“Horror, guilt and shame” – Uncomfortable Experiences in Digital Games

Gameplay frequently involves a combination of positive and negative emotions, where there is increasing interest in how to design for more complex forms of player experience. However, despite the risk that some of these experiences may be uncomfortable, there has been little empirical investigation into how discomfort manifests during play and its impact on engagement. We conducted a qualitative investigation using an online survey (N=95), that focused on uncomfortable interactions across three games: Darkest Dungeon, Fallout 4 and Papers, Please. The findings suggest games create discomfort in a variety of ways; through providing high-pressure environments with uncertain outcomes and difficult decisions to make, to the experience of loss and exposing players to disturbing themes. However, while excessive discomfort can jeopardize player engagement, the findings also indicate that discomfort can provide another facet to gameplay, leading to richer forms of experience and stimulating wider reflections on societal issues and concerns

Community-led initiatives bridging the gap to provide linguistically and culturally tailored health and social services in Parc-Extension, Montréal

Background: Parc-Extension (PE) has the greatest immigrant population in Montréal. PE had a lower proportion of vaccinations compared to the rest of Montreal (19.9% vs 30.8%), during Québec’s first rollout of COVID-19 vaccines. By August 2021 PE’s proportion of first dose vaccinations surpassed Montreal’s (77.9% vs 74%). This is attributable to building vaccine acceptance through community-led strategies that addressed social determinants of health (SDOH) impacting immigrant and asylum seeker communities. Objective: To examine the perspectives of PE residents around how SDOH influence their access to health and social services, including COVID-19 vaccines. Methods: We conducted semi-structured interviews with PE residents to explore which SDOH contributed to the accessibility to health and social services during all waves of the pandemic to date. The interviews were recorded and transcribed using Otter.ai and HappyScribe for English and French transcripts, respectively. We performed thematic content analysis. Coding was done by three co-authors and discrepancies were resolved during analysis meetings with all study authors. Results: We conducted 47 interviews (French: 27, English: 17, Urdu: 3) between June and October 2022. Three themes were identified: inadequate governmental support for immigrants and asylum seekers exacerbate SDOH; language barriers influence care; and inaccessibility to healthcare providers creates a “clinical desert”. Discussion: Due to inadequate support at the governmental level, there is an unjust burden placed on PE community organizations to ensure that PE residents are receiving appropriate care. Improving access to services amongst immigrant groups requires consideration of SDOH and fostering trusting partnerships between governments and community organizations.

Rural and urban differences in quality of dementia care of persons with dementia and caregivers across all domains: a systematic review

Abstract Background There are challenges in healthcare service delivery in rural areas, and this may be especially true for persons with dementia, who have higher needs to access to the healthcare system, and may have difficulties to commute easily and safely to these services. There is a growing body of literature regarding geographical disparities, but there is no comprehensive systematic review of geographical differences in persons with dementia across all domains of care quality. Therefore, the objective of this study is to conduct a systematic review of the literature on rural and urban differences in quality of dementia care outcomes of persons with dementia across all quality-of-care domains. Methods We performed a digital search in Ovid MEDLINE on July 16, 2019, updated on May 3, 2021, for French or English records. We selected studies that reported outcome from at least one domain of quality of dementia care (Access, Integration, Effective Care, Efficient Care, Population Health, Safety, and Patient-Centered) in both rural and urban persons with dementia or caregivers. We used rigorous, systematic methods for screening, selection, data extraction and we analyzed outcomes reported by at least two studies using vote counting and appraised the certainty of evidence. Finally, we explored sources of heterogeneity. Results From the 38 included studies, we found differences in many dementia care domains. Rural persons with dementia had higher mortality rates (Population Health), lower visits to any physicians (Access), more hospitalizations but shorter stays (Integration), higher antipsychotic medications (Safety), lower use of home care services and higher use of nursing home (Patient-Centered Care) compared to urban persons with dementia. Conclusions This comprehensive portrait of rural–urban differences in dementia care highlights possible geographically based inequities and can be used by researchers and decision makers to guide development of more equitable dementia care policies

Accuracy of mammographic and sonographic assessment of preoperative breast cancer size

Evaluation of breast cancer size is important for preoperative surgical planning and determining response to neoadjuvant chemotherapy. Due to the limitations of clinical breast examination, imaging assessment of tumor size is important. The purpose of this study is to compare preoperative breast cancer size as determined by mammography and sonography and correlate to pathologic size. In 117 invasive breast cancers, tumor size was measured mammographically and sonographically prior to surgery and correlated with postexcisional pathologic measurement by regression linear analysis. The tumor histologic type was considered in the correlations. Mammographic (r = 0.8585) and sonographic (r = 0.8701) measurements of tumor size correlated well with pathologic size. The correlation persisted when evaluating the differing histopathologic types of breast cancer and was greater for infiltrating lobular carcinoma than infiltrating ductal carcinoma. Both mammography and sonography can accurately measure tumor size preoperatively, regardless of breast cancer histopathology

Simvastatin Reduces Protection and Intestinal T Cell Responses Induced by a Norovirus P Particle Vaccine in Gnotobiotic Pigs

Noroviruses (NoVs) are a leading cause of acute gastroenteritis worldwide. P particles are a potential vaccine candidate against NoV. Simvastatin is a cholesterol-reducing drug that is known to increase NoV infectivity. In this study, we examined simvastatin’s effects on P particle-induced protective efficacy and T-cell immunogenicity using the gnotobiotic pig model of human NoV infection and diarrhea. Pigs were intranasally inoculated with three doses (100 µg/dose) of GII.4/VA387-derived P particles together with monophosphoryl lipid A and chitosan adjuvants. Simvastatin-fed pigs received 8 mg/day orally for 11 days prior to challenge. A subset of pigs was orally challenged with 10 ID50 of a NoV GII.4/2006b variant at post-inoculation day (PID) 28 and monitored for 7 days post-challenge. Intestinal and systemic T cell responses were determined pre- and postchallenge. Simvastatin abolished the P particle’s protection and significantly increased diarrhea severity after NoV infection. Simvastatin decreased proliferation of virus-specific and non-specific CD8 T cells in duodenum and virus-specific CD4 and CD8 T cells in spleen and significantly reduced numbers of intestinal mononuclear cells in vaccinated pigs. Furthermore, simvastatin significantly decreased numbers of duodenal CD4+IFN-γ+, CD8+IFN-γ+ and regulatory T cells and total duodenal activated CD4+ and CD8+ T cells in vaccinated pigs pre-challenge at PID 28. Following challenge, simvastatin prevented the IFN-γ+ T cell response in spleen of vaccinated pigs. These results indicate that simvastatin abolished P particle vaccine-induced partial protection through, at least in part, impairing T cell immunity. The findings have specific implications for the development of preventive and therapeutic strategies against NoV gastroenteritis, especially for the elderly population who takes statin-type drugs

Probiotic Lactobacillus rhamnosus GG enhanced Th1 cellular immunity but did not affect antibody responses in a human gut microbiota transplanted neonatal gnotobiotic pig model.

This study aims to establish a human gut microbiota (HGM) transplanted gnotobiotic (Gn) pig model of human rotavirus (HRV) infection and diarrhea, and to verify the dose-effects of probiotics on HRV vaccine-induced immune responses. Our previous studies using the Gn pig model found that probiotics dose-dependently regulated both T cell and B cell immune responses induced by rotavirus vaccines. We generated the HGM transplanted neonatal Gn pigs through daily feeding of neonatal human fecal suspension to germ-free pigs for 3 days starting at 12 hours after birth. We found that attenuated HRV (AttHRV) vaccination conferred similar overall protection against rotavirus diarrhea and virus shedding in Gn pigs and HGM transplanted Gn pigs. HGM promoted the development of the neonatal immune system, as evidenced by the significantly enhanced IFN-γ producing T cell responses and reduction of regulatory T cells and their cytokine production in the AttHRV-vaccinated pigs. The higher dose Lactobacillus rhamnosus GG (LGG) feeding (14 doses, up to 109 colony-forming-unit [CFU]/dose) effectively increased the LGG counts in the HGM Gn pig intestinal contents and significantly enhanced HRV-specific IFN-γ producing T cell responses to the AttHRV vaccine. Lower dose LGG (9 doses, up to 106 CFU/dose) was ineffective. Neither doses of LGG significantly improved the protection rate, HRV-specific IgA and IgG antibody titers in serum, or IgA antibody titers in intestinal contents compared to the AttHRV vaccine alone, suggesting that an even higher dose of LGG is needed to overcome the influence of the microbiota to achieve the immunostimulatory effect in the HGM pigs. This study demonstrated that HGM Gn pig is an applicable animal model for studying immune responses to rotavirus vaccines and can be used for studying interventions (i.e., probiotics and prebiotics) that may enhance the immunogenicity and protective efficacy of vaccines through improving the gut microbiota

Probiotic as Adjuvant Significantly Improves Protection of the Lanzhou Trivalent Rotavirus Vaccine against Heterologous Challenge in a Gnotobiotic Pig Model of Human Rotavirus Infection and Disease

This preclinical study in the gnotobiotic (Gn) pig model of human rotavirus (HRV) infection and disease evaluates the effect of probiotic Lactobacillus rhamnosus GG (LGG) as a mucosal adjuvant on the immunogenicity and cross-protective efficacy of the Lanzhou live oral trivalent (G2, G3, G4) vaccine (TLV, aka LLR3). Gn pigs were immunized with three doses of TLV with or without concurrent administration of nine doses of LGG around the time of the first dose of the TLV vaccination, and were challenged orally with the virulent heterotypic Wa G1P[8] HRV. Three doses of TLV were highly immunogenic and conferred partial protection against the heterotypic HRV infection. LGG significantly enhanced the intestinal and systemic immune responses and improved the effectiveness of protection against the heterotypic HRV challenge-induced diarrhea and virus shedding. In conclusion, we demonstrated the immune-stimulating effects of probiotic LGG as a vaccine adjuvant and generated detailed knowledge regarding the cross-reactive and type-specific antibody and effector B and T cell immune responses induced by the TLV. Due to the low cost, ease of distribution and administration, and favorable safety profiles, LGG as an adjuvant has the potential to play a critical role in improving rotavirus vaccine efficacy and making the vaccines more cost-effective