ObjectiveIn diabetes, vascular dysfunction is characterized by impaired endothelial function due to increased oxidative stress. Empagliflozin, as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), offers a novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with empagliflozin improves endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated vascular oxidative stress.MethodsType I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection empagliflozin (10 and 30 mg/kg/d) was administered via drinking water for 7 weeks. Vascular function was assessed by isometric tension recording, oxidative stress parameters by chemiluminescence and fluorescence techniques, protein expression by Western blot, mRNA expression by RT-PCR, and islet function by insulin ELISA in serum and immunohistochemical staining of pancreatic tissue. Advanced glycation end products (AGE) signaling was assessed by dot blot analysis and mRNA expression of the AGE-receptor (RAGE).ResultsTreatment with empagliflozin reduced blood glucose levels, normalized endothelial function (aortic rings) and reduced oxidative stress in aortic vessels (dihydroethidium staining) and in blood (phorbol ester/zymosan A-stimulated chemiluminescence) of diabetic rats. Additionally, the pro-inflammatory phenotype and glucotoxicity (AGE/RAGE signaling) in diabetic animals was reversed by SGLT2i therapy.ConclusionsEmpagliflozin improves hyperglycemia and prevents the development of endothelial dysfunction, reduces oxidative stress and improves the metabolic situation in type 1 diabetic rats. These preclinical observations illustrate the therapeutic potential of this new class of antidiabetic drugs.
Background The success of any COVID-19 vaccine program ultimately depends on high vaccine uptake. This study determined overall intention to receive a COVID-19 vaccine and identified factors that predict intentions to be vaccinated against COVID-19 in Canada, specifically in key priority groups identified by the American Committee on Immunization Practice (ACIP) and the National Advisory Committee on Immunization (NACI) for early immunization. Methods Individuals from research cohorts from the general population of British Columbia aged 25–69 were invited complete an online survey based on validated scales and theoretical frameworks to explore intention to receive a COVID-19 vaccine. Two multivariable logistic regression models were conducted to determine factors associated with intention to receive the COVID-19 vaccine. Results Of 4948 respondents, 79.8% intended to receive a COVID-19 vaccine. In multivariable modeling, respondents who intended to receive the vaccine had higher vaccine attitudinal scores (p < 0.001), reported greater influence of direct social norms (p = 0.001), and indirect social norms, including their family physician (p = 0.024), and Provincial Health Officer (p = 0.011). Older individuals (> 60 years) were more likely to intend to receive the vaccine, while females (95%CI 0.57,0.93), those with less than high school education (95%CI 0.5,0.76), those who self-identified as non-white (95%CI 0.60,0.92), self-identified as Indigenous (95%CI 0.36,0.84) and essential non-health care workers (95%CI 0.59,0.86) had lower adjusted odds of intending to receive a COVID-19 vaccine. Conclusions To optimize vaccine coverage, public health should focus on key messages around vaccine safety and benefit, and leverage trusted practitioners for messaging. As certain key populations identified by NACI and ACIP for early immunization report a lower intention to vaccinate, there is a need for in-depth education and support for these communities to ensure optimal uptake.
PurposeCervical cancer rates in Latin America are higher than those in developed countries, likely because of the lower prevalence of screening. Specifically, less than 40% of women in Guatemala are regularly screened and even fewer women are screened in indigenous communities. Current screening strategies—Pap smears and visual inspection with acetic acid—might not be the most effective methods for controlling cancer in these settings. We thus investigated the potential of self-collection of cervical samples with testing for human papillomavirus (HPV) to help prevent cervical cancer in an indigenous community in Guatemala.Patients and MethodsA community representative random sample of 202 indigenous women age 18 to 60 years residing in Santiago Atitlan, Guatemala, were surveyed to assess knowledge of and risk factors for HPV and cervical cancer. Women were then invited to self-collect a cervical sample using HerSwab collection kits to assess the prevalence of HPV and the acceptability of self-sampling.ResultsOf 202 women who completed the survey, 178 (89%) provided a self-sample. In all, 79% of these women found the test comfortable, 91% found the test easy to use, and 100% reported they were willing to perform the test periodically as a screening method. Thirty-one samples (17%) were positive for at least one of 13 high-risk HPV types, and eight (4.5%) were positive for HPV 16/18.ConclusionHPV testing by using self-collected samples was well accepted, suggesting that it is a plausible modality for cervical cancer screening in indigenous communities. Further studies are needed to assess rates of follow-up after a positive test and to determine whether these findings extend to other indigenous and nonindigenous communities in Guatemala and Latin America.
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