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ObjectiveEfforts to describe the current state of research are needed to advance the field of physical-mental multimorbidity (ie, the co-occurrence of at least one physical illness and at least one mental disorder) among children and youth. Our objective was to systematically explore the breadth of physical-mental multimorbidity research in children and youth and to provide an overview of existing literature topics.DesignScoping review.MethodsWe conducted a systematic search of four key databases: PubMed, EMBASE, PsycINFO and Scopus as well as a thorough scan of relevant grey literature. We included studies of any research design, published in English, referring to physical-mental multimorbidity among children and youth aged ≤18 years. Studies were screened for eligibility and data were extracted, charted and summarised narratively by research focus. Critical appraisal was employed using the modified Quality Index (QI).ResultsWe included 431 studies and 2 sources of grey literature. Existing research emphasises the co-occurrence of anxiety, mood and attention disorders among children with epilepsy, asthma and allergy. Evidence consists of mostly small, observational studies that use cross-sectional data. The average QI score across applicable studies was 9.1 (SD=1.8).ConclusionsThere is a pressing need for more robust research within the field of child physical-mental multimorbidity.

Opioid use disorder (OUD) and opioid overdoses are public health emergencies. In 2021, 80,000 opioid overdose associated deaths were reported in the United States. Despite the availability of treatment strategies, including medications for opioid use disorder (MOUD) and naloxone, opioid overdoses continue to increase at an alarming rate. Opioid vaccines are a novel approach to combat the growing crisis with several candidates recently entering human clinical trials. In this study, we investigated Qβ bacteriophage virus-like particles (VLPs) as a vaccine platform for immunogenic display of oxycodone. A derivative of oxycodone was conjugated to pre-formed Qβ VLPs using a sulfhydryl-amine reactive heterobifunctional crosslinker with high loading of oxycodone. In mice, intramuscular immunization with Qβ-oxycodone elicited high-titer, high-avidity and long-lasting antibody responses. Qβ-oxycodone was also immunogenic after storage at ambient room temperature for over two weeks, demonstrating that the vaccine is highly thermostable. In mice, immunization with Qβ-oxycodone elicited antibodies that sequester oxycodone in the serum, an important mechanism for preventing the adverse effects of opioid activity. Finally, Qβ-oxycodone is immunogenic in nonhuman primates, eliciting serum oxycodone antibodies after intramuscular immunization of rhesus macaques. These data establish Qβ-oxycodone as a promising opioid vaccine candidate.

Objective The aim of this research was to examine the bidirectional association between self-reported symptoms of mental disorder and physical activity among a large sample of Canadian secondary school students over time. Methods Linked survey data were obtained from 28,567 grade 9 to 12 students across Canada participating in two waves of the COMPASS Study (2017–18; 2018–19). Autoregressive cross-lagged models were run to examine the reciprocal relationships between self-reported moderate-to-vigorous physical activity (MVPA) and symptoms of depression (CESD-10) and anxiety (GAD-7). Models were stratified by gender, and accounted for grade, ethno-racial identity, and school-level clustering. Results Autoregressive associations show that neither symptoms of anxiety nor depression, at baseline, were predictive of mean MVPA at follow-up – consistent for the full sample and among both males and females. Higher MVPA among males at baseline was associated with lower symptoms of both anxiety (β = − 0.03, p  = 0.002) and depression (β = − 0.05, p  < 0.001) at follow-up. However, among females, higher MVPA at baseline was associated with greater symptoms of anxiety (β = 0.03, p  < 0.001), but not symptoms of depression (β = 0.01, p  = 0.073), at follow-up. Conclusion In our large sample of Canadian secondary school students, associations between physical activity and symptoms of mental disorder were not bi-directional, and these relationships differed in males and females. This study illustrates the complex nature of the relationship between physical activity and symptoms of mental disorder among youth. While results support the benefits of promoting physical activity among males to prevent or manage internalizing symptoms, the relationship among females warrants further investigation.

Background/Objectives: Intramuscular immunization elicits systemic IgG and is the primary route of vaccine administration in humans. However, there is growing interest in utilizing other routes of administration to tailor antibody profiles, increase immunity at primary sites of infection, simplify administration, and eliminate needle waste. Here, we investigated the antibody profiles elicited by immunization with bacteriophage virus-like particle vaccine platforms at various routes of administration. Methods: We chose two model bacteriophage vaccines for investigation: bacteriophage MS2 virus-like particles (VLPs) recombinantly displaying a short, conserved peptide from Chlamydia trachomatis major outer membrane protein (MS2) and bacteriophage Qβ VLPs displaying oxycodone through chemical conjugation (Qβ). We comprehensively characterized the antibodies elicited systemically and at various mucosal sites when the vaccines were administered intramuscularly, intranasally or periocularly with or without an intramuscular prime using various prime/boost schemes. Results: Intranasal and periocular immunization elicited robust mucosal and systemic IgA responses for both MS2 and Qβ. The intramuscular prime followed by intranasal or periocular boosts elicited broad antibody responses, and increased antibodies titers at certain anatomical sites. Conclusions: These findings demonstrate the tractability of bacteriophage VLP-based vaccines in generating specific antibody profiles based on the prime–boost regimen and route of administration.

Intracranial vascular calcification has been observed in the setting of both Alzheimer's disease (AD) and vascular dementia. Increased calcification in intracranial and extracranial arteries is associated with an increased risk of dementia; however, less is known about the prevalence and implications of microvascular calcification in AD and related dementias. In this study, we compared microvascular calcification in AD-relevant brain regions between human donors with vs. without dementia and/or late-onset AD diagnoses. Brain tissue was sampled bilaterally from basal ganglia, hippocampus, posterior cingulate cortex, substantia nigra, and subventricular zone, along with bilateral carotid arteries in a cohort of human donor cadavers with and without dementia at death ( = 23, 61% females, 86.4 ± 7.9 years of age). An additional cohort included postmortem posterior cingulate cortex samples from NIH NeuroBioBank donors with and without confirmed late-onset AD ( = 10, 40% females, 78.3 ± 2.1 years of age). All samples were scanned by micro-computed tomography. Vascular calcification was quantified as the sum of voxels at an intensity of ≥130 Hounsfield units in a standardized tissue volume. Findings were confirmed by histology. Our findings indicate higher odds of dementia per one quartile increase in microvascular calcification volume in the hippocampus [OR 9.601 (CI 2.518, 86.803), = 0.0091], posterior cingulate cortex [OR 2.894 (CI 1.222, 8.923), = 0.0302], and subventricular zone [OR 2.851 (CI 1.153, 9.482), = 0.0427]. Similarly, in posterior cingulate cortex samples from the NeuroBioBank, significantly higher microvascular calcification was observed in late-onset AD cases [median 0.0153 (IQR 0.0075, 0.0581), % by volume] compared to controls [median 0.0024 (IQR 0.0016, 0.0104), % by volume; = 0.0265]. Internal carotid calcification was significantly associated with microvascular calcification in the basal ganglia [OR 1.699 (CI 1.156, 2.496), = 0.0093], hippocampus [OR 1.580 (CI 1.056, 2.366), = 0.0281], and posterior cingulate cortex [OR 1.524 (CI 1.009, 2.299), = 0.0452]. Our findings indicate that microvascular calcification impacts brain regions relevant to morphologic changes (hippocampus) and hypoperfusion (posterior cingulate cortex) in AD. Our study expands on a recent report of increased brain calcification in the setting of AD, suggesting that microvascular calcification carries pathophysiological significance in the development and/or progression of AD and related dementias.

Opioid overdoses and opioid use disorder (OUD) are major public health concerns. Current treatment approaches for OUD have failed to slow the growth of the opioid crisis. Opioid vaccines have shown pre-clinical success in targeting multiple different opioid drugs. However, the need for many immunizations can limit their clinical implementation. In this study, we investigate the development of novel opioid vaccines by independently targeting fentanyl and the active metabolites of heroin using a bacteriophage virus-like particle (VLP) vaccine platform. We establish the successful conjugation of haptens to bacteriophage Qβ VLPs and demonstrate immunogenicity of Qβ-fentanyl, Qβ-morphine, and Qβ-6-acetylmorphine in animal models after one or two immunizations. We show that these vaccines elicit high-titer, high-avidity, and durable antibody responses. Moreover, we reveal their protective capacities against heroin or fentanyl challenge after two immunizations. Overall, these findings establish Qβ-VLP conjugated vaccines for heroin and fentanyl as promising opioid vaccine candidates.

As a largely social behaviour, substance use may have decreased for some youth overall in Canada during the COVID-19 pandemic; however, continued use may indicate nonadherence to pandemic-related restrictions and social distancing measures. In a sample of Canadian adolescents (aged 12-19 years), our objective was to examine how substance use (cannabis, binge drinking, cigarettes, vaping) is associated with perceptions of, and adherence to, early COVID-19-related public health measures, taking into consideration sociodemographic factors. Cross-sectional data were retrieved from online data collected during Year 8 of the COMPASS school-based study, during the early months of the COVID-19 pandemic (May-July 2020) in British Columbia, Ontario and Quebec. We fitted two models using generalized estimating equations to examine how substance use was associated with separate measures of (1) perceptions of, and (2) adherence to early COVID-19 restrictions. In our sample, 10% of adolescents perceived COVID-19 restrictions as too weak and 14% perceived them as too strict. Nearly half (46%) reported taking restrictions very seriously, and 5% did not take them seriously at all. Binge drinking, cigarette use and vaping were associated with perceptions that restrictions were too strict and with nonadherence. However, adolescents who used cannabis were less likely to perceive COVID-19-related restrictions as too strict. This study highlights the association of adolescent substance use with perceptions of, and adherence to, COVID-19-related public health restrictions in Canada. Our findings emphasize a need for continual monitoring of substance use behaviours during the COVID-19 pandemic to better characterize adolescent risk and further inform targeted public health strategies accordingly.

Indigenous children in Canada are less likely to be breastfed compared to non-Indigenous children; however, little information about rates and correlates of breastfeeding exist. We used a nationally representative survey to examine breastfeeding initiation (n = 9,330) and duration (n = 6,760) among First Nations, Métis, and Inuit children. In our sample, 72.5% of children had been breastfed, and 57.9% of these individuals were breastfed until six months. Factors associated with increased breastfeeding included mothers’ educational attainment, children’s weight at birth, mothers' residential school attendance, and region of residence. Having Indian Status and lower household income were associated with lower breastfeeding initiation and duration. Our findings suggest that targeted efforts to encourage and support breastfeeding among Indigenous women are needed. Additional research using contemporary data are required in Canada.

Introduction Fixed ratio combination of insulin degludec and liraglutide (IDegLira) represents an option to revise inappropriate therapies in patients with poorly controlled type 2 diabetes. This study aimed to assess the pattern of use and 1-year effectiveness of IDegLira. Methods A retrospective chart review was performed to assess changes in glycated hemoglobin (HbA1c) (primary endpoint), fasting blood glucose (FBG), body weight, estimated glomerular filtration rate (eGFR), and lipid profile following IDegLira initiation. Previous versus concomitant diabetes treatments were also compared. Results Overall, 87 patients (mean age 73.9 ± 9.2 years, diabetes duration 18.2 ± 6.7 years, 62.1% men, HbA1c 8.3 ± 1.3%, BMI 30.4 ± 5.5 kg/m 2 ) initiated IDegLira. Previously, 21.8% of patients were treated with oral hypoglycemic agents (OHA group), 47.1% with basal insulin ± OHA (BOT group), 5.8% with GLP-1 RA ± basal insulin (GLP1-RA group), and 25.3% with basal-bolus schemes (BB group). At the first prescription of IDegLira, secretagogues and schemes including two or more OHA were substantially reduced, leaving metformin as the most prevalent OHA (81.6%) used in combination with IDegLira. Starting dose of IDegLira ranged from 18.7 ± 3.1 U (OHA group) to 24.1 ± 4.4 U (BB group). After 1 year, HbA1c was significantly reduced by 1.25% (95% CI − 1.48; − 1.03), FBG by 52.9 mg/dl, and body weight by 2.0 kg. Also, eGFR levels and lipid profile significantly improved. No severe hypoglycemia occurred. Conclusion It is possible to proactively review suboptimal or inappropriate diabetes treatment according to the most recent guidelines. Results suggest that initiation of IDegLira was associated with a reduction in drugs to be administered daily and relevant improvements in clinical outcomes.