Search

Japanese encephalitis virus (JEV) is transmitted by Culex species of mosquitoes. In 2022, JEV belonging to a previously unrecognized lineage of genotype IV (GIV) caused a major outbreak of JE in South-eastern Australia, resulting in human cases and affecting piggeries. Cx. annulirostris has previously been implicated as the major vector of JEV in northern Australia where the virus has circulated since its first detection in 1995. Here, we showed that experimental infection of a laboratory colony of Australian Cx. annulirostris with the isolate JEV NSW/22 resulted in a 100% mosquito infection rate, with 87% of mosquito saliva samples testing positive by RT-qPCR at 14 days post-infection. Immunohistochemistry confirmed the presence of a replicating virus in the mosquito midgut and dissemination throughout the body, including the salivary glands. Our results also showed evidence of transovarial transmission of this virus; however, transstadial transmission from the eggs to the adult stage was not found. Comparison with an Indonesian isolate of GIV JEV and previous Australian isolates belonging to genotypes I and II showed that infection with JEV NSW/22 resulted in higher viral titres in the early stage of infection and higher proportions of mosquitoes with JEV-positive saliva, indicating a greater transmission potential compared to other isolates. This study provides compelling experimental evidence that Australian Cx. annulirostris is a highly efficient vector for the 2022 Australian JEV GIV outbreak strain.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Background: Thermal burns during pregnancy are rare but life-threatening emergencies associated with significant morbidity and mortality. Currently, principles of management center around fluid resuscitation based on formulas established for nonpregnant patients and supportive care, as data on the optimal management of pregnant burn patients is limited. Case report: We present the case of a 23-year-old G2P1 at 26 weeks gestational age who presented to the emergency department with 52 % total body surface area (TBSA) burns and inhalation injury sustained during a house fire. She was initially managed with both standard burn fluid resuscitation and vasopressors to maintain perfusion before undergoing an emergent delivery 3 h after her initial presentation. Ultimately, she underwent five surgical debridements with split-thickness skin grafting before being discharged on hospital day 60. Her infant was treated for prematurity-associated respiratory distress syndrome and was discharged on hospital day 82 without any other major complications. Why should an emergency physician be aware of this?: Thermal burns in pregnancy are high-risk, low-frequency events that require the competent, rapid consideration of numerous factors to optimize outcomes for both the mother and fetus. This case describes the effective management of maternal hemodynamics with early standard fluid resuscitation and vasopressors, though highlights the need for future studies identifying the role of fluids and vasopressors in supporting pregnant patients with burn injuries and their fetuses.

Background and objective: Postoperative pulmonary rehabilitation in non-small cell lung cancer (NSCLC) patients following thoracic surgery can be an important strategy for restoring functional exercise capacity. This study aimed to evaluate the changes in the Glittre-ADL test (TGlittre) in patients with NSCLC undergoing thoracic surgery and early home-based pulmonary rehabilitation and, subsequently, to assess the associations of the test results with muscle strength and quality of life (QoL). Methods: This observational study evaluated 18 patients with NSCLC before and after home-based pulmonary rehabilitation. Before thoracic surgery and 3 months after pulmonary rehabilitation, the participants underwent the following assessments: St. George's Respiratory Questionnaire (SGRQ), spirometry, measurement of the diffusion capacity of the lung for carbon monoxide (DLCO), respiratory muscle strength, handgrip strength (HGS), quadriceps muscle strength, and TGlittre. Results: When comparing the preoperative and postpulmonary rehabilitation periods, there was a significant increase in HGS [21.6 (19–29) vs. 28.5 (26–33) kgf, p = 0.011] with preservation of TGlittre time [3.6 (3.2–4) vs. 3.6 (3–4.1) min, p = 0.87]. In addition, there was a significant decrease in lung function and SGRQ scores. Preoperative TGlittre time significantly correlated with maximum inspiratory pressure (MIP, rs = −0.491, p = 0.038) and DLCO (rs = −0.621, p = 0.006). TGlittre time measured in postpulmonary rehabilitation was significantly correlated with HGS (rs = −0.664, p = 0.002) and the MIP (rs = −0.478, p = 0.045). Conclusion: In patients with NSCLC undergoing thoracic surgery and pulmonary rehabilitation, there was an increase in muscle strength and preservation of functional exercise capacity, although there was a decrease in lung function and QoL. There were interrelations of TGlittre time with MIP and pulmonary diffusion in the preoperative period and of TGlittre time with HGS and MIP following the home-based pulmonary rehabilitation. Although the results are promising, additional studies with a larger number of patients and a control group are needed to further support these findings.

The term ‘MENA’ refers to ‘Menores Extranjeros No Acompañados’ (‘unaccompanied foreign minors’) who are child immigrants to Spain who entered alone without legal documentation. Over the years, ‘mena’ has become a pejorative term associated with criminality, a view especially promoted by some on the political far right. In this article, we describe an experiment where virtual reality (VR) was used to place people among a group of young adults with a ‘MENA’ background (‘ex-mena’) to explore how their experience might alter their attitudes about the plight of the MENA. In particular, we were interested in the different influence of a 360 3D video or the same video on a 2D large screen, both experienced through the same VR head-mounted display. There were 51 people recruited for the experimental study, 28 of whom experienced the video in the screen condition and 23 in the 360 video condition. In addition to questionnaires, a sentiment analysis was carried out on short essays that participants wrote after their experience. The results show that sentiment was greater for the 360 video condition than the screen. Lower sentiment scores are associated with sadness, media bias, feeling bad about the conditions of the MENA, the difficulty of integration, and the utility of understanding and empathy. Higher sentiment scores are associated with empathy due to being closer to the situation, knowing the story of the migrants better, politicization, prejudging, feeling sorry for the manipulation of the migrants, and failure of action by the authorities. The 360 video approach used could be an important tool for documentary journalism.

ABSTRACT Background Despite advances made in targeted biomarker‐based therapy for acute myeloid leukemia (AML) treatment, remission is often short and followed by relapse and acquired resistance. Functional precision medicine (FPM) efforts have been shown to improve therapy selection guidance by incorporating comprehensive biological data to tailor individual treatment. However, effectively managing complex biological data, while also ensuring rapid conversion of actionable insights into clinical utility remains challenging. Methods We have evaluated the clinical applicability of quadratic phenotypic optimization platform (QPOP), to predict clinical response to combination therapies in AML and reveal patient‐centric insights into combination therapy sensitivities. In this prospective study, 51 primary samples from newly diagnosed (ND) or refractory/relapsed (R/R) AML patients were evaluated by QPOP following ex vivo drug testing. Results Individualized drug sensitivity reports were generated in 55/63 (87.3%) patient samples with a median turnaround time of 5 (4–10) days from sample collection to report generation. To evaluate clinical feasibility, QPOP‐predicted response was compared to clinical treatment outcomes and indicated concordant results with 83.3% sensitivity and 90.9% specificity and an overall 86.2% accuracy. Serial QPOP analysis in a FLT3‐mutant patient sample indicated decreased FLT3 inhibitor (FLT3i) sensitivity, which is concordant with increasing FLT3 allelic burden and drug resistance development. Forkhead box M1 (FOXM1)—AKT signaling was subsequently identified to contribute to resistance to FLT3i. Conclusion Overall, this study demonstrates the feasibility of applying QPOP as a functional combinatorial precision medicine platform to predict therapeutic sensitivities in AML and provides the basis for prospective clinical trials evaluating ex vivo‐guided combination therapy.

ABSTRACT The objective of the study was to ascertain an optimal Helicobacter pylori diagnostic strategy using population-level laboratory data comparing the performance of serology against urea breath test (UBT). H. pylori diagnostic test results for serology and UBT from two laboratories over a 12-year period (2006–20017) were extracted, linked, and analyzed. A subset of this population underwent both methods of testing within days of each other, enabling a direct comparison of the two methods. The average prevalence of H. pylori positivity was 21.3% by serology and 17.5% by UBT. There were 2,612 individuals who had serology performed first, followed by UBT within 14 days. For this subset, the sensitivity of serology compared with UBT was 96.5% with a specificity of 79.2%. The negative predictive value for serology was 98.4%. Contrary to various recent clinical guidelines, the data show that serology still has utility as a sensitive enough test to be used as an initial H. pylori screening test in a lower prevalence population. Negative serology can be used with confidence to rule out active infection, whereas a positive serology could be followed up with a UBT or a similar performing test such as stool antigen to differentiate active from past infection. For population-based diagnostic recommendations, such a strategy may be ideal since serology generally costs less than UBT and may be combined with a blood draw being done for other diagnostic tests. Continuing to offer serology increases options for patients and may provide economic benefits for single-payer health care systems or health maintenance organizations.IMPORTANCEThis study compares the performance of serology with urea breath test in the diagnosis of Helicobacter pylori in a population-level data set and mimics a head-to-head direct comparison as the study population had both tests performed within 2 weeks of each other. This provides new information supporting the use of serology in a diagnostic algorithm. There are several instances where serology could be preferable to patients to rule out disease, despite some guidelines suggesting serology should not be used.

Abstract BackgroundDigital health interventions (DHIs) could support prevention and management of cardiometabolic disease. However, those who may benefit most often experience barriers to awareness and adoption of these interventions. ObjectiveAmong South Asian individuals, we evaluated user experience of DHIs for prevention and management of cardiometabolic disease, aiming to understand barriers and facilitators to initial and ongoing use. MethodsAmong South Asian individuals recruited via primary care, community organizations, and snowball methods (n=18), we conducted “think-aloud” interviews using a reflective and reactive approach. Participants included nonusers, as well as those that used a range of DHIs as part of monitoring and improving their health. Participants were asked to think aloud while completing a task they routinely do in a familiar DHI, as well as while setting up and completing a search task in a novel DHI; they were encouraged to behave as if unobserved. ResultsLack of cultural specificity was highlighted as reducing relevance and usability, particularly relating to dietary change. Preferred features reflected individual health beliefs and behaviors, digital skills, and trust in DHIs. For example, tracking blood glucose was considered by some to be positive, while for others it caused distress and anxiety. Similarly, some users found the novel DHI to be extremely simple to set up and use, and others grew frustrated navigating through initial interfaces. Many participants raised concerns about data privacy and needing to agree to terms and conditions that they did not understand. Participants expressed that with information and support from trusted sources, they would be interested in using DHIs as part of self-management. ConclusionsDHIs may support South Asians to prevent and manage cardiometabolic disease, but it is important to consider the needs of specific user groups in DHI development, design, and implementation. Despite motivation to make health changes, digital barriers are common. Cultural appropriateness and trusted sources (such as health care providers and community organizations) have roles in increasing awareness and enabling individuals to access and use DHIs.

Abstract BackgroundTelemonitoring (TM), as part of telehealth, allows physiotherapists to monitor and coach their patients using remotely collected data. The use of TM requires a different approach compared with face-to-face treatment. Although a telehealth capability framework exists for health care professionals, it remains unclear what specific capabilities are required to use TM during physiotherapy treatments. ObjectiveThis study aims to identify the capabilities required to use TM in physiotherapy treatment. MethodsAn exploratory qualitative study was conducted following a constructivist semistructured grounded theory approach. Three heterogeneous focus groups were conducted with 15 lecturers of the School of Physiotherapy (Bachelor of Science Physiotherapy program) from the Amsterdam University of Applied Sciences. Focus group discussions were audiotaped and transcribed verbatim. Capabilities for using TM in physiotherapy treatment were identified during an iterative process of data collection and analysis, based on an existing framework with 4 different domains. Team discussions supported further conceptualization of the findings. ResultsSixteen capabilities for the use of TM in physiotherapy treatment were found addressing 3 different domains. Four capabilities were identified in the “digital health technologies, systems, and policies” domain, 7 capabilities in the “clinical practice and application” domain, and 5 capabilities in the “data analysis and knowledge creation” domain. No capabilities were identified in the “system and technology implementation” domain. ConclusionsThe use of TM in physiotherapy treatment requires specific skills from physiotherapists. To best use TM in physiotherapy treatment, it is important to integrate these capabilities into the education of current and future physiotherapists.

Resumo Nascida na capital paulista, a Bacio di Latte é uma das referências brasileiras no segmento de sorvetes - ou gelato, como eles preferem - de alto valor agregado. Em pouco mais de 10 anos de uma trajetória bem-sucedida, a sorveteria se estabeleceu em todo o território brasileiro, com mais de 130 unidades próprias, além de uma crescente e vitoriosa operação de distribuição em supermercados. Você acaba de ser contratado como head de marketing e encontra uma empresa que tem passado por um período delicado em suas operações, dado o fechamento das lojas e dos shoppings em virtude da pandemia. Porém, percebe também que a crise acelerou os negócios de alimentação em direção aos canais digitais, o que traz oportunidades e desafios. Caberá a você a liderança desse projeto, que pode representar o próximo salto de crescimento da Bacio di Latte.

Abstract Background The Good Life with osteoArthritis: Denmark (GLA:D™), an evidence-based education and exercise program designed for conservative management of knee and hip osteoarthritis (OA), has been shown to benefit participants by reducing pain, improving function, and quality of life. Standardized reporting in the GLA:D databases enabled the measurement of self-reported and performance-based outcomes. There is a paucity of qualitative research on the participants’ perceptions of this program, and it is important to understand whether participants’ perceptions of the benefits of the program align with reported quantitative findings. Methods We conducted semi-structured telephone interviews with individuals who participated in the GLA:D program from January 2017 to December 2018 in Alberta, Canada. Data were analyzed using an interpretive description approach and thematic analysis to identify emergent themes and sub-themes associated with participants perceived benefits of the GLA:D program. We analyzed the data using NVivo Pro software. Member checking and bracketing were used to ensure the rigour of the analysis. Results 30 participants were interviewed (70% female, 57% rural, 73% knee OA). Most participants felt the program positively benefited them. Two themes emerged from the analysis: wellness and self-efficacy. Participants felt the program benefited their wellness, particularly with regard to pain relief, and improvements in mobility, strength, and overall well-being. Participants felt the program benefited them by promoting a sense of self-efficacy through improving the confidence to perform exercise and routine activities, as well as awareness, and motivation to manage their OA symptoms. Twenty percent of participants felt no benefits from the program due to experiencing increased pain and feeling their OA was too severe to participate. Discussion The GLA:D program was viewed as beneficial to most participants, this study also identified factors (e.g., severe OA, extreme pain) as to why some participants did not experience meaningful improvements. Early intervention with the GLA:D program prior to individuals experiencing severe OA could help increase the number of participants who experience benefits from their participation. Conclusion As the GLA:D program expands across jurisdictions, providers of the program may consider recruitment earlier in disease progression and targeting those with mild and moderate OA.

Abstract Background Although availability and utilisation of digital health interventions (DHIs) for management of diabetes and cardiovascular disease (“cardiometabolic disease”) have increased, they may exacerbate health inequalities. South Asians have increased cardiometabolic risk, but their experiences of DHIs are poorly investigated and characterised. Objective To explore facilitators and barriers to DHI uptake and use in South Asian individuals in the UK with cardiometabolic disease. Methods Mixed-methods approach encompassing online/face-to-face/individual interviews (n = 45) and survey (n = 100). After informed consent, transcription and coding, we conducted a thematic analysis informed by a guide for understanding inequalities in DHIs to examine perceptions at the individual, healthcare professional, societal and intervention level. Results Participants described an intersection of factors resulting in varied digital skills and confidence within the community, including individual characteristics, awareness, and support. COVID-19 restrictions acted as both a positive (use of online shopping and social media increasing digital confidence) and negative (lack of access to health services) drivers to DHI uptake. Participants made recommendations for improving DHI uptake in the health service and policy area, such as promotion and upskilling through culturally and language-appropriate avenues such as community organisations and outlets. Participants suggested DHI design improvements should focus on literacy, numeracy, accessibility, and cultural appropriateness. Conclusions DHIs have the potential to support South Asian populations in the UK to prevent and manage cardiometabolic disease. To improve their uptake, approaches to their implementation should consider community diversity to provide appropriate promotion, education, and support.

Abstract Background Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse. Methods STORY follows 720 young people aged 16–25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings (‘Ōura ring’) unobtrusively measures individuals’ daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months. Discussion By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families.

Abstract To evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 (ACE2) inhibition surrogate neutralization and antibody dependent cellular phagocytosis (ADCP)), as well as S-specific T cells were quantified via activation induced marker (AIM) assay in response to two-dose series. Eighty-four adults were vaccinated with either: mRNA/mRNA (mRNA-1273 and/or BNT162b2); ChAdOx1-S/mRNA; or ChAdOx1-S/ChAdOx1-S. Anti-S IgG concentrations, ADCP scores and ACE2 inhibiting antibody concentrations were highest at one-month post-second dose and declined by four-months post-second dose for all groups. mRNA/mRNA and ChAdOx1-S/mRNA schedules had significantly higher antibody responses than ChAdOx1-S/ChAdOx1-S. CD8+ T-cell responses one-month post-second dose were associated with increased ACE2 surrogate neutralization. Antibody avidity (total relative avidity index) did not change between one-month and four-months post-second dose and did not significantly differ between groups by four-months post-second dose. In determining COVID-19 correlates of protection, a measure that considers both antibody concentration and avidity should be considered.

Abstract Background Hepatitis C virus (HCV) is a major health threat in Canada. In British Columbia (BC) province, 1.6% of the population had been exposed to HCV by 2012. Prevalence and incidence of HCV are very high in populations of people who use drugs (PWUD) and sex workers (SW), who may experience unique barriers to healthcare. Consequently, they are less likely to be treated for HCV. Overcoming these barriers is critical for HCV elimination. This research sought to explore the healthcare experiences of PWUD and SW and how these experiences impact their willingness to engage in healthcare in the future, including HCV care. Methods Interpretive Description guided this qualitative study of healthcare experiences in BC, underpinned by the Health Stigma and Discrimination framework. The study team included people with living/lived experience of drug use, sex work, and HCV. Twenty-five participants completed in-depth semi-structured interviews on their previous healthcare and HCV-related experiences. Thematic analysis was used to identify common themes. Results Three major themes were identified in our analysis. First, participants reported common experiences of delay and refusal of care by healthcare providers, with many negative healthcare encounters perceived as rooted in institutional culture reflecting societal stigma. Second, participants discussed their choice to engage in or avoid healthcare. Many avoided all but emergency care following negative experiences in any kind of healthcare. Third, participants described the roles of respect, stigma, dignity, fear, and trust in communication in healthcare relationships. Conclusions Healthcare experiences shared by participants pointed to ways that better understanding and communication by healthcare providers could support positive change in healthcare encounters of PWUD and SW, who are at high risk of HCV infection. More positive healthcare encounters could lead to increased healthcare engagement which is essential for HCV elimination.

Several barriers exist in Alberta, Canada to providing accurate and accessible diagnoses for patients presenting with acute knee injuries and chronic knee problems. In efforts to improve quality of care for these patients, an evidence-informed clinical decision-making tool was developed. Forty-five expert panelists were purposively chosen to represent stakeholder groups, various expertise, and each of Alberta Health Services’ 5 geographical health regions. A systematic rapid review and modified Delphi approach were executed with the intention of developing standardized clinical decision-making processes for acute knee injuries, atraumatic/overuse conditions, knee arthritis, and degenerative meniscus. Standardized criteria for screening, history-taking, physical examination, diagnostic imaging, timelines, and treatment were developed. This tool standardizes and optimizes assessment and diagnosis of acute knee injuries and chronic knee problems in Alberta. This project was a highly collaborative, province-wide effort led by Alberta Health Services’ Bone and Joint Health Strategic Clinical Network (BJH SCN) and the Alberta Bone and Joint Health Institute (ABJHI).

Abstract Acute compartment syndrome is a surgical emergency requiring rapid recognition in the emergency department to minimize morbidity and mortality. It is most commonly caused by traumatic extremity fractures, which account for about 75% of cases. Atraumatic acute compartment syndrome is substantially less common with current evidence mostly limited to case reports, and diagnosis is made more challenging by the absence of an obvious traumatic injury. We present the case of a young adult female patient with IgA vasculitis who developed recurrent, atraumatic acute compartment syndrome and was successfully managed with prompt fasciotomy. This is the first case of spontaneous intramuscular hemorrhage, a rare sequela of IgA vasculitis, leading to recurrent, atraumatic acute compartment syndrome. This case highlights the importance of both a thorough physical exam and maintaining a high suspicion for acute compartment syndrome in the absence of injury to ensure patients receive prompt surgical evaluation for definitive care.

Summary: Background: We evaluated the association of hepatitis B virus (HBV) treatment with all-cause, and liver-related mortality among individuals with HBV and cirrhosis in British Columbia (BC), Canada. Methods: This analysis included people diagnosed with HBV and had cirrhosis in the BC Hepatitis Testers Cohort, including data on all individuals diagnosed with HBV from 1990 to 2015 in BC and integrated with healthcare administrative data. We followed people with cirrhosis from the first cirrhosis diagnosis date until death or December 31, 2020. We compared all-cause and liver related mortality between those who received treatment and those who did not. HBV treatment was considered a time-varying variable. We performed multivariable Cox proportional hazards model and competing risk regression models to assess the association of HBV treatment with all causes, and liver-related mortality respectively using inverse probability of treatment weighted population. Findings: Among 4962 individuals with HBV and cirrhosis, 48.1% received HBV treatment. Treated individuals had a median follow-up of 2.97 years, compared to 2.87 years for untreated individuals. The treated group was older (median age 57 vs 54 years), had higher proportion of treated of males [1802 (75.50%) vs 1766 (68.8%)], from urban area [2318 (97.2%) vs 2355 (91.8%)], and from East and South Asian ethnicity [1506 (63.1%) vs 709 (27.5%)] compared to untreated group. Untreated people experienced higher all-cause mortality (115.47 vs. 35.72 per 1000 person-years) and liver-related mortality (49.86 vs. 11.39 per 1000 person-years). Multivariable models showed that HBV treatment significantly lowered the risk of all-cause mortality (adjusted hazard ratio (aHR) 0.74; 95% CI: 0.65, 0.84) and liver-related mortality (adjusted subdistribution hazard ratio (asHR) 0.72; 95% CI: 0.58, 0.89) compared to untreated individuals. Among untreated individuals with HBV, those with HCV coinfection had a higher risk of both all-cause and liver-related mortality (aHR 1.57; 95% CI: 1.22, 2.04, and asHR 1.60; 95% CI: 1.25, 2.05, respectively). Interpretation: HBV treatment was associated with a significant reduction in all-cause and liver-related mortality among individuals with cirrhosis. The findings highlight the need for treatment among individuals with HBV related cirrhosis especially those with coinfection with hepatitis C virus. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-142832, PJT-156066, and SC1 -178736]. JDM has received doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and doctoral fellowship from the CanHepC. CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

BackgroundExposure therapy (ET) for anxiety disorders involves introducing the participant to an anxiety-provoking situation over several treatment sessions. Each time, the participant is exposed to a higher anxiety-provoking stimulus; for example, in the case of fear of heights, the participant would successively experience being at a greater height. ET is effective, and its counterpart, virtual reality (VR) exposure therapy (VRET), where VR substitutes real-world exposure, is equally so. However, ET is time-consuming, requiring several sessions. ObjectiveThis study aimed to compare the results of single-session exposure with those of traditional VRET with regard to reducing public speaking anxiety. MethodsWe introduced a paradigm concerned with public speaking anxiety where the VR exposure occurred in a single session while the participant interacted with a virtual therapist. Over time, the therapist transformed into an entire audience with almost imperceptible changes. We carried out a feasibility study with 45 participants, comparing 3 conditions: single-session exposure (n=16, 36%); conventional multiple-session exposure (n=14, 31%), where the same content was delivered in successive segments over 5 sessions; and a control group (n=15, 33%), who interacted with a single virtual character to talk about everyday matters. A week later, the participants were required to speak on a stage in front of a large audience in VR. ResultsAcross most of the series of conventional public speaking anxiety measures, the single-session exposure was at least as effective in reducing anxiety as the multiple-session exposure, and both these conditions were better than the control condition. The 12-item Personal Report of Confidence as a Speaker was used to measure public speaking anxiety levels, where higher values indicated more anxiety. Using a Bayesian model, the posterior probabilities of improvement compared to a high baseline were at least 1.7 times greater for single- and multiple-session exposures compared to the control group. The State Perceived Index of Competence was used as a measure of anticipatory anxiety for speaking on a stage in front of a large audience, where lower values indicated higher anxiety. The probabilities of improvement were just over 4 times greater for single- and multiple-session exposures compared to the control group for a low baseline and 489 (single) and 53 (multiple) times greater for a middle baseline. ConclusionsOverall, the results of this feasibility study show that for moderate public speaking anxiety, the paradigm of gradual change in a single session is worth following up with further studies with more severe levels of anxiety and a larger sample size, first with a randomized controlled trial with nonpatients and subsequently, if the outcomes follow those that we have found, with a full clinical trial with patients.

Abstract Background and objectives Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC). Methods We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults

The agri-food sector is undergoing a comprehensive transformation as it transitions towards net zero. To achieve this, fundamental changes and innovations are required, including changes in how food is produced and delivered to customers, new technologies, data and physical infrastructures, and algorithmic advancements. In this paper, we explore the opportunities and challenges of deploying AI-based data infrastructures for sustainability in the agri-food sector by focusing on two case studies: soft-fruit production and brewery operations. We investigate the potential benefits of incorporating Internet of Things (IoT) sensors and AI technologies for improving the use of resources, reducing carbon footprints, and enhancing decision-making. We identify user engagement with new technologies as a key challenge, together with issues in data quality arising from environmental volatility, difficulties in generalising models, including those designed for carbon calculators, and socio-technical barriers to adoption. We highlight and advocate for user engagement, more granular availability of sensor, production, and emissions data, and more transparent carbon footprint calculations. Our proposed future directions include semantic data integration to enhance interoperability, the generation of synthetic data to overcome the lack of real-world farm data, and multi-objective optimisation systems to model the competing interests between yield and sustainability goals. In general, we argue that AI is not a silver bullet for net zero challenges in the agri-food industry, but at the same time, AI solutions, when appropriately designed and deployed, can be a useful tool when operating in synergy with other approaches.

Objective To investigate current care for people with Long COVID in England.Design In-depth, semistructured interviews with people living with Long COVID and Long COVID healthcare professionals; data analysed using thematic analysis.Setting National Health Service England post-COVID-19 services in six clinics from November 2022 to July 2023.Participants 15 healthcare professionals and 21 people living with Long COVID currently attending or discharged (18 female; 3 male).Results Health professionals and people with lived experience highlighted the multifaceted nature of Long COVID, including its varied symptoms, its impact on people’s lives and the complexity involved in managing this condition. These impacts encompass physical, social, mental and environmental dimensions. People with Long COVID reported barriers in accessing primary care, as well as negative general practitioner consultations where they felt unheard or invalidated, though some positive interactions were also noted. Peer support or support systems proved highly valuable and beneficial for individuals, aiding their recovery and well-being. Post-COVID-19 services were viewed as spaces where overlooked voices found validation, offering more than medical expertise. Despite initial challenges, healthcare providers’ increasing expertise in diagnosing and treating Long COVID has helped refine care approaches for this condition.Conclusion Long COVID care in England is not uniform across all locations. Effective communication, specialised expertise and comprehensive support systems are crucial. A patient-centred approach considering the unique complexities of Long COVID, including physical, mental health, social and environmental aspects is needed. Sustained access to post-COVID-19 services is imperative, with success dependent on offering continuous rehabilitation beyond rapid recovery, acknowledging the condition’s enduring impacts and complexities.

Abstract Background and Aim Long Covid is often stigmatised, particularly in people who are disadvantaged within society. This may prevent them from seeking help and could lead to widening health inequalities. This coproduced study with a Community Advisory Board (CAB) of people with Long Covid aimed to understand healthcare and wider barriers and stigma experienced by people with probable Long Covid. Methods An active case finding approach was employed to find adults with probable, but not yet clinically diagnosed, Long Covid in two localities in London (Camden and Merton) and Derbyshire, England. Interviews explored the barriers to care and the stigma faced by participants and were analysed thematically. This study forms part of the STIMULATE‐ICP Collaboration. Findings Twenty‐three interviews were completed. Participants reported limited awareness of what Long Covid is and the available pathways to management. There was considerable self‐doubt among participants, sometimes reinforced by interactions with healthcare professionals (HCPs). Participants questioned their deservedness in seeking healthcare support for their symptoms. Hesitancy to engage with healthcare services was motivated by fear of needing more investigation and concerns regarding judgement about the ability to carry out caregiving responsibilities. It was also motivated by the complexity of the clinical presentation and fear of all symptoms being attributed to poor mental health. Participants also reported trying to avoid overburdening the health system. These difficulties were compounded by experiences of stigma and discrimination. The emerging themes reaffirmed a framework of epistemic injustice in relation to Long Covid, where creating, interpreting and conveying knowledge has varied credibility based on the teller's identity characteristics and/or the level of their interpretive resources. Conclusion We have codeveloped recommendations based on the findings. These include early signposting to services, dedicating protected time to listening to people with Long Covid, providing a holistic approach in care pathways, and working to mitigate stigma. Regardless of the diagnosis, people experiencing new symptoms must be encouraged to seek timely medical help. Clear public health messaging is needed among communities already disadvantaged by epistemic injustice to raise awareness of Long Covid, and to share stories that encourage seeking care and to illustrate the adverse effects of stigma. Patient or Public Contribution This study was coproduced with a CAB made up of 23 members including HCPs, people with lived experience of Long Covid and other stakeholders.

IntroductionIn the scientific research domain, the Open Science movement stands as a fundamental pillar for advancing knowledge and innovation globally. This article presents the design and implementation of the GITCE Open Data Ecosystem (GITCE-ODE) Research Data Management System (RDMS), developed by the Research Group on Emerging Computational Technologies (GITCE) at the Technological University of Panama, as a platform for the long-term storage, publication, and dissemination of research products.MethodsThe architecture of the GITCE-ODE RDMS encompasses the entire data engineering lifecycle, facilitating information processing stages such as extraction, transformation, loading (ETL), as well as the management and analysis of diverse datasets and metadata.ResultsCompliance with the FAIR principles ensures that published data and products are Findable, Accessible, Interoperable, and Reusable, promoting automation in the discovery and reuse of digital resources. Key considerations of the web portal include file format standardization, data categorization, treatment of semantic context, and organization of resources to ensure efficient management and administration of open research data.DiscussionThrough this platform, GITCE aims to foster collaboration, transparency, and accessibility in scientific research, contributing to the ongoing advancement of knowledge transfer and innovation.

BackgroundVirtual reality (VR) interventions, based on cognitive behavioral therapy principles, have been proven effective as complementary tools in managing obesity and have been associated with promoting healthy behaviors and addressing body image concerns. However, they have not fully addressed certain underlying causes of obesity, such as a lack of motivation to change, low self-efficacy, and the impact of weight stigma interiorization, which often impede treatment adherence and long-term lifestyle habit changes. To tackle these concerns, this study introduces the VR self-counseling paradigm, which incorporates embodiment and body-swapping techniques, along with motivational strategies, to help people living with obesity effectively address some of the root causes of their condition. ObjectiveThis study aims to assess the clinical efficacy of ConVRself (Virtual Reality self-talk), a VR platform that allows participants to engage in motivational self-conversations. MethodsA randomized controlled trial was conducted with 68 participants from the bariatric surgery waiting list from the obesity unit of the Vall d’Hebron University Hospital in Barcelona, Spain. Participants were assigned to 1 of 3 groups: a control group (CG), which only received treatment as usual from the obesity unit; experimental group 1 (EG1), which, after intensive motivational interviewing training, engaged in 4 sessions of VR-based self-conversations with ConVRself, and underwent embodiment and body-swapping techniques; and experimental group 2 (EG2), which engaged in 4 VR-based sessions led by a virtual counselor with a prerecorded discourse, and only underwent the embodiment technique. In the case of both EG1 and EG2, the VR interventions were assisted by a clinical researcher. Readiness to change habits, eating habits, and psychological variables, as well as adherence and satisfaction with ConVRself were measured at baseline, after the intervention, 1 week after the intervention, and 4 weeks after the intervention. ResultsRegarding the primary outcomes, EG1 (24/68, 35%) and EG2 (22/68, 32%) showed significant improvements in confidence to lose weight compared to the CG (22/68, 32%) at all assessment points (β=−.16; P=.02). Similarly, EG1 demonstrated a significant increase after the intervention in readiness to exercise more compared to the CG (β=−.17; P=.03). Regarding the secondary outcomes, EG1 participants showed a significant reduction in uncontrolled eating (β=.71; P=.01) and emotional eating (β=.29; P=.03) compared to the CG participants, as well as in their anxiety levels compared to EG2 and CG participants (β=.65; P=.01). In addition, participants from the experimental groups reported high adherence and satisfaction with the VR platform (EG1: mean 59.82, SD 4.00; EG2: mean 58.43, SD 5.22; d=0.30, 95% CI −0.30 to 0.89). ConclusionsThis study revealed that using VR self-conversations, based on motivational interviewing principles, may have benefits in helping people with obesity to enhance their readiness to change habits and self-efficacy, as well as reduce dysfunctional eating behaviors and anxiety. Trial RegistrationClinicalTrials.gov NCT05094557; https://www.clinicaltrials.gov/study/NCT05094557

Abstract Aβ peptides derived from the amyloid precursor protein (APP) have been strongly implicated in the pathogenesis of Alzheimer’s disease. However, the normal function of APP and the importance of that role in neurodegenerative disease is less clear. We recover the Drosophila ortholog of APP, Appl, in an unbiased forward genetic screen for neurodegeneration mutants. We perform comprehensive single cell transcriptional and proteomic studies of Appl mutant flies to investigate Appl function in the aging brain. We find an unexpected role for Appl in control of multiple cellular pathways, including translation, mitochondrial function, nucleic acid and lipid metabolism, cellular signaling and proteostasis. We mechanistically define a role for Appl in regulating autophagy through TGFβ signaling and document the broader relevance of our findings using mouse genetic, human iPSC and in vivo tauopathy models. Our results demonstrate a conserved role for APP in controlling age-dependent proteostasis with plausible relevance to Alzheimer’s disease.

Abstract Chemotherapy-related cognitive impairment (CRCI) is a common adverse effect of treatment and is characterized by deficits involving multiple cognitive domains including memory. Despite the significant morbidity of CRCI and the expected increase in cancer survivors over the coming decades, the pathophysiology of CRCI remains incompletely understood, highlighting the need for new model systems to study CRCI. Given the powerful array of genetic approaches and facile high throughput screening ability in Drosophila, our goal was to validate a Drosophila model relevant to CRCI. We administered the chemotherapeutic agents cisplatin, cyclophosphamide, and doxorubicin to adult Drosophila. Neurologic deficits were observed with all tested chemotherapies, with doxorubicin and in particular cisplatin also resulting in memory deficits. We then performed histologic and immunohistochemical analysis of cisplatin-treated Drosophila tissue, demonstrating neuropathologic evidence of increased neurodegeneration, DNA damage, and oxidative stress. Thus, our Drosophila model relevant to CRCI recapitulates clinical, radiologic, and histologic alterations reported in chemotherapy patients. Our new Drosophila model can be used for mechanistic dissection of pathways contributing to CRCI (and chemotherapy-induced neurotoxicity more generally) and pharmacologic screens to identify disease-modifying therapies.

Abstract We sought to evaluate the rates and predictors of SARS-CoV-2 vaccination among members of a structurally-marginalized population of people who use drugs (PWUD) during a targeted, community-wide, vaccination campaign in Vancouver, Canada. Interviewer-administered data were collected from study participants between June 2021 and March 2022. Generalized estimating equation analysis was used to identify factors associated with SARS-CoV-2 vaccine uptake, ascertained through a province-wide vaccine registry. Among 223 PWUD, 107 (48.0%) reported receipt of at least two SARS-CoV-2 vaccine doses at baseline and this increased to 151 (67.7%) by the end of the study period. Using social media as a source of vaccine information was negatively associated with SARS-CoV-2 vaccine uptake (Adjusted odds ratio [AOR] 0.27, 95% confidence interval [CI] 0.09–0.81) and HIV seropositivity (AOR 2.68, 95% CI 1.12–6.39) and older age (AOR 1.27, 95% CI 1.07–1.51) were positively associated with SARS-CoV-2 vaccine uptake. These findings suggest that the targeted vaccination campaign in Vancouver may be an effective model to promote SARS-CoV-2 vaccination in other jurisdictions. However, using social media as a source of vaccine information likely reduced SARS-CoV-2 vaccine uptake in PWUD arguing for further efforts to promote accessible and evidence-based vaccine information among marginalized populations.

Abstract Background Long-term antiretroviral therapy (ART) perpetually suppresses HIV load and has dramatically altered the prognosis of HIV infection, such that HIV is now regarded as a chronic disease. Side effects of ART in Patients With HIV (PWH), has introduced new challenges including “metabolic” (systemic) and oral complications. Furthermore, inflammation persists despite great viral load suppression and normal levels of CD4+ cell count. The impact of ART on the spectrum of oral diseases among PWH is often overlooked relative to other systemic complications. There is paucity of data on oral complications associated with ART use in PWH. This is in part due to limited prospective longitudinal studies designed to better understand the range of oral abnormalities observed in PWH on ART. Methods We describe here the study design, including processes associated with subject recruitment and retention, study visit planning, oral health assessments, bio-specimen collection and preprocessing procedures, and data management and statistical plan. Discussion We present a procedural roadmap that could be modelled to assess the extent and progression of oral diseases associated with ART in PWH. We also highlight the rigors and challenges associated with our ongoing participant recruitment and retention. A rigorous prospective longitudinal study requires proper planning and execution. A great benefit is that large data sets are collected and biospecimen repository can be used to answer more questions in future studies including genetic, microbiome and metabolome-based studies. Trial registration National Institute of Health Clinical Trials Registration (NCT) #: NCT04645693.

Abstract Background Non-memory-led dementias such as posterior cortical atrophy (PCA), primary progressive aphasia (PPA) and behavioural variant frontotemporal dementia (bvFTD) are low prevalent and often affect individuals under the age of 65. Tailored educational and support resources for caregivers of people living with these dementia phenotypes are scarce and unevenly distributed geographically. Web-based educational programmes are emerging as promising alternatives to improve caregiver self-efficacy and well-being. Here, we present the protocol of a study aiming to assess the feasibility of a co-produced online educational programme for caregivers of people living PCA, PPA and bvFTD: the Better Living with Non-memory-led Dementia programme. Methods A randomised controlled feasibility trial will be conducted on a sample of 30 caregivers of people living with PCA, PPA and bvFTD. Participants will be recruited among members of the support organisation Rare Dementia Support (based at UCL in the UK). The intervention group will be given access to an 8-week co-produced web-based educational programme consisting of 6 modules addressing education about PCA, PPA and bvFTD and support strategies for the person with dementia and for the caregiver. The control group will receive treatment as usual (TAU). Feasibility will be measured through feasibility of recruitment, clinical measurement tools and acceptability. Clinical measures will be used to assess preliminary efficacy and data on completion rates, missing data and variability used to decide on measures to be included in a full-scale trial. Allocation ratio will be 2:1 (intervention:control) stratified by diagnosis. Feasibility of recruitment and acceptability will be assessed. Clinical measures will be administered at baseline and 8-week and 3-month post-randomisation. The control group will be offered access to the intervention at the completion of data collection. Participants will be unblinded, and all measures will be self-reported online. Discussion Online-delivered educational programmes show potential for improving care competency of caregivers and may contribute to overcoming geographical inequalities in local provision of support services. This pilot study will inform a fully powered international trial to determine the effectiveness of Better Living with Non-memory-led Dementia. Trial registration This trial has been registered prospectively on the Clinical Trials Registry on 1st September 2022, registration number NCT05525377.

Hermeneutic phenomenology’s aim is to bring forth that which needs to be thought about. It is an invitation to think. To articulate thinking, one needs to listen in the corners and the shadows of the lived experience(s) of the phenomenon being investigated. The method simultaneously holds numerous perspectives and adopts an embodied approach to embracing experiential knowledge. This paper explores the power of hermeneutical phenomenology, as a methodological approach for understanding what it means to be intersex. Intersex people have bodies that are born different to typical male-female ones. Intersex is an umbrella term that includes more than thirty ways the human body may differ according to its sex characteristics (i.e., genitalia, hormones, chromosomes, sex organs). From interviews with intersex people, we confirm that employing a hermeneutic phenomenological approach did not just answer our research questions, but also became a powerful and empowering means through which some participants were effectively able to navigate, share and ‘own’ their personal story. Indeed, the method’s person-centred and ethical underpinnings permitted some to engage in the research in ways that became empowering and transformational.

Abstract Cancer cell populations evolve by a stepwise process involving natural selection of the fittest variants within a tissue ecosystem context and as modified by therapy. Genomic scrutiny of patient samples reveals an extraordinary diversity of mutational profiles both between patients with similar cancers and within the cancer cell population of individual patients. Does this signify highly divergent evolutionary trajectories or are there repetitive and predictable patterns? Major evolutionary innovations or adaptations in different species are frequently repeated, or convergent, reflecting both common selective pressures and constraints on optimal solutions. We argue this is true of evolving cancer cells, especially with respect to the TP53 gene. Functional loss variants in TP53 are the most common genetic change in cancer. We discuss the likely microenvironmental selective pressures involved and the profound impact this has on cell fitness, evolvability and probability of subsequent drug resistance.

Abstract Introduction Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future. Methods A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: “adoptive cell therapy”, “patient-reported outcomes” and “cancer”. Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated. Results One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1–2 weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3 months. Discussion None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.

Abstract Little is known about circular RNAs (circRNAs) in specific brain cells and human neuropsychiatric disease. Here, we systematically identify over 11,039 circRNAs expressed in vulnerable dopamine and pyramidal neurons laser-captured from 190 human brains and non-neuronal cells using ultra-deep, total RNA sequencing. 1526 and 3308 circRNAs are custom-tailored to the cell identity of dopamine and pyramidal neurons and enriched in synapse pathways. 29% of Parkinson’s and 12% of Alzheimer’s disease-associated genes produced validated circRNAs. circDNAJC6, which is transcribed from a juvenile-onset Parkinson’s gene, is already dysregulated during prodromal, onset stages of common Parkinson’s disease neuropathology. Globally, addiction-associated genes preferentially produce circRNAs in dopamine neurons, autism-associated genes in pyramidal neurons, and cancers in non-neuronal cells. This study shows that circular RNAs in the human brain are tailored to neuron identity and implicate circRNA-regulated synaptic specialization in neuropsychiatric diseases.

There is a wide spectrum of craniofacial bone disorders and dysplasias because embryological development of the craniofacial region is complex. Classification of craniofacial bone disorders and dysplasias is also complex because they exhibit complex clinical, pathological, and molecular heterogeneity. Most craniofacial disorders and dysplasias are rare but they present an array of phenotypes that functionally impact the orofacial complex. Management of craniofacial disorders is a multidisciplinary approach that involves the collaborative efforts of multiple professionals. This review provides an overview of the complexity of craniofacial disorders and dysplasias from molecular, clinical, and management perspectives.

IntroductionThe Good Life with osteoArthritis: Denmark (GLA:DTM) is an evidence-based program designed for individuals with symptomatic hip and knee osteoarthritis (OA). This program has reported improvement in pain, quality of life and self-efficacy, as well as delays in joint replacement surgery for adults with moderate to severe hip or knee OA. Evaluations of GLA:DTM implementation in several countries have focused on effectiveness, training, and feasibility of the program primarily from the provider perspective. Our objective was to examine how the GLA:DTM program was perceived and experienced by individuals with hip and knee OA to inform on-going program refinement and implementation.MethodsThirty semi-structured telephone interviews were conducted with participants who completed the GLA:DTM program in Alberta. An interpretive description approach was used to frame the study and thematic analysis was used to code the data and identify emergent themes and sub-themes associated with participants' experience and perception of the GLA:DTM program.ResultsMost participants had a positive experience of the GLA:DTM program and particularly enjoyed the group format, although some participants felt the group format prevented one-on-one support from providers. Three emergent themes related to acceptability were identified: accessible, adaptable, and supportive. Participants found the program to be accessible in terms of location, cost, and scheduling. They also felt the program was adaptable and allowed for individual attention and translatability into other settings. Finally, most participants found the group format to be motivating and fostered connections between participants.ConclusionThe GLA:DTM program was perceived as acceptable by most participants, yet the group format may not be useful for all individuals living with OA. Recommended improvements included adapting screening to identify those suited for the group format, providing program access earlier in the disease progression trajectory, modifying educational content based on participants' knowledge of OA and finally, providing refresher sessions after program completion.

Amidst the global growth of the ageing demographic in the world, an inclusive assessment of the care needs of the older lesbian, gay, bisexual, transgender, and intersex (LGBTI) population is receiving increasing attention, especially in view of reported health inequalities for these minority groups and the position of their sexual orientations and gender identities within a predominantly heteronormative health and social system. This literature review aims to identify and analyse previous research on older LGBTI people’s views, experiences, and perceptions of homecare provision. We searched the CINAHL, Medline, and PsychINFO databases and found a total of 337 records. After an eligibility assessment, 12 studies were selected, comprising 11 qualitative studies, and one mixed methods study. Under an overarching theme of fears of discrimination and of receiving suboptimal care, we further categorised our findings in the following three interlinked subthemes: (a) disclosure of gender identity and sexual orientation; (b) emerging meanings of LGBTI‐competent care; and (c) recommendations for improved quality of LGBTI‐friendly services. The overall surfacing outcome of our analysis of the participants’ experiences described in the studies examined is an aspiration for homecare services ensuring quality of holistic, person‐centred care that recognises this population’s distinct set of requirements, including knowledge and consideration of their histories of inequalities and oppression. Wider awareness about the need to re‐imagine more inclusive care for the LGBTI community has the potential to improve services and practices, reduce access barriers, and prevent inequalities.

Resumo No início de 2023, um grande revés abala o mercado acionário brasileiro: a Americanas, empresa quase centenária e uma das maiores varejistas do Brasil, anuncia ao mercado, em um Fato Relevante, que haviam sido encontradas “inconsistências contábeis”, estimadas em R$ 20 bilhões, na sua conta fornecedores. A empresa é gerida há mais de 30 anos pelo trio Jorge Paulo Lemann, Marcel Telles e Beto Sicupira, considerados, até então, uma referência no capitalismo brasileiro. Neste momento, em que o caso ainda se desdobra diante de nós e atrai imensa atenção da mídia pelos números superlativos - milhares de pontos de vendas, 45.000 empregos, bilhões em dívidas com fornecedores e uma perda de R$ 8 bilhões em ações -, é fundamental que a academia qualifique o debate e faça uma discussão de seus impactos e desdobramentos de forma estruturada em sala de aula.

Summary: Background: HCV infection is associated with mortality due to extrahepatic manifestations (EHM). Sustained virologic response (SVR) following direct-acting antiviral (DAA) therapy has been linked to decreased all-cause and liver-related mortality. However, evidence regarding the impact of DAA on EHM-related deaths is lacking. This study aimed to assess the impact of DAA and SVR on EHM-related mortality. Methods: The British Columbia Hepatitis Testers Cohort comprises ∼1.7 million people tested for HCV between 1990 and 2015 and is linked with administrative health data. Among individuals diagnosed with HCV by 12/31/2020, those who received at least one DAA treatment were matched to those who never received treatment by the year of their first HCV RNA positive date. We compared three groups: treated & SVR, treated & no-SVR, and untreated; and generated EHM mortality rates and incidence curves. To account for differences in baseline characteristics, we used inverse probability of treatment weights (IPTW). IPTW-weighted multivariable cause-specific Cox regression models were adjusted for competing risk and confounders. Findings: Study population included 12,815 treated (12,287 SVR, 528 no-SVR) and 12,815 untreated individuals (median follow-up 3.4 years, IQR 2.9). The untreated group had the highest EHM mortality rate (30.9 per 1000 person-years [PY], 95% CI 29.2–32.8), followed by the treated & no-SVR group (21.2 per 1000 PY, 95% CI 14.9–30.1), while the treated & SVR group had the lowest EHM mortality rate (7.9 per 1000 PY, 95% CI 7.1–8.7). In the multivariable model, EHM mortality in the treated & SVR group was significantly decreased (adjusted cause-specific hazard ratio [acsHR] 0.20, 95% CI 0.18–0.23). The treated & SVR group had significant reductions in mortality related to each of the EHMs (78–84%). Interpretation: Treatment of HCV with DAA was associated with significant reductions in EHM-related mortality. These findings emphasize the critical importance of timely diagnosis and treatment of HCV to prevent deaths associated with EHM, and have important implications for clinical practice and public health. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-348216, PJT-156066, and PHE-337680]. DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and Doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

Background: In locally-advanced breast cancers (LABC), the previous primary goal of neoadjuvant systemic therapy was to improve resectability and achieve better margins. Currently, it can also provide important prognostic information based on actual response to therapy. Achieving pathologic complete response (pCR) after neoadjuvant therapy is targeted because it is associated with favorable disease-free survival (DFS) and overall survival (OS). The purpose of this study is to report the 5-year disease-free survival rate and overall survival rate among patients with LABC treated with neoadjuvant treatment followed by surgery. Methods: All patients with histologically diagnosed locally advanced breast cancer, who completed neoadjuvant therapy and surgery at St. Luke’s Medical Center from January 2007 to December 2017 where included. Response to neoadjuvant therapy were categorized using post-surgical pathologic reports. Survival curves were generated by the Kaplan-Meier method and compared using the log-rank test. Results: The cohort included 231 women, most were diagnosed with stage III disease (n=151). Pathologic complete response to neoadjuvant treatment had a significantly greater 5-year disease-free survival at 73.17% compared to those with residual disease after neoadjuvant treatment at 51.25% (Log-rank test p=0.0107). The locoregional recurrence-free survival and distant metastasis-free survival were 83.20% and 62.0% at 5 years, respectively. No deaths were recorded at 5 years for patients who achieved pathologic complete response after neoadjuvant chemotherapy. Conclusion: Pathologic complete response has better outcomes in terms of disease-free survival compared to those who did not achieve complete pathologic response after neoadjuvant therapy. Disease-free survival among patients who achieved pathologic complete response does not significantly differ among the different molecular phenotypes. The overall survival of the patients in this cohort does not differ in terms of phenotypic subtypes and mortality is seen among patients with disease progression.

Background: Chronic/latent viral infections may accelerate immunological aging, particularly among people living with HIV (PLWH). We characterized chronic/latent virus infections across their lifespan and investigated their associations with leukocyte telomere length (LTL). Methods: Participants enrolled in the CARMA cohort study were randomly selected to include n = 15 for each decade of age between 0 and >60 y, for each sex, and each HIV status. Cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpesvirus 8 (HHV-8), herpes simplex virus 1 (HSV-1), and HSV-2 infection were determined serologically; HIV, hepatitis C (HCV), and hepatitis B (HBV) were self-reported. LTLs were measured using monochrome multiplex qPCR. Associations between the number of viruses, LTL, and sociodemographic factors were assessed using ordinal logistic and linear regression modeling. Results: The study included 187 PLWH (105 female/82 male) and 190 HIV-negative participants (105 female/84 male), ranging in age from 0.7 to 76.1 years. Living with HIV, being older, and being female were associated with harbouring a greater number of chronic/latent non-HIV viruses. Having more infections was in turn bivariately associated with a shorter LTL. In multivariable analyses, older age, living with HIV, and the female sex remained independently associated with having more infections, while having 3–4 viruses (vs. 0–2) was associated with a shorter LTL. Conclusions: Our results suggest that persistent viral infections are more prevalent in PLWH and females, and that these may contribute to immunological aging. Whether this is associated with comorbidities later in life remains an important question.

We investigated the impacts of the COVID-19 pandemic on hepatitis C (HCV) treatment initiation, including by birth cohort and injection drug use status, in British Columbia (BC), Canada. Using population data from the BC COVID-19 Cohort, we conducted interrupted time series analyses, estimating changes in HCV treatment initiation following the introduction of pandemic-related policies in March 2020. The study included a pre-policy period (April 2018 to March 2020) and three follow-up periods (April to December 2020, January to December 2021, and January to December 2022). The level of HCV treatment initiation decreased by 26% in April 2020 (rate ratio 0.74, 95% confidence interval [CI] 0.60 to 0.91). Overall, no statistically significant difference in HCV treatment initiation occurred over the 2020 and 2021 post-policy periods, and an increase of 34.4% (95% CI 0.6 to 75.8) occurred in 2022 (equating to 321 additional people initiating treatment), relative to expectation. Decreases in HCV treatment initiation occurred in 2020 for people born between 1965 and 1974 (25.5%) and people who inject drugs (24.5%), relative to expectation. In summary, the pandemic was associated with short-term disruptions in HCV treatment initiation in BC, which were greater for people born 1965 to 1974 and people who inject drugs.

Background: Multidisciplinary transitional care interventions aim to improve the coordination and continuity of healthcare during hospitalization and after discharge for patients with complex care needs related to physical, nutritional, or psychosocial status. Implementing such interventions is complex as they involve many stakeholders across multiple settings. Numerous studies have evaluated patients’, family members’, and healthcare professionals’ experiences with multidisciplinary transitional care interventions, which can provide insight into facilitators and barriers to their implementation. Objective: To provide an overview of facilitators and barriers to implementing multidisciplinary transitional care interventions, which could be considered before developing implementation strategies. Design: A qualitative systematic review using the Consolidated Framework for Implementation Research. Setting(s): Hospitals and primary care Participants: Adult patients admitted to a hospital, regardless of their diagnosis, as well as their family members and hospital and primary care healthcare professionals Methods: Embase, CINAHL, and Medline were searched for qualitative studies evaluating multidisciplinary transitional care interventions through patients', family members', and healthcare professionals' experiences and views from inception until June 2024. The methodological rigor was assessed with the Critical Appraisal Skills Program. We identified facilitators and barriers to the successful implementation of multidisciplinary transitional care interventions with the Consolidated Framework for Implementation Research. Facilitators and barriers were categorized into pre- or post-discharge or general factors. Results: Twelve studies were included and appraised. We identified 79 factors, mostly linked to three domains of the Consolidated Framework for Implementation Research: Innovation, Inner setting, and Individuals involved. Facilitators included ''comprehensive follow-up care needs assessment''(pre-discharge), ''immediate, tailored follow-up care''(post-discharge), and ''improved communication between stakeholders''(general). Barriers included ''shortage of hospital beds'' and ''lack of time''(pre-discharge), ''lack of available primary care professionals''(post-discharge), ''inconsistencies of stakeholders' schedules'' and ''intervention costs''(general). Conclusions: The factors identified could serve as a non-exhaustive inventory list to inspire readers who wish to implement a multidisciplinary transitional care intervention in their settings. Digital tools and alternative financing models might overcome cost and reimbursement issues, the increasing complexity of patient care, and shortcomings, such as the lack of available hospital beds or professionals. Further research should identify effective implementation strategies, considering the pre-, post-discharge, and general factors identified. Registration: The protocol was registered in PROSPERO (CRD42023421423). Tweetable abstract: Effective communication aids in implementing transitional care interventions, but patient care complexity and healthcare system pressures present challenges.

Background: We tested the hypothesis that overexpression of cellular-prion-protein in adipose-derived mesenchymal stem cells (PrPC OE -ADMSCs) effectively protected the kidney against ischemia-reperfusion (IR) injury in rat. Methods: Part I of cell culture was categorized into A1(ADMSCs)/A2(ADMSCs+p-Cresol)/A3(PrPC OE in ADMSCs)/A4 (PrPC OE in ADMSCs+p-Cresol). Part II of cell culture was divided into B1(ADMSCs)/B2[ADMSCs+lipopolysaccharide (LPS)]/B3(PrPC OE in ADMSCs)/B4(PrPC OE in ADMSCs+LPS). Sprague-Dawley (SD) rats (n = 50) were equally categorized into groups 1 (sham-operated-control)/2 (IR)/3 (IR+ADMSCs/6.0 × 10 5 equally divided into bilateral-renal arteries and 6.0 × 10 5 intravenous administration by 1 h after IR)/4 [IR+PrPC OE -ADMSCs (identical dosage administered as group 3)]/5 [IR+silencing PRNP -ADMSCs (identical dosage administered as group 3)], and kidneys were harvested post-day 3 IR injury. Results: Part I results demonstrated that the cell viability at 24/48/72 h, BrdU uptake/number of mitDNA/APT concentration/mitochondrial-cytochrome-C+ cells and the protein expressions of ki67/PrPC at 72 h-cell culturing were significantly higher in PrPC OE -ADMSCs than in ADMSCs (all P < 0.001). The protein expressions of oxidative-stress (NOX-1/NOX2/NOX4/oxidized protein)/mitochondrial-damaged (p22-phox/cytosolic-cytochrome-C)/inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers were lowest in A1/A3 and significantly higher in A2 than in A4 (all P < 0.001). Part II result showed that the protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers exhibited an identical pattern of part I among the groups (all P < 0.001). The protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized-protein)/mitochondrial-damaged (cytosolic-cytochrome-C/p22-phox)/apoptotic (cleaved caspase-3/cleaved-PARP/mitochondrial-Bx)/autophagic (beclin-1/ratio of LC3B-II/LC3B-I)/fibrotic (Smad3/TGF-ß) biomarkers and kidney-injury-score/creatinine level were lowest in group 1, highest in group 2, significantly higher in group 5 than in groups 3/4 (all P < 0.0001). Conclusion: PrPC OE in ADMSCs rejuvenated these cells and played a cardinal role on protecting the kidney against IR injury.

Antivirals with broad coronavirus activity are important for treating high-risk individuals exposed to the constantly evolving SARS-CoV-2 variants of concern (VOCs) as well as emerging drug-resistant variants. We developed and characterized a novel class of active-site-directed 3-chymotrypsin-like protease (3CLpro) inhibitors (C2–C5a). Our lead direct-acting antiviral (DAA), C5a, is a non-covalent, non-peptide with a dissociation constant of 170 nM against recombinant SARS-CoV-2 3CLpro. The compounds C2–C5a exhibit broad-spectrum activity against Omicron subvariants (BA.5, BQ.1.1, and XBB.1.5) and seasonal human coronavirus-229E infection in human cells. Notably, C5a has median effective concentrations of 30–50 nM against BQ.1.1 and XBB.1.5 in two different human cell lines. X-ray crystallography has confirmed the unique binding modes of C2–C5a to the 3CLpro, which can limit virus cross-resistance to emerging Paxlovid-resistant variants. We tested the effect of C5a with two of our newly discovered host-directed antivirals (HDAs): N-0385, a TMPRSS2 inhibitor, and bafilomycin D (BafD), a human vacuolar H+-ATPase [V-ATPase] inhibitor. We demonstrated a synergistic action of C5a in combination with N-0385 and BafD against Omicron BA.5 infection in human Calu-3 lung cells. Our findings underscore that a SARS-CoV-2 multi-targeted treatment for circulating Omicron subvariants based on DAAs (C5a) and HDAs (N-0385 or BafD) can lead to therapeutic benefits by enhancing treatment efficacy. Furthermore, the high-resolution structures of SARS-CoV-2 3CLpro in complex with C2–C5a will facilitate future rational optimization of our novel broad-spectrum active-site-directed 3C-like protease inhibitors.

Research has shown that incorporating haptics into virtual environments can increase sensory fidelity and provide powerful and immersive experiences. However, current studies on haptics in virtual interactions primarily focus on one-on-one scenarios, while kinesthetic haptic interactions in large virtual gatherings are underexplored. This study aims to investigate the impact of kinesthetic haptics on eliciting emotional responses within crowded virtual reality (VR) scenarios. Specifically, we examine the influence of type or quality of the haptic feedback on the perception of positive and negative emotions. We designed and developed different combinations of tactile and torque feedback devices and evaluated their effects on emotional responses. To achieve this, we explored different combinations of haptic feedback devices, including “No Haptic,” “Tactile Stimulus” delivering tactile cues, and “Haptic Stimulus” delivering tactile and torque cues, in combination with two immersive 360-degree video crowd scenarios, namely, “Casual Crowd” and “Aggressive Crowd.” The results suggest that varying the type or quality of haptic feedback can evoke different emotional responses in crowded VR scenarios. Participants reported increased levels of nervousness with Haptic Stimulus in both virtual scenarios, while both Tactile Stimulus and Haptic Stimulus were negatively associated with pleasantness and comfort during the interaction. Additionally, we observed that participants’ sense of touch being real was enhanced in Haptic Stimulus compared to Tactile Stimulus. The “Haptic Stimulus” condition had the most positive influence on participants’ sense of identification with the crowd.

Moving through a virtual environment that is larger than the physical space in which the participant operates has been a challenge since the early days of virtual reality. Many different methods have been proposed, such as joystick-based navigation, walking in place where the participant makes walking movements but is stationary in the physical space, and redirected walking where the environment is surreptitiously changed giving the illusion of walking in a long straight line in the virtual space but maybe a circle in the physical space. Each type of method has its limitations, ranging from simulator sickness to still requiring more physical space than is available. Stimulated by the COVID-19 lockdown, we developed a new method of locomotion which we refer to as interactive redirected walking. Here, the participant really walks but, when reaching a boundary, rotates the virtual world so that continuation of walking is always within the physical boundary. We carried out an exploratory study to compare this method with walking in place with respect to presence using questionnaires as well as qualitative responses based on comments written by the participants that were subjected to sentiment analysis. Surprisingly, we found that smaller physical boundaries favor interactive redirected walking, but for boundary lengths more than approximately 7 adult paces, the walking-in-place method is preferable.

Summary: Change blindness (CB) is the perceptual phenomenon whereby people are blind to dramatic changes in their visual environment. In virtual reality (VR) a person’s body can be substituted by a life-sized virtual one that moves synchronously with their real body movements as their self-representation. We consider whether CB occurs in VR, and whether there are differences in the case of changes to their own virtual body compared with the body of another. Forty people took part in a Qi Gong lesson in VR led by a virtual instructor. During the lesson both their own and the instructor’s face dramatically changed in appearance. Overall, 73% and 85% did not notice the changes to their own and instructor’s face respectively. People make iconic inferences about their visual surroundings without sampling detail, and reduced CB in the case of their own body may be a marker for self-representation.