Effects of Maintenance on Quality of Performance of Cryotherapy Devices for Treatment of Precancerous Cervical Lesions.

OBJECTIVE: The aim of the study was to evaluate the impact of maintenance on performance of cryosurgical equipment used in El Salvador primary health clinics. MATERIALS AND METHODS: Nine gynecological cryotherapy devices used in El Salvador were bench tested against a new machine of the same make and model. The devices were run for five successive double-freeze cycles. The El Salvador machines then received maintenance by a specialized engineer and another double-freeze cycle was performed. Temperature at the device probe tip was recorded throughout each cycle and ballistic gelatin was used as the tissue analogue to measure freeze ball dimensions achieved by the devices. Outcome measures were mean lowest-sustained temperatures and freeze ball mean weight, depth, and diameter. Paired and unpaired t tests were used to compare results premaintenance versus postmaintenance and postmaintenance versus the reference, respectively. RESULTS: Premaintenance versus postmaintenance freeze ball dimensions were significantly different (mean differences in weight = 2.31 g, p = .01; depth = 2.29 mm, p = .03; diameter = 3.51 mm, p = .02). However, postmaintenance dimensions were not significantly different than those of the reference (weight = 7.44 g vs. 8.39 g, p = .07; depth = 10.71 vs. 11.24 mm, p = .1; diameter = 31.38 mm vs. 32.05 mm, p = .3). Postmaintenance, minimum, and lowest-sustained temperatures were within the recommended clinical range. CONCLUSIONS: Specialized maintenance was necessary for heavily used cryotherapy devices to perform adequately, highlighting the challenges of gas-based cryotherapy in low- and middle-income countries.

IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic dysfunction in a mouse model of lupus-associated atherosclerosis.

Premature atherosclerosis is a severe complication of lupus and other systemic autoimmune disorders. Gain-of-function polymorphisms in IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing lupus, and IRF5 deficiency in lupus mouse models ameliorates disease. However, whether IRF5 deficiency also protects against atherosclerosis development in lupus is not known. In this study, we addressed this question using the gld.apoE(-/-) mouse model. IRF5 deficiency markedly reduced lupus disease severity. Unexpectedly, despite the reduction in systemic immune activation, IRF5-deficient mice developed increased atherosclerosis and also exhibited metabolic dysregulation characterized by hyperlipidemia, increased adiposity, and insulin resistance. Levels of the atheroprotective cytokine IL-10 were reduced in aortae of IRF5-deficient mice, and in vitro studies demonstrated that IRF5 is required for IL-10 production downstream of TLR7 and TLR9 signaling in multiple immune cell types. Chimera studies showed that IRF5 deficiency in bone marrow-derived cells prevents lupus development and contributes in part to the increased atherosclerosis. Notably, IRF5 deficiency in non-bone marrow-derived cells also contributes to the increased atherosclerosis through the generation of hyperlipidemia and increased adiposity. Together, our results reveal a protective role for IRF5 in lupus-associated atherosclerosis that is mediated through the effects of IRF5 in both immune and nonimmune cells. These findings have implications for the proposed targeting of IRF5 in the treatment of autoimmune disease as global IRF5 inhibition may exacerbate cardiovascular disease in these patients.

Family Medicine Resident Perceptions on Racial Justice Training in Residency: A CERA Study.

Introduction: Structural racism is a root cause of health disparities. While family medicine residency programs recognize the importance of addressing race in medicine, it is unclear how many programs have established racial justice training (RJT). This study examines residents' views on the current state of RJT in their respective programs. Methods: This survey was part of the Council of Academic Family Medicine Educational Research Alliance (CERA) 2021 national survey of family medicine residents. Questions addressed RJT, resident reported barriers to implementing such training, and recommendations for change. Results: Of the family medicine residents who responded (n=266), the majority of individuals (91.5%) and their residency programs (65.0%) stated that addressing racism in medicine is an educational priority. Residents reported a minority of their programs (17.3%) have a longitudinal curriculum. Residents who received RJT in residency are more likely to be in communities of color (P=.03). The top requests included recruiting faculty and residents of color, and establishing community-based partnerships. Conclusions: Few residencies have been able to implement RJT to the extent that residents' desire. Lack of curricular time and faculty training were commonly cited barriers. Strategies to address these barriers and implement RJT across residencies are needed to combat structural racism.

Modulation of lupus phenotype by adiponectin deficiency in autoimmune mouse models.

Adiponectin is an adipocyte-derived cytokine with anti-inflammatory properties. Paradoxically, circulating adiponectin levels are increased in a number of inflammatory diseases. Thus, we sought to define the role of adiponectin deficiency in mouse models of autoimmunity. Adiponectin-deficient mice on a C57BL/6 background do not develop an autoimmune phenotype. Autoimmunity was also not observed in adiponectin-deficient mice generated on the permissive MRL background. However, adiponectin deficiency exacerbated the autoimmune phenotype of MRL-lpr mice. Compared with MRL-lpr mice, MRL-lpr.apn(-/-) mice displayed greater lymphadenopathy and splenomegaly, as well as increased anti-nuclear antibody and anti-dsDNA production. In addition, evaluation of the kidney revealed larger glomerular tuft size, crescent formation, increased IgG and C3 deposits, and mesangial expansion in the MRL-lpr.apn(-/-) mice. The effects of adiponectin deficiency on the autoimmune phenotypes were more pronounced in female versus male mice. These data show that, while adiponectin deficiency is not sufficient to confer autoimmunity, adiponectin acts as a negative modulator of the autoimmune phenotype in a murine model of lupus.

A pilot study of community-based self-sampling for HPV testing among non-attenders of cervical cancer screening programs in El Salvador.

OBJECTIVE: To establish the feasibility and acceptability of home-based HPV self-sampling among women who did not attend screening appointments in rural El Salvador. METHODS: In a cross-sectional study, data were collected from May 2015 to January 2016 among 60 women aged 30-59 years who were not pregnant, provided informed consent, had not been screened in 2 years, had no history of pre-cancer treatment, and did not attend a scheduled HPV screening. Participants completed questionnaires and received educational information before being given an opportunity to self-sample with the Hybrid Capture 2 High Risk HPV DNA Test. RESULTS: Self-sampling was accepted by 41 (68%) participants. Almost all women chose to self-sample because the process was easy (40/41, 98%), could be performed at home (40/41, 98%), and saved time (38/41, 93%), and because they felt less embarrassed (33/41, 80%). The most common reason for declining the test was not wanting to be screened (8/19, 42%). The prevalence of high-risk HPV types among women who accepted self-sampling was 17% (7/41). CONCLUSION: For most women, community-based self-sampling was an acceptable way to participate in a cervical cancer screening program. In low-resource countries, incorporating community-based self-sampling into screening programs might improve coverage of high-risk women.

Interferon regulatory factor-5 deficiency ameliorates disease severity in the MRL/lpr mouse model of lupus in the absence of a mutation in DOCK2.

Interferon regulatory factor 5 (IRF5) polymorphisms are strongly associated with an increased risk of developing the autoimmune disease systemic lupus erythematosus. In mouse lupus models, IRF5-deficiency was shown to reduce disease severity consistent with an important role for IRF5 in disease pathogenesis. However these mouse studies were confounded by the recent demonstration that the IRF5 knockout mouse line contained a loss-of-function mutation in the dedicator of cytokinesis 2 (DOCK2) gene. As DOCK2 regulates lymphocyte trafficking and Toll-like receptor signaling, this raised the possibility that some of the protective effects attributed to IRF5 deficiency in the mouse lupus models may instead have been due to DOCK2 deficiency. We have therefore here evaluated the effect of IRF5-deficiency in the MRL/lpr mouse lupus model in the absence of the DOCK2 mutation. We find that IRF5-deficient (IRF5-/-) MRL/lpr mice develop much less severe disease than their IRF5-sufficient (IRF5+/+) littermates. Despite markedly lower serum levels of anti-nuclear autoantibodies and reduced total splenocyte and CD4+ T cell numbers, IRF5-/- MRL/lpr mice have similar numbers of all splenic B cell subsets compared to IRF5+/+ MRL/lpr mice, suggesting that IRF5 is not involved in B cell development up to the mature B cell stage. However, IRF5-/- MRL/lpr mice have greatly reduced numbers of spleen plasmablasts and bone marrow plasma cells. Serum levels of B lymphocyte stimulator (BLyS) were markedly elevated in the MRL/lpr mice but no effect of IRF5 on serum BLyS levels was seen. Overall our data demonstrate that IRF5 contributes to disease pathogenesis in the MRL/lpr lupus model and that this is due, at least in part, to the role of IRF5 in plasma cell formation. Our data also suggest that combined therapy targeting both IRF5 and BLyS might be a particularly effective therapeutic approach in lupus.