guidelines. METHODS: Certainty of evidence and strength of recommendations were rated by experts according to the Grading of Recommendation Assessment, Development, and Evaluation approach. PICO (patient population, intervention, comparator, and outcome) questions were developed and voted on by the group. Recommendations were formulated using the Evidence to Decision framework. RESULTS: The current literature supports many of the previous recommendations and several new recommendations. Invasive testing with strain antimicrobial susceptibility analysis is recommended for the diagnosis and selection of eradication therapy for H. pylori infection. Molecular methods are acceptable for detection of infection and of antibiotic resistance in gastric biopsy specimens. Reliable, noninvasive tests can be used as a screening method for children with history of gastric cancer in a first-degree relative. When investigating causes of chronic immune thrombocytopenic purpura, testing for H. pylori is no longer recommended. When investigating other diseases such as inflammatory bowel disease, celiac disease, or eosinophilic esophagitis, specific diagnostic biopsies for H. pylori infection are not indicated. However, if H. pylori is an incidental finding, treatment may be considered after discussing the risks and benefits. Treatment should be based on antibiotic antimicrobial susceptibility testing and, if unavailable, regimens containing clarithromycin should be avoided. CONCLUSIONS: Due to decreasing prevalence of infection, increasing challenges with antibiotic resistance, and emerging evidence regarding complications of infection, clinicians must be aware of these recommended changes to appropriately manage H. pylori infection and its clinical sequelae in children.

International consensus on fasting terminology.

Although fasting is increasingly applied for disease prevention and treatment, consensus on terminology is lacking. Using Delphi methodology, an international, multidisciplinary panel of researchers and clinicians standardized definitions of various fasting approaches in humans. Five online surveys and a live online conference were conducted with 38 experts, 25 of whom completed all 5 surveys. Consensus was achieved for the following terms: "fasting" (voluntary abstinence from some or all foods or foods and beverages), "modified fasting" (restriction of energy intake to max. 25% of energy needs), "fluid-only fasting," "alternate-day fasting," "short-term fasting" (lasting 2-3 days), "prolonged fasting" (≥4 consecutive days), and "religious fasting." "Intermittent fasting" (repetitive fasting periods lasting ≤48 h), "time-restricted eating," and "fasting-mimicking diet" were discussed most. This study provides expert recommendations on fasting terminology for future research and clinical applications, facilitating communication and cross-referencing in the field.

Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood.

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.

Modifiable lifestyle factors and the risk of post-COVID-19 multisystem sequelae, hospitalization, and death.

Effective prevention strategies for post-COVID complications are crucial for patients, clinicians, and policy makers to mitigate their cumulative burden. This study evaluated the association of modifiable lifestyle factors (smoking, alcohol intake, BMI, physical activity, sedentary time, sleep duration, and dietary habits) with COVID-19 multisystem sequelae, death, and hospitalization in the UK Biobank cohort (n = 68,896). A favorable lifestyle (6-10 healthy factors; 46.4%) was associated with a 36% lower risk of multisystem sequelae (HR, 0.64; 95% CI, 0.58-0.69; ARR at 210 days, 7.08%; 95% CI, 5.98-8.09) compared to an unfavorable lifestyle (0-4 factors; 12.3%). Risk reductions spanned all 10 organ systems, including cardiovascular, coagulation, metabolic, gastrointestinal, kidney, mental health, musculoskeletal, respiratory disorders, and fatigue. This beneficial effect was largely attributable to direct lifestyle impacts independent of corresponding pre-infection comorbidities (71% for any sequelae). A favorable lifestyle was also related to the risk of post-COVID death (HR 0.59, 0.52-0.66) and hospitalization (HR 0.78, 0.73-0.84). These associations persisted across acute and post-acute infection phases, irrespective of hospitalization status, vaccination, or SARS-CoV-2 variant. These findings underscore the clinical and public health importance of adhering to a healthy lifestyle in mitigating long-term COVID-19 adverse impacts and enhancing future pandemic preparedness.

The effect of hydrostatic pressure on lipid membrane lateral structure.

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.

Behavioral Intervention that Extends Sleep Duration Leads to Greater Self-Control in School-Aged Children.

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.

Examining the interplay between physical activity, problematic internet use and the negative emotional state of depression, anxiety and stress: insights from a moderated mediation path model in university students.

BACKGROUND: The aim of this study was to investigate the relationship between Problematic Internet Use (PIU), emotional states of stress, anxiety and depression, and the practice of physical activity among Tunisian students. METHODS: Cross-sectional data were collected from 976 university students aged 20.76 ± 1.63 years (46.8% female). They filled out an online survey comprised of a socio-demographic questionnaire, the depression, anxiety and stress scale- 21 items (DASS-21), the international physical activity questionnaire (IPAQ) and the compulsive internet use scale (CIUS). Students were divided, based on their economic levels, into three groups: low (n = 256, 26.23%), medium (n = 523, 53.59%) and high (n = 197, 20.18%). RESULTS: Mediation analysis: Indirect effects of IPAQ and gender on DASS-21 were highlighted: ß= -0.18 (p < 0.01) and ß= -0.04, P < 0.01) respectively. In addition, a significant and negative effect of IPAQ on CIUS was demonstrated (ß = -0.45, P < 0.01). In addition, the effect of CIUS on DASS-21 was significant (ß = 0.39, P < 0.01). Also, the effect of gender on CIUS was significant (ß=-0.10, P < 0.01) However, its effect on DASS-21 was not significant (ß = 0.05, p = 0.078). The total effect of IPAQ on DASS21 was significant (ß= -0.52, p < 0.01) but the effect of Gender on DASS-21 was not significant (ß = 0.01, p = 0.817). Moderation analysis: the results showed a significant moderation effect of the interaction between IPAQ and Gender on CIUS (ß = 0.07, p < 0.01). However, it was not significant between Gender and CIUS on DASS-21 (ß = 0.09, p = 0.390) and between IPAQ and Gender on DASS21 (ß = 0.01, p = 0.736) Also, the interaction between IPAQ and CIUS did not have a significant moderation effect on DASS-21 (ß = 0.15, p = 0.115). CONCLUSIONS: Findings suggest that relationships between PIU and negative emotional state of depression, anxiety and stress are mediated via physical exercise. These results underscore the importance of the physical activity factor in the studies analyzing longitudinal effects of PIU on mental health outcomes.

Understanding the impact of HIV on mpox transmission in the MSM population: A mathematical modeling study.

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.

f-Block hydride complexes - synthesis, structure and reactivity.

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.

O le tagata ma lona aiga, o le tagata ma lona fa'asinomaga (Every person belongs to a family and every family belongs to a person): Development of a parenting framework for adolescent mental wellbeing in American Samoa.

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.

Activated eosinophils in early life impair lung development and promote long-term lung damage.

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.

Neuropsychological Profiles of Deployment-Related Mild Traumatic Brain Injury: A LIMBIC-CENC Study.

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.

Noncommunicable disease risk behaviors and protective factors among children in Samoa: Retrospective trend analysis of global school-based health surveys in 2011 and 2017.

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.

The Impact of the COVID-19 Pandemic on Incidence and Short-Term Survival for Common Solid Tumours in the United Kingdom: A Cohort Analysis.

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.

Factors influencing imaging clinical decision-making in low back pain management. A scoping review.

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.

Longitudinal associations of time-varying homeboundness and life satisfaction after traumatic brain injury.

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).

Associations between fasting glucose rate-of-change and the missense variant, rs373863828, in an adult Samoan cohort.

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.