Introduction Non-alcoholic fatty liver disease (NAFLD) has emerged as a leading cause of chronic liver disease worldwide. The global prevalence of NAFLD is expected to increase dramatically with the increasing prevalence of obesity and type 2 diabetes mellitus (T2DM). The role of NAFLD as a cardiometabolic risk factor or component of metabolic syndrome on the heart remains unclear. Thus, the independent effect of NAFLD on structural and functional heart parameters warrants validation. Our goal was to study cardiac structure and function in subjects with obesity and NAFLD. Methods A total of 164 patients were examined in this cross-sectional study. Participants were grouped based on BMI and the presence or absence of abdominal obesity (AO) and/or NAFLD. The subjects were divided into four groups: group 1: normal BMI without AO and NAFLD; group 2: BMI ≥ 25 kg/m2 or AO without NAFLD; group 3: BMI ≥ 25 kg/m2 and AO without NAFLD; group 4: patients with BMI ≥ 25 kg/m2, AO, and NAFLD. We performed a thorough clinical examination, a biochemical blood analysis, and echocardiography. Indices of liver steatosis and fibrosis were calculated. A study of liver assessment of the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) was conducted. Statistical analysis was performed using IBM SPSS Statistics version 26 (IBM Corp., Armonk, NY). Results The mean age of the participants was 35.0 (31.0-38.5) years. We found a higher frequency of multiple cardiometabolic risk factors in the general cohort. However, on comparing groups 3 and 4, we found a higher frequency of hyperinsulinemia, homeostatic model assessment of insulin resistance (HOMA-IR), and obesity (p < 0.05). To assess the role of NAFLD independent of obesity, we conducted further analyses after adjusting for BMI. Among patients with NAFLD, we observed a similar trend for parameters of carbohydrate metabolism (p < 0.005). In individuals with NAFLD, an increase in left atrial (LA) volume, interventricular septal (IVS) thickness, and left ventricular (LV) myocardial mass, and a decrease in LV ejection fraction and LV stroke volume index were found (p < 0.005). The hepatic steatosis index (HSI) correlated with LA volume, LV end-systolic volume (ESV) and LV end-diastolic volume (EDV), stroke volume, and LV myocardial mass. An association between an increase in CAP score and an increase in the LA volume, stroke volume index, IVS thickness, LV myocardial mass, and the values of LSM with an increase in the LA volume was established. Conclusion The presence of NAFLD without cardiovascular disease and diabetes mellitus revealed an association with the structural and functional parameters of the heart. The results of this study can also be used to improve the effectiveness of a comprehensive assessment of patients and to develop strategies for the primary and secondary prevention of heart failure with preserved ejection fraction in NAFLD.

The ketogenic diet (KD) restricts carbohydrate consumption, leading to an increase in ketone bodies, such as acetoacetate, β-hydroxybutyrate, and acetone, which are utilized as energy substrates. This dietary approach impacts several biochemical processes, resulting in improved clinical management of various disorders, particularly in childhood. However, the exact mechanisms underlying the efficacy of KD remain unclear. Interestingly, KD may also impact the gut microbiota, which plays a pivotal role in metabolism, nutrition, and the development of the immune and nervous systems. KD has gained popularity for its potential benefits in weight loss, blood sugar control, and certain neurological conditions. This narrative review sums up KD-related studies published over 30 years. While short-term studies have provided valuable insights into the effects of KD on the gut microbiota, persistent uncertainties surround its long-term efficacy and potential for inducing dysbiosis. The significant influence of KD on epigenetic mechanisms, intracellular pathways, and gut microbial composition underscores its potential as a therapeutic choice. However, a judicious consideration of the potential risks associated with the strict adherence to a low-carbohydrate, high-fat, and high-protein regimen over prolonged periods is imperative. As KDs gain popularity among the adolescent and young adult demographic for weight management, it becomes imperative to undertake additional research to comprehensively assess their impact on nutritional status and gut microbiota, ensuring a holistic and sustainable approach to medical nutrition.

Idiopathic nephrotic syndrome is the most common glomerular disease in children. Corticosteroids are the cornerstone of its treatment, and steroid response is the main prognostic factor. Most children respond to a cycle of oral steroids, and are defined as having steroid-sensitive nephrotic syndrome. Among the children who do not respond, defined as having steroid-resistant nephrotic syndrome, most respond to second-line immunosuppression, mainly with calcineurin inhibitors, and children in whom a response is not observed are described as multidrug resistant. The pathophysiology of nephrotic syndrome remains elusive. In cases of immune-mediated origin, dysregulation of immune cells and production of circulating factors that damage the glomerular filtration barrier have been described. Conversely, up to a third of cases of steroid-resistant nephrotic syndrome have a monogenic origin. Multidrug resistant nephrotic syndrome often leads to kidney failure and can cause relapse after kidney transplant. Although steroid-sensitive nephrotic syndrome does not affect renal function, most children with steroid-sensitive nephrotic syndrome have a relapsing course that requires repeated steroid cycles with significant side-effects. To minimise morbidity, some patients require steroid-sparing immunosuppressive agents, including levamisole, mycophenolate mofetil, calcineurin inhibitors, anti-CD20 monoclonal antibodies, and cyclophosphamide. Close monitoring and preventive measures are warranted at onset and during relapse to prevent acute complications (eg, hypovolaemia, acute kidney injury, infections, and thrombosis), whereas long-term management requires minimising treatment-related side-effects. A subset of patients have active disease into adulthood.

Despite 20 years of improvement in acute coronary syndromes care, patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains a major clinical challenge with a stable incidence and mortality. While intra-aortic balloon pump (IABP) did not meet its expectations, percutaneous mechanical circulatory supports (pMCS) with higher hemodynamic support, large availability and quick implementation may improve AMICS prognosis by enabling early hemodynamic stabilization and unloading. Both interventional and observational studies suggested a clinical benefit in selected patients of the IMPELLA[Ⓡ] CP device within in a well-defined therapeutic strategy. While promising, these preliminary results are challenged by others suggesting a higher rate of complications and possible poorer outcome. Given these conflicting data and its high cost, a randomized clinical trial is warranted to delineate the benefits and risks of this new therapeutic strategy.

Hallucinogenic mushrooms have been used in religious and cultural ceremonies for centuries. Of late, psilocybin, the psychoactive compound in hallucinogenic mushrooms, has received increased public interest as a novel drug for treating mood and substance use disorders (SUDs). In addition, in recent years, some states in the United States have legalized psilocybin for medical and recreational use. Given this, clinicians need to understand the potential benefits and risks related to using psilocybin for therapeutic purposes so that they can accurately advise patients. This expert narrative review summarizes the scientific basis and clinical evidence on the safety and efficacy of psilocybin-assisted therapy for treating psychiatric disorders and SUDs. The results of this review are structured as a more extensive discussion about psilocybin's history, putative mechanisms of action, and recent legislative changes to its legal status. There is modest evidence of psilocybin-assisted therapy for treating depression and anxiety disorders. In addition, early data suggest that psilocybin-assisted therapy may effectively reduce harmful drinking in patients with alcohol use disorders. The evidence further suggests psilocybin, when administered under supervision (psilocybin-assisted therapy), the side effects experienced are mild and transient. The occurrence of severe adverse events following psilocybin administration is uncommon. Still, a recent clinical trial found that individuals in the psilocybin arm had increased suicidal ideations and non-suicidal self-injurious behaviors. Given this, further investigation into the safety and efficacy of psilocybin-assisted therapy is warranted to determine which patient subgroups are most likely to benefit and which are most likely to experience adverse outcomes related to its use.

Recently, studies have examined COVID-19 vaccine acceptance and/or hesitancy amongst adult populations across the globe. However, there is a paucity of literature illustrating children's voices in vaccination debates. This article draws on qualitative data collected via a mixed-methods study that explored South Africans' experiences during the COVID-19 pandemic between 2020 and 2021. Interviews were conducted with a purposive sample (N = 29) of children (>18 years) and their parents regarding their initial perspectives on COVID-19 vaccines. Given the dyadic nature of our study, we explored the intergenerational influence that parents' perspectives had on children's vaccine acceptability and the role that vaccine literacy, or lack thereof, played in vaccine decision making. Findings showed a great level of vaccine acceptability among children and parents, where many placed hopes in the vaccines to promote societal health and wellbeing. Intergenerational transfer of perspectives was observed where children's willingness to receive a vaccine was intrinsically linked to their parents' vaccine acceptability. Some participants also expressed concerns about COVID-19 vaccines, related to misinformation, mistrust, and limited vaccine literacy. We discuss the findings as they relate to vaccine and health literacy, also considering the prospective implications of this work as we enter the "recovery" period of the pandemic.

mRNA vaccine technology is the most interesting final product of decades of research. This new platform for public health is simple to transfer to low-income countries and can be used against diverse agents, including cancer. It is environmentally clean, relatively low-cost, and does not use animals for its production. Most importantly, mRNA vaccines have been highly efficacious in avoiding serious disease and death from COVID-19. Yet, at the highest point of the pandemic, many voices, including some from prominent positions, opposed their use. Similarly, the Human Papillomavirus (HPV) vaccines, which are highly effective, very safe, and probably confer long life protection against its HPV types, faced strong parents' hesitancy. Vaccine hesitancy has been the subject of extensive research, focusing primarily on factors associated with the public, the political environment, and messaging strategies. However, the issue of unfair worldwide access to the COVID-19 vaccines has recently sparked significant debate about the vaccine industry's role. Recent data demonstrated that the system's perceived unfairness with the masses is behind the growing populist anti-vaccine movements worldwide. The association between populism and antivaccine attitudes has been reported at country and individual levels. The anti-science attitudes behind vaccine hesitancy emerge when the scientist is not found credible due to the suspicion that they had monetary investments in pharmaceutical companies. Here, I argue that the obscurity of the vaccine market, but also its unfairness, are important factors contributing to vaccine hesitancy. The purpose of this commentary is to stimulate a review of current market regulations and to improve its transparency and fairness, particularly in the context of public health emergencies. By doing so, a new pandemic would find us better prepared. The general population and much of the healthcare community often ignore the years of dedicated work and substantial public funding that enabled the discovery and design of vaccines. Conversely, pharmaceutical companies often over-emphasize their investments in research and development. A decade ago, Marcia Angell provided a detailed breakdown of pharmaceutical expenses, revealing that marketing and administration costs were 2.5 times higher than research and development expenses; recently, Olivier Wouters confirmed the high expenditures of the pharmaceutical industry in lobbying and political campaign contributions. In this commentary, I will present the cases of HPV and COVID-19 vaccines as examples of when vaccines, instead of being public health goods, became market goods, creating large inequities and health costs. This failure is a structural cause behind more ideological vaccine hesitancy, less studied so far.

Over the past few years, numerous anti-phage defense systems have been discovered in bacteria. Although the mechanism of defense for some of these systems is understood, a major unanswered question is how these systems sense phage infection. To systematically address this question, we isolated 177 phage mutants that escape 15 different defense systems. In many cases, these escaper phages were mutated in the gene sensed by the defense system, enabling us to map the phage determinants that confer sensitivity to bacterial immunity. Our data identify specificity determinants of diverse retron systems and reveal phage-encoded triggers for multiple abortive infection systems. We find general themes in phage sensing and demonstrate that mechanistically diverse systems have converged to sense either the core replication machinery of the phage, phage structural components, or host takeover mechanisms. Combining our data with previous findings, we formulate key principles on how bacterial immune systems sense phage invaders.

To understand the impact of kidney disease in Canada and the priority areas of kidney research that can benefit from patient-oriented, precision medicine research using novel technologies.

This study assessed the attitudes and needs of physicians and health professional staff at a tertiary care hospital in Canada regarding the introduction of physician assisted dying (PAD) during 2015-16. This research aimed to develop an understanding of the wishes, concerns and hopes of stakeholders related to handling requests for PAD; to determine what supports/structures/resources health care professionals (HCP) require in order to ensure high quality and compassionate care for patients requesting PAD, and a supportive environment for all healthcare providers across the moral spectrum. This study constituted a mixed methods design with a qualitative descriptive approach for the study's qualitative component. A total of 303 HCPs working in a tertiary care hospital completed an online survey and 64 HCPs working in hospital units with high mortality rates participated in 8 focus group discussions. Both focus group and survey data coalesced around several themes to support the implementation of PAD following the decriminalization of this practice: the importance of high quality care; honoring moral diversity; supporting values (such as autonomy, privacy, beneficence); and developing resources, including collaboration with palliative care, education, policies and a specialized team. This study provided the foundational evidence to support the development of the PAD program described in other papers in this collection, and can be a model for gathering evidence from stakeholders to inform the implementation of PAD in any healthcare organization.

Coronavirus disease 2019 (COVID-19), the highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a catastrophic effect on the world’s demographics resulting in more than 3.8 million deaths worldwide, emerging as the most consequential global health crisis since the era of the influenza pandemic of 1918. After the first cases of this predominantly respiratory viral illness were first reported in Wuhan, Hubei Province, China, in late December 2019, SARS-CoV-2  rapidly disseminated across the world in a short span of time, compelling the World Health Organization (WHO) to declare it as a global pandemic on March 11, 2020. Since being declared a global pandemic, COVID-19 has ravaged many countries worldwide and has overwhelmed many healthcare systems. The pandemic has also resulted in the loss of livelihoods due to prolonged shutdowns, which have had a rippling effect on the global economy. Even though substantial progress in clinical research has led to a better understanding of SARS-CoV-2 and the management of COVID-19, limiting the continuing spread of this virus and its variants has become an issue of increasing concern, as SARS-CoV-2 continues to wreak havoc across the world, with many countries enduring a second or third wave of outbreaks of this viral illness attributed mainly due to the emergence of mutant variants of the virus.  Like other RNA viruses, SARS-CoV-2, while adapting to their new human hosts, is prone to genetic evolution with the development of mutations over time, resulting in mutant variants that may have different characteristics than its ancestral strains. Several variants of SARS-CoV-2 have been described during the course of this pandemic, among which only a few are considered variants of concern (VOCs) by the WHO, given their impact on global public health. Based on the recent epidemiological update by the WHO, as of June 22, 2021, four SARS-CoV-2 VOCs have been identified since the beginning of the pandemic: Alpha (B.1.1.7): first variant of concern described in the United Kingdom (UK) in late December 2020. Beta (B.1.351): first reported in South Africa in December 2020. Gamma(P.1): first reported in Brazil in early January 2021. Delta (B.1.617.2): first reported in India in December 2020. Despite the unprecedented speed of vaccine development against the prevention of COVID-19 and robust global mass vaccination efforts, the emergence of these new SARS-CoV-2 variants threatens to overturn the significant progress made so far in limiting the spread of this viral illness. This review article aims to comprehensively describe the etiology, epidemiology, pathophysiology, clinical features, diagnostic methods, and the latest novel therapeutics in the management of COVID-19. This review also briefly provides an overview of the different variants of SARS-CoV-2 and the efficacy of different available vaccines for prevention against COVID-19 and its variants. 

Recent advances in functional neuroimaging have demonstrated novel potential for informing diagnosis and prognosis in the unresponsive wakeful syndrome and minimally conscious states. However, these technologies come with considerable expense and difficulty, limiting the possibility of wider clinical application in patients. Here, we show that high density electroencephalography, collected from 104 patients measured at rest, can provide valuable information about brain connectivity that correlates with behaviour and functional neuroimaging. Using graph theory, we visualize and quantify spectral connectivity estimated from electroencephalography as a dense brain network. Our findings demonstrate that key quantitative metrics of these networks correlate with the continuum of behavioural recovery in patients, ranging from those diagnosed as unresponsive, through those who have emerged from minimally conscious, to the fully conscious locked-in syndrome. In particular, a network metric indexing the presence of densely interconnected central hubs of connectivity discriminated behavioural consciousness with accuracy comparable to that achieved by expert assessment with positron emission tomography. We also show that this metric correlates strongly with brain metabolism. Further, with classification analysis, we predict the behavioural diagnosis, brain metabolism and 1-year clinical outcome of individual patients. Finally, we demonstrate that assessments of brain networks show robust connectivity in patients diagnosed as unresponsive by clinical consensus, but later rediagnosed as minimally conscious with the Coma Recovery Scale-Revised. Classification analysis of their brain network identified each of these misdiagnosed patients as minimally conscious, corroborating their behavioural diagnoses. If deployed at the bedside in the clinical context, such network measurements could complement systematic behavioural assessment and help reduce the high misdiagnosis rate reported in these patients. These metrics could also identify patients in whom further assessment is warranted using neuroimaging or conventional clinical evaluation. Finally, by providing objective characterization of states of consciousness, repeated assessments of network metrics could help track individual patients longitudinally, and also assess their neural responses to therapeutic and pharmacological interventions.