Search

Background: Most adults with sickle cell disease will experience a silent cerebral infarction (SCI) or overt stroke. Identifying patient subgroups with increased stroke incidence is important for future clinical trials focused on stroke prevention. Our 3-center prospective cohort study tested the primary hypothesis that adults with sickle cell disease and SCIs have a greater incidence of new stroke or SCI compared with those without SCI. A secondary aim focused on identifying additional risk factors for progressive infarcts, particularly traditional risk factors for stroke in adults., Methods and Results: This observational study included adults with sickle cell disease and no history of stroke. Magnetic resonance imaging scans of the brain completed at baseline and >1 year later were reviewed by 3 radiologists for baseline SCIs and new or progressive infarcts on follow-up magnetic resonance imaging. Stroke risk factors were abstracted from the medical chart. Time-to-event analysis was utilized for progressive infarcts. Median age was 24.1 years; 45.3% of 95 participants had SCIs on baseline magnetic resonance imaging. Progressive infarcts were present in 17 participants (17.9%), and the median follow-up was 2.1 years. Incidence of new infarcts was 11.95 per 100 patient-years (6.17-20.88) versus 3.74 per 100 patient-years (1.21-8.73) in those with versus without prior SCI. Multivariable Cox regression showed that baseline SCI predicts progressive infarcts (hazard ratio, 3.46 [95% CI, 1.05-11.39]; P =0.041); baseline hypertension was also associated with progressive infarcts (hazard ratio, 3.23 [95% CI, 1.16-9.51]; P =0.025)., Conclusions: Selecting individuals with SCIs and hypertension for stroke prevention trials in sickle cell disease may enrich the study population with those at highest risk for infarct recurrence.

Objectives: To increase diversity and inclusion in graduate medical education (GME), the Accreditation Council for Graduate Medical Education (ACGME) issued new diversity standards requiring programs to engage in practices that focus on systematic recruitment and retention of a diverse workforce of trainees and faculty. The literature on how program directors (PDs) can incorporate and prepare for this standard is limited., Methods: We developed a diversity, equity, and inclusion (DEI) toolkit for PDs as an example of an institutional GME-led effort to promote inclusive recruitment and DEI awareness among residency and fellowship programs at a large academic center., Results: A survey was sent to 80 PDs before the launch of the toolkit and 6 months afterwards with response rates of 27% (22/80) and 97% (78/80), respectively. At baseline, 45% (10/22) anticipated that the DEI toolkit might provide better resources than those currently available to them and 41% (9/22) perceived that the toolkit might improve recruitment outcomes. At 6 months, 63% (49/78) found the toolkit helpful in the 2021-2022 recruitment season. By contrast, 2% (2/78) of PDs did not find the toolkit helpful, and 33% (26/78) said they did not access the toolkit. When asked if a PD changed their program's recruitment practices because of the toolkit, 31% (24/78) responded yes. Programs that changed recruitment practices started to require unconscious bias training for all faculty and residents involved in the residency interviews and ranking. Others worked on creating a standardized scoring rubric for interviews focused on four main domains: Experiences, Attributes, Competencies, and Academic Metrics., Conclusion: There is a need to support PDs in their DEI journey and their work to recruit a diverse workforce in medicine. Utilizing a DEI toolkit is one option to increase DEI knowledge, skills, awareness, and self-efficacy among PDs and can be adopted by other institutions and leaders in academic medicine., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Sexual trauma is common. Consequences of sexual trauma can include deterioration of mental and physical health and it can also affect future romantic and sexual relationships. Previous studies have identified common healthy and destructive coping mechanisms to recover after experiencing sexual trauma, but few studies have investigated useful strategies to move into a healthy sexual relationship focused on resilience. In-depth semi-structured interviews were conducted with 41 women with a history of sexual trauma who were in a healthy sexual relationship at the time of participation. Participants provided strategies that helped them move beyond the sexually traumatic event(s) toward a healthy sexual relationship. Reflexive thematic analysis identified 5 effective and 6 ineffective strategies reported by the participants. Rich examples of resilience and empowerment were overarching in the effective strategies used for moving toward healthy sexual relationships. Women were also able to reflect on the strategies that were ineffective for them with kindness and understanding for their coping at that time, a normalizing theme for women working through sexual trauma. The results of this study will help therapists and researchers working with women who have experienced sexual trauma learn from their experiences in working beyond trauma toward a healthy sexual relationship., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mark et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Noroviruses are highly diverse viruses that are the major viral cause of acute gastroenteritis in humans. Although these viruses can infect multiple mammalian species, their potential for zoonosis is not well understood, especially within Genogroup IV (GIV), which contains viruses that infect humans, canines, and felines. The study of GIV viruses has been, in part, hindered by the limited number of complete genomes. Here, we developed a full-genome amplicon-based platform that facilitated the sequencing of canine noroviruses circulating in the United States. Eight novel nearly full-length canine norovirus genomes and two nearly complete VP1 sequences, including four GIV.2, three GVI.1, and three GVI.2 viruses, were successfully obtained. Only animal strains exhibited GVI/GIV chimeric viruses, demonstrating restrictions in norovirus recombination. Using genomic, phylogenetic, and structural analyses, we show that differences within the major capsid protein and the non-structural proteins of GIV and GVI noroviruses could potentially limit cross-species transmission between humans, canines, and felines.

Gastroenteritis caused by bacterial and viral pathogens constitutes a major public health threat in the United States accounting for 35% of hospitalizations. In particular, Salmonella enterica and noroviruses cause the majority of gastroenteritis infections, with emergence of sporadic outbreaks and incidence of increased infections. Although mechanisms underlying infections by these pathogens have been individually studied, little is known about the mechanisms regulating co-infection by these pathogens. In this study, we utilized RAW 264.7 murine macrophage cells to investigate the mechanisms governing co-infection with S. enterica serovar Heidelberg and murine norovirus (MNV). We demonstrate that infection of RAW 264.7 cells with S. enterica reduces the replication of MNV, in part by blocking virus entry early in the virus life cycle, and inducing antiviral cytokines later in the infection cycle. In particular, bacterial infection prior to, or during MNV infection affected virus entry, whereas MNV entry remained unaltered when the virus infection preceded bacterial invasion. This block in virus entry resulted in reduced virus replication, with the highest impact on replication observed during conditions of co-infection. In contrast, bacterial replication showed a threefold increase in MNV-infected cells, despite the presence of antibiotic in the medium. Most importantly, we present evidence that the infection of MNV-infected macrophages by S. enterica blocked MNV-induced apoptosis, despite allowing efficient virus replication. This apoptosis blockade was evidenced by reduction in DNA fragmentation and absence of poly-ADP ribose polymerase (PARP), caspase 3 and caspase 9 cleavage events. Our study suggests a novel mechanism of pathogenesis whereby initial co-infection with these pathogens could result in prolonged infection by either of these pathogens or both together.

Simian varicella virus (SVV) causes a natural varicella-like disease in nonhuman primates. Outbreaks of simian varicella occur sporadically in primate facilities. Simian varicella is used as a model for investigation of varicella-zoster virus (VZV) pathogenesis and latency. In this study, SVV gene expression and histopathology were analysed in tissues of acutely infected vervet monkeys. RT-PCR analysis demonstrated expression of specific SVV immediate early, early and late genes in the skin, lung, liver and ganglia tissues of acutely infected monkeys. Viral antigen expression and histopathology, including necrosis and inflammation, were detected in the skin, lungs, liver and spleen of infected monkeys by immunohistochemical analysis. Viral antigen expression, but little or no histopathology, was evident in the neural ganglia, the eventual site of viral latency. The study provides a foundation for further investigation on the role of viral genes in varicella pathogenesis and latency.