A Preliminary Study of the Attitudes and Barriers of Family Physicians to Prescribing HIV Preexposure Prophylaxis

Introduction. Attitudes of individuals who provide HIV caretowards prescribing Preexposure Prophylaxis (PrEP) to at-riskpopulations have been studied, but few studies indicate if familyphysicians would be willing to prescribe PrEP as most familyphysicians do not specialize in HIV medicine. Few data existon the perceived barriers preventing family physicians fromprescribing PrEP. The purpose of this project was to assess theattitudes and perceived barriers of family physicians in Kansastowards prescribing PrEP to high risk patient populations. Methods. This study was a descriptive, observational,and cross-sectional survey of family physicians who respondto email surveys issued through the Family MedicineResearch and Data Information Office (FM RADIO). Results. Fifty-three percent of family physicians take a sexualhistory on new patients less than frequently, and only35% frequently ask about the use of safe sex practices. Only29% frequently ask if the patient has sex with men, women,or both. Seventy-six percent of respondents would be willingto prescribe PrEP to men who have sex with men, and anequal percentage would be willing to prescribe to heterosexuallyactive men and women who are at substantial risk of acquiringHIV. While 59% of participants agreed that PrEP belongsin the primary care domain of treatment, 71% agreedthat they had limited or no knowledge of PrEP guidelines. Conclusions. This preliminary study indicated a need for increasedfamily physician screening of new patients for high risksexual behaviors who would be eligible for PrEP. The limitedknowledge of PrEP guidelines and its use in clinical practiceare significant limiting factors to increasing prescribing practicesin the family medicine community rather than a perceivedethical dilemma of prescribing PrEP to men who have sex withmen. As a result, an increase in continuing medical educationabout PrEP could significantly increase its prescribing inthe family medicine community. KS J Med 2017;10(2):40-42

Speech-Language and Cognitive Findings in Patients with HIV/AIDS

BACKGROUND: Few adult patients with HIV/AIDS are screened regularly for speech-language and cognitive disorders even though they may manifest communication difficulties. No comprehensive studies assessing the broad range of speech-language and cognitive disorders of adults with HIV/AIDS appear in the literature. As such, clinicians may be unfamiliar with the types of communication disorders that may be manifested. This study assessed the prevalence of speech-language and cognitive disorders in adults with HIV/AIDS using a broad inventory of speech, language, and cognitive skills. METHODS: A cross-sectional design was used to investigate communication disorders in a convenience sample of patients living with HIV/AIDS. Adult patients from a general internal medicine clinic in Wichita, Kansas were recruited as they presented for medical appointments. Each participant received a speech-language and cognitive test battery consisting of 10 assessments. RESULTS: The primary outcomes were: (1) presence of any speech-language or cognitive disorder, and (2) degree of communication disorder, as measured by the number of positive results. Eighty-two adults with HIV/AIDS were evaluated for communication disorders. Prevalence was 95%; 78 out of 82 participants manifested abnormal findings on at least one assessment in the test battery. Test results revealed a variety of cognitive and language issues, mostly related to integrating information on the picture description task (45%), timed word generation (44%), and memory-related story retelling (35%). Two participants revealed abnormal results on all ten assessments. CONCLUSION: Speech-language and cognition deficits are common in adult patients with HIV/AIDS. Every patient with HIV/AIDS should be assessed to determine the impact of these communication deficits on their daily living skills

Silence Is Not Golden: Invisible Latinas Living with HIV in the Midwest

This qualitative study was conducted to better understand the health needs and concerns of immigrant HIV-infected Latinas residing in the Midwest United States. Individual interviews (n = 18) were conducted in Spanish with Latinas in Kansas, Oklahoma and Missouri. Women were at different stages of acceptance about their HIV diagnosis and four common themes emerged from the data: pregnancy as a death sentence, HIV is taboo, God as their only resource, and living in isolation. Silence was an over-arching theme present throughout all the narratives and many women had never shared their stories about HIV with anyone. Depressive symptoms and suicidal ideation were common. These findings have implications for strategies to address the HIV prevention and HIV-related healthcare needs of this population of women. Results from this study further suggest that efforts are needed to break the silence surrounding HIV and to reduce HIV-related stigma in smaller Midwestern Hispanic communities

Mechanisms Establishing TLR4-Responsive Activation States of Inflammatory Response Genes

Precise control of the innate immune response is required for resistance to microbial infections and maintenance of normal tissue homeostasis. Because this response involves coordinate regulation of hundreds of genes, it provides a powerful biological system to elucidate the molecular strategies that underlie signal- and time-dependent transitions of gene expression. Comprehensive genome-wide analysis of the epigenetic and transcription status of the TLR4-induced transcriptional program in macrophages suggests that Toll-like receptor 4 (TLR4)-dependent activation of nearly all immediate/early- (I/E) and late-response genes results from a sequential process in which signal-independent factors initially establish basal levels of gene expression that are then amplified by signal-dependent transcription factors. Promoters of I/E genes are distinguished from those of late genes by encoding a distinct set of signal-dependent transcription factor elements, including TATA boxes, which lead to preferential binding of TBP and basal enrichment for RNA polymerase II immediately downstream of transcriptional start sites. Global nuclear run-on (GRO) sequencing and total RNA sequencing further indicates that TLR4 signaling markedly increases the overall rates of both transcriptional initiation and the efficiency of transcriptional elongation of nearly all I/E genes, while RNA splicing is largely unaffected. Collectively, these findings reveal broadly utilized mechanisms underlying temporally distinct patterns of TLR4-dependent gene activation required for homeostasis and effective immune responses

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe