A Narrative Synthesis of Literature on the Barriers to Timely Diagnosis and Treatment of Cancer in Sub-Saharan Africa.

Poor cancer survival outcomes in sub-Saharan Africa (SSA) have been linked to delays in diagnosis and treatment. Here we present a detailed overview of the qualitative literature evaluating the barriers to receiving timely diagnosis and treatment of cancer in SSA. The PubMed, EMBASE, CINAHL, PsycINFO databases were searched to identify qualitative studies reporting on barriers to timely diagnosis of cancer in SSA published between 1995 and 2020. A systematic review methodology was applied, including quality assessment and narrative data synthesis. We identified 39 studies, of which 24 focused on breast or cervical cancer. Only one study focused on prostate cancer and one on lung cancer. When exploring factors contributing to delays, six key themes emerged from the data. The first theme was health service barriers, which included: (i) inadequate numbers of trained specialists; (ii) limited knowledge of cancer among healthcare providers; (iii) poor co-ordination of care; (iv) inadequately resourced health facilities; (v) negative attitudes of healthcare providers towards patients; (vi) high cost of diagnostic and treatment services. The second key theme was patient preference for complementary and alternative medicine; the third was the limited understanding of cancer among the population. The fourth barrier was a patient's personal and family obligations; the fifth was the perceived impact of cancer and its treatment on sexuality, body image and relationships. Finally, the sixth was the stigma and discrimination faced by patients following a diagnosis of cancer. In conclusion, health system, patient level and societal factors all influence the likelihood of timely diagnosis and treatment for cancer in SSA. The results provide a focus for targeting health system interventions, particular with regards to awareness and understanding of cancer in the region.

Conceptualization, detection, and management of psychological distress and mental health conditions among people with tuberculosis in Zambia: a qualitative study with stakeholders' and TB health workers.

BACKGROUND: In recent years, there has been increased recognition of the need to integrate mental health services into routine tuberculosis (TB) care. For successful integration, policymakers need to first understand the practices of TB health workers in the management of mental health conditions, including depression, anxiety, and psychological distress, and use this to decide how best mental health services could be delivered in tandem with TB services. In this qualitative study we aimed to understand how TB health workers and other stakeholders viewed mental health conditions linked to TB and how they screened and treated these in their patients. METHODS: The study draws on qualitative data collected in 2018 as part of the Tuberculosis Reduction through Expanded Antiretroviral Treatment and Screening for active TB trial (TREATS), conducted in eight urban communities in Zambia. Data were collected through 17 focus group discussions with local health committee members (n = 96) and TB stakeholders (n = 57) present in the communities. Further in-depth interviews were held with key TB health workers (n = 9). Thematic analysis was conducted. RESULTS: TB stakeholders and health workers had an inadequate understanding of mental health and commonly described mental health conditions among TB patients by using stigmatizing terminology and overtones, for example "madness", which often implied a characterological flaw rather an actual illness. Psychological distress was also described as "overthinking", which participants attributed to psychosocial stressors, and was not perceived as a condition that would benefit from mental health intervention. There were no standard screening and treatment options for mental health conditions in TB patients and most TB health workers had no mental health training. TB Stakeholders and health workers understood the negative implications of mental health conditions on TB treatment adherence and overall wellbeing for TB patients. CONCLUSIONS: TB stakeholders and health workers in Zambia have a complex conceptualisation of mental health and illness, that does not support the mental health needs of TB patients. The integration of mental health training in TB services could be beneficial and shift negative attitudes about mental health. Further, TB patients should be screened for mental health conditions and offered treatment. Trial registration number NCT03739736-Registered on the 14th of November 2018- Retrospectively registered- https://clinicaltrials.gov/ct2/results?cond=&term=NCT03739736&cntry=&state=&city=&dist.

Qualitative study of patient experiences of mental distress during TB investigation and treatment in Zambia.

BACKGROUND: The mental health and TB syndemic is a topic that remains under-researched with a significant gap in acknowledging and recognizing patient experiences, particularly in the sub-Saharan African region. In this qualitative study conducted in Zambia, we aimed to explore the lived mental health experiences of TB patients focusing on their multi-layered drivers of distress, and by so doing highlighting contextual factors that influence mental distress in TB patients in this setting. METHODS: The study draws on qualitative data collected in 2018 as part of the Tuberculosis Reduction through Expanded Antiretroviral Treatment and Screening for active TB trial (TREATS) being conducted in Zambia. The data was collected through in-depth interviews with former TB patients (n = 80) from 8 urban communities participating in the TREATS trial. Thematic analysis was conducted. Additional quantitative exploratory analysis mapping mental distress symptoms on demographic, social, economic and TB characteristics of participants was conducted. RESULTS: Most participants (76%) shared that they had experienced some form of mental distress during their TB investigation and treatment period. The reported symptoms ranged in severity. Some participants reported mild distress that did not disrupt their daily lives or ability to adhere to their TB medication, while other participants reported more severe symptoms of distress, for example, 15% of participants shared that they had suicidal ideation and thoughts of self-harm during their time on treatment. Mental distress was driven by unique interactions between individual, social and health level factors most of which were inextricably linked to poverty. Mental distress caused by individual level drivers such as TB morbidity often abated once participants started feeling better, however social, economic and health system level drivers of distress persisted during and beyond TB treatment. CONCLUSION: The findings illustrate that mental distress during TB is driven by multi-layered and intersecting stresses, with the economic stress of poverty often being the most powerful driver. Measures are urgently needed to support TB patients during the investigation and treatment phase, including increased availability of mental health services, better social security safety nets during TB treatment, and interventions targeting TB, HIV and mental health stigma. Trial registration ClinicalTrials.gov NCT03739736 . Trial registration date: November 14, 2018.

Intimate Partner Violence (IPV) and Associated Factors in HPTN 071 (PopART) Study Communities in Zambia and South Africa-A Comparison by HIV Status.

The HPTN 071(PopART) study was a community-randomised trial in Zambia and South Africa, examining the impact of combination-prevention including universal testing and treatment (UTT), on HIV-incidence. This sub-study evaluated factors associated with IPV (physical and/or sexual) to identify differences by HIV status. During 2015-16, a random subset of adults who participated in the first year of the PopART intervention were recruited and standardised questionnaires were administered. Logistic regression was performed to estimate odds ratios of factors associated with IPV. Among > 700 women studied (300 HIV-negative;400 HIV-positive), ~ 20% reported experiencing physical and/or sexual violence in the last 12-months. Sexual violence was similar by HIV status, but physical violence and reporting both physical/sexual violence was more common among HIV-positive women. Spending nights away from the community in the last 12-months was associated with higher odds of IPV among both HIV-negative (aOR 3.17, 95% CI 1.02-9.81) and HIV-positive women (aOR 1.79, 95% CI 0.99-3.24). Among HIV-positive women, financial autonomy was associated with reduced IPV (aOR:0.41,95%CI:0.23-0.75) while pregnancy in the last 12-months (aOR 2.25, 95% CI 1.07-4.74), risk of alcohol dependence (aOR 2.75, 95% CI 1.51-5.00) and risk of mental distress (aOR 2.62, 95% CI 1.33-5.16) were associated with increased IPV. Among HIV-negative women reporting sex in the last 12-months, transactional sex (aOR 3.97, 95% CI 1.02-15.37) and not knowing partner's HIV status (aOR 3.01, 95% CI 1.24-7.29) were associated with IPV. IPV was commonly reported in the study population and factors associated with IPV differed by HIV status. The association of mobility with IPV warrants further research. The high prevalence of harmful alcohol use and mental distress, and their association with IPV among HIV-positive women require urgent attention.

RESUMEN: El estudio HPTN 071 (PopART) fue un ensayo aleatorio-comunitario realizado en Zambia y Sudáfrica, que examinó el impacto de la prevención combinada, incluyendo las pruebas y tratamiento universal (UTT), en la incidencia del VIH. Este subestudio evaluó los factores asociados con la IPV (físicos y / o sexuales) para identificar diferencias en el estado del VIH. Durante 2015-16, un subconjunto aleatorio de adultos fueron reclutados para participar en el primer año de intervención de PopART, donde se administraron cuestionarios estandarizados. Se realizó una regresión logística para estimar las ratios de probabilidad de los factores asociados con la VPI. Entre las > 700 mujeres estudiadas (300 VIH negativas; 400 VIH positivas), ~ 20% informó haber experimentado violencia física y / o sexual en los últimos 12 meses. La violencia sexual fue similar en cuanto al estado del VIH. La denuncia de violencia física y sexual fue más común entre las mujeres VIH positivas. Pasar noches fuera de la comunidad en los últimos 12 meses, se asoció con mayores probabilidades de VPI entre las mujeres VIH negativas (ORa 3,17, 95% IC 1,02­9,81) y las mujeres VIH positivas (ORa 1,79, 95% IC 0,99­3,24). Entre las mujeres VIH positivas, la autonomía financiera se asoció con una reducción de la VPI (ORa 0,41; IC del 95% 0,23-0,75) mientras que en el embarazo en los últimos 12 meses (ORa 2,25; IC del 95% 1,07­4,74), riesgo a la dependencia del alcohol (ORa 2,75% IC 1,51­5,00) y el riesgo de angustia mental (ORa 2,62% IC del 95% 1,33­5,16) se asociaron con un aumento de la VPI. Entre las mujeres VIH negativas que informaron haber tenido relaciones sexuales en los últimos 12 meses, el sexo transaccional (ORa 3.97, 95% CI 1.02­15.37) y el desconocimiento del estado de VIH de la pareja (ORa 3.01, 95% CI 1.24­7.29) se asociaron con IPV. La IPV fue notificada mayoritariamente en la población de estudio y los factores asociados con la IPV diferían según el estado del VIH. La asociación de la movilidad con la IPV justifica una mayor investigación. La alta prevalencia de l consumo nocivo de alcohol y la angustia mental, y su asociación con la VPI entre las mujeres seropositivas, requieren atención urgente.

Does tuberculosis screening improve individual outcomes? A systematic review.

BACKGROUND: To determine if tuberculosis (TB) screening improves patient outcomes, we conducted two systematic reviews to investigate the effect of TB screening on diagnosis, treatment outcomes, deaths (clinical review assessing 23 outcome indicators); and patient costs (economic review). METHODS: Pubmed, EMBASE, Scopus and the Cochrane Library were searched between 1/1/1980-13/4/2020 (clinical review) and 1/1/2010-14/8/2020 (economic review). As studies were heterogeneous, data synthesis was narrative. FINDINGS: Clinical review: of 27,270 articles, 18 (n=3 trials) were eligible. Nine involved general populations. Compared to passive case finding (PCF), studies showed lower smear grade (n=2/3) and time to diagnosis (n=2/3); higher pre-treatment losses to follow-up (screened 23% and 29% vs PCF 15% and 14%; n=2/2); and similar treatment success (range 68-81%; n=4) and case fatality (range 3-11%; n=5) in the screened group. Nine reported on risk groups. Compared to PCF, studies showed lower smear positivity among those culture-confirmed (n=3/4) and time to diagnosis (n=2/2); and similar (range 80-90%; n=2/2) treatment success in the screened group. Case fatality was lower in n=2/3 observational studies; both reported on established screening programmes. A neonatal trial and post-hoc analysis of a household contacts trial found screening was associated with lower all-cause mortality. Economic review: From 2841 articles, six observational studies were eligible. Total costs (n=6) and catastrophic cost prevalence (n=4; range screened 9-45% vs PCF 12-61%) was lower among those screened. INTERPRETATION: We found very limited patient outcome data. Collecting and reporting this data must be prioritised to inform policy and practice. FUNDING: WHO and EDCTP.

Role of γ-adducin in actin cytoskeleton rearrangements in podocyte pathophysiology.

We recently reported that the enhanced susceptibility to chronic kidney disease (CKD) in the fawn-hooded hypertensive (FHH) rat is caused, at least in part, by a mutation in γ-adducin (ADD3) that attenuates renal vascular function. The present study explored whether Add3 contributes to the modulation of podocyte structure and function using FHH and FHH.Add3 transgenic rats. The expression of ADD3 on the membrane of primary podocytes isolated from FHH was reduced compared with FHH.Add3 transgenic rats. We found that F-actin nets, which are typically localized in the lamellipodia, replaced unbranched stress fibers in conditionally immortalized mouse podocytes transfected with Add3 Dicer-substrate short interfering RNA (DsiRNA) and primary podocytes isolated from FHH rats. There were increased F/G-actin ratios and expression of the Arp2/3 complexes throughout FHH podocytes in association with reduced synaptopodin and RhoA but enhanced Rac1 and CDC42 expression in the renal cortex, glomeruli, and podocytes of FHH rats. The expression of nephrin at the slit diaphragm and the levels of focal adhesion proteins integrin-α3 and integrin-ß1 were decreased in the glomeruli of FHH rats. Cell migration was enhanced and adhesion was reduced in podocytes of FHH rats as well as in immortalized mouse podocytes transfected with Add3 DsiRNA. Mean arterial pressures were similar in FHH and FHH.Add3 transgenic rats at 16 wk of age; however, FHH rats exhibited enhanced proteinuria associated with podocyte foot process effacement. These results demonstrate that reduced ADD3 function in FHH rats alters baseline podocyte pathophysiology by rearrangement of the actin cytoskeleton at the onset of proteinuria in young animals.

20-HETE Enzymes and Receptors in the Neurovascular Unit: Implications in Cerebrovascular Disease.

20-HETE is a potent vasoconstrictor that is implicated in the regulation of blood pressure, cerebral blood flow and neuronal death following ischemia. Numerous human genetic studies have shown that inactivating variants in the cytochrome P450 enzymes that produce 20-HETE are associated with hypertension, stroke and cerebrovascular disease. However, little is known about the expression and cellular distribution of the cytochrome P450A enzymes (CYP4A) that produce 20-HETE or the newly discovered 20-HETE receptor (GPR75) in the brain. The present study examined the cell types and regions in the rat forebrain that express CYP4A and GPR75. Brain tissue slices from Sprague Dawley (SD), Dahl Salt-Sensitive (SS) and CYP4A1 transgenic rat strains, as well as cultured human cerebral pericytes and cerebral vascular smooth muscle cells, were analyzed by fluorescent immunostaining. Tissue homogenates from these strains and cultured cells were examined by Western blot. In the cerebral vasculature, CYP4A and GPR75 were expressed in endothelial cells, vascular smooth muscle cells and the glial limiting membrane of pial arteries and penetrating arterioles but not in the endothelium of capillaries. CYP4A, but not GPR75, was expressed in astrocytes. CYP4A and GPR75 were both expressed in a subpopulation of pericytes on capillaries. The diameters of capillaries were significantly decreased at the sites of first and second-order pericytes that expressed CYP4A. Capillary diameters were unaffected at the sites of other pericytes that did not express CYP4A. These findings implicate 20-HETE as a paracrine mediator in various components of the neurovascular unit and are consistent with 20-HETE's emerging role in the regulation of cerebral blood flow, blood-brain barrier integrity, the pathogenesis of stroke and the vascular contributions to cognitive impairment and dementia. Moreover, this study highlights GPR75 as a potential therapeutic target for the treatment of these devastating conditions.

Impaired renal hemodynamics and glomerular hyperfiltration contribute to hypertension-induced renal injury.

Recently, we reported a mutation in γ-adducin (ADD3) was associated with an impaired myogenic response of the afferent arteriole and hypertension-induced chronic kidney disease (CKD) in fawn hooded hypertensive (FHH) rats. However, the mechanisms by which altered renal blood flow (RBF) autoregulation promotes hypertension-induced renal injury remain to be determined. The present study compared the time course of changes in renal hemodynamics and the progression of CKD during the development of DOCA-salt hypertension in FHH 1BN congenic rats [wild-type (WT)] with an intact myogenic response versus FHH 1BNAdd3KO (Add3KO) rats, which have impaired myogenic response. RBF was well autoregulated in WT rats but not in Add3KO rats. Glomerular capillary pressure rose by 6 versus 14 mmHg in WT versus Add3KO rats when blood pressure increased from 100 to 150 mmHg. After 1 wk of hypertension, glomerular filtration rate increased by 38% and glomerular nephrin expression decreased by 20% in Add3KO rats. Neither were altered in WT rats. Proteinuria doubled in WT rats versus a sixfold increase in Add3KO rats. The degree of renal injury was greater in Add3KO than WT rats after 3 wk of hypertension. RBF, glomerular filtration rate, and glomerular capillary pressure were lower by 20%, 28%, and 19% in Add3KO rats than in WT rats, which was associated with glomerular matrix expansion and loss of capillary filtration area. The results indicated that impaired RBF autoregulation and eutrophic remodeling of preglomerular arterioles increase the transmission of pressure to glomeruli, which induces podocyte loss and accelerates the progression of CKD in hypertensive Add3KO rats.

Secondary analysis of tuberculosis stigma data from a cluster randomised trial in Zambia and South Africa (ZAMSTAR).

SETTING: Zambian and South African TB and HIV Reduction (ZAMSTAR) cluster-randomised trial (CRT) communities, 2006-2009. OBJECTIVES: To develop TB stigma items, and evaluate changes in them in response to a household intervention aimed at reducing TB transmission and prevalence but not tailored to reduce stigma. DESIGN: TB stigma was measured at baseline and 18 months later among 1826 recently diagnosed TB patients and 1235 adult members of their households across 24 communities; 12 of 24 communities were randomised to receive the household intervention. We estimated the impact of the household intervention on TB stigma using standard CRT analytical methods. RESULTS: Among household members, prevalence of blame and belief in transmission myths fell in both study arms over time: adjusted prevalence ratios (aPRs) comparing the household intervention with the non-household intervention arm were respectively 0.61 (95%CI 0.26-1.44) and 0.77 (95%CI 0.48-1.25) at 18-month follow-up. Among TB patients, at baseline a low percentage experienced social exclusion and poor treatment by health staff and a relatively high percentage reported 'being made fun of', with little change over time. Disclosure of TB status increased over time in both study arms. Internalised stigma was less prevalent in the household arm at both baseline and follow-up, with an aPR of 0.85 (95%CI 0.41-1.76). Variability in stigma levels between countries and across communities was large. CONCLUSION: Robust TB stigma items were developed. TB stigma was not significantly reduced by the household intervention, although confidence intervals for estimated intervention effects were wide. We suggest that stigma-specific interventions are required to effectively address TB stigma.

Defining the research agenda to measure and reduce tuberculosis stigmas.

Crucial to finding and treating the 4 million tuberculosis (TB) patients currently missed by national TB programmes, TB stigma is receiving well-deserved and long-delayed attention at the global level. However, the ability to measure and evaluate the success of TB stigma-reduction efforts is limited by the need for additional tools. At a 2016 TB stigma-measurement meeting held in The Hague, The Netherlands, stigma experts discussed and proposed a research agenda around four themes: 1) drivers: what are the main drivers and domains of TB stigma(s)?; 2) consequences: how consequential are TB stigmas and how are negative impacts most felt?; 3) burden: what is the global prevalence and distribution of TB stigma(s) and what explains any variation? 4): intervention: what can be done to reduce the extent and impact of TB stigma(s)? Each theme was further subdivided into research topics to be addressed to move the agenda forward. These include greater clarity on what causes TB stigmas to emerge and thrive, the difficulty of measuring the complexity of stigma, and the improbability of a universal stigma 'cure'. Nevertheless, these challenges should not hinder investments in the measurement and reduction of TB stigma. We believe it is time to focus on how, and not whether, the global community should measure and reduce TB stigma.

Does childbirth alter the reflex pelvic floor response to coughing?

OBJECTIVE: To determine the prevalence of and to quantify the effect of reflex pelvic floor activation on coughing in nulliparous pregnant women, and to assess peripartal changes and any association with stress urinary incontinence. METHODS: Between April 2008 and March 2010, 131 nulliparous pregnant women were recruited from an antenatal clinic. All participants were interviewed and underwent four-dimensional translabial ultrasound examination at antepartum (35.8 (mean) weeks' gestation) and postpartum (4.6 (mean) months) visits. Four-dimensional ultrasound volume datasets of the pelvic floor during coughs were obtained at a minimum frame rate of 16 Hz, using a 10° volume acquisition angle. To quantify a reflex levator contraction we measured the midsagittal hiatal diameter at multiple time points. Levator integrity was determined using tomographic ultrasound imaging. RESULTS: From 131 women recruited, 47 datasets were technically suboptimal, leaving 84. There was a visible pelvic floor reflex in 82 (98%) cases. At the postpartum visit this was reduced to 63/84, i.e. 75% (P < 0.001). The magnitude of a reflex contraction was markedly reduced postpartum, from 4.8 mm to 2.0 mm (P < 0.001), and this effect was associated with delivery mode (P = 0.042). There was a trend towards an association between lower reflex contraction magnitude and stress incontinence (0.87 ± 3.18 mm vs. 2.36 ± 3.5 mm; P = 0.08) at the postpartum follow-up visit. CONCLUSIONS: Pelvic floor reflexes are altered by childbirth. This alteration may be associated with vaginal delivery. Reflex magnitude may be associated with postpartum stress urinary incontinence. The clinical significance of this finding is uncertain.

HIV Type 1 Nef is released from infected cells in CD45(+) microvesicles and is present in the plasma of HIV-infected individuals.

HIV-1 Nef has been demonstrated to be integral for viral persistence, infectivity, and the acceleration of disease pathogenesis (AIDS) in humans. Nef has also been detected in the plasma of HIV-infected individuals and is released from infected cells. The form in which Nef is released from infected cells is unknown. However, Nef is a myristoylated protein and has been shown to interact with the intracellular vesicular trafficking network. Here we show that Nef is released in CD45-containing microvesicles. This microvesicular Nef (mvNef) is detected in the plasma of HIV-infected individuals at relatively high concentrations (10 ng/ml). It is also present in tissue culture supernatants of Jurkat cells infected with HIV(MN). Interestingly, plasma mvNef levels in HIV(+) patients did not significantly correlate with viral load or CD4 count. Microvesicular Nef levels persisted in the plasma of HIV-infected individuals despite the use of antiretroviral therapy, even in individuals with undetectable viral loads. Using cell lines, we found Nef microvesicles induce apoptosis in Jurkat T-lymphocytes but had no observed effect on the U937 monocytic cell line. Given the large amount of mvNef present in the plasma of HIV-infected individuals, the apoptotic effect of mvNef on T cells, and the observed functions of extracellular soluble Nef in vitro, it seems likely that in vivo mvNef may play a significant role in the pathogenesis of AIDS.

Children's role in enhanced case finding in Zambia.

OBJECTIVE: To evaluate information dissemination by children and attitudes among children towards a school-based tuberculosis (TB) reduction strategy that asked children to address TB symptoms, testing and stigma in their homes. SETTING AND DESIGN: Qualitative research was conducted with schoolchildren before, and 2 years into, an intervention to promote early detection of TB using sputum microscopy in Zambia. The baseline study in 2005 involved 38 children at five sites. The evaluation in 2008 included 209 children in schools at four sites. Research with schoolchildren included discussions, drawings, role plays and narratives. RESULTS: The baseline study revealed children's enthusiasm to learn about TB and the human immunodeficiency virus (HIV), but it also revealed children's anxieties about the possible conflicts related to discussing HIV and TB with adults. Children in the evaluation demonstrated more accurate knowledge about TB and HIV than in the baseline study. Children were enthusiastic about discussing TB and HIV at home. Their responses suggested that they did so with respect and adult approval, circumventing the intergenerational conflict expected during the baseline study. CONCLUSION: The present study demonstrates that schoolchildren have a role to play in enhanced case finding. Schoolchildren are already familiar with TB in areas of high burden, but they need more information about the link between TB and HIV and about antiretroviral treatment.

A multidisciplinary method to map potential tuberculosis transmission 'hot spots' in high-burden communities.

BACKGROUND: Global control of the tuberculosis (TB) epidemic remains poor, especially in high-burden settings where ongoing transmission sustains the epidemic. In such settings, a significant amount of transmission takes place outside the household, and practical approaches to understanding transmission at community level are needed. OBJECTIVE: To identify and map potential TB transmission 'hot spots' across high-burden communities. SETTING AND DESIGN: Our method draws on data that qualitatively describe a high-burden community in Cape Town, South Africa. Established transmission principles are applied to grade the potential TB transmission risk posed by congregate settings in the community. Geographic information systems (GIS) technology then creates a visual map, locating potential transmission 'hot spots' in the community. RESULTS: Drinking places (shebeens), clinics and churches (often gatherings in confined homes) emerge as gathering places that potentially pose a high transmission risk, particularly if located in overcrowded and impoverished areas of the community. CONCLUSION: This proof-of-concept study demonstrates that combining qualitative techniques with GIS mapping may improve our understanding of potential TB transmission within a community and guide public health interventions to enhance TB control efforts.

Association of GNB3 C825T polymorphism with peak oxygen consumption.

The C825T single nucleotide polymorphism (SNP) in the guanine nucleotide-binding protein, beta polypeptide 3 ( GNB3) gene gives rise to a splice variant, GNB3s that has enhanced G protein activation and signal transduction activity. This variant has been reported to be associated with cardiovascular disease, diabetes and obesity. We studied this SNP in 95 healthy 18 to 30 year-old African American university students to determine its association with aerobic capacity and cardiorespiratory fitness as measured by peak oxygen consumption (VO (2)peak). We also tested the effect of heart rate variability (HRV) as an independent predictor of VO (2)peak. We tested the association of the SNP and HRV with VO (2)peak in a multivariate regression analysis with appropriate adjustments of covariates, under dominant and recessive models. We found a significant independent association of the 825T allele with VO (2)peak under the dominant model (beta-coef.=-0.101, P=0.0442). We also observed that HRV marginally influenced VO (2)peak. This finding suggests that GNB3 C825T polymorphism is associated with VO (2)peak which is influenced by autonomic modulation of heart rate in African Americans.

Exercise training favourably affects autonomic and blood pressure responses during mental and physical stressors in African-American men.

Aerobic exercise is a powerful mechanism by which cardiovascular and autonomic parameters may be improved. We sought to quantify the extent of benefit that could be achieved by a short-term monitored exercise regimen on several autonomic parameters during recognized mental and physical stressors in young normotensive African-American men matched for a family history of hypertension, a group at high risk for the development of hypertension. Autonomic modulations were derived using spectral decomposition of the electrocardiogram and beat-to-beat blood pressures (BPs). Arterial compliance was obtained using contour analysis of the radial artery pulse wave. The analysis of variance revealed that compared with a matched sedentary control group, aerobic capacity of the trained group significantly increased by 16%. Autonomic modulations, arterial compliance and BP responses significantly improved during some of the stressors, whereas no such improvements were seen in the control group. Attenuated responses, mediated through a favourable shift in sympathovagal balance and enhanced arterial compliance, provide mechanistic evidence of how certain variables may be improved due to aerobic conditioning in a population at high risk for the development of hypertension.

'Kuyendela odwala TB'--visiting TB patients: the widening role of home-based care organisations in the management of tuberculosis patients in Lusaka, Zambia.

OBJECTIVE: To explore the widening role of home-based care (HBC) organisations in the management of TB patients in Lusaka, Zambia, in 1999. DESIGN: In a purposeful sample of eight HBC organisations and 1 hospice in Lusaka, 142 TB patients under HBC, 54 care givers, 42 TB patients not under HBC and 9 managers were interviewed. RESULTS: At least 50% of TB patients in Lusaka are cared for by HBC. The role of HBC in management of TB patients included food aid, practical and emotional support through the visits of voluntary care givers and, often, medical advice and treatment. TB diagnosis is carried out within the government health facilities. Five HBC organisations supplied anti-tuberculosis drugs, and three tried to carry out direct observation of treatment. The majority of the TB patients said their situation improved under HBC. Management was undermined by poor record keeping, sporadic anti-tuberculosis drug supplies, stigmatising preventive messages, limited supervision of care givers and poor coordination with the District Health Services. CONCLUSION: HBC organisations have become a key partner in TB control, looking after half the TB patients in Lusaka from diagnosis onwards, and complementing the public system. However, the quality of their management of TB and their partnership with government need to improve.

Mother-to-child discordance in HLA-G exon 2 is associated with a reduced risk of perinatal HIV-1 transmission.

Definitive genetic parameters correlating with mother-to-child transmission (MCT) of HIV have not been fully established. We screened for the potential correlation between HLA-G variants and MCT, in a cohort of mother-child pairs. Discordance in exon 2 of HLA-G was significantly more common among non-transmitting (93%) than transmitting mother-child pairs (40%). Our results suggest that mother-child pairs both carrying the identical mutation in HLA-G exon 2 may be at higher risk of MCT of HIV-1.

Physical activity and blood pressure responsiveness to the cold pressor test in normotensive young adult African-American males.

The aim of our study was to examine whether there is an association between blood pressure reactivity to the cold pressor test in African Americans who engaged in different levels of physical activity. We examined the systolic pressure, diastolic pressure, mean arterial blood pressure, heart rate, cardiac index, total peripheral resistance, and forearm blood flow during a two-minute cold pressor test in 15 aerobic, physically active and 15 physically inactive, normotensive young adult African-American males. Peak oxygen consumption varied as a function of physical activity, and was significantly higher in the physically active than in the physically inactive subjects (54.5 +/- 1.5 vs 36.8 +/- 0.7 ml kg(-1) min(-1)) (P<.05). During the cold pressor test, consisting of immersing the foot in ice water, the change in cardiovascular responses were similar between the physically active and the physically inactive groups. These results suggest that regular physical activity may not contribute to an attenuated blood pressure response to behavioral stress of the cold pressor test in normotensive young adult African-American males.