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Methylammonium lead iodide (CH3NH3PbI3), an organic-inorganic perovskite widely used for optoelectronic applications, is known to dissociate under illumination with light at photon energies around 2.7 eV and higher. Here, we show that photo-induced dissociation is not limited to ambient temperatures but can be observed even at 5 K. The photo-induced dissociation of N–H bonds results in the formation of metastable states. Photoluminescence (PL) measurements reveal the formation of defect states that are located 100 meV within the bandgap. This is accompanied by a quenching of the band-to-band PL by one order of magnitude. Defect generation is reversible and annealing at 30 K recovers the band-to-band PL, while the light-induced defect states disappear concurrently. [ABSTRACT FROM AUTHOR]

Abstract Background The majority of patients with idiopathic pulmonary arterial hypertension (IPAH) in functional classes II and III are currently being treated with non-parenteral therapies, including endothelin receptor antagonists (ERA), phosphodiesterase (PDE)-5 inhibitors, inhaled iloprost or combinations of these substances. If these treatments fail, current guidelines recommend the addition of parenteral prostanoid therapy. There is, however, limited evidence for the efficacy of parenteral prostanoids when added to combinations of non-parenteral therapies. Methods In this retrospective, multicentre study we collected data from consecutive IPAH patients receiving intravenous iloprost in addition to optimized non-parenteral therapy between Jan 2002 and Dec 2009. Analyses included 6 min walk distance (6MWD), functional class, need for transplantation, and survival. Results During the observation period, 50 patients were treated with intravenous iloprost in addition to non-parenteral therapy; 44% of the patients were on dual combination therapy and 52% on triple combination. Three months after initiation of iloprost, functional class had improved in 24% of the patients and the median 6MWD had increased from 289 m to 298 m (n.s.). During the observation period, 22 patients (44%) died and 14 (28%) underwent lung transplantation. The probabilities of LuTx-free survival at 1, 3 and 5 years following iloprost initiation were 38%, 17% and 17%, respectively. A 6MWD < 300 m and persistent functional class IV at 3 months after initiation of intravenous iloprost were predictors of an adverse outcome. Conclusion In essence, late initiation of intravenous iloprost in IPAH patients who previously failed to respond to non-parenteral therapies appears to be of limited efficacy in the majority patients. Alternative therapeutic options are currently not available, underlying the need for the development of new drugs.

Abstract Background Growth-differentiation factor-15 (GDF-15) is a stress-responsive, transforming growth factor-β-related cytokine, which has recently been reported to be elevated in serum of patients with idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to examine the expression and biological roles of GDF-15 in the lung of patients with pulmonary arterial hypertension (PAH). Methods GDF-15 expression in normal lungs and lung specimens of PAH patients were studied by real-time RT-PCR and immunohistochemistry. Using laser-assisted micro-dissection, GDF-15 expression was further analyzed within vascular compartments of PAH lungs. To elucidate the role of GDF-15 on endothelial cells, human pulmonary microvascular endothelial cells (HPMEC) were exposed to hypoxia and laminar shear stress. The effects of GDF-15 on the proliferation and cell death of HPMEC were studied using recombinant GDF-15 protein. Results GDF-15 expression was found to be increased in lung specimens from PAH patients, com-pared to normal lungs. GDF-15 was abundantly expressed in pulmonary vascular endothelial cells with a strong signal in the core of plexiform lesions. HPMEC responded with marked upregulation of GDF-15 to hypoxia and laminar shear stress. Apoptotic cell death of HPMEC was diminished, whereas HPMEC proliferation was either increased or decreased depending of the concentration of recombinant GDF-15 protein. Conclusions GDF-15 expression is increased in PAH lungs and appears predominantly located in vascular endothelial cells. The expression pattern as well as the observed effects on proliferation and apoptosis of pulmonary endothelial cells suggest a role of GDF-15 in the homeostasis of endothelial cells in PAH patients.

The charge transport in Schottky-type solar cells fabricated from graphene/methyl-passivated silicon heterojunctions is studied in detail. The electrical device characteristics are affected by ambient temperature and illumination conditions. Moreover, the presence of deep and shallow interface states influences the current across the junction at forward and reverse bias. In the dark, thermionic emission over the potential barrier is clearly affected by the recombination via interface states, while under illumination those states become electrically inactive. [ABSTRACT FROM AUTHOR]

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disability diagnosed in an increasing number of children. Psychotropic medication use has also increased among Canadian children and may be more common among children with intellectual disabilities. However, psychotropic medications are not strongly recommended for use among children and have been associated with significant adverse events. ASD has few effective treatment options, yet psychotropic medications are used to manage challenging behaviours in some children with ASD. Objectives: This study describes ASD prevalence and use of psychotropic medications in the pediatric population of Manitoba. Populations of children with and without ASD are described and compared to determine difference in psychotropic medication use and population characteristics. Methods: Administrative data from the Repository at the Manitoba Centre for Health Policy were used to create a cohort of children born in Manitoba. Diagnoses of ASD were based on medical claim records, hospital abstracts or special education funding data. Results: Between 2010 and 2014, 3079 Manitoba children aged 0 to 14 years had an ASD diagnosis (1% prevalence). Among children with ASD aged 0 to 18 years, 80% are boys, almost 60% were diagnosed before age 5, with 85% diagnosed before age 10, and almost 50% received special education funding. Close to 50% of all children with ASD received a psychotropic prescription before age 18, compared to only 12% in the population of children in Manitoba without ASD or an intellectual disability. Children with ASD are more likely than those in the general population of children to live in Winnipeg, be involved with child welfare services and receive psychotropic medications. Conclusion: In Manitoba, ASD is diagnosed in preschool or early school years, when treatment and services can have the greatest impact on functioning. Children with ASD are more likely to use psychotropic medications and have different population characteristics when compared to children in the general population. This epidemiological information is important to understand risk factors, assess current treatment strategies and direct future intervention planning. [ABSTRACT FROM AUTHOR]

Graphene has become an extremely prospective material for numerous applications because of its excellent electrical and optical properties. The combination of conductivity and high transparency and the ability of large‐area production render graphene suitable as a contact layer and transparent electrode in solar cells. Graphene brought into direct contact with n‐type silicon introduces a built‐in electric field at the heterojunction interface and forms a Schottky contact. Solar cells utilizing this effect show a conversion efficiency of 4.2%. However, the graphene‐Si Schottky diodes are not stable and degrade strongly during the first days. In the study by Brus et al. (pp. 843–847) the influence of the graphene‐silicon interface on the solar cell properties is investigated. The quality of this interface is crucial since the concentration of localized states and its ability to block minority carriers influence the device performance significantly. Passivation of the silicon surface with methyl groups prior to graphene deposition reduces recombination loss at the graphene/Si heterojunction. In addition, it enhances and stabilizes the photoelectric performance of undoped graphene/n‐type c‐Si(111) solar cells. [ABSTRACT FROM AUTHOR]

Macrophages in the B cell lymphoma microenvironment represent a functional node in progression and therapeutic response. We assessed metabolic regulation of macrophages in the context of therapeutic antibody-mediated phagocytosis. Pentose phosphate pathway (PPP) inhibition induces increased phagocytic lymphoma cell clearance by macrophages in vitro, in primary human chronic lymphocytic leukemia (CLL) patient co-cultures, and in mouse models. Addition of the PPP inhibitor S3 to antibody therapy achieves significantly prolonged overall survival in an aggressive B cell lymphoma mouse model. PPP inhibition induces metabolic activation and pro-inflammatory polarization of macrophages while it decreases macrophages' support for survival of lymphoma cells empowering anti-lymphoma function. As a mechanism of macrophage repolarization, the link between PPP and immune regulation was identified. PPP inhibition causes decreased glycogen level and subsequent modulation of the immune modulatory uridine diphosphate glucose (UDPG)-Stat1-Irg1-itaconate axis. Thus, we hypothesize the PPP as a key regulator and targetable modulator of macrophage activity in lymphoma to improve efficacy of immunotherapies and prolong survival., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Despite decades of Inuit accessing services in Manitoba, Inuit-centric services remain scant and have only begun to emerge. This article reports on Inuit utilisation of mental health services in Manitoba. In this study, we focused on two interrelated cohorts: Inuit living in Manitoba and Inuit from the Kivalliq region who come to Winnipeg to access specialised services. We used administrative data routinely collected by Manitoban agencies. The study was conducted in partnership with the Manitoba Inuit Association, and Inuit Elders from Nunavut and Manitoba. Our results show that mental health-related consults represent between 1 in 5 and 1 in 3 of all consults made by Inuit in Manitoba. Rates of hospitalisation for mental health conditions are considerably lower than those of residents from the Manitoba northern health authority. Given that Nunavut has the highest rate of suicide in the world, our results suggest underserved needs rather than lower needs. Kivalliq and Manitoba Inuit utilise mental health services in Manitoba extensively, yet these services for the most part remain western-centric. Epistemological accommodations in the provision of mental health services have yet to be implemented. This is now the focus of our work.

Purpose: The Food and Nutrition for Manitoba Youth (FANS) study examined dietary intakes, food behaviours, food security status, health indicators, and body mass index of a cohort of grade 9 students. This paper describes regional differences and similarities in dietary intake (food and nutrients) and quality of youth participants in the FANS study. Methods: Grade 9 students completed a web-based survey on dietary intakes (24-hour recall), food behaviours, self-reported health indicators, and sociodemographic variables. Nutrient intakes were compared with national guidelines and diet quality was assessed using a modified Healthy Eating Index. Results: A total of 1587 students participated from northern, rural, and urban regions in Manitoba. Northern and rural students had higher intakes of sugar, sodium, and saturated fat compared with urban. Northern students consumed fewer grain products compared to urban, and more servings of "other" foods compared with rural and urban. While most participants were classified into the "needs improvement" or "poor" Healthy Eating Index categories, significantly more northern participants were in the "poor" category. Conclusions: Most adolescents in the study are at nutritional risk; however, there are additional vulnerabilities for those in rural and northern communities. Dietitians can use results to advocate for and plan interventions to improve adolescent nutrition.

Canada legalized the use of non-medical cannabis in 2018. This study examines youth and young adults' knowledge and perceptions of harms, benefits, and education around cannabis use since legalization. An online survey was completed by a convenience sample of 1,759 individuals aged 12-25 years living in Manitoba, Canada. Most participants ( n  = 1,525, 86.7%) reported receiving education on the potential effects/harms related to cannabis; the most common topics included driving and cannabis use (79.9%), the mental harms of cannabis (67.4%), and addiction and dependency (66.3%). Youth who reported using cannabis more than once ( n  = 1,203) were more knowledgeable about the effects of cannabis than youth who never used cannabis or used cannabis once ( n  = 580; mean score: 6.6 versus 5.7 out of 8, respectively; p  < .001). Vaping cannabis oil was perceived as the most harmful cannabis product among all participants. Among participants with experience using cannabis, the most frequently reported benefits were relaxation, improved sleep, and enhanced enjoyment of food/music. Half of the participants reported ever being in a car with someone driving high, of which, 40% of these participants reported doing so in the last 30 days. Future tailored education is needed to address knowledge related to cannabis use among youth and young adults who use and do not use cannabis.

Objective: Breastfeeding is associated with reduced postpartum depression, stronger parent-child relationships, and fewer behavioral disorders in early childhood. We tested the mediating roles of postpartum depression and parent-child relationship in the association between breastfeeding practices and child behavior., Study Design: We used standardized questionnaire data from a subset of the CHILD Cohort Study (n = 1,573) to measure postpartum depression at 6 months, 1 year and 2 years, parent-child relationship 1 year and 2 years, and child behavior at 5 years using the Child Behavior Checklist (range 0-100). Breastfeeding practices were measured at 3 months (none, partial, some expressed, all direct at the breast), 6 months (none, partial, exclusive), 12 months, and 24 months (no, yes). Confounders included birth factors, maternal characteristics, and socioeconomic status., Results: Breast milk feeding at 3 or 6 months was associated with - 1.13 (95% CI: -2.19-0.07) to -2.14 (95% CI: -3.46, -0.81) lower (better) child behavior scores. Reduced postpartum depression at 6 months mediated between 11.5% and 16.6% of the relationship between exclusive breast milk feeding at 3 months and better child behavior scores. Together, reduced postpartum depression at 1 year and reduced parent-child dysfunction at 2 years mediated between 21.9% and 32.1% of the relationship between breastfeeding at 12 months and better child behavior scores., Conclusion: Postpartum depression and parent-child relationship quality partially mediate the relationship between breastfeeding practices and child behavior. Breastfeeding, as well as efforts to support parental mental health and parent-child relationships, may help to improve child behavior., (© 2024. The Author(s).)

Thermoelectric materials have garnered significant interest for their potential to efficiently convert waste heat into electrical energy at room temperature without moving parts or harmful emissions. This study investigated the impact of the HOMO-LUMO (H-L) gap on the thermoelectric properties of three distinct classes of organic compounds: conjugated aromatics (isoindigos (IIGs)), quinoidal molecules (benzodipyrrolidones (BDPs)), and donor-acceptor systems (bis(pyrrol-2-yl)squaraines (BPSs)). These compounds were chosen for their structural simplicity and linear π-conjugated conductance paths, which promote high electrical conductance and minimize complications from quantum interference. Single-molecule thermoelectric measurements revealed that despite their low H-L gaps, the Seebeck coefficients of these compounds remain low. The alignment of the frontier orbitals relative to the Fermi energy was found to play a crucial role in determining the Seebeck coefficients, as exemplified by the BDP compounds. Theoretical calculations support these findings and suggest that anchor group selection could further enhance the thermoelectric behavior of these types of molecules., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Smoking is a risk factor for many chronic diseases. Multiple smoking status ascertainment algorithms have been developed for population-based electronic health databases such as administrative databases and electronic medical records (EMRs). Evidence syntheses of algorithm validation studies have often focused on chronic diseases rather than risk factors. We conducted a systematic review and meta-analysis of smoking status ascertainment algorithms to describe the characteristics and validity of these algorithms., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. We searched articles published from 1990 to 2022 in EMBASE, MEDLINE, Scopus, and Web of Science with key terms such as validity, administrative data, electronic health records, smoking, and tobacco use. The extracted information, including article characteristics, algorithm characteristics, and validity measures, was descriptively analyzed. Sources of heterogeneity in validity measures were estimated using a meta-regression model. Risk of bias (ROB) in the reviewed articles was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool., Results: The initial search yielded 2086 articles; 57 were selected for review and 116 algorithms were identified. Almost three-quarters (71.6%) of algorithms were based on EMR data. The algorithms were primarily constructed using diagnosis codes for smoking-related conditions, although prescription medication codes for smoking treatments were also adopted. About half of the algorithms were developed using machine-learning models. The pooled estimates of positive predictive value, sensitivity, and specificity were 0.843, 0.672, and 0.918 respectively. Algorithm sensitivity and specificity were highly variable and ranged from 3 to 100% and 36 to 100%, respectively. Model-based algorithms had significantly greater sensitivity (p = 0.006) than rule-based algorithms. Algorithms for EMR data had higher sensitivity than algorithms for administrative data (p = 0.001). The ROB was low in most of the articles (76.3%) that underwent the assessment., Conclusions: Multiple algorithms using different data sources and methods have been proposed to ascertain smoking status in electronic health data. Many algorithms had low sensitivity and positive predictive value, but the data source influenced their validity. Algorithms based on machine-learning models for multiple linked data sources have improved validity., (© 2024. The Author(s).)

Importance: Alcohol-related hospitalizations are common and associated with significant cost to the health care system. We have a limited understanding of the characteristics of individuals who experience alcohol-related hospitalizations, which limits our capacity to prioritize those at the highest risk of postdischarge harm., Objective: To identify and characterize the clinical subgroups of individuals who are hospitalized for alcohol-related harms., Design, Setting, and Participants: This cohort study used latent class analysis (LCA) to identify clinical subgroups of individuals experiencing alcohol-related hospitalizations in 2 provinces in Canada. All individuals between ages 10 and 105 years who were hospitalized for an alcohol-related harm between January 2017 and December 2018 (ie, the index hospitalization) were eligible. Data were analyzed between June 2023 and August 2023., Exposures: The exposure of interest was the clinical subgroup that an individual belonged to. These subgroups were identified using an LCA based on (1) the characteristics of the index hospitalization and (2) the history of alcohol-related health service use., Main Outcomes and Measures: In-hospital mortality, alcohol-related hospital readmission, and all-cause mortality in the year following discharge from the index hospitalization. The association between subgroup membership and the risk of in-hospital and postdischarge outcomes was evaluated using multivariable regression., Results: A total of 34 043 individuals were included in analysis, 4753 from Manitoba (median [IQR] age, 49 [40-58] years; 1786 female [37.6%]) and 29 290 from Ontario (median [IQR] age, 57 [45-67] years; 8527 female [29.1%]). Seven subgroups were identified following a gradient from low-frequency service use for acute intoxication to high-frequency service use for severe alcohol use disorder and liver disease. In Ontario, there were 4431 individuals in the liver disease subgroup representing 15.5% of the cohort who were at the highest risk of 1-year mortality (1382 [31.2%]) relative to the acute intoxication subgroup (42 [4.0%]) (adjusted hazard ratio [aHR], 3.83; 95% CI, 2.80-5.24). There was also a small subgroup (10.6%) of individuals with high-frequency alcohol-related health service use who had a much higher hazard of readmission following the index hospitalization (1-year readmission: 703 of 1526 [46.1%] vs 104 of 1058 [9.8%] in the acute intoxication subgroup; aHR, 5.09; 95% CI, 4.11-6.31)., Conclusions and Relevance: In this population-based cohort study of individuals experiencing alcohol-related hospitalizations, we identified several small, clinically distinct subgroups that were at a disproportionately high risk of readmission and mortality. These groups could merit prioritization in strategies aimed at reducing the risk of adverse outcomes following alcohol-related hospitalizations.

Across Canada, the COVID-19 pandemic placed considerable stress on territorial and provincial healthcare systems. For Nunavut, the need to continue to provide access to critical care to its citizens meant that medical travel to provincial points of care (Edmonton, Winnipeg and Ottawa) had to continue through the pandemic. This complexity created challenges related to the need to keep Nunavut residents safe while accessing care, and to manage the risk of outbreaks in Nunavut resultant from patients returning home. A number of strategies were adopted to mitigate risk, including the expansion of virtual care, self-isolation requirements before returning from Winnipeg, and a level of cross-jurisdictional coordination previously unprecedented. Structural limitations in Nunavut however limited opportunities to expand virtual care, and to allow providers from Manitoba to access the Nunavut's electronic medical records of patients requiring follow up. Thus, known and long-standing issues exacerbated vulnerabilities within the Nunavut healthcare system. We conclude that addressing cross-jurisdictional issues would be well served by the development of a more formal Nunavut-Manitoba agreement (with similar agreements with Ontario and Alberta), outlining mutual obligations and accountabilities.

We document community responses to the COVID-19 pandemic among Inuit living in the province of Manitoba, Canada. This study was conducted by the Manitoba Inuit Association and a Council of Inuit Elders, in partnership with researchers from the University of Manitoba. We present findings from 12 health services providers and decision-makers, collected in 2021.Although Public Health orders led to the closure of the Manitoba Inuit Association's doors to community events and drop-in activities, it also created opportunities for the creation of programming and events delivered virtually and through outreach. The pandemic exacerbated pre-existing health and social system's shortcomings (limited access to safe housing, food insecurity) and trauma-related tensions within the community. The Manitoba Inuit Association achieved unprecedented visibility with the provincial government, receiving bi-weekly reports of COVID-19 testing, results and vaccination rates for Inuit. We conclude that after over a decade of advocacy received with at best tepid enthusiasm by federal and provincial governments, the Manitoba Inuit Association was able effectively advocate for Inuit-centric programming, and respond to Inuit community's needs, bringing visibility to a community that had until then been largely invisible. Still, many programs have been fueled with COVID-19 funding, raising the issue of sustainability.

A laryngeal mask is one of the most widely used airway management devices. The Singularity TM Air is a second-generation laryngeal mask whose shaft angle can be adjusted after insertion. Since the device's performance has been assessed on mannequins only, this study aimed to evaluate Singularity TM Air's effectiveness in the clinical setting. The prospective single-center cohort study included 100 adults undergoing elective surgery under general anesthesia and suitable for airway securing with a laryngeal mask. The primary endpoint was the oropharyngeal leak pressure, and the secondary endpoints were the ease of insertion and the patient's comfort. Laryngeal mask insertion was successful in 97%, and mechanical ventilation was possible in 96% of patients. After insertion, the median (IQR) oropharyngeal leak pressure was 25 (18-25) cm H 2 O, which remained stable at 25 (25-25) cm H 2 O after 20 min. The median (IQR) time for successful manual bag ventilation was 42 (34-50) seconds. Nineteen patients complained of side effects (e.g., sore throat, difficulty swallowing), but none persisted. The Singularity TM Air performed well in a clinical setting, and its oropharyngeal leak pressure was comparable to that of other masks reported in the literature. The time for successful manual ventilation was slightly longer, and patients reported more temporary side effects.

Background: Addressing the risk of people from gender and sexual minority (GSM) groups experiencing inequities throughout the cancer continuum requires a robust evidence base. In this scoping review, we aim to map the literature on cancer outcomes among adults from GSM groups and the factors that influence them along the cancer continuum., Methods: This mixed-methods scoping review will follow the approach outlined by JBI. We will systematically search electronic databases for literature in collaboration with a health sciences librarian. Two reviewers will screen titles and abstracts to determine eligibility based on inclusion criteria, and then retrieve full text articles for data extraction. Results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Quantitative data will be qualitized through a narrative interpretation and pooled with qualitative data. We will use meta-aggregation to synthesize findings. This protocol was developed in collaboration with GSM patient and public advisors. We will engage people from GSM groups, community organizations and knowledge users in disseminating results., Interpretation: This review will direct future research efforts by expanding the wider body of research examining cancer disparities across the cancer continuum that GSM groups experience, identifying literature gaps and limitations, and highlighting relevant social determinants of health that influence cancer outcomes for adults from GSM groups., Competing Interests: Competing interests: Nathan Nickel reports grants or contracts from the Canadian Institutes of Health Research, Health Canada and the Government of Manitoba; a leadership or fiduciary role with Health Data Research Network Canada and Sexuality Education Resource Centre, Manitoba. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Purpose of Review: Obstructive sleep apnea (OSA) is associated with several cardiovascular risk predictors that have only recently begun to be studied in detail. The strong association between OSA and hypertension, coronary artery disease, congestive heart failure, and sudden cardiac death underscores its significant impact on cardiovascular health. This brief review considers the links between OSA and cardiovascular risk., Recent Findings: OSA is an important contributor to endothelial dysfunction and damage, while repetitive hypoxia and hypercarbia contribute to autonomic dysfunction and sympathetic stimulation. In turn, these derangements have deleterious hematologic effects, including hypercoagulability and abnormal platelet aggregability, which are important in the pathogenesis of atherothrombotic disease., Summary: The varied deleterious effects of OSA on cardiovascular health stem from a unique 'perfect storm' of hypoxic oxidative stress, autonomic dysregulation, endothelial damage, and inflammation occurring at the microvascular level. Further research may disentangle these multiple etiologic threads and provide a better understanding of the underlying pathophysiological relationship between OSA and cardiovascular disease., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There are gaps in our understanding of treatment needs among people who use methamphetamine. We examined the demographics, perceived treatment needs, barriers to accessing care, and stigma experienced by an inpatient sample of people who use methamphetamine., Methods: This study surveyed a convenience sample of patients admitted to psychiatry wards with a history of methamphetamine use in Winnipeg, Canada, between May 1 and July 31, 2019. The Perceived Need for Care Questionnaire (PNCQ-9) was used to assess treatment needs and barriers to care, and the Substance Use Stigma Mechanisms Scale (SU-SMS) was used to assess enacted, anticipated, and internalized stigma. Prevalence rates of perceived need, stigma, and demographic variables were determined., Results: A total of 103 potential participants were identified, with 34 completing the survey. The most common age group was 21-30 years of age (41.2%); an approximate equal number of men and women; and almost all were single and never married (91.1%). Rates of perceived need for care were very high across all treatment types, including 91% identifying a need for medication treatment for their mental health or substance use. Despite the majority receiving care across the seven types of care described in the PNCQ-9, most felt they did not receive enough care. Unmet need for care was therefore high in many categories, including rates of 87% for counselling and skills training. The most common barriers to having needs met were a desire to self-manage substance use, and not receiving care after asking for help. Almost all participants reported experiencing stigma (94%). Stigma from family was endorsed significantly more than stigma from health care providers (p = 0.005)., Conclusions: The average hospitalized person who uses methamphetamine in this sample is young, single, and has not completed any post-secondary education. High rates of perceived treatment need suggest an awareness of problems with methamphetamine, yet most interventions are perceived as inadequate. People who used methamphetamine felt highly stigmatized, particularly by their family members. Trial registration Registered with the Health Research Ethics Board at the University of Manitoba (Number HS22605 (H2019:072), renewed February 14, 2022)., (© 2023. The Author(s).)

Background and Objectives: Guidance around maternity care practices and infant feeding during the COVID-19 pandemic changed over time and was sometimes conflicting. Hospital maternity practices influence breastfeeding, an important preventive strategy against viral illness. Most birthing hospitals in Mississippi are enrolled in CHAMPS, a quality improvement initiative to support breastfeeding and continuously collect maternity care data. The aims of this study were to (1) assess changes to maternity care policies in response to COVID-19, and (2) compare hospital-level breastfeeding, skin-to-skin, and rooming-in rates, at cohort hospitals, before and during the pandemic, overall and stratified by race. Methods: Hospitals responded to a survey on maternity policies in May and September 2020 (Aim 1); hospitals submitted data on breastfeeding and maternity care practices before and during the pandemic (Aim 2). We tested for differences in survey responses using chi-squared statistics and performed an interrupted time series analysis on breastfeeding and maternity care practices data. Results: Twenty-six hospitals responded to the May and September 2020 surveys. Hospitals used different sources to create maternity care policies, and policies differed between institutions. Trends in rates of any and exclusive breastfeeding in the hospital cohort plateaued during the pandemic, in comparison to previous gains, and rates of skin-to-skin and hospital rooming-in decreased. No differences were evident between races. Conclusions: Policies (Aim 1) and practices in the quality improvement cohort hospitals were inconsistent during the COVID-19 pandemic, and changes measured to practices were detrimental (Aim 2). Ongoing monitoring is recommended.

Adolescence is a vital period of growth and development, both of which are dependent on adequate nutrition; however, concerns persist about poor nutrition and inappropriate food behaviours. In addition to nutrition assessment, the context of food and health behaviour is necessary to understand how dietary choices are shaped and related to diet quality. This study describes food-related behaviours and health indicators associated with dietary quality among adolescents in Manitoba, Canada. A stratified two-stage sampling method was used to collect data on the diet, food behaviours and health indicators of 1587 grade nine students. Diet quality was analysed using the Healthy Eating Index-Canada. Several food behaviours and health indicators varied by gender and school region (urban, rural, northern). The Independent Samples t-test and one-way ANOVA (analysis of variance) assessed differences between groups on the Healthy Eating Index-Canada. Higher Healthy Eating Index-Canada scores were found for those eating family dinners more frequently; consuming breakfast and lunch more frequently; consuming breakfast at home; eating lunch and morning snacks at school; purchasing fewer meals and snacks from cafeterias and vending machines; believing that food and nutrition education is important; not attempting to lose weight; being classified as 'healthy weight'; and getting more sleep. Many Manitoba youth are exhibiting food and health behaviours that increase their risk of having a poor diet.

Pulmonary hypertension (PH) associated with left heart disease (LHD) is a complex cardiopulmonary condition where a variable degree of pulmonary congestion, arterial vasoconstriction and vascular remodeling can lead to PH and right heart strain. Right heart dysfunction has a significant prognostic impact on these patients. Therefore, preserving right ventricular (RV) function is an important treatment goal. However, the treatment of PH in patients with left heart disease has produced conflicting evidence. The transition from pure LHD to LHD with PH is a continuum and clinically challenging. The heart failure with preserved ejection fraction (HFpEF) patient population is heterogeneous when it comes to PH and RV function. Appropriate clinical and hemodynamic phenotyping of patients with HFpEF and concomitant PH is paramount to making the appropriate treatment decision. This manuscript will summarize the current evidence for the use of pulmonary arterial vasodilators in patients with HFpEF., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

There is a notable lack of research related to trends in Inuit accessing health services throughout the land known as Canada. Given Nunavut's reliance on specialised services provided in the Northwest Territories, Alberta, Manitoba, and Ontario, this gap is particularly problematic, making it more difficult for Nunangat to proactively plan new programs for emerging needs, and for provinces to respond to those needs. The Qanuinngitsiarutiksait study aimed to address this gap by developing detailed profiles of Inuit accessing health services in Manitoba. We used administrative data routinely collected by Manitoba agencies, to support the development of Inuit-centric services. It was conducted in partnership with the Manitoba Inuit Association, and Inuit Elders from Nunavut Canada and Manitoba. We focused on two interrelated cohorts: Kivallirmiut (Inuit from the Kivalliq region of Nunavut) who come to Winnipeg to access specialised services; and Manitobamiut (Inuit already living in Manitoba). Findings show that health services are primarily accessed in Winnipeg. Half of health services accessed by Kivallirmiut are for in-patient care at facilities with the Winnipeg Regional Health Authority. The other half are for advanced out-patient care including specialist consults. For Kivallirmiut, hospitalisation for pregnancy and birth are the most prevalent reasons for hospitalisation, followed by diseases of the respiratory system. Noteworthy, rates of hospitalisation for conditions treatable in primary healthcare for Kivallirmiut are considerably lower than those for Manitobans living in the northern part of the province (where comparable constraints exist). For Inuit adults, rates of hospitalisation for these conditions are comparable to those of Manitobans living in small communities. Inuit living in Manitoba are most often hospitalised for mental health reasons, although other reasons are nearly as prevalent. Our results support the need for more Inuit-centric health programming in Winnipeg.

Background: The Qanuinngitsiarutiksait study aimed to develop detailed profiles of Inuit health service utilization in Manitoba, by Inuit living in Manitoba (approximately 1,500) and by Inuit from the Kivalliq region of Nunavut who travel to Manitoba to access care not available in Nunavut (approximately 16,000 per year)., Methods: We used health administrative data routinely collected in Manitoba for all services provided and developed an algorithm to identify Inuit in the dataset. This paper focused on health services used by Inuit from the Kivalliq for prenatal care and birthing., Results: Our study found that approximately 80 percent of births to women from the Kivalliq region occur in Manitoba, primarily in Winnipeg. When perinatal care and birthing are combined, they constitute one third of all consults happening by Kivalliq residents in Manitoba. For scale, hospitalizations for childbirths to Kivalliq women about to only 5 percent of all childbirth-related hospitalizations in Manitoba., Conclusions: The practice of evacuating women from the Kivalliq for perinatal care and birthing is rooted in colonialism, rationalized as ensuring that women whose pregnancy is at high risk have access to specialized care not available in Nunavut. While defendable, this practice is costly, and does not provide Inuit women a choice as to where to birth. Attempts at relocating birthing to the north have proven complex to operationalize. Given this, there is an urgent need to develop Inuit-centric and culturally appropriate perinatal and birthing care in Manitoba., (© 2022. The Author(s).)

The discovery of quantum interference (QI) is widely considered as an important advance in molecular electronics since it provides unique opportunities for achieving single-molecule devices with unprecedented performance. Although some pioneering studies suggested the presence of spin qubit coherence and QI in collective systems such as thin films, it remains unclear whether the QI can be transferred step-by-step from single molecules to different length scales, which hinders the application of QI in fabricating active molecular devices. Here, we found that QI can be transferred from a single molecule to their assemblies. We synthesized and investigated the charge transport through the molecular cages using 1,3-dipyridylbenzene (DPB) as a ligand block with a destructive quantum interference (DQI) effect and 2,5-dipyridylfuran (DPF) as a control building block with a constructive quantum interference (CQI) effect using both single-molecule break junction and large area junction techniques. Combined experiments and calculations revealed that both DQI and CQI had been transferred from the ligand blocks to the molecular cages and the monolayer thin film of the cages. Our work introduced QI effects from a ligand to the molecular cage comprising 732 atoms and even their monolayers, suggesting that the quantum interference could be scaled up within the phase-coherent distance.

Objective: Our neonatal intensive care unit (NICU) saw an increase in Staphylococcus aureus (SA) infections-methicillin-resistant SA (MRSA) infections increased from 2.1/10,000 patient days (PD) to 5.1/10,000 PD, and methicillin-sensitive SA (MSSA) infections from 1.2/10,000 PD to 3.9/10,000 PD. This quality improvement project aimed to decrease the rates of SA infections to less than 2.0/10,000 PD, and to determine the rate of SA decolonization., Methods: Infection prevention interventions targeted patient factors (SA surveillance, patient cohorting, decolonization protocol), provider factors (provider cohorting, enhanced hand hygiene) and environmental factors (room structure, equipment optimization)., Results: The rates of MRSA and MSSA infections decreased to 0.6/10,000 PD and 0.7 infections/10,000 PD respectively. Persistent decolonization of SA was successful in 67% of colonized patients., Conclusions: Specific interventions targeting patient, provider, and environmental factors, including the implementation of a SA decolonization protocol, were successful in decreasing the incidence of SA infections in neonates., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Good nutrition and access to healthy foods are essential for child growth and development. However, there are concerns that Canadian children do not have a healthy diet, which may be related to dietary choices as well as lack of access to healthy foods. The FANS (Food and Nutrition Security for Children and Youth) study examined the nutrition and food security status of youth in the province of Manitoba, Canada. This paper describes methods, dietary intakes, and body mass index for the FANS study.  METHODS: This cross-sectional study included 1587 Manitoba grade nine students who completed a self-administered web-based survey. Data was collected on demographic characteristics, dietary intake (24-h recall), food behaviors, food security, and self-report health indicators. Dietary data was compared to national dietary guidelines (Dietary Reference Intakes and Canada's Food Guide). Mean and median nutrient and food group intakes were calculated with corresponding measures of variability. Chi-square tests compared percentage of respondents not meeting key nutrients and food groups. Significant differences in percentage of total servings for each food group were determined by a Kruskal-Wallis test, and differences between different caloric groups were assessed using Dunn's test for post-hoc comparisons.  RESULTS: Half of study respondents were female (50.5%). Median energy intake was higher in males (2281 kcal) compared with females (1662 kcal), with macronutrient distribution of 52%, 16%, and 32% for carbohydrates, protein, and fats respectively. Most participants consumed inadequate fibre (94%), vitamin D (90%), and calcium (73%), while median sodium intakes exceeded recommendations for males but not females. A majority of participants did not meet Health Canada's recommendations for food group servings: Vegetables and Fruit (93%), Milk and Alternatives (74%), Meat and Alternatives (57%) and Grain Products (43%). Other Foods, including sugar sweetened beverages and juice, were consumed by most participants. Higher energy consumers had a greater proportion of food servings coming from Other Foods. 72.1% of students were classified as having a healthy weight and 25% were classified as overweight or obese., Conclusion: Poor dietary intakes and body mass index values indicate an urgent need for policy and program strategies to support healthy eating habits and food awareness in Manitoba youth., (© 2022. The Author(s).)

Communities and Hospitals Advancing Maternity Practices (CHAMPS) is a public health initiative, operating in Mississippi since 2014, to improve maternal and child health practices and reduce racial disparities in breastfeeding. Using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, this study assessed CHAMPS, which used a Quality Improvement intervention at hospitals, and engaged intensively with local community partners. The study team assessed outcomes through quantitative data (2014-2020) from national sources, Mississippi hospitals, community partners and CHAMPS programme records, and qualitative data from focus groups. With 95% of eligible Mississippi hospitals enrolled into CHAMPS, the programme reached 98% of eligible birthing women in Mississippi, and 65% of breastfeeding peer counsellors in Mississippi's Special Supplemental Nutrition Programme for Women, Infants and Children. Average hospital breastfeeding initiation rates rose from 56% to 66% (p < 0.05), the proportion of hospitals designated Baby-Friendly or attaining the final stages thereof rose from 15% to 90%, and 80% of Mississippi Special Supplemental Programme for Women, Infants, and Children districts engaged with CHAMPS. CHAMPS also maintains a funded presence in Mississippi, and all designated hospitals have maintained Baby-Friendly status. These findings show that a breastfeeding-focused public health initiative using broad-based strategic programming involving multiple stakeholders and a range of evaluation criteria can be successful. More breastfeeding promotion and support programmes should assess their wider impact using evidence-based implementation frameworks., (© 2022 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Genetic alterations in the DNA damage response (DDR) pathway are a frequent mechanism of resistance to chemoimmunotherapy (CIT) in B-cell malignancies. We have previously shown that the synergy of CIT relies on secretory crosstalk elicited by chemotherapy between the tumor cells and macrophages. Here, we show that loss of multiple different members of the DDR pathway inhibits macrophage phagocytic capacity in vitro and in vivo. Particularly, loss of TP53 led to decreased phagocytic capacity ex vivo across multiple B-cell malignancies. We demonstrate via in vivo cyclophosphamide treatment using the Eμ-TCL1 mouse model that loss of macrophage phagocytic capacity in Tp53-deleted leukemia is driven by a significant downregulation of a phagocytic transcriptomic signature using small conditional RNA sequencing. By analyzing the tumor B-cell proteome, we identified a TP53-specific upregulation of proteins associated with extracellular vesicles (EVs). We abrogated EV biogenesis in tumor B-cells via clustered regularly interspaced short palindromic repeats (CRISPR)-knockout (KO) of RAB27A and confirmed that the EVs from TP53-deleted lymphoma cells were responsible for the reduced phagocytic capacity and the in vivo CIT resistance. Furthermore, we observed that TP53 loss led to an upregulation of both PD-L1 cell surface expression and secretion of EVs by lymphoma cells. Disruption of EV bound PD-L1 by anti-PD-L1 antibodies or PD-L1 CRISPR-KO improved macrophage phagocytic capacity and in vivo therapy response. Thus, we demonstrate enhanced EV release and increased PD-L1 expression in TP53-deficient B-cell lymphomas as novel mechanisms of macrophage function alteration in CIT resistance. This study indicates the use of checkpoint inhibition in the combination treatment of B-cell malignancies with TP53 loss., (© 2022 by The American Society of Hematology.)

Mississippi CHAMPS addressed racial inequities in breastfeeding by implementing community and hospital-based practice changes in accordance with the BFHI and by parallel community work., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

Background and Aims: High-risk alcohol consumption is associated with compromised health. This study aimed to compare the incidence of alcohol-related cancers, diabetes, ischemic heart disease (IHD) and mortality between those with and without an indication of alcohol use disorder (AUD)., Design: Retrospective, population-based, matched cohort study using data from the Manitoba Population Research Data Repository. Rates were modeled using generalized linear models with either negative binomial distribution or Poisson distribution and a log offset of person-years to account for each person's time to follow-up., Setting: Manitoba, Canada., Participants: Individuals aged ≥ 12 years with a first indication of AUD (index date) between 1 April 1990 and 31 March 2015 were matched to five controls based on age, sex and geographical region at index. This study included 53 410 individuals with AUD and 264 857 matched controls., Measurements: Adjusted rate ratios (aRR) and 95% confidence intervals (CI) were determined for each outcome from 5 years prior to and 20 years after AUD detection., Findings: Alcohol-related cancers (aRR = 4.85, 95% CI = 3.88-6.07 and aRR = 1.85, 95% CI = 1.35-2.53 for men and women, respectively), diabetes (aRR = 1.74, 95% CI = 1.50-2.02 and aRR = 2.43, 95% CI = 2.20-2.68) and IHD (aRR = 3.59, 95% CI = 3.31-3.90 and aRR = 2.92, 95% CI = 2.50-3.41) peaked in the 1 year prior to index for those with AUD compared with matched controls. All-cause mortality (aRR = 3.31, 95% CI = 3.09-3.55 and aRR =3.61, 95% CI = 3.21-4.04) was highest in the year of index and remained higher among cases compared with controls throughout the 20-year follow-up., Conclusion: People with alcohol use disorder appear to have higher rates of adverse health outcomes in the year before alcohol use disorder recognition, and death at the time of alcohol use disorder recognition, compared with matched controls., (© 2021 Society for the Study of Addiction.)

Background: Heart failure is the leading cause of morbidity and mortality worldwide. With improved longevity, the incidence and prevalence of heart failure continue to rise with an estimated prevalence of around 26 million worldwide. Heart failure with preserved ejection fraction (HFpEF) constitutes around 50% of the total heart failure cases and is the most common cause of heart failure in the elderly population. The cost of heart failure care continues to rise with care for heart failure hospitalization taking the major bulk. The cost was around 30 billion in the US in 2012 and is projected to reach 70 billion by 2030., Objective: This study aims to provide updated pharmacotherapy of heart failure with a preserved ejection fraction (HFpEF)., Methods: We performed a comprehensive literature review to examine the available pharmacotherapeutics in the management of heart failure with a preserved ejection fraction using online databases (PubMed and Embase)., Results: We reviewed multiple studies examining pharmacotherapeutics in the management of HFpEF and reducing heart failure hospitalizations in this cohort. Until recently, our management mainly focused on aggressively managing diabetes, hypertension, atrial fibrillation, and coronary artery disease anticipating improving the outcome. Beta-blockers, Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, sildenafil, digoxin, vericiguat, praliciguat, and Ivabradine did not improve heart failure hospitalization in this cohort., Conclusion: EMPEROR-PRESERVED (Empagliflozin) and PRESERVED-HF (Dapagliflozin) results in the management of HFpEF look promising irrespective of diabetes status. Sacubitrilvalsartan and Empagliflozon are the only medications approved for its management as per the PARAGON-HF and EMPEROR-PRESERVED studies, respectively., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cefepime is a fourth-generation, cephalosporin antibiotic commonly used as a first-line empirical treatment in a wide range of bacterial infections. It is predominantly excreted renally; therefore, a reduction in kidney function allows for the accumulation of cefepime to potentially toxic levels. Here we present a case of cefepime-induced encephalopathy (CIE) in a 67 years old male patient with advanced-stage renal insufficiency and cirrhosis who was admitted to our hospital for altered mental status (AMS). The patient was initially treated for hepatic encephalopathy (HE) given an elevated ammonia level (105 µg/dL), which had significantly improved. He was also placed on intravenous (IV) cefepime for Pseudomonas bacteremia. Four days later, the patient became drowsy and confused. A detailed workup for secondary causes of AMS was performed however no significant acute abnormalities were detected. The ammonia level remained within the normal range. There was no acute intracranial pathology reported on a head computerized tomography (CT). Furthermore, an electroencephalograph (EEG) was obtained which showed generalized periodic discharge with a tri-phasic wave pattern suggesting non-convulsive status epilepticus (NCSE). CIE was suspected at that point and cefepime administration was stopped. Following cefepime discontinuation, there was a remarkable improvement in the patient's mental status for several days after cefepime discontinuation that supported the diagnosis of CIE in our patient. Although the exact pathophysiology is unclear, CIE should be suspected in elderly patients, patients with renal dysfunction, and critical illness. Meanwhile, liver dysfunction can be an additional risk factor for CIE as it increases the permeability of the blood-brain barrier (BBB), altered neurotransmission, and neuro-inflammation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Ortega et al.)

Background: First Nations (FN) women have a higher risk of diabetes than non-FN women in Canada. Prenatal education and breastfeeding may reduce the risk of diabetes in mothers and offspring. The rates of breastfeeding initiation and participation in the prenatal program are low in FN communities., Methods: A prenatal educational website, social media-assisted prenatal chat groups and community support teams were developed in three rural or remote FN communities in Manitoba. The rates of participation of pregnant women in prenatal programs and breastfeeding initiation were compared before and after the start of the remote prenatal education program within 2014-2017., Findings: The participation rate of FN pregnant women in rural or remote communities in the prenatal program and breastfeeding initiation during 1-year after the start of the community-based remote prenatal education program were significantly increased compared to that during 1-year before the start of the program (54% versus 36% for the participation rate, 50% versus 34% for breastfeeding initiation, p  < 0·001). Availability of high-speed Wi-Fi and/or postpartum supporting team were associated with favorite study outcomes. Positive feedback on the remote prenatal education was received from participants., Interpretation: The findings suggest that remote prenatal education is feasible and effective for improving the breastfeeding rate and engaging pregnant women to participate in the prenatal program in rural or remote FN communities. The remote prenatal education remained active during COVID-19 in the participating communities, which suggests an advantage to expand remote prenatal education in other Indigenous communities., Funding: Canadian Institutes of Health Research, the Lawson Foundation and University of Manitoba., Competing Interests: No conflicting interest exists between the content of the manuscript and all authors., (© 2021 The Authors.)

Objective: This quality improvement project aimed to improve the accuracy and efficiency of handoff communication among NICU medical providers with an Electronic Medical Record (EMR)-based handoff tool (HT)., Study Design: Three Plan-Do-Study-Act (PDSA) cycles were utilized following the implementation of a NICU-specific EMR-based HT and a standardized handoff process. Primary measures included accuracy of demographic components: patient name, bed, age, gestational age, postmenstrual age; and medical components: active diagnoses, weight, vascular access, respiratory support, diet, total fluid goal, medications. Secondary measures included environmental components (start time, duration, location, and distractions) as indicators of efficiency., Results: Accuracy of handoff components improved from 68% to 99% (p < 0.001). Efficiency of the handoff improved with time needed to complete patient handoff decreasing from 78 to 47 s per patient (p < 0.001)., Conclusions: Standardizing the NICU handoff process using an EMR-based HT allowed for increased accuracy of handoff components and improved efficiency, which may promote enhanced patient safety.

The interaction and crosstalk of Toll-like receptors (TLRs) is an established pathway in which the innate immune system recognises and fights pathogens. In a single nucleotide polymorphisms (SNP) analysis of an Indian cohort, we found evidence for both TLR4-399T and TRL8-1A conveying increased susceptibility towards tuberculosis (TB) in an interdependent manner, even though there is no established TLR4 ligand present in Mycobacterium tuberculosis (Mtb), which is the causative pathogen of TB. Docking studies revealed that TLR4 and TLR8 can build a heterodimer, allowing interaction with TLR8 ligands. The conformational change of TLR4-399T might impair this interaction. With immunoprecipitation and mass spectrometry, we precipitated TLR4 with TLR8-targeted antibodies, indicating heterodimerisation. Confocal microscopy confirmed a high co-localisation frequency of TLR4 and TLR8 that further increased upon TLR8 stimulation. The heterodimerisation of TLR4 and TLR8 led to an induction of IL12p40, NF-κB, and IRF3. TLR4-399T in interaction with TLR8 induced an increased NF-κB response as compared to TLR4-399C, which was potentially caused by an alteration of subsequent immunological pathways involving type I IFNs. In summary, we present evidence that the heterodimerisation of TLR4 and TLR8 at the endosome is involved in Mtb recognition via TLR8 ligands, such as microbial RNA, which induces a Th1 response. These findings may lead to novel targets for therapeutic interventions and vaccine development regarding TB.