Evaluating the Effect of Maternal Opioid Maintenance Dose on the NOWS-COS Outcome Criteria: A Pilot Study.

This retrospective cohort study included 77 mother-infant dyads that delivered term pregnancies at a single tertiary care institution. The primary objective was to investigate whether maternal dose of opioid maintenance therapy during pregnancy affects infant outcomes. All infants had prenatal exposure to opioid maintenance therapies. Maternal dose was converted into morphine milligram equivalents (MMEs) and stratified into high- (MME >1000 mg) and low-dose groups (MME ≤1000 mg). Associations between infant outcomes and MME dosage were examined using Wilcoxon rank-sum and Fisher's Exact tests. Days to symptom control were significantly higher in the high MME group (5 days vs 2.8 days, P = .016). Rates of developmental delay at 24 months were higher in the high MME group (21.2% vs 4.5%, P = .0335). Maternal MME did not predict need for NOWS treatment. Higher MME-exposed infants should have optimized nonpharmacologic interventions for consolation and be increasingly observed for signs of developmental delay.

A Light Touch: Solar Photocatalysis Detoxifies Oil Sands Process-Affected Waters Prior to Significant Treatment of Naphthenic Acids.

Environmental reclamation of Canada's oil sands tailings ponds is among the single largest water treatment challenges globally. The toxicity of oil sands process-affected water (OSPW) has been associated with its dissolved organics, a complex mixture of naphthenic acid fraction components (NAFCs). Here, we evaluated solar treatment with buoyant photocatalysts (BPCs) as a passive advanced oxidation process (P-AOP) for OSPW remediation. Photocatalysis fully degraded naphthenic acids (NAs) and acid extractable organics (AEO) in 3 different OSPW samples. However, classical NAs and AEO, traditionally considered among the principal toxicants in OSPW, were not correlated with OSPW toxicity herein. Instead, nontarget petroleomic analysis revealed that low-polarity organosulfur compounds, composing <10% of the total AEO, apparently accounted for the majority of waters' toxicity to fish, as described by a model of tissue partitioning. These findings have implications for OSPW release, for which a less extensive but more selective treatment may be required than previously expected.

A compendium of multi-omics data illuminating host responses to lethal human virus infections.

Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For comparison, we have included transcriptomics datasets from cells treated with type I and type II human interferon. Raw multi-omics data and metadata were deposited in public repositories, and we provide a central location linking the raw data with experimental metadata and ready-to-use, quality-controlled, statistically processed multi-omics datasets not previously available in any public repository. This compendium of infection-induced host response data for reuse will be useful for those endeavouring to understand viral disease pathophysiology and network biology.

"You Can Do So Much Better Than What They Expect": An Arts-Based Engagement Ethnography on School Integration With Newcomer Youth.

Newcomer adolescents make up a large minority of Canada's population and their positive integration experiences with education systems across the country are critical for both their development and the country's long-term success. The current study examined newcomer adolescents' (n = 4, between 16 and 18 years old) integration experiences using an arts-based engagement ethnography to understand what influences their positive integration into the school system. Artifacts, interview, and focus group data were analyzed systematically using ethnographic research guidelines. Five structures were identified: (1) barriers to advancement at individual, school, and macro levels, (2) fluctuating relationship with cultural identity, (3) limited trust in systems, (4) resilience through independent learning, and (5) facilitating factors to positive integration experiences at the family and school level. In keeping with a relational developmental systems theory framework, each structure accounts for multiple inter- and intra-individual factors at multiple environmental levels. These findings outline considerations for systemic issues in academic institutions and offer suggestions for how institutions can better support newcomer adolescents.

Self-reported knowledge of tetrahydrocannabinol and cannabidiol concentration in cannabis products among cancer patients and survivors.

PURPOSE: Cannabis use may introduce risks and/or benefits among people living with cancer, depending on product type, composition, and nature of its use. Patient knowledge of tetrahydrocannabinol (THC) or cannabidiol (CBD) concentration could provide information for providers about cannabis use during and after treatment that may aide in risk and benefit assessments. This study aimed to examine knowledge of THC or CBD concentration among patients living with cancer who consume cannabis, and factors associated with knowledge of cannabinoid concentrations. METHODS: People living with cancer who consumed cannabis since their diagnosis (n = 343) completed an anonymous, mixed-mode survey. Questions assessed usual mode of delivery (MOD), knowledge of THC/CBD concentration, and how source of acquisition, current cannabis use, and source of instruction are associated with knowledge of THC/CBD concentration. Chi-square and separate binary logistic regression analyses were examined and weighted to reflect the Roswell Park patient population. RESULTS: Less than 20% of people living with cancer had knowledge of THC and CBD concentration for the cannabis products they consumed across all MOD (smoking- combustible products, vaping- vaporized products (e-cigarettes), edibles-eating or drinking it, and oral- taking by mouth (pills)). Source of acquisition (smoking-AOR:4.6, p < 0.01, vaping-AOR:5.8, p < 0.00, edibles-AOR:2.6, p < 0.04), current cannabis use (edibles-AOR:5.4, p < 0.01, vaping-AOR: 11.2, p < 0.00, and oral-AOR:9.3, p < 0.00), and source of instruction (vaping only AOR:4.2, p < 0.05) were found to be variables associated with higher knowledge of THC concentration. CONCLUSION: Self-reported knowledge of THC and CBD concentration statistically differed according to MOD, source of acquisition, source of instruction, and current cannabis use.

Legionella pneumophila usurps host cell lipids for vacuole expansion and bacterial growth.

Vacuolar pathogens reside in membrane-bound compartments within host cells. Maintaining the integrity of this compartment is paramount to bacterial survival and replication as it protects against certain host surveillance mechanisms that function to eradicate invading pathogens. Preserving this compartment during bacterial replication requires expansion of the vacuole membrane to accommodate the increasing number of bacteria, and yet, how this is accomplished remains largely unknown. Here, we show that the vacuolar pathogen Legionella pneumophila exploits multiple sources of host cell fatty acids, including inducing host cell fatty acid scavenging pathways, in order to promote expansion of the replication vacuole and bacteria growth. Conversely, when exogenous lipids are limited, the decrease in host lipid availability restricts expansion of the replication vacuole membrane, resulting in a higher density of bacteria within the vacuole. Modifying the architecture of the vacuole prioritizes bacterial growth by allowing the greatest number of bacteria to remain protected by the vacuole membrane despite limited resources for its expansion. However, this trade-off is not without risk, as it can lead to vacuole destabilization, which is detrimental to the pathogen. However, when host lipid resources become extremely scarce, for example by inhibiting host lipid scavenging, de novo biosynthetic pathways, and/or diverting host fatty acids to storage compartments, bacterial replication becomes severely impaired, indicating that host cell fatty acid availability also directly regulates L. pneumophila growth. Collectively, these data demonstrate dual roles for host cell fatty acids in replication vacuole expansion and bacterial proliferation, revealing the central functions for these molecules and their metabolic pathways in L. pneumophila pathogenesis.

Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours.

Hypoxia is a common feature of solid tumours affecting their biology and response to therapy. One of the main transcription factors activated by hypoxia is hypoxia-inducible factor (HIF), which regulates the expression of genes involved in various aspects of tumourigenesis including proliferative capacity, angiogenesis, immune evasion, metabolic reprogramming, extracellular matrix (ECM) remodelling, and cell migration. This can negatively impact patient outcomes by inducing therapeutic resistance. The importance of hypoxia is clearly demonstrated by continued research into finding clinically relevant hypoxia biomarkers, and hypoxia-targeting therapies. One of the problems is the lack of clinically applicable methods of hypoxia detection, and lack of standardisation. Additionally, a lot of the methods of detecting hypoxia do not take into consideration the complexity of the hypoxic tumour microenvironment (TME). Therefore, this needs further elucidation as approximately 50% of solid tumours are hypoxic. The ECM is important component of the hypoxic TME, and is developed by both cancer associated fibroblasts (CAFs) and tumour cells. However, it is important to distinguish the different roles to develop both biomarkers and novel compounds. Fibronectin (FN), collagen (COL) and hyaluronic acid (HA) are important components of the ECM that create ECM fibres. These fibres are crosslinked by specific enzymes including lysyl oxidase (LOX) which regulates the stiffness of tumours and induces fibrosis. This is partially regulated by HIFs. The review highlights the importance of understanding the role of matrix stiffness in different solid tumours as current data shows contradictory results on the impact on therapeutic resistance. The review also indicates that further research is needed into identifying different CAF subtypes and their exact roles; with some showing pro-tumorigenic capacity and others having anti-tumorigenic roles. This has made it difficult to fully elucidate the role of CAFs within the TME. However, it is clear that this is an important area of research that requires unravelling as current strategies to target CAFs have resulted in worsened prognosis. The role of immune cells within the tumour microenvironment is also discussed as hypoxia has been associated with modulating immune cells to create an anti-tumorigenic environment. Which has led to the development of immunotherapies including PD-L1. These hypoxia-induced changes can confer resistance to conventional therapies, such as chemotherapy, radiotherapy, and immunotherapy. This review summarizes the current knowledge on the impact of hypoxia on the TME and its implications for therapy resistance. It also discusses the potential of hypoxia biomarkers as prognostic and predictive indictors of treatment response, as well as the challenges and opportunities of targeting hypoxia in clinical trials.

Human Paenibacillus Infections: A Systematic Review with Comparison of Adult and Infant Cases.

Neonatal infections due to Paenibacillus species have increasingly been reported over the last few years. We performed a structured literature review of human Paenibacillus infections in infants and adults to compare the epidemiology of infections between these distinct patient populations. Thirty-nine reports describing 176 infections met our inclusion criteria and were included. There were 37 Paenibacillus infections occurring in adults caused by 23 species. The clinical presentations of infections were quite variable. In contrast, infections in infants were caused by only 3 species: P. thiaminolyticus (112/139, 80%), P. alvei (2/139, 1%) and P. dendritiformis (2/139, 1%). All of the infants with Paenibacillus infection presented with a sepsis syndrome or meningitis, often complicated by extensive cerebral destruction and hydrocephalus. Outcomes were commonly poor with 17% (24/139) mortality. Cystic encephalomalacia due to brain destruction was common in both Ugandan and American cases and 92/139 (66%) required surgical management of hydrocephalus following their infection. Paenibacillus infections are likely underappreciated in infants and effective treatments are urgently needed.

Intracranial Relapse in Pediatric Sarcoma.

Advances in local control techniques, chemotherapy regimens, and imaging modalities have led to improvements in both morbidity and mortality in pediatric sarcoma patients. However, approximately one-third of patients develop disease relapse and intracranial metastasis was considered rare. The incidence of sarcoma brain metastasis is thought to have increased and is associated with grim outcomes. This was a retrospective study of 3 deidentified patient charts illustrating the possibility of the central nervous system as a potential site for pediatric sarcoma relapse and investigate the patterns of such relapses. We note this is the first report of infantile fibrosarcoma brain metastasis and a rare report of sarcoma lymph node metastasis. In addition, each patient was treated with targeted therapies, including entrectinib, Ruxolitnib, and pazopanib. Caregivers in cases 2 and 3 reported new-onset neurological manifestations before identification of new brain metastasis, indicating a lag in detection of new intracranial relapse in asymptomatic sarcoma patients. We suggest implementing a brief review of systems screening tool focused on concerning neurological manifestations to screen for new brain metastasis.

A blood-based marker of mitochondrial DNA damage in Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, and neuroprotective or disease-modifying interventions remain elusive. High-throughput markers aimed at stratifying patients on the basis of shared etiology are required to ensure the success of disease-modifying therapies in clinical trials. Mitochondrial dysfunction plays a prominent role in the pathogenesis of PD. Previously, we found brain region-specific accumulation of mitochondrial DNA (mtDNA) damage in PD neuronal culture and animal models, as well as in human PD postmortem brain tissue. To investigate mtDNA damage as a potential blood-based marker for PD, we describe herein a PCR-based assay (Mito DNADX) that allows for the accurate real-time quantification of mtDNA damage in a scalable platform. We found that mtDNA damage was increased in peripheral blood mononuclear cells derived from patients with idiopathic PD and those harboring the PD-associated leucine-rich repeat kinase 2 (LRRK2) G2019S mutation in comparison with age-matched controls. In addition, mtDNA damage was elevated in non-disease-manifesting LRRK2 mutation carriers, demonstrating that mtDNA damage can occur irrespective of a PD diagnosis. We further established that Lrrk2 G2019S knock-in mice displayed increased mtDNA damage, whereas Lrrk2 knockout mice showed fewer mtDNA lesions in the ventral midbrain, compared with wild-type control mice. Furthermore, a small-molecule kinase inhibitor of LRRK2 mitigated mtDNA damage in a rotenone PD rat midbrain neuron model and in idiopathic PD patient-derived lymphoblastoid cell lines. Quantifying mtDNA damage using the Mito DNADX assay may have utility as a candidate marker of PD and for measuring the pharmacodynamic response to LRRK2 kinase inhibitors.

Parent-Child Vaccination Concordance and Its Relationship to Child Age, Parent Age and Education, and Perceived Social Norms.

Researchers established that parental vaccination status often predicts that of their children, but a limited number of studies have examined factors influencing dyadic concordance or discordance (i.e., same or different vaccination status or intent for both members). We investigated how child versus parent age as well as parents' perceptions of their respective friends' immunization behavior impacted un/vaccinated parents' decisions regarding vaccinating their child. An online survey obtained the COVID-19 vaccination status and views of 762 parents of 5-17-year-old children. More than three-quarters of all dyads were concordant; 24.1% of vaccinated parents would not vaccinate their child, with greater hesitancy for younger children and among younger or less educated parents. Children of vaccinated parents and of parents who thought most of their child's friends were vaccinated were 4.7 and 1.9 times, respectively, more likely to be vaccinated; unvaccinated parents were 3.2 times more likely to accept the vaccine for their child if they believed most of their friends would vaccinate their children. Further, parents who reported that most of their friends were vaccinated were 1.9 times more likely to have obtained the vaccine themselves, illustrating the influence of social norms. Regardless of their own vaccination status, parents of unvaccinated children were more likely to be politically conservative. If communities or circles of friends could achieve or convey a vaccinated norm, this might persuade undecided or reluctant parents to vaccinate their children. Future research should examine the effects of community behavior and messages highlighting social norms on pediatric vaccine uptake.

Prevalence of depressive symptoms and cannabis use among adult cigarette smokers in Canada: cross-sectional findings from the 2020 International Tobacco Control Policy Evaluation Project Canada Smoking and Vaping Survey.

BACKGROUND: Tobacco smoking and cannabis use are independently associated with depression, and evidence suggests that people who use both tobacco and cannabis (co-consumers) are more likely to report mental health problems, greater nicotine dependence and alcohol misuse than those who use either product exclusively. We examined prevalence of cannabis use and depressive symptoms among Canadian adults who smoke cigarettes and tested whether co-consumers of cannabis and tobacco were more likely to report depressive symptoms than cigarette-only smokers; we also tested whether cigarette-only smokers and co-consumers differed on cigarette dependence measures, motivation to quit smoking and risky alcohol use by the presence or absence of depressive symptoms. METHODS: We analyzed cross-sectional data from adult (age ≥ 18 yr) current (≥ monthly) cigarette smokers from the Canadian arm of the 2020 International Tobacco Control Policy Evaluation Project Four Country Smoking and Vaping Survey. Canadian respondents were recruited from Leger's online probability panel across all 10 provinces. We estimated weighted percentages for depressive symptoms and cannabis use among all respondents and tested whether co-consumers (≥ monthly use of cannabis and cigarettes) were more likely to report depressive symptoms than cigarette-only smokers. Weighted multivariable regression models were used to identify differences between co-consumers and cigarette-only smokers with and without depressive symptoms. RESULTS: A total of 2843 current smokers were included in the study. The prevalence of past-year, past-30-day and daily cannabis use was 44.0%, 33.2% and 16.1%, respectively (30.4% reported using cannabis at least monthly). Among all respondents, 30.0% screened positive for depressive symptoms, with co-consumers being more likely to report depressive symptoms (36.5%) than those who did not report current cannabis use (27.4%, p < 0.001). Depressive symptoms were associated with planning to quit smoking (p = 0.01), having made multiple attempts to quit smoking (p < 0.001), the perception of being very addicted to cigarettes (p < 0.001) and strong urges to smoke (p = 0.001), whereas cannabis use was not (all p ≥ 0.05). Cannabis use was associated with high-risk alcohol consumption (p < 0.001), whereas depressive symptoms were not (p = 0.1). INTERPRETATION: Co-consumers were more likely to report depressive symptoms and high-risk alcohol consumption; however, only depression, and not cannabis use, was associated with greater motivation to quit smoking and greater perceived dependence on cigarettes. A deeper understanding of how cannabis, alcohol use and depression interact among people who smoke cigarettes is needed, as well as how these factors affect cessation activity over time.

Validating Wave 1 (2014) Urinary Cotinine and TNE-2 Cut-points for Differentiating Wave 4 (2017) Cigarette Use from Non-use in the United States Using Data from the PATH Study.

BACKGROUND: Sex and racial/ethnic identity-specific cut-points for validating tobacco use using Wave 1 (W1) of the Population Assessment of Tobacco and Health (PATH) Study were published in 2020. The current study establishes predictive validity of the W1 (2014) urinary cotinine and total nicotine equivalents-2 (TNE-2) cut-points on estimating Wave 4 (W4; 2017) tobacco use. METHODS: For exclusive and polytobacco cigarette use, weighted prevalence estimates based on W4 self-report alone and with exceeding the W1 cut-point were calculated to identify the percentage missed without biochemical verification. Sensitivity and specificity of W1 cut-points on W4 self-reported tobacco use status were examined. ROC curves were used to determine the optimal W4 cut-points to distinguish past 30-day users from non-users, and evaluate whether the cut-points significantly differed from W1. RESULTS: Agreement between W4 self-reported use and exceeding the W1 cut-points was high overall and when stratified by demographic subgroups (0.7%-4.4% of use was missed if relying on self-report alone). The predictive validity of using the W1 cut-points to classify exclusive cigarette and polytobacco cigarette use at W4 was high (>90% sensitivity and specificity, except among polytobacco Hispanic smokers). Cut-points derived using W4 data did not significantly differ from the W1-derived cut-points [e.g., W1 exclusive = 40.5 ng/mL cotinine (95% confidence interval, CI: 26.1-62.8), W4 exclusive = 29.9 ng/mL cotinine (95% CI: 13.5-66.4)], among most demographic subgroups. CONCLUSIONS: The W1 cut-points remain valid for biochemical verification of self-reported tobacco use in W4. IMPACT: Findings from can be used in clinical and epidemiologic studies to reduce misclassification of cigarette smoking status.

Associations between biomarkers of nicotine/tobacco exposure and respiratory symptoms among adults who exclusively smoke cigarettes in the U.S.: Findings from the PATH Study Waves 1-4 (2013-2017).

Significance: Determining if tobacco-related biomarkers of exposure (BOE) are associated with respiratory symptoms is an important public health tool that can be used to evaluate the potential harm of different tobacco products. Methods: Adult data from people who exclusively smoked cigarettes (N = 2,438) in Waves 1-4 (2013-2017) of the Population Assessment of Tobacco and Health Study were stacked to examine associations between baseline and follow-up within wave pairs (W1-W2, W2-W3, W3-W4). Weighted generalized estimating equation models were used to evaluate associations between biomarkers of nicotine, tobacco-specific nitrosamines, acrolein, acrylonitrile, cadmium, and lead at baseline/follow-up and respiratory symptom(s) (wheezing/whistling in the chest, wheezing during exercise, and/or dry cough in the past 12 months) at follow-up. Results: Higher acrolein metabolite (CEMA) levels at follow-up were associated with increased odds of respiratory symptoms at follow-up for people who exclusively smoked cigarettes (aOR = 1.34; 95% CI = 1.06, 1.70), including when limited to those without a diagnosed respiratory disease (aOR = 1.46; 95% CI = 1.12, 1.90) and those who smoked daily (aOR = 1.40; 95% CI = 1.06, 1.84). Higher cadmium levels at baseline (while controlling for follow-up levels) were associated with reduced odds of respiratory symptoms at follow-up (aOR = 0.80; 95% CI = 0.65, 0.98) among people who exclusively smoked cigarettes without a respiratory disease. There were no significant associations between baseline/follow-up BOE and follow-up respiratory symptoms for people who smoked cigarettes non-daily. Conclusions: This research supports measuring biomarkers of acrolein, such as CEMA, as a potential intermediate measurement for increased respiratory symptom development. Measuring these biomarkers could help alleviate the clinical burden of respiratory disease.

Pregnancy intentions of young women in Canada in the era of climate change: a qualitative auto-photography study.

BACKGROUND: Climate change poses a global health risk through consequences such as sea level rise, wildfires, and increased air pollution. Children born today and in the future may be disproportionately affected by climate change. As a result, many young adults are rethinking having children. The impacts of the climate crisis on the decision-making of parents is an understudied area of research. This study aims to be one of the first to explore how climate change impacts the pregnancy intentions of young women in Canada and their perspectives towards childbearing. METHODS: We conducted auto-photography and qualitative interviews. Participants were recruited using social media, and were aged 18-25, nulliparous, assigned female at birth, and were either current or previous residents of British Columbia, Canada. We asked participants to take photos that responded to the question, "Show us how climate change impacts your decision to have a family," then complete a virtual, one-on-one interview during which photo-elicitation was employed to guide conversation about participants' decision-making related to childbearing and climate change. We subjected all transcribed interviews to qualitative thematic analysis. RESULTS: We conducted in-depth interviews with seven participants who discussed a total of 33 photographs. Analysis of participants' interviews and photographs identified themes of eco-anxiety, hesitancy towards having children, sense of loss, and a desire for systemic change. Participants experienced anxiety, grief, and loss when faced with thoughts of change associated with their environments. Climate change impacted all but two participants' childbearing decision making, which was found to be interrelated with social-environmental factors, such as cost of living. CONCLUSION: We aimed to identify the ways in which climate change may impact youth decisions to have a family. Further research on this topic is needed to understand the prevalence of this phenomenon, and to build such considerations into climate action policy and family planning tools used among young people.

Digital Intervention Barriers Scale-7 (DIBS-7): Development, Evaluation, and Preliminary Validation.

BACKGROUND: The translation of mental health services into digital formats, deemed digital mental health interventions (DMHIs), has the potential to address long-standing obstacles to accessing care. However, DMHIs have barriers of their own that impact enrollment, adherence, and attrition in these programs. Unlike in traditional face-to-face therapy, there is a paucity of standardized and validated measures of barriers in DMHIs. OBJECTIVE: In this study, we describe the preliminary development and evaluation of such a scale, the Digital Intervention Barriers Scale-7 (DIBS-7). METHODS: Following an iterative QUAN → QUAL mixed methods approach, item generation was guided by qualitative analysis of feedback from participants (n=259) who completed a DMHI trial for anxiety and depression and identified barriers related to self-motivation, ease of use, acceptability, and comprehension of tasks. Item refinement was achieved through DMHI expert review. A final item pool was administered to 559 treatment completers (mean age 23.02 years; 438/559, 78.4% female; 374/559, 69.9% racially or ethnically minoritized). Exploratory factor analyses and confirmatory factor analyses were estimated to determine the psychometric properties of the measure. Finally, criterion-related validity was examined by estimating partial correlations between the DIBS-7 mean score and constructs related to treatment engagement in DMHIs. RESULTS: Statistical analyses estimated a 7-item unidimensional scale with high internal consistency (α=.82, ω=0.89). Preliminary criterion-related validity was supported by significant partial correlations between the DIBS-7 mean score and treatment expectations (pr=-0.25), number of modules with activity (pr=-0.55), number of weekly check-ins (pr=-0.28), and treatment satisfaction (pr=-0.71). CONCLUSIONS: Overall, these results provide preliminary support for the use of the DIBS-7 as a potentially useful short scale for clinicians and researchers interested in measuring an important variable often associated with treatment adherence and outcomes in DMHIs.

Assessing Efficacy and Use Patterns of Medical Cannabis for Symptom Management in Elderly Cancer Patients.

OBJECTIVES: Our study sought to further characterize patterns of medical cannabis use in elderly cancer patients. Furthermore, we sought to assess efficacy of medical cannabis for the treatment of pain, nausea, anorexia, insomnia and anxiety in elderly cancer patients. BACKGROUND: Medical cannabis use is growing for symptom management in cancer patients, but limited data exists on the safety or efficacy of use in elderly patients. METHODS: A retrospective chart review assessing changes in numerical symptom scores reported at clinic visits before and after medical cannabis initiation. RESULTS: There was no statistically significant difference in pain, nausea, appetite, insomnia or anxiety scores reported before and after initiation of medical cannabis. Oil was the most common form used, followed by vape, and the most common ratios used were high tetrahydrocannabinol (THC) to cannabidiol (CBD) and equal parts THC/CBD products. CONCLUSION: This study did not find a statistically significant change in symptom scores with medical cannabis use, although further study is warranted given the limitations of the present study. Elderly patients most commonly are using equal parts THC/CBD or high THC ratio products initially.

Developmental programming of mitochondrial substrate metabolism in skeletal muscle of adult sheep by cortisol exposure before birth.

Prenatal glucocorticoid overexposure causes adult metabolic dysfunction in several species but its effects on adult mitochondrial function remain largely unknown. Using respirometry, this study examined mitochondrial substrate metabolism of fetal and adult ovine biceps femoris (BF) and semitendinosus (ST) muscles after cortisol infusion before birth. Physiological increases in fetal cortisol concentrations pre-term induced muscle- and substrate-specific changes in mitochondrial oxidative phosphorylation capacity in adulthood. These changes were accompanied by muscle-specific alterations in protein content, fibre composition and abundance of the mitochondrial electron transfer system (ETS) complexes. In adult ST, respiration using palmitoyl-carnitine and malate was increased after fetal cortisol treatment but not with other substrate combinations. There were also significant increases in protein content and reductions in the abundance of all four ETS complexes, but not ATP synthase, in the ST of adults receiving cortisol prenatally. In adult BF, intrauterine cortisol treatment had no effect on protein content, respiratory rates, ETS complex abundances or ATP synthase. Activity of citrate synthase, a marker of mitochondrial content, was unaffected by intrauterine treatment in both adult muscles. In the ST but not BF, respiratory rates using all substrate combinations were significantly lower in the adults than fetuses, predominantly in the saline-infused controls. The ontogenic and cortisol-induced changes in mitochondrial function were, therefore, more pronounced in the ST than BF muscle. Collectively, the results show that fetal cortisol overexposure programmes mitochondrial substrate metabolism in specific adult muscles with potential consequences for adult metabolism and energetics.