Response Biomedical (Canada)

As mpox spread continues across several endemic and non-endemic countries around the world, vaccination has become an integral part of the global response to control the epidemic. Some vaccines have been recommended for use against mpox by the World Health Organization (WHO). As the roll-out of mpox vaccines continue across the globe, it is imperative to develop mathematical models to support public health officials and governments agencies in optimizing vaccination strategies to curtail the resurgence of mpox. In this article, we develop a compartmental mathematical model to investigate the impact of vaccination in controlling a potential mpox resurgence in Canada. The model categorizes individuals into high- and low-risk groups and incorporates pre-exposure vaccination in the high-risk group and post-exposure vaccination in the high- and low-risk groups. The vaccine-free version of the model was calibrated to the daily reported cases of mpox in Canada from April to October 2022, from which we estimated key model parameters, including the sexual and non-sexual transmission rates. Furthermore, we calibrated the full model to the daily reported cases of mpox in Canada in 2024, to estimate the current mpox vaccination rates in Canada. Our results highlight the importance of pre-exposure vaccination in the high-risk group on controlling a potential resurgence of mpox in Canada, and the minimal effects of post-exposure vaccination in the high- and low-risk groups on the outbreak. In addition, our model predicts the possibility of mpox becoming endemic in Canada, in the absence of pre-exposure vaccination in the high-risk group. Overall, our modeling result suggests that pre-exposure vaccination in the high-risk group is crucial in controlling mpox outbreak in Canada. Stepping up this vaccination is sufficient to avert a potential mpox resurgence in Canada.Clinical trial number Not applicable.

Background/Objectives: The ongoing avian influenza (H5N1) outbreak, one of the most widespread and persistent in recent history, has significantly impacted public health and the poultry and dairy cattle industries. This review covers lessons from past outbreaks, risk factors for transmission, molecular epidemiology, clinical features, surveillance strategies, and socioeconomic impacts. Since 1997, H5N1 has infected over 900 individuals globally, with a fatality rate exceeding 50%. Key factors influencing infection rates include demographic, socioeconomic, environmental, and ecological variables. The virus’s potential for sustained human-to-human transmission remains a concern. The current outbreak, marked by new viral clades, has complicated containment efforts. Methods: This review discusses how to integrate technological advances, such as mathematical modeling and artificial intelligence (AI), to improve forecasting, hotspot detection, and early warning systems. Results: We provide inventories of data sources, covering both conventional and unconventional data streams, as well as those of mathematical and AI models, which can be vital for comprehensive surveillance and outbreak responses. Conclusion: In conclusion, integrating AI, mathematical models, and technological innovations into a One-Health approach is essential for improving surveillance, forecasting, and response strategies to mitigate the impacts of the ongoing avian influenza outbreak. Strengthening international collaboration and biosecurity measures will be pivotal in controlling future outbreaks and protecting both human and animal populations from this evolving global threat.

Abstract N-acetylglucosamine (GlcNAc) is an endogenous compound whose intracellular concentration is closely associated with the biosynthesis of acetyllactosamine-rich N-linked oligosaccharides. These oligosaccharides interact with mammalian lectin galectin-3, mediating cell surface receptor dynamics as well as cell-to-cell and cell-to-extracellular matrix interactions. Our previous and recent studies suggest that GlcNAc, in conjunction with galectin-3, augments muscle regenerationin vitro. We have also demonstrated that intraperitoneal GlcNAc administration improves muscle strength in a murine model of Duchenne muscular dystrophy (DMD) (mdxmice). Here, we show that oral administration of GlcNAc significantly improves the spontaneous locomotor activity of mdx mice. Administering GlcNAc at concentrations of 0.6, 1.2, 1.8, and 2.4 g/kg body weight per day for 35 days significantly improved nocturnal spontaneous locomotor activity at all those doses, with the 1.2 g/kg body weight dose reducing damages of extensor digitorum longus muscle by nearly 50%. While consecutive forced exercises, including horizontal and downhill treadmill running, reduced GlcNAc-promoted locomotor activity, treatment with 0.6 and 1.2 g/kg body weight treatment results in increased spontaneous locomotor activity. These results suggest that GlcNAc enhances overall muscle health, likely through promoting muscle repair/regeneration rather than preventing damage formation. Notably, co-administration of GlcNAc with prednisolone, a corticosteroid commonly used in DMD patients, further enhanced spontaneous locomotor improvement inmdxmice compared to prednisolone alone. These findings suggest that GlcNAc has the potential to improve the clinical status of DMD patients, either as a monotherapy or in combination with corticosteroids.

Abstract BackgroundMpox (formerly Monkeypox) virus has affected the lives of thousands of individuals both in endemic and non-endemic countries. Before the May 2022 outbreak, Mpox infections were sporadically endemic in Central and Western Africa, still research into Mpox has been limited and lacking epidemiological data. Thus, identification of potential risk factors to better understand who is at risk of being infected is critical for future prevention and control.ObjectiveTo synthesize comprehensive evidence on risk factors associated with human Mpox transmission both in endemic and non-endemic countries from inception to March 31, 2024.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in conducting the systematic review. Electronic databases were searched. Two reviewers sifted the articles that were included in the review: firstly, by title and abstract, and secondly, by full text. We used the Newcastle-Ottawa Scale (NOS) to assess the risk of bias for included articles. Fixed or random effects meta-analysis were conducted when at least two studies reported odds ratios (OR), relative risks (RR), with 95% confidence intervals (CI). Heterogeneity was assessed using theI2statistic and sensitivity analysis was also done. The study protocol has been registered under PROSPERO with ID:CRD42023459895.Results947 articles were identified from the database search and 31 articles were eligible to be included in the systematic review. The findings of the meta-analysis showed that interaction with infected animals (OR= 5.61, 95%CI= 2.83, 11.13), HIV (OR= 4.46, 95%CI= 3.27, 6.08), other STIs (OR= 1.76, 95%CI= 1.42, 2.91), sexual contact/activities (OR = 1.53, 95% CI = 1.13, 4.82), contact with an infected person (OR = 2.39, 95%CI = 1.87, 3.05), being identified as men who have sex with men (MSM) (OR = 2.18, 95%CI = 1.88, 2.51), and having multiple sexual partners Mpox (OR = 1.61, 95%CI = 1.24, 2.09), were associated with an increased risk of contracting Mpox. However, patients who were vaccinated against smallpox had a lower risk of Mpox infection (OR = 0.24, 95%CI = 0.11, 0.55).ConclusionThis study is the first meta-analysis on reported risk factors for Mpox. Our analysis demonstrated that certain factors were associated with increased risk of Mpox, whereas smallpox vaccination had a protective role against contracting Mpox. The study findings could facilitate future strategic public health planning and targeted intervention.Key messages of this articleWhat is already known on this topicMpox (monkeypox) is a zoonotic infectious disease of notable global public health importance due to recent outbreaks in non-endemic countries.Prior outbreaks of Mpox have been associated with travel to endemic areas in Western and Central Africa, contact with infected animals, and close contact with infectious lesions, particularly among household members.What this study addsThis study is the first meta-analysis on reported risk factors for Mpox. Our study findings add to the body of evidence on Mpox research efforts and could assist in future Mpox global strategic intervention and control.Our meta-analysis revealed a strong correlation between increased risk of Mpox infection, HVI, other STIs, physical and sexual contacts, and being identified as MSM.While HIV infection may be a risk factor for Mpox, Mpox lesions could also facilitate the transmission of HIV and other STIs.How this study might affect research, practice or policyThe results of this systematic review and meta-analysis provide evidence to support policymakers in future Mpox intervention and prevention in both endemic and non-endemic countries based on identified risk factors.

Abstract BackgroundEmergency shelters offer temporary sleeping accommodation to people deprived of housing and connect them to services. Service restriction is the practice of limiting or denying someone access to emergency shelters. This parallel convergent mixed methods study describes the characteristics, healthcare utilization, and morbidity of people experiencing service restrictions in Hamilton, Ontario, and explores the relationship between health and service restriction.MethodsWe recruited 20 people who had experienced service restriction and accessed healthcare from the Shelter Health Network clinic. We conducted semi-structured interviews and performed reflexive thematic analysis. We reviewed participants’ medical records from January 1, 2018 to December 31, 2021 to calculate simple descriptive statistics. Mixing our qualitative and quantitative results, we generated narrative metainferences. We employed community-based research principles, including a research team with lived and living experiences of being service restricted, implementing service restrictions, or providing care to people experiencing service restrictions.ResultsWe generated six themes: 1) Losing your home shouldn’t mean losing your humanity, 2) Where am I supposed to go?, 3) The snakes and ladders of service restrictions, 4) Abandoned to survive, 5) Constantly criminalized, 6) Harnessing the wisdom of community. Participants averaged 17.4 primary care visits, 11 emergency department visits, and 4 hospital admissions over 4 years. The most common reasons for visit were infections, traumatic injuries, and substance use-related concerns. Narrative metainferences highlighted how people experience dehumanization when accessing shelters or healthcare; how service restrictions and encampment living contribute to infections; the lack of practical supports for people using substances in shelters; the ubiquitous criminalization of people experiencing homelessness; and the care people practice for one another to reduce substance-related harms.ConclusionsParticipants’ high healthcare need and utilization was shaped by criminalization, stigma, societal abandonment, and abstinence-based substance use policies. Participants practiced care for themselves and others to navigate these barriers. Shelters should have a transparent service restriction process and employ harm reduction practices. Healthcare should provide affirming and accessible treatment for common conditions. Social and health services must contend with broader social forces while building on the strengths of people with lived experience to improve the health of people who are service restricted.

PurposeThis study aimed to determine the organ-specific accuracy of [18F]FDG-PET/CT in identifying immune-related adverse events (irAEs) in patients with high-risk (stage III/IV) surgically resected melanoma treated with an adjuvant immune checkpoint inhibitor (ICI) and determine the incidence of irAEs within the first year after starting treatment.Materials and methodsThis registry-based study included individuals who had undergone surgical removal of melanoma and were undergoing adjuvant ICI treatment (either nivolumab or pembrolizumab). The study specifically enrolled patients who had undergone both a baseline and at least one subsequent follow-up [18F]FDG-PET/CT scan. Follow-up scans were performed every third month in the first year after surgery to screen for disease recurrence. We retrospectively compared the follow-up scans with baseline scans to identify irAEs. Clinical information on irAEs was obtained from medical records and served as a reference standard for determining the accuracy of [18F]FDG-PET/CT.ResultsA total of 123 patients with 363 [18F]FDG-PET/CT scans were included, and 65 patients (52.8%) developed irAEs. In decreasing order, the organ-specific incidences of irAEs were: skin 26/65 (40%), muscle and joints 21/65 (32.3%), intestines 13/65 (20%), thyroid gland 12/65 (18.5%), lungs 4/65 (6.2%), and heart 2/65 (3.1%). The sensitivities and specificities of [18F]FDG-PET/CT for diagnosing irAEs were: skin 19% (95% CI: 7–39%) and 95% (88–98%), muscles and joints 71% (48–89%) and 83% (75–90%), intestines 100% (75–100%) and 85% (77–91%); thyroid gland 92% (62–99%) and 95% (89–98%), lungs 75% (19–99%) and 90% (83–95%), and heart 50% (13–99%) and 97% (92–99%), respectively.Conclusion[18F]FDG-PET/CT generally had moderate to high sensitivities (except for skin and heart) and specificities in diagnosing irAEs in patients receiving adjuvant ICI; this could be suggested to be systematically assessed and reported in scan reports.

ABSTRACT Background: Healthcare workers (HCWs) across the globe have reported symptoms of Post-Traumatic Stress Disorder (PTSD) during the COVID-19 pandemic. Moral Injury (MI) has been associated with PTSD in military populations, but is not well studied in healthcare contexts. Moral Distress (MD), a related concept, may enhance understandings of MI and its relation to PTSD among HCWs. This study examined the independent and combined impact of MI and MD on PTSD symptoms in Canadian HCWs during the pandemic. Methods: HCWs participated in an online survey between February and December 2021, with questions regarding sociodemographics, mental health and trauma history (e.g. MI, MD, PTSD, dissociation, depression, anxiety, stress, childhood adversity). Structural equation modelling was used to analyze the independent and combined impact of MI and MD on PTSD symptoms (including dissociation) among the sample when controlling for sex, age, depression, anxiety, stress, and childhood adversity. Results: A structural equation model independently regressing both MI and MD onto PTSD accounted for 74.4% of the variance in PTSD symptoms. Here, MI was strongly and significantly associated with PTSD symptoms (β = .412, p < .0001) to a higher degree than MD (β = .187, p < .0001), after controlling for age, sex, depression, anxiety, stress and childhood adversity. A model regressing a combined MD and MI construct onto PTSD predicted approximately 87% of the variance in PTSD symptoms (r 2 = .87, p < .0001), with MD/MI strongly and significantly associated with PTSD (β = .813, p < .0001), after controlling for age, sex, depression, anxiety, stress, and childhood adversity. Conclusion: Our results support a relation between MI and PTSD among HCWs and suggest that a combined MD and MI construct is most strongly associated with PTSD symptoms. Further research is needed better understand the mechanisms through which MD/MI are associated with PTSD.

Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but their existence and relative frequency in clinical disease are unclear, as is how to target resistance. Longitudinal mutation and methylation profiling of circulating tumour (ct)DNA was carried out in 47 patients with metastatic BRCA1-, BRCA2- or PALB2-mutant breast cancer treated with HRD-targeted therapy who developed progressive disease-18 patients had primary resistance and 29 exhibited response followed by resistance. ctDNA isolated at multiple time points in the patient treatment course (before, on-treatment and at progression) was sequenced using a novel >750-gene intron/exon targeted sequencing panel. Where available, matched tumour biopsies were whole exome and RNA sequenced and also used to assess nuclear RAD51. BRCA1/2 reversion mutations were present in 60% of patients and were the most prevalent form of resistance. In 10 cases, reversions were detected in ctDNA before clinical progression. Two new reversion-based mechanisms were identified: (i) intragenic BRCA1/2 deletions with intronic breakpoints; and (ii) intragenic BRCA1/2 secondary mutations that formed novel splice acceptor sites, the latter being confirmed by invitro minigene reporter assays. When seen before commencing subsequent treatment, reversions were associated with significantly shorter time to progression. Tumours with reversions retained HRD mutational signatures but had functional homologous recombination based on RAD51 status. Although less frequent than reversions, nonreversion mechanisms [loss-of-function (LoF) mutations in TP53BP1, RIF1 or PAXIP1] were evident in patients with acquired resistance and occasionally coexisted with reversions, challenging the notion that singular resistance mechanisms emerge in each patient. These observations map the prevalence of candidate drivers of resistance across time in a clinical setting, information with implications for clinical management and trial design in HRD breast cancers.

Our objective was to explore whether consuming the same high-fat/sugar beverage affects endothelial function differently depending on whether it is presented as "unhealthy" [accurate high calorie (kcal), fat, and sugar information displayed] versus "healthy" (inaccurate low kcal, fat, and sugar information displayed). Twenty-five, young (21 ± 2 yr), healthy, food-stress/shame-prone women completed three conditions: milkshake consumption (540 kcal, 80 g sugar, and 14 g fat) where correct, "unhealthy" nutritional information was shown to participants (milkshake condition), consumption of the same milkshake but with incorrect, "healthy" information shown to participants (100 kcal, 3 g sugar, and 4 g fat; sham-nutrishake condition), and water consumption (control condition). Pre- and postbeverage we assessed 1) endothelial function via standard brachial artery flow-mediated dilation (FMD); 2) perceived shame, stress, beverage healthiness, and harm; and 3) blood (plasma) glucose, insulin, triglycerides and oral fluid cortisol, and tumor necrosis factor-alpha (TNFα) receptor binding. Glucose, triglycerides, and insulin increased in the milkshake and sham-nutrishake conditions (P < 0.05). The milkshake was perceived as less healthy (P < 0.001) and more harmful (P < 0.001) than the sham-nutrishake. Shame, stress, oral fluid cortisol and TNFα receptor binding did not increase postconsumption. FMD decreased after the milkshake condition (pre: 7.4 ± 3.3%; post-60 min: 4.9 ± 2.9%; post-90 min: 4.5 ± 3.1%, P < 0.001) but not the sham-nutrishake (pre: 5.7 ± 2.2%; post-60 min: 5.5 ± 2.6%; post-90 min: 5.0 ± 2.4%, P = 0.43) or control conditions (pre: 7.0 ± 2.6%; post-60 min: 6.6 ± 4.1%; post-90 min: 6.0 ± 3.2%, P = 0.29). Shear rate stimulus covariation did not alter FMD results. Lower perceived beverage healthiness was significantly associated with a greater reduction in FMD (ρ = 0.36, P = 0.002). In conclusion, a high-fat/sugar milkshake reduced FMD only when presented as high in fat, sugar, and calories. This suggests that perceptions about nutritional information contribute to the impact of food intake on endothelial function and that nocebo effects could be involved in cardiovascular disease etiology.NEW & NOTEWORTHY This was the first study to investigate how perceived nutritional content influences the impact of a high-sugar/fat beverage on endothelial function. We found that a high-sugar/fat beverage only reduced endothelial function when it was presented to participants as high in calories, fat, and sugar. This suggests that perceived nutritional information contributes to the impact of high sugar and fat intake on endothelial function.