Support for smoke-free public places among adults in four countries in sub-Saharan Africa.

INTRODUCTION: There is no known safe level of secondhand smoke exposure; yet, less than 30% of the global population is covered by comprehensive smoke-free policies as of 2016 and there are few smoke-free policies in sub-Saharan Africa (SSA). This study examines the support for smoke-free public places in SSA and delineates their correlates. METHODS: Data collected through the Global Adult Tobacco Survey (2012-2017) were analyzed using SAS for descriptive and multivariable analyses, with a significance level set at p < .05. RESULTS: No SSA country had comprehensive smoke-free policies, defined as a prohibition of smoking in eight public places. In the four countries whose Global Adult Tobacco Survey data were analyzed (Nigeria, Cameroon, Kenya, and Uganda), support for the prohibition of smoking in public places was over 90% in all eight public places except bars. Support for smoking prohibition in bars was 65.8%, 81.1%, 81.4%, and 91.0% in Nigeria, Cameroon, Kenya, and Uganda, respectively. Factors associated with support for smoke-free bars differed across the four countries, but in all countries, current smokers had decreased odds of support for smoke-free bars. Knowledge of secondhand smoke harm and living in smoke-free homes were associated with increased odds of support for smoke-free bars in all countries except Kenya. CONCLUSION: The high support for smoke-free public places should inform the efforts of the public health community and policymakers in these four SSA countries toward meeting their obligations of Article 8 of the World Health Organization Framework Convention on Tobacco Control (WHO FCTC). IMPLICATIONS: Much of the population in SSA is not protected by comprehensive smoke-free policies. It was found that the overwhelming majority of adults in four large countries in SSA support the prohibition of smoking in public places and that knowledge of the health dangers of smoking and exposure to secondhand smoke and home smoking rules increased support for the prohibition. High support for the prohibition of smoking in these four SSA countries suggests tobacco control proponents should advocate for comprehensive smoke-free policies.

Cardiovascular Diseases Health Literacy among Patients, Health Professionals, and Community-Based Stakeholders in a Predominantly Medically Underserved Rural Environment.

OBJECTIVE: The central Appalachian region of the United States is disproportionately burdened with cardiovascular disease (CVD); however, the level of literacy about CVD among residents has not been well studied. This study aimed to examine the prevalence and factors of CVD health literacy (HL) among a sample of patients/caregivers, providers/professionals, and community stakeholders. METHODS: In 2018, data were collected from central Appalachian residents in six states: Kentucky, North Carolina, Ohio, Tennessee, Virginia, and West Virginia. CVD HL status was determined by assessing correct responses to five interrelated questions about basic knowledge of CVD. Multiple logistic regression analyses were used to examine the associations between potential factors and CVD HL status. RESULTS: Of the total respondents (N = 82), <50% correctly answered all 5 CVD HL questions. Multiple logistic regression analyses showed that compared with respondents with advanced college degrees, those with a college degree or less were more likely to have low HL for "typical symptom of CVD," "physical exercise and CVD," "blood pressure and CVD," and "stress and CVD." In addition, compared with respondents younger than 50 years, those 50 years and older were 3.79 times more likely to have low HL for "physical exercise and CVD." CONCLUSIONS: These results suggest the incorporation of CVD HL into CVD care and that educational attainments should be part of CVD policies and programs in the region.

Chloride co-transporters as possible therapeutic targets for stroke.

Stroke is one of the major causes of death and disability worldwide. The major type of stroke is an ischaemic one, which is caused by a blockage that interrupts blood flow to the brain. There are currently very few pharmacological strategies to reduce the damage and social burden triggered by this pathology. The harm caused by the interruption of blood flow to the brain unfolds in the subsequent hours and days, so it is critical to identify new therapeutic targets that could reduce neuronal death associated with the spread of the damage. Here, we review some of the key molecular mechanisms involved in the progression of neuronal death, focusing on some new and promising studies. In particular, we focus on the potential of the chloride co-transporter (CCC) family of proteins, mediators of the GABAergic response, both during the early and later stages of stroke, to promote neuroprotection and recovery. Different studies of CCCs during the chronic and recovery phases post-stroke reveal the importance of timing when considering CCCs as potential neuroprotective and/or neuromodulator targets. The molecular regulatory mechanisms of the two main neuronal CCCs, NKCC1 and KCC2, are further discussed as an indirect approach for promoting neuroprotection and neurorehabilitation following an ischaemic insult. Finally, we mention the likely importance of combining different strategies in order to achieve more effective therapies.

Setting Patient-Centered Priorities for Cardiovascular Disease in Central Appalachia: Engaging Stakeholder Experts to Develop a Research Agenda.

The disproportionate burden of cardiovascular diseases (CVD) and associated risk factors continues to exist in the Central Appalachian Region (CAR) of the United States. Previous studies to gather data about patient-centered care for CVD in the region were conducted through focus group discussions. There have not been any studies that used a collaborative framework where patients, providers, and community stakeholders were engaged as panelists. The objective of this study was to identify patient-centered research priorities for CVD in the CAR. We used a modified Delphi approach to administer questionnaires to forty-two stakeholder experts in six states representing the CAR between the fall of 2018 and the summer of 2019. Their responses were analyzed for rankings and derived priorities by research gaps. Six of the fifteen research priorities identified were patient-centered. These patient-centered priorities included shorter wait times for appointments; educating patients at their level; empowering patients to take responsibility for their health; access to quality providers; heart disease specialists for rural areas; and lifestyle changes. The participants' commitments to identify patient-centered research priorities indicate the potential to engage in community-based collaboration to address the burden of CVD in the CAR.

Perceptions and Understanding of Patients with Cardiovascular Disease and Non-Licensed Caregivers about Patient-Centered Care: An Exploratory Study in Central Appalachia.

This study explored knowledge, understanding, and perceptions of patient-centered care (PCC) among patients with cardiovascular diseases and their non-licensed caregivers (NLCs) in Central Appalachia, a medically underserved rural environment. Seven focus group discussions (FGDs) involving 78 patients/NLCS were conducted across the six states of the region. Focus group discussions were audio-recorded, transcribed, and thematically coded. Major themes were: 1) access to quality health care providers (HCPs) and 2) patientprovider interactions. Subthemes for access to quality HCPs included a) long-term relationships with providers, b) high turnover of cardiovascular specialists, c) lack of traditional family physicians, and d) physician assistants/nurse practitioners versus physicians as primary providers. Subthemes for patient-provider interactions included a) reciprocal communication, b) individualized care, and c) meaningful voice in care decisions. These results underscore the importance of interpersonal relationships with providers in the delivery of medical care in the region.

The co-existence of diabetes and subclinical atherosclerosis in rural central Appalachia: Do residential characteristics matter?

Aim Disparities exist in cardiovascular diseases (CVD) and diabetes in the United States (U.S.) with Central Appalachia having disproportionate burden. This study examined prevalence and correlates of CVD risk-factors among patients with diabetes/subclinical atherosclerosis in Central Appalachia. METHODS: During 2012-2016, 3000 patients from Central Appalachia were screened for subclinical atherosclerosis, using coronary artery calcium (CAC) scores; 419 participants had diabetes. Patients were categorized into four groups, with emphasis on those having subclinical atherosclerosis, CAC score ≥ 1. Descriptive statistics and multilevel multinomial logistic regression were conducted to identify CVD risk and spatial factors associated with co-existence of diabetes and subclinical atherosclerosis. RESULTS: Among participants, prevalence of CVD risk-factors ranged from 11.7% for current smokers to 69.2% for those with CVD family history. Average BMI was 29.8. Compared to patients with diabetes only, age [RR = 1.07; p ≤ 0.0001], being male [RR = 5.33; p ≤ 0.0001], having hypertension [RR = 2.37; p ≤ 0.05] and being a former smoker were associated with increased likelihood of having diabetes/subclinical atherosclerosis. At the zip-code level, unemployment rate [RR = 1.37; p ≤ 0.05] was significantly associated with having diabetes/subclinical atherosclerosis. CONCLUSION: Consistent with clinical guidelines, study results suggest the need to integrate CAC screening into primary care diabetes programs while addressing spatial issues that predispose patients to have diabetes/subclinical atherosclerosis.

Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer.

Radiotherapy remains an important treatment modality in nearly two thirds of all cancers, including the primary curative or palliative treatment of breast cancer. Unfortunately, largely due to tumor heterogeneity, tumor radiotherapy response rates can vary significantly, even between patients diagnosed with the same tumor type. Although in recent years significant technological advances have been made in the way radiation can be precisely delivered to tumors, it is proving more difficult to personalize radiotherapy regimens based on cancer biology. Biomarkers that provide prognostic or predictive information regarding a tumor's intrinsic radiosensitivity or its response to treatment could prove valuable in helping to personalize radiation dosing, enabling clinicians to make decisions between different treatment options whilst avoiding radiation-induced toxicity in patients unlikely to gain therapeutic benefit. Studies have investigated numerous ways in which both patient and tumor radiosensitivities can be assessed. Tumor molecular profiling has been used to develop radiosensitivity gene signatures, while the assessment of specific intracellular or secreted proteins, including circulating tumor cells, exosomes and DNA, has been performed to identify prognostic or predictive biomarkers of radiation response. Finally, the investigation of biomarkers related to radiation-induced toxicity could provide another means by which radiotherapy could become personalized. In this review, we discuss studies that have used these methods to identify or develop prognostic/predictive signatures of radiosensitivity, and how such assays could be used in the future as a means of providing personalized radiotherapy.

hASH1 nuclear localization persists in neuroendocrine transdifferentiated prostate cancer cells, even upon reintroduction of androgen.

Neuroendocrine prostate cancer (NEPC) is thought to arise as prostate adenocarcinoma cells transdifferentiate into neuroendocrine (NE) cells to escape potent anti-androgen therapies however, the exact molecular events accompanying NE transdifferentiation and their plasticity remain poorly defined. Cell fate regulator ASCL1/hASH1's expression was markedly induced in androgen deprived (AD) LNCaP cells and prominent nuclear localisation accompanied acquisition of the NE-like morphology and expression of NE markers (NSE). By contrast, androgen-insensitive PC3 and DU145 cells displayed clear nuclear hASH1 localisation under control conditions that was unchanged by AD, suggesting AR signalling negatively regulated hASH1 expression and localisation. Synthetic androgen (R1881) prevented NE transdifferentiation of AD LNCaP cells and markedly suppressed expression of key regulators of lineage commitment and neurogenesis (REST and ASCL1/hASH1). Post-AD, NE LNCaP cells rapidly lost NE-like morphology following R1881 treatment, yet ASCL1/hASH1 expression was resistant to R1881 treatment and hASH1 nuclear localisation remained evident in apparently dedifferentiated LNCaP cells. Consequently, NE cells may not fully revert to an epithelial state and retain key NE-like features, suggesting a "hybrid" phenotype. This could fuel greater NE transdifferentiation, therapeutic resistance and NEPC evolution upon subsequent androgen deprivation. Such knowledge could facilitate CRPC tumour stratification and identify targets for more effective NEPC management.

The Progress of Tobacco Control Research in Sub-Saharan Africa in the Past 50 Years: A Systematic Review of the Design and Methods of the Studies.

Over one billion of the world's population are smokers, with increasing tobacco use in low- and middle-income countries. However, information about the methodology of studies on tobacco control is limited. We conducted a literature search to examine and evaluate the methodological designs of published tobacco research in Sub-Saharan Africa (SSA) over the past 50 years. The first phase was completed in 2015 using PubMed, Embase, CINAHL, and Cochrane Central Register of Controlled Trials. An additional search was completed in February 2017 using PubMed. Only tobacco/smoking research in SSA countries with human subjects and published in English was selected. Out of 1796 articles, 447 met the inclusion criteria and were from 26 countries, 11 of which had one study each. Over half of the publications were from South Africa and Nigeria. The earliest publication was in 1968 and the highest number of publications was in 2014 (n = 46). The majority of publications used quantitative methods (91.28%) and were cross-sectional (80.98%). The commonest data collection methods were self-administered questionnaires (38.53%), interviews (32.57%), and observation (20.41%). Around half of the studies were among adults and in urban settings. We conclud that SSA remains a "research desert" and needs more investment in tobacco control research and training.

Preferential activation of HIF-2α adaptive signalling in neuronal-like cells in response to acute hypoxia.

Stroke causes severe neuronal damage as disrupted cerebral blood flow starves neurons of oxygen and glucose. The hypoxia inducible factors (HIF-1α and HIF-2α) orchestrate oxygen homeostasis and regulate specific aspects of hypoxic adaptation. Here we show the importance of HIF-2α dependant signalling in neuronal adaptation to hypoxic insult. PC12 and NT2 cells were differentiated into neuronal-like cells using NGF and retinoic acid, and exposed to acute hypoxia (1% O2). Gene and protein expression was analysed by qPCR and immunoblotting and the neuronal-like phenotype was examined. PC12 and NT2 differentiation promoted neurite extension and expression of neuronal markers, NSE and KCC2. Induction of HIF-1α mRNA or protein was not detected in hypoxic neuronal-like cells, however marked induction of HIF-2α mRNA and protein expression was observed. Induction of HIF-1α target genes was also not detected in response to acute hypoxia, however significant induction of HIF-2α transcriptional targets was clearly evident. Furthermore, hypoxic insult dramatically reduced both neurite number and length, and attenuated expression of neuronal markers, NSE and KCC2. This correlated with an increase in expression of the neural progenitor and stem cell-like markers, CD44 and vimentin, suggesting HIF-2α molecular mechanisms could potentially promote regression of neuronal-like cells to a stem-like state and trigger neuronal recovery following ischaemic insult. Our findings suggest the HIF-2α pathway predominates over HIF-1α signalling in neuronal-like cells following acute hypoxia.

GABA(A) receptor chloride channels are involved in the neuroprotective role of GABA following oxygen and glucose deprivation in the rat cerebral cortex but not in the hippocampus.

Assays on "ex vivo" sections of rat hippocampus and rat cerebral cortex, subjected to oxygen and glucose deprivation (OGD) and a three-hour reperfusion-like (RL) recovery, were performed in the presence of either GABA or the GABA(A) receptor binding site antagonist, bicuculline. Lactate dehydrogenase (LDH) and propidium iodide were used to quantify cell mortality. We also measured, using real-time quantitative polymerase chain reaction (qPCR), the early transcriptional response of a number of genes of the glutamatergic and GABAergic systems. Specifically, glial pre- and post-synaptic glutamatergic transporters (namely GLAST1a, EAAC-1, GLT-1 and VGLUT1), three GABAA receptor subunits (α1, ß2 and γ2), and the GABAergic presynaptic marker, glutamic acid decarboxylase (GAD65), were studied. Mortality assays revealed that GABAA receptor chloride channels play an important role in the neuroprotective effect of GABA in the cerebral cortex, but have a much smaller effect in the hippocampus. We also found that GABA reverses the OGD-dependent decrease in GABA(A) receptor transcript levels, as well as mRNA levels of the membrane and vesicular glutamate transporter genes. Based on the markers used, we conclude that OGD results in differential responses in the GABAergic presynaptic and postsynaptic systems.