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This article explains the importance of a communities of practice (CoP) model for continually aligning medical education and clinical transformation with contemporary health issues. It describes the evolution and advantages of using CoP as a model for transforming medical education and clinical practice and applies the CoP methodology to addressing the changing needs of socially vulnerable populations (LGBTQ [lesbian, gay, bisexual, transgender, and queer/questioning], persons experiencing homelessness, and migrant farm workers). In conclusion, this article describes CoP-led activities, achievements, and value creation in medical education by the National Center for Medical Education Development and Research established at the Meharry Medical College.
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Educação Médica , Minorias Sexuais e de Gênero , Feminino , Humanos , Faculdades de Medicina , Bissexualidade , Serviços de Saúde ComunitáriaRESUMO
Transgender and gender-diverse (TGD) patients experience a greater burden of health disparities compared with their heterosexual/cisgender counterparts. Some of the poorer health outcomes observed in these populations are known to be associated with the prevalence of implicit bias, bullying, emotional distress, alcoholism, drug abuse, intimate partner violence, sexually transmitted infections (eg, human immunodeficiency virus and human papilloma virus), and cancer. The TGD populations face unique barriers to receiving both routine and gender-affirming health care (acquiring hormones and gender-affirming surgeries). Additional barriers to implementing affirming care training for TGD patients are lack of expertise among medical education faculty and preceptors both in undergraduate and in graduate medical education programs. Drawing on a systematic review of the literature, we propose a policy brief aimed at raising awareness about gender-affirming care among education planners and policy makers in government and advisory bodies.
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Educação Médica , Pessoas Transgênero , Humanos , Políticas , Educação de Pós-Graduação em Medicina , EscolaridadeRESUMO
Background: Currently, the capacity to provide buprenorphine treatment (BT) is not sufficient to treat the growing number of people in the United States with opioid use disorder (OUD). We sought to examine participant retention in care rates of primary care delivered BT programs and to describe factors associated with retention/attrition for participants receiving BT in this setting.Objectives: A PRISMA-guided search of various databases was performed to identify the articles focusing on efficacy of BT treatment and OUD.Method: A systematic literature search identified 15 studies examining retention in care in the primary care setting between 2002 and 2020. Random effects meta-regression were used to identify retention rates across studies.Results: Retention rates decreased across time with a mean 0.52 rate at one year. Several factors were found to be related to retention, including: race, use of other drugs, receipt of counseling, and previous treatment with buprenorphine.Conclusions: While we only investigate BT through primary care, our findings indicate retention rates are equivalent to the rates reported in the specialty care literature. More work is needed to examine factors that may impact primary care delivered BT specifically and differentiate participants that may benefit from care delivered in specialty over primary care as well as the converse.
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Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Humanos , Estados Unidos , Buprenorfina/uso terapêutico , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/complicações , Resultado do Tratamento , Atenção Primária à Saúde , Analgésicos Opioides/uso terapêuticoRESUMO
BACKGROUND: A wealth of scientific evidence supports the effectiveness of HIV prophylaxis and treatment. Homelessness is strongly associated with the health status and viral suppression among underserved populations and can undermine the national plan to eliminate HIV by 2030. This retrospective observational study examined the extent in which homelessness affects HIV treatment in an underserved urban area of Middle Tennessee in 2014-2019. RESULTS: Among 692 HIV-seropositive patients, the proportion of homeless patients increased from 13.5% in 2014 to 27.7% in 2019, thrice the national average for HIV-seropositive people (8.4%) and twice that of HIV positive patients who are participating in Ryan White programs nationwide (12.9%). Our findings suggest that homeless patients were half as likely to achieve viral suppression as compared to those who had a permanent/stable home [OR 0.48 (0.32-0.72), p-value < 0.001]. CONCLUSION: Our study indicates that homelessness may play an important role in viral suppression among persons living with HIV/AIDS in Middle Tennessee.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Pessoas Mal Alojadas , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Tennessee/epidemiologiaRESUMO
BACKGROUND: The most common measure of association between two continuous variables is the Pearson correlation (Maronna et al. in Safari an OMC. Robust statistics, 2019. https://login.proxy.bib.uottawa.ca/login?url=https://learning.oreilly.com/library/view/-/9781119214687/?ar&orpq&email=^u). When outliers are present, Pearson does not accurately measure association and robust measures are needed. This article introduces three new robust measures of correlation: Taba (T), TabWil (TW), and TabWil rank (TWR). The correlation estimators T and TW measure a linear association between two continuous or ordinal variables; whereas TWR measures a monotonic association. The robustness of these proposed measures in comparison with Pearson (P), Spearman (S), Quadrant (Q), Median (M), and Minimum Covariance Determinant (MCD) are examined through simulation. Taba distance is used to analyze genes, and statistical tests were used to identify those genes most significantly associated with Williams Syndrome (WS). RESULTS: Based on the root mean square error (RMSE) and bias, the three proposed correlation measures are highly competitive when compared to classical measures such as P and S as well as robust measures such as Q, M, and MCD. Our findings indicate TBL2 was the most significant gene among patients diagnosed with WS and had the most significant reduction in gene expression level when compared with control (P value = 6.37E-05). CONCLUSIONS: Overall, when the distribution is bivariate Log-Normal or bivariate Weibull, TWR performs best in terms of bias and T performs best with respect to RMSE. Under the Normal distribution, MCD performs well with respect to bias and RMSE; but TW, TWR, T, S, and P correlations were in close proximity. The identification of TBL2 may serve as a diagnostic tool for WS patients. A Taba R package has been developed and is available for use to perform all necessary computations for the proposed methods.
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Correlação de Dados , Simulação por Computador , HumanosRESUMO
This pilot study investigates the correlation between psychological stress and antiretroviral therapy (ART) adherence and plasma HIV RNA (viral load) as mediated by psychological flexibility among Black men in the south. Data were collected from 48 HIV-positive, low income Black men. Results indicate a strong positive correlation between perceived stress and psychological inflexibility (adjusted for age and income rs = 0.67; p < 0.001), a negative correlation between psychological inflexibility and ART adherence (adjusted rs = - 0.32; p = 0.03), a negative correlation between perceived stress and ART adherence (adjusted rs = - 0.45; p = 0.006), and a negative correlation between ART adherence and viral load (adjusted rs = - 0.37; p = 0.04). Our findings suggest stress decreases adherence to ART and viral suppression among Black men living with HIV. However, psychological flexibility did not mediate the relationship between stress and treatment adherence. Hair cortisol concentrations were high (mean of 34.2 pg/mg), but uncorrelated with adherence.
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Fármacos Anti-HIV , Infecções por HIV , Adesão à Medicação , Negro ou Afro-Americano , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Hidrocortisona , Masculino , Projetos Piloto , Carga ViralRESUMO
BACKGROUND: Lesbian, gay, bisexual, transgender and questioning (LGBTQ) individuals experience higher rates of health disparities. These disparities may be driven, in part, by biases of medical providers encountered in health care settings. Little is known about how medical, nursing, or dental students are trained to identify and reduce the effects of their own biases toward LGBTQ individuals. Therefore, a systematic review was conducted to determine the effectiveness of programs to reduce health care student or provider bias towards these LGBTQ patients. METHODS: The authors performed searches of online databases (MEDLINE/PubMed, PsycINFO, Web of Science, Scopus, Ingenta, Science Direct, and Google Scholar) for original articles, published in English, between March 2005 and February 2017, describing intervention studies focused on reducing health care student or provider bias towards LGBTQ individuals. Data extracted included sample characteristics (i.e., medical, nursing, or dental students or providers), study design (i.e., pre-post intervention tests, qualitative), program format, program target (i.e., knowledge, comfort level, attitudes, implicit bias), and relevant outcomes. Study quality was assessed using a five-point scale. RESULTS: The search identified 639 abstracts addressing bias among medical, nursing, and dental students or providers; from these abstracts, 60 articles were identified as medical education programs to reduce bias; of these articles, 13 described programs to reduce bias towards LGBTQ patients. Bias-focused educational interventions were effective at increasing knowledge of LGBTQ health care issues. Experiential learning interventions were effective at increasing comfort levels working with LGBTQ patients. Intergroup contact was effective at promoting more tolerant attitudes toward LGBTQ patients. Despite promising support for bias education in increasing knowledge and comfort levels among medical, nursing, and dental students or providers towards LGBTQ persons, this systematic review did not identify any interventions that assessed changes in implicit bias among students or providers. CONCLUSIONS: Strategies for assessing and mitigating implicit bias towards LGBTQ patients are discussed and recommendations for medical, nursing, and dental school curricula are presented.
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Atitude do Pessoal de Saúde , Relações Médico-Paciente , Preconceito/prevenção & controle , Minorias Sexuais e de Gênero , Estudantes de Odontologia/psicologia , Estudantes de Medicina/psicologia , Estudantes de Enfermagem/psicologia , Homofobia/prevenção & controle , HumanosRESUMO
BACKGROUND/PURPOSE: Intimate partner violence (IPV) is a global public health epidemic that initiates/exacerbates health consequences affecting a victim's lifespan. IPV can significantly predispose women to a lifetime risk of developing cardiovascular disease (CVD) due to the effects of stress and inflammation. This study investigates the correlation among IPV exposure, in-vivo CVD events, and inflammatory biomarkers as predictor indices(s) for CVD in female dental patients. METHODS: Of 37 women enrolled in this study, 19 were African-American (AA) and 18 non-African-American (non-AA) and their ages ranged from 19 to 63 years. IPV-exposure and stress-induced in-vivo CVD events such as Chest Pain (CP) and Heart palpitations were recorded from all enrolled subjects. Cardiovascular events were obtained through surveys by patient self-report. Saliva specimens were obtained from all women and were analyzed for CVD biomarkers using multiplex-ELISA. RESULTS: The prevalence of IPV was 51% (19/37) and statistically equivalent for AA and non-AA. The results show differences in experience of 1) CP (p < 0.01) and 2) heart palpitations (p < 0.02) when IPV + participants are compared with IPV- AA and non-AA cohorts. Of 10 CVD biomarkers analyzed, significant correlations between IPV+ and IPV- subjects were observed for biomarkers that include Interleukin-1ß/sCD40L; TNFα/sCD40L; Myoglobin/IL-1ß; CRP/sCD40L; CRP/IL-6; CRP/TNFα; TNFα/siCAM; CRP/MMP9; TNF-α/Adiponectin (p < 0.01). DISCUSSION/IMPLICATIONS: Analysis of in vivo CVD status showed that significant race/health disparities exist in IPV + cohorts, as well as increased expression of inflammatory mediators, specifically CRP, IL-1ß, IL-6, MMP9. Women who have experienced IPV may be a target cohort for primary prevention of CVD. The use of salivary biomarkers and our protocol may provide a less invasive method to help increase identification of victims at risk for IPV and CVD and potentially decrease other health injuries associated with IPV exposure.
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Biomarcadores/metabolismo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Violência por Parceiro Íntimo , Saliva/metabolismo , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Doenças Cardiovasculares/metabolismo , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Disparidades nos Níveis de Saúde , Humanos , Violência por Parceiro Íntimo/etnologia , Violência por Parceiro Íntimo/estatística & dados numéricos , Modelos Logísticos , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco , AutorrelatoRESUMO
OBJECTIVES: Meta-analysis is a statistical appraisal of the data analytic implications of published articles (Y), estimating parameters including the odds ratio and relative risk. This information is helpful for evaluating the significance of the findings. The Higgins I2 index is often used to measure heterogeneity among studies. The objectives of this article are to amend the Higgins I2 index score in a novel and innovative way and to make it more useful in practice. METHODS: Heterogeneity among study populations can be affected by many sources, including the sample size and study design. They influence the Cochran Q score and, thus, the Higgins I2 score. In this regard, the I2 score is not an absolute indicator of heterogeneity. Q changes by bound as Y increases unboundedly. An innovative methodology is devised to show the conditional and unconditional probability structures. RESULTS: Various properties are derived, including showing that a zero correlation between Q and Y does not necessarily mean that they are independent. A new alternative statistic, S2, is derived and applied to mild cognitive impairment and coronavirus disease 2019 vaccination for meta-analysis. CONCLUSIONS: A hidden shortcoming of the Higgins I2 index is overcome in this article by amending the Higgins I2 score. The usefulness of the proposed methodology is illustrated using 2 examples. The findings have potential health policy implications.
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COVID-19 , Disfunção Cognitiva , Humanos , COVID-19/epidemiologiaRESUMO
Purpose: The goal of the National Center for Medical Education Development and Research Center (NCMEDR) is to support the education and training of medical students in the care of vulnerable populations. Access to primary care services in the US is fundamental to the health and wellness of all people regardless of their socioeconomic status. LGBQ+ persons, (lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority), Persons Experiencing Homelessness (PEH), and Migrant Farm Workers (MFW) are among the most underserved, marginalized, and socially vulnerable groups in the US. NCMEDR in the Department of Family and Community Medicine at Meharry Medical College was established in part, with funding from the Department of Health and Human Services (DHHS) and the Health Resources and Services Administration (HRSA). NCMEDR was developed to provide educational pathways for transforming medical education and clinical practice in the US by ascertaining whether medical students were being trained to provide primary care, and behavioral health services to LGBTQ+ persons, PEH, and MFW. Here we focus on the impact of the COVID-19 pandemic on these specific populations because they represent marginalized groups that have been heavily impacted by the pandemic, have poor social determinants of health (SDOH), and are more likely to be uninsured, and are less likely to engage primary care providers outside of emergency room care. Methods: In this study, a scoping literature review was conducted to assess the impact of COVID-19 on primary care of LQBTQ+ persons, PEH, and MFW. Results and Discussion: The pandemic provided a serious health disparities gap for the defined vulnerable populations under review by the NCMEDR. The pandemic identified the need for transformative measures for clinical practices, medical education, and health care policies required for implementation to improve health care for vulnerable groups. We make recommendations for interventions with defined populations that may influence clinical, environmental health, and SDOH in the COVID era. Conclusions: The COVID pandemic directed the need for medical schools, health care and social organizations to intervene in new and different ways in vulnerable and marginalized communities. The recommendations provide a model for advancing health equity, access, quality, utilization, care coordination, and treatment.
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BACKGROUND: African American (AA) women with type 2 diabetes (T2D) carry disproportionate diabetes-related morbidity and mortality burdens. Diabetes medical nutrition therapy (MNT) improves glycemic, blood pressure, and cholesterol control, all critical in preventing and reducing diabetes complications. Yet, MNT does not address low motivation for dietary intake management, which is frequently reported among AA women with T2D living in the Southeastern US. METHODS: A randomized controlled trial will be used to test the central hypothesis that diabetes MNT plus culturally-tailored motivational interviewing (MI) (diabetes MNT plus MI) is more effective than diabetes MNT alone (diabetes MNT). Two hundred ninety-one Southeastern AA women who are at risk for development and/or progression of T2D complications will be randomized to diabetes MNT plus MI or diabetes MNT. Both groups will include: 1) a 3-month active intervention period, consisting of group-based, nutritionist-facilitated MNT sessions; 2) a 3-month maintenance intervention period, including one group-based, nutritionist-facilitated maintenance support session; and 3) a 6-month inactive period. Culturally-adapted MI exercises will be integrated into the diabetes MNT plus MI group only. Primary (HbA1c) and secondary (systolic blood pressure, LDL cholesterol) outcomes will be assessed at baseline and 3, 6, and 12 months following the active intervention period. DISCUSSION: The results from this study, called the SISTER (Sisters Inspiring Sisters to Engage in Relevant Diabetes Self-Care) Diabetes Study, are vital to the adoption and uptake of rigorously-tested MNT interventions that address motivation among AA women with T2D as a way to reduce their risk and/or progression of diabetes-related complications.
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Diabetes Mellitus Tipo 2 , Terapia Nutricional , Humanos , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Negro ou Afro-Americano , Autocuidado , Glicemia , Terapia Nutricional/métodos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Increases in fatal synthetic opioid overdoses over the past 8 years have left states scrambling for effective means to curtail these deaths. Many states have implemented policies and increased service capacity to address this rise. To better understand the effectiveness of policy level interventions we estimated the impact of the presence of naloxone access laws (NALs) on synthetic opioid fatalities at the state level. METHODS: A multivariable longitudinal linear mixed model with a random intercept was used to determine the relationship between the presence of NALs and synthetic opioid overdose death rates, while controlling for, Good Samaritan laws, opioid prescription rate, and capacity for medication for opioid use disorder (MOUD), utilizing a quadratic time trajectory. Data for the study was collected from the National Vital Statistics System using multiple cause-of-death mortality files linked to drug overdose deaths. RESULTS: The presence of an NAL had a significant (univariate P-value = .013; multivariable p-value = .010) negative relationship to fentanyl overdose death rates. Other significant controlling variables were quadratic time (univariate and multivariable P-value < .001), MOUD (univariate P-value < .001; multivariable P-value = .009), and Good Samaritan Law (univariate P-value = .033; multivariable P-value = .018). CONCLUSION: Naloxone standing orders are strongly related to fatal synthetic opioid overdose reduction. The effect of NALs, MOUD treatment capacity, and Good Samaritan laws all significantly influenced the synthetic opioid overdose death rate. The use of naloxone should be a central part of any state strategy to reduce overdose death rate.
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Overdose de Drogas , Overdose de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Humanos , Naloxona/uso terapêutico , Analgésicos Opioides/uso terapêutico , Overdose de Opiáceos/tratamento farmacológico , Overdose de Opiáceos/epidemiologia , Overdose de Drogas/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológicoRESUMO
BACKGROUND: The objective of the study was to measure the risk of death due to COVID-19 in relation to individuals' characteristics, and severity of their disease during the dominant periods of Alpha, Delta, and Omicron variants have influenced mortality rates. METHODS: This study was conducted using COVID-19 Centers for Disease Control and Prevention (CDC) Case Surveillance Public Data Taskforce for 57 states, and United States territories between January 1, 2020 and March 20, 2022. Multivariable binary Hyperbolastic regression of type I was used to analyzes the data. RESULTS: Seniors and ICU-admitted patients had the highest risk of death. For each additional percent increase in fully vaccinated individuals, the odds of death deceased by 1%. The odds of death prior to vaccine availability, compared to post vaccine availability, was 1.27. When comparing the time periods each variant was dominant, the odds of death was 3.45-fold higher during Delta compared to Alpha. All predictor variables had P-values ≤.001. CONCLUSION: There was a noticeable difference in the odds of death among subcategories of age, race/ethnicity, sex, PMCs, hospitalization, ICU, vaccine availability, variant, and percent of fully vaccinated individuals.
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COVID-19 , Estados Unidos/epidemiologia , Humanos , SARS-CoV-2 , Centers for Disease Control and Prevention, U.S. , EtnicidadeRESUMO
BACKGROUND: Literature presents limited information on histological subtypes and their association with other factors influencing the survival of melanoma patients. To explore the risk of death due to melanoma associated with histological subtypes, this retrospective study used the Surveillance, Epidemiology, and End Results program (SEER) data from 1998 to 2019. METHODS: A total of 27,532 patients consisting of 15,527 males and 12,005 females. The Hypertabastic Accelerated Failure Time model was used to analyze the impact of histology on the survival of patients with cutaneous or mucosal melanoma. RESULTS: The median survival time (MST) for cutaneous patients was 149 months, whereas those diagnosed with mucosal melanoma was 34 months. Nodular melanoma had a hazard ratio of 3.40 [95% CI: (2.94, 3.94)] compared to lentigo maligna melanoma. Across all histological subtypes, females had a longer MST, when compared to males. The hazard ratio (HR) of distant to localized melanoma was 9.56 [95% CI: (7.58, 12.07)]. CONCLUSIONS: Knowledge of patients' histological subtypes and their hazard assessment would enable clinicians and healthcare providers to perform personalized treatment, resulting in a lower risk of complication and higher survivability of melanoma patients. Significant factors were stage of the disease, age, histology, sex, and income. Focus should be placed on high-risk populations with severe and aggressive histological subtypes. Programs that emphasize preventive measures such as awareness, education, and early screening could reduce risk.
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Melanoma , Neoplasias Cutâneas , Masculino , Feminino , Humanos , Estados Unidos/epidemiologia , Estudos Retrospectivos , Melanoma/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Modelos de Riscos Proporcionais , Programa de SEERRESUMO
COVID-19 vaccine hesitancy and uptake among Southern states in the US has been problematic throughout the pandemic. To characterize COVID-19 vaccine hesitancy and uptake among medically underserved communities in Tennessee. We surveyed 1482 individuals targeting minority communities in Tennessee from 2 October 2021 to 22 June 2022. Participants who indicated that they did not plan to receive or were unsure whether to receive the COVID-19 vaccine were considered vaccine-hesitant. Among participants, 79% had been vaccinated, with roughly 5.4% not likely at all to be vaccinated in the next three months from the date that the survey was conducted. When focusing particularly on Black/AA people and white people, our survey results revealed a significant association between race (Black/AA, white, or people of mixed Black/white ancestry) and vaccination status (vaccinated or unvaccinated) (p-value = 0.013). Approximately 79.1% of all participants received at least one dose of a COVID-19 vaccine. Individuals who were concerned with personal/family/community safety and/or wanted a return to normalcy were less likely to be hesitant. The study found that the major reasons cited for refusing the COVID-19 vaccines were distrust in vaccine safety, concerns about side effects, fear of needles, and vaccine efficacy.
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The American College of Obstetricians and Gynecologists (AGOG) recommends the FDA-approved Pfizer and Moderna mRNA COVID-19 vaccines and boosters for all eligible pregnant women in the US. However, COVID-19 vaccine confidence and uptake among pregnant minority women have been poor. While the underlying reasons are unclear, they are likely to be associated with myths and misinformation about the vaccines. Direct and indirect factors that deter minority mothers in the US from receiving the mRNA COVID-19 vaccines require further investigation. Here, we examine the historical perspectives on vaccinations during pregnancy. We will examine the following aspects: (1) the influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccinations during pregnancy; (2) the exclusion of pregnant and lactating women from COVID-19 vaccine trials; (3) COVID-19 vaccine safety during pregnancy, obstetric complications associated with symptomatic COVID-19 during pregnancy, COVID-19 vaccine hesitancy among pregnant minority women, and racial disparities experienced by pregnant minority women due to the COVID-19 pandemic as well as their potential impact on pregnancy care; and (4) strategies to improve COVID-19 vaccine confidence and uptake among pregnant minority women in the US. COVID-19 vaccine hesitancy among minority mothers can be mitigated by community engagement efforts that focus on COVID-19 vaccine education, awareness campaigns by trusted entities, and COVID-19-appropriate perinatal counseling aimed to improve COVID-19 vaccine confidence and uptake.
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The incidence of COVID-19 breakthrough infections-an infection that occurs after you have been vaccinated-has increased in frequency since the Delta and now Omicron variants of the SARS-CoV-2 coronavirus have become the dominant strains transmitted in the United States (US). Evidence suggests that individuals with breakthrough infections, though rare and expected, may readily transmit COVID-19 to unvaccinated populations, posing a continuing threat to the unvaccinated. Here, we examine factors contributing to breakthrough infections including a poor immune response to the vaccines due to the fact of advanced age and underlying comorbidities, the natural waning of immune protection from the vaccines over time, and viral variants that escape existing immune protection from the vaccines. The rise in breakthrough infections in the US and how they contribute to new infections, specifically among the unvaccinated and individuals with compromised immune systems, will create the need for additional booster vaccinations or development of modified vaccines that directly target current variants circulating among the general population. The need to expedite vaccination among the more than 49.8 million unvaccinated eligible people in the US is critical.
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Diabetic gastroparesis (DG) exhibits delayed gastric emptying (GE) due to impaired gastric non-adrenergic, non-cholinergic (NANC) relaxation. These defects are due to loss or reduction of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that causes reduced expression and/or dimerization of neuronal nitric oxide synthase alpha (nNOSα) gene expression and function. We investigated the effect of potent Nrf2 activators (cinnamaldehyde [CNM] & curcumin [CUR]) on GE in obesity-induced diabetic female mice. We fed adult female homozygous Nfe2l2-/- (Nrf2 KO) and wild-type (WT) female mice with either a high-fat diet (HFD) or a normal diet (ND) for a period of 16 weeks. Groups of HFD mice were fed with CUR or CNM either at 6th or 10th week respectively. Our results demonstrate that supplementation of CNM or CUR restored impaired nitrergic relaxation and attenuated delayed GE in HFD fed mice. Supplementation of CNM or CUR normalized altered gastric antrum protein expression of (1) p-ERK/p-JNK/MAPK/p-GSK-3ß, (2) BH4 (Cofactor of nNOS) biosynthesis enzyme GCH-1 and the GSH/GSSG ratio, (3) nNOSα protein & dimerization and soluble guanylate cyclase (sGC), (4) AhR and ER expression, (5) inflammatory cytokines (TNF α, IL-1ß, IL-6), (6)TLR-4, as well as (7) reduced oxidative stress markers in WT but not in Nrf2 KO obesity-induced chronic diabetic female mice. Immunoprecipitation experiments revealed an interaction between nNOS and Nrf2 proteins. Our results conclude that Nrf2 activation restores nitrergic-mediated gastric motility and GE by normalizing inflammation and oxidative stress induced by obesity-induced chronic diabetes.
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Antioxidantes/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Dieta Hiperlipídica , Esvaziamento Gástrico/efeitos dos fármacos , Acroleína/análogos & derivados , Acroleína/farmacologia , Animais , Curcumina/farmacologia , Diabetes Mellitus Experimental/genética , Feminino , Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Óxido Nítrico/fisiologia , Óxido Nítrico Sintase Tipo I/biossíntese , Estresse Oxidativo/efeitos dos fármacos , Antro Pilórico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacosRESUMO
Pre-Exposure Prophylaxis (PrEP) has been shown to be an effective method of HIV prevention for men who have sex with-men (MSM) and -transgender women (MSTGWs), serodiscordant couples, and injection drug users; however fewer than 50 000 individuals currently take this regimen. Knowledge of PrEP is low among healthcare providers and much of this lack of knowledge stems from the lack or exposure to PrEP in medical school. We conducted a cross sectional survey of medical schools in the United States to assess the degree to which PrEP for HIV prevention is taught. The survey consisted Likert scale questions assessing how well the students were prepared to perform each skill associated with PrEP delivery, as well as how PrEP education was delivered to students. We contacted 141 medical schools and 71 responded to the survey (50.4%). PrEP education was only reported to be offered at 38% of schools, and only 15.4% reported specific training for Lesbian, Gay, Bisexual, and Transgender (LGBT) patients. The most common delivery methods of PrEP content were didactic sessions with 11 schools reporting this method followed by problem-based learning, direct patient contact, workshops, and small group discussions. Students were more prepared to provide PrEP to MSM compared to other high-risk patients. Few medical schools are preparing their students to prescribe PrEP upon graduation. Further, there is a need to increase the number of direct patient contacts or simulations for students to be better prepared.