The transcription factor sex-determining region Y-box 2 (SOX2) in bladder cancer.

Sex-determining region Y-box 2 (SOX2) is a transcription factor with a central role in embryologic development. SOX2 is also an oncogene in several cancer types. Prior work by our group has shown SOX2 activity associates with cell cycle dysregulation in early-stage bladder cancer. The present study was thus undertaken to broadly investigate SOX2 in bladder cancer, with emphasis on associations with tumor stage, clinical outcomes, and tumorigenicity. Gene expression was quantified by immunohistochemistry in an established tissue microarray (n=303 cystectomy specimens, all stages) and whole tissue sections of noninvasive papillary urothelial carcinoma (n=25). Gene expression by RNA sequencing was evaluated in non-muscle invasive and muscle-invasive cohorts from publicly available repositories. By immunohistochemistry, SOX2 was expressed in 40% of whole tissue sections of noninvasive papillary carcinoma, which correlated with SOX2 expression by RNA sequencing (r=0.6, P=0.001, Spearman correlation). Expression tended to be focal (median H-score =6). SOX2 was expressed in only 9% of TMA cases, consistent with focal expression. SOX2 expression was substantially higher in muscle-invasive compared with noninvasive papillary urothelial carcinoma by RNA sequencing (P<0.001, Wilcoxon rank sum test). SOX2 expression associated with stage progression in lamina-propria invasive cancers (hazard ratio =2, P=0.05, Cox model, binary, RNA sequencing) but not noninvasive papillary cancers (P=0.5, Cox model, binary, RNA sequencing). SOX2 expression did not associate with overall survival in muscle-invasive carcinoma. Activity of SOX2 in bladder cancer was tested in vivo using murine allografts created with MB49 cells that express human SOX2 (MB49-SOX). MB49-SOX allografts expressed this protein focally by immunohistochemistry, much like human tumors. Compared with controls, MB49 allografts demonstrated larger tumor size (P=0.03, Wilcoxon rank sum test) and higher tumor burden in mesenteric metastases (P=0.009, Wilcoxon rank sum test). Though SOX2 expression is focal within tumors, it may drive tumorigenesis, increase growth rate, and promote aggressive features of bladder cancer, particularly stage progression of early-stage disease.

Severe Anemia in Sprague-Dawley Rats After Roux-en-Y Gastric Bypass Surgery.

Roux-en-Y gastric bypass (RYGB) surgery is one of the most commonly performed bariatric procedures for weight loss in humans. However, this procedure is not risk-free, and patients may experience complications that include small bowel obstruction, gastrointestinal bleeding, chronic diarrhea, ulcers, malnutrition, and anemia. In particular, anemia is a recognized long-term complication and can be severe. Rats have been used as a model to study the effects of gastric bypass surgeries. They can experience similar complications as people, but the development of severe anemia has not previously been reported in rats. We observed 2 cases of severe anemia in female Sprague-Dawley rats after RYGB surgery. These cases prompted us to further investigate the frequency and severity of anemia after RYGB in rats. Blood work and necropsies were performed on 9 additional female Sprague-Dawley rats (5 with RYGB, 4 with sham surgery). In these 9 rats, only one had signs of clinical anemia. These 3 anemic rats displayed moderate to severe pallor of the eyes and ears. Necropsy findings in anemic RYGB rats included pale internal organs and eccentric heart enlargement, which led to a significantly higher heart:body weight ratio in RYGB rats as compared with sham controls. Anemic rats had either a macrocytic normochromic anemia, consistent with vitamin B12 or folate deficiency, or microcytic hypochromic anemia, indicative of iron deficiency. Researchers who perform RYGB surgery in rats should be aware of the potential complication of severe anemia. Plans for the diagnosis and management of this complication and the development of criteria for humane endpoints for severe anemia are recommended as a refinement to these studies.

Left ventricular functional improvement appears to contribute to lower rates of device thrombosis in patients on durable mechanical circulatory support.

By unloading the failing heart, left ventricular (LV) assist devices (LVADs) provide a favorable environment for reversing adverse structural and functional cardiac changes. Prior reports have suggested that an improved native LV function might contribute to the development of LVAD thrombosis. We used the Interagency Registry for Mechanically Assisted Circulatory Support and found that LV functional improvement is associated with a lower risk for device thrombosis. The risk for cerebrovascular accident and transient ischemic attack was comparable across post-LVAD LV function subgroups, while the risk of hemolysis was lower in subgroups of patients with better LV function on LVAD support.

A Health Equity Lens Contributes to an Effective Pandemic Response: A Canadian Regional Perspective.

As cases of COVID-19 began to increase in Ontario, Canada, throughout 2020, early evidence from surveillance and media highlighted disproportionately higher rates of COVID-19 infection, hospitalization and mortality among racialized and low-income populations. This disproportionate impact on underserved populations calls for a shift in approach away from what has traditionally occurred in health protection, that is the use of a universal approach which assumes everyone is affected and benefits equally from the same type and intensity of interventions. In this article, public health agencies are, therefore, being called to consider moving away from using a purely universal approach, often used in the control of communicable diseases, and apply a more tailored approach and use principles of health equity and proportionate universalism to reduce COVID-19 cases and their impacts among underserved groups and address health inequities exacerbated by the pandemic. We highlight examples from York Region Public Health, one of the largest health units in Ontario, to demonstrate areas of possible impact of this paradigm shift. It is clear that with a health equity lens applied to the pandemic response, the impact of COVID-19 can be further reduced and health inequities that predated the global pandemic can improve.

Identification of a Hypomorphic FANCG Variant in Bernese Mountain Dogs.

Bernese mountain dogs (BMDs), have an overall cancer incidence of 50%, half of which is comprised of an otherwise rare tumor, histiocytic sarcoma (HS). While recent studies have identified driver mutations in the MAPK pathway, identification of key predisposing genes has been elusive. Studies have identified several loci to be associated with predisposition to HS in BMDs, including near the MTAP/CDKN2A region, but no causative coding variant has been identified. Here we report the presence of a coding polymorphism in the gene encoding FANCG, near the MTAP/CDKN2A locus. This variant is in a conserved region of the protein and appears to be specific to BMDs. Canine fibroblasts derived from dogs homozygous for this variant are hypersensitive to cisplatin. We show this canine FANCG variant and a previously defined hypomorphic FANCG allele in humans impart similar defects in DNA repair. However, our data also indicate that this variant is neither necessary nor sufficient for the development of HS. Furthermore, BMDs homozygous for this FANCG allele display none of the characteristic phenotypes associated with Fanconi anemia (FA) such as anemia, short stature, infertility, or an earlier age of onset for HS. This is similar to findings in FA deficient mice, which do not develop overt FA without secondary genetic mutations that exacerbate the FA deficit. In sum, our data suggest that dogs with deficits in the FA pathway are, like mice, innately resistant to the development of FA.

How Food Insecurity and Financial Difficulty Relate to Emotional Well-Being and Social Functioning.

OBJECTIVES: Medically uninsured individuals living in poverty experience poor health and face social barriers that negatively affect their health. The purpose of this study was to examine the association between social barriers, particularly healthy food availability and financial difficulty, and well-being among uninsured free clinic patients in the United States. METHODS: Data were collected using a self-administered paper survey at a free clinic from adult patients who spoke and read English or Spanish (N = 666) from January to April 2019. RESULTS: Better neighborhood healthy food availability is associated with better self-reported general health. Food security is related to better emotional well-being and social functioning. Having difficulty paying rent or a mortgage is linked to worse emotional well-being and social functioning. CONCLUSIONS: Providing health education programs may not be sufficient to promote healthy eating among underserved populations because of the social barriers that they experience, such as food insecurity and financial difficulty. Future research could be performed to determine how these social factors influence those of different social and cultural backgrounds than the participants in this study.

The Effects of Ketamine on the Gut Microbiome on CD1 Mice.

The intestinal microbiota of an organism can significantly alter outcome data in otherwise identical experiments. Occasionally, animals may require sedation or anesthesia for scientific or health-related purposes, and certain anesthetics, such as ketamine, can profoundly affect the gastrointestinal system. While many factors can alter the gut microbiome (GM), the effects of anesthetics on the composition or diversity of the GM have not been established. The goal of the current study was to determine whether daily administration of ketamine would significantly alter the microbiome of CD1 mice. To achieve this goal, female CD1 mice received daily injections of ketamine HCl (100 mg/kg) or the equivalent volume of 0.9% saline for 10 consecutive days. Fecal samples were collected before the first administration and 24 h after the final dose of either ketamine or saline. Samples were analyzed by 16S rRNA sequencing to identify changes between groups in diversity or composition of GM. The study found no significant changes to the GM after serial ketamine administration when treated mice were housed with controls. Therefore, ketamine administration is unlikely to alter the GM of a CD1 mouse and should not serve be a confounding factor in reproducibility of research.

Patients' Perspectives on Psychiatric Pharmacogenetic Testing.

INTRODUCTION: There is growing interest to adopt pharmacogenetic (PGx) testing in psychiatric medicine, despite mixed views regarding its clinical utility. Nevertheless, providers are utilizing PGx testing among patients with mental health disorders. This study sought to assess genotyped patients' perspectives and experiences with psychiatric PGx testing. METHODS: Individual semi-structured interviews were conducted among patients with depression who had undergone psychiatric PGx testing. The audio-recorded interviews were transcribed and analyzed inductively and deductively for salient themes. RESULTS: Twenty patients (100% Caucasian, 60% female, mean age 39±18 years) were interviewed. The majority of the PGx tests were provider-initiated for patients who failed multiple pharmacotherapies (50%) and/or had medication intolerances (45%). Patients' pre-testing expectations ranged from hopefulness to indifference to skepticism. Their post-testing experiences varied from optimism to disappointment, with the perceived value of the test influenced by the results and cost of the test. DISCUSSION: Genotyped patients had mixed perspectives, expectations, and experiences with psychiatric PGx testing. Their perceived value of the test was influenced by the test outcomes and its cost.

Therapeutic groups via video teleconferencing and the impact on group cohesion.

BACKGROUND: The use of synchronous telemental health for therapy group is a relatively new area of exploration. While telegroups have demonstrated they can be helpful in providing psychoeducation, there is less known about whether synchronous remote groups can develop group cohesion and whether patients can receive the benefit of a supportive group setting. METHODS: A pilot study was conducted comparing group cohesion between patients who participated in a dialectical behavior therapy (DBT) group via video teleconferencing (VTC) and patients who participated in an in-person group. RESULTS: Findings indicate that while both groups felt equally connected to the facilitator, there were significant differences between the online and in-person groups on the group cohesion scale. Those in the online group did not feel as connected to other group members as those in the in-person group. Qualitative statements indicate that while an in-person group may have been preferable, the convenience of the online group outweighed any negative effects. Attendance was significantly better in the online group, suggesting that use of this technology may help to overcome barriers preventing treatment participation. The focus of this study was on group cohesion and changes in psychiatric symptoms were not evaluated. CONCLUSIONS: The use of telemental health for group therapy appears to be a viable alternative to traditional in-person groups, especially when no other treatment options are available. However, facilitators may need to take extra steps to build group cohesion when members are participating remotely.

Technology-Based Mental Health Treatment and the Impact on the Therapeutic Alliance.

PURPOSE OF REVIEW: Telemental health, which is treatment mediated by technology, is an increasingly common method of delivering mental health care. However, its impact on the therapeutic alliance is unclear. This review examines studies of telemental health and its impact on therapeutic alliance. RECENT FINDINGS: Findings indicate that a therapeutic alliance can be maintained through a variety of communication technologies, with some caveats. Considerations on maintaining a successful therapeutic alliance include using technology as an adjunct to treatment and ensuring patients and providers have back-up plans for continuing communication in the event of technical difficulties. Overall, the studies found that clinicians often have more concerns about alliance than patients do, suggesting that clinicians could make some changes to feel more comfortable. Recommendations are offered for implementing techniques into practice that will help clinicians increase their awareness of ways to support the therapeutic alliance when using telemental health.

The disgrace of commodification and shameful convenience: a critical race critique of the NBA.

This essay positions sport as a pedagogical social institution from which people learn about race, gender, power, and privilege. The National Basketball Association is examined closely with a critical race lens with regard to the commodification of Black masculinity. A critical race analysis reveals the sharp contradictions between the league's progressive image as an "industry leader" of racial diversity (Lapchick, Bustamante, & Ruiz, 2007, p.1) and the actualization of league discourse, policy, and practice.