Unexpected brain lesions in lactating Sprague-Dawley rats in a Two-generation Inhalation Reproductive Toxicity Study with pentafluoropropane (HFC-245fa)

The study presented was conducted following the reproductive study guideline OECD Guideline 416 Two-Generation Reproduction Toxicity Study. Sprague-Dawley rats were exposed to 2000, 10,000 and 50,000 ppm of HFC-245fa. There was an unexpected mortality of lactating dams in the medium and high dose group beginning at day 10 of lactation. Statistically significant histopathological alterations were observed in the cerebellum of a total of 9/30 females of the high dose group of the F₀-generation and in 10/27 females of the high dose group of the F₁-generation. In contrast there were no brain lesions found in males or non-pregnant females of all dose groups. Neuronal necrosis and degeneration in the cerebellar cortex were observed as the most severe finding. Furthermore vacuolation of the neuropil in different degrees was diagnosed in 7/30 females of the F₀-generation and in 9/30 females of the F₁-generation. Acute hemorrhages – in particular perivascular – occurred in 5/30 females of the F₀- and in 5/30 females of the F1-generation indicating a disturbed vascular integrity. The main lesions found in the cerebrum were glial scars in the corpus callosum and restricted to 2/30 females of the F₀-generation of the high dose group. The increased incidence of myocardial fibrosis and mononuclear cell infiltration in males – indicating myocarditis – was only seen in the F₀-generation of the high dose group. Females of the F₁-generation of the high dose group showed an increased incidence of minimal myocardial fibrosis. In summary, histopathology revealed that the brain, particularly the cerebellum, and to a minor degree the heart turned out to be the toxicological target organs of the substance. Presumably substance-related energy deprivation may be responsible for the observed changes. One of the metabolites, 3,3,3-trifluoropropanoic acid has been shown to be capable of causing this effect.     

Feeding of a well‐cooked beef diet containing a high heterocyclic amine content enhances colon and stomach carcinogenesis in 1,2‐dimethylhydrazine‐treated rats

Epidemiologic studies have linked the consumption of red meat and the consumption of highly browned meats containing high levels of heterocyclic aromatic amines (HCAs) to increased risk of colorectal cancer or polyps. The present study determined the effects of long‐term feeding of beef‐containing diets with low and high levels of HCAs (in the context of a low or high beef tallow diet) on a standard 1,2‐dimethylhydrazine (DMH)‐induced colon tumorigenesis protocol. Very lean beef was cooked by a variety of methods at different temperatures, and the levels of the major HCAs (2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline, 2‐amino‐3,4,8‐trimethylimidazo[4,5‐f]quinoxaline, and 2‐amino‐l‐methyl‐6‐phenylimidazo[4,5‐f]pyridine) were measured by high‐performance liquid chromatogra‐phy. Diets incorporating beef containing low or high levels of HCAs were fed for 12 weeks, during which DMH was administered to induce colon tumors, followed by various dietary regimens as promotional stimuli. Feeding of a beef diet high in HCAs resulted in more DMH‐induced colon adenocarcinomas, but only in the context of a low‐fat diet. The high‐HCA diets increased stomach tumors in all DMH‐treated rats. An apparent interaction of high HCA with a high fat level reduced the colon tumor incidence and tumor numbers in those diets containing both factors. These results support the epidemiologic data linking well‐cooked meat to increased risk for colon and stomach cancer, but the role of dietary fat level remains puzzling.     

The contribution of self‐help/mutual aid groups to mental well‐being

This article explores the contribution of self‐help/mutual aid groups to mental well‐being. Self‐help/mutual aid groups are self‐organising groups where people come together to address a shared a health or social issue through mutual support. They are associated with a range of health and social benefits, but remain poorly understood. This article draws on data from stage one of ESTEEM, a project which runs from 2010 to 2013. Stage one ran from 2010 to 2011 and involved participatory, qualitative research carried out in two UK sites. Twenty‐one groups were purposively selected to include a range of focal issues, longevity, structures and ethnic backgrounds. Researchers carried out 21 interviews with group coordinators and twenty group discussions with members to explore the groups' purpose, nature and development. Preliminary analysis of the data suggested that mental well‐being was a common theme across the groups. Subsequently the data were re‐analysed to explore the groups' contribution to mental well‐being using a checklist of protective factors for mental well‐being as a coding framework. The findings showed that groups made a strong contribution to members' mental well‐being by enhancing a sense of control, increasing resilience and facilitating participation. Group members were uplifted by exchanging emotional and practical support; they gained self‐esteem, knowledge and confidence, thereby increasing their control over their situation. For some groups, socio‐economic factors limited their scope and threatened their future. The article provides an evidence‐base which illustrates how self‐help/mutual aid groups can enhance mental well‐being. If supported within a strategy for social justice, these groups enable people with varied concerns to develop a tailored response to their specific needs. The authors suggest that policy‐makers engage with local people, investing in support proportionate to the needs of different populations, enabling them to develop their own self‐help/mutual aid groups to enhance their sense of mental well‐being.     

Addressing Oncofertility Needs: Views of Female Cancer Patients in Fertility Preservation

A total of 41 questionnaires were returned from 64 respondents who consented to receive a questionnaire through the mail. Almost all valued the opportunity to receive consultation to address their fertility concerns and discuss fertility preservation options. Psychological stress, time pressure, and costs were identified as main factors affecting respondents’ decision to proceed with in-vitro fertilization to cryopreserve oocytes or embryos. About one third indicated that the discussion of fertility matters was initiated by themselves, their friends, and families rather than their health care providers. The findings have identified several major barriers encountered by female cancer patients when seeking fertility preservation services.     

Evidence-Based Strategies for Clinical Organizations to Address COVID-19 Vaccine Hesitancy

The success of vaccination programs is contingent upon irrefutable scientific safety data combined with high rates of public acceptance and population coverage. Vaccine hesitancy, characterized by lack of confidence in vaccination and/or complacency about vaccination that may lead to delay or refusal of vaccination despite the availability of services, threatens to undermine the success of coronavirus disease 2019 (COVID-19) vaccination programs. The rapid pace of vaccine development, misinformation in popular and social media, the polarized sociopolitical environment, and the inherent complexities of large-scale vaccination efforts may undermine vaccination confidence and increase complacency about COVID-19 vaccination. Although the experience of recent lethal surges of COVID-19 infections has underscored the value of COVID-19 vaccines, ensuring population uptake of COVID-19 vaccination will require application of multilevel, evidence-based strategies to influence behavior change and address vaccine hesitancy. Recent survey research evaluating public attitudes in the United States toward the COVID-19 vaccine reveals substantial vaccine hesitancy. Building upon efforts at the policy and community level to ensure population access to COVID-19 vaccination, a strong health care system response is critical to address vaccine hesitancy. Drawing on the evidence base in social, behavioral, communication, and implementation science, we review, summarize, and encourage use of interpersonal, individual-level, and organizational interventions within clinical organizations to address this critical gap and improve population adoption of COVID-19 vaccination.