The chronic stress risk phenotype mirrored in the human retina as a neurodegenerative condition.

The brain is the key organ that orchestrates the stress response which translates to the retina. The retina is an extension of the brain and retinal symptoms in subjects with neurodegenerative diseases substantiated the eye as a window to the brain. The retina is used in this study to determine whether chronic stress reflects neurodegenerative signs indicative of neurodegenerative conditions. A three-year prospective cohort (n = 333; aged 46 ± 9 years) was stratified into stress-phenotype cases (n = 212) and controls (n = 121) by applying the Malan stress-phenotype index. Neurodegenerative risk markers included ischemia (astrocytic S100 calcium-binding protein B/S100B); 24-h blood pressure, proteomics; inflammation (tumor-necrosis-factor-α/TNF-α); neuronal damage (neuron-specific-enolase); anti-apoptosis of retinal-ganglion-cells (beta-nerve-growth-factor), astrocytic activity (glial-fibrillary-acidic-protein); hematocrit (viscosity) and retinal follow-up data [vessels; stress-optic-neuropathy]. Stress-optic-neuropathy risk was calculated from two indices: a newly derived diastolic-ocular-perfusion-pressure cut-point ≥68 mmHg relating to the stress-phenotype; combined with an established cup-to-disk ratio cut-point ≥0.3. Higher stress-optic-neuropathy (39% vs. 17%) and hypertension (73% vs. 16%) prevalence was observed in the stress-phenotype cases vs. controls. Elevated diastolic-ocular-perfusion-pressure, indicating hypoperfusion, was related to arterial narrowing and trend for ischemia increases in the stress-phenotype. Ischemia in the stress-phenotype at baseline, follow-up and three-year changes was related to consistent inflammation (TNF-α and cytokine-interleukin-17-receptor-A), neuron-specific-enolase increases, consistent apoptosis (chitinase-3-like protein 1, low beta-nerve-growth-factor), glial-fibrillary-acidic-protein decreases, elevated viscosity, vein widening as risk marker of endothelial dysfunction in the blood-retinal barrier, lower vein count, and elevated stress-optic-neuropathy. The stress-phenotype and related neurodegenerative signs of ongoing brain ischemia, apoptosis and endothelial dysfunction compromised blood-retinal barrier permeability and optic nerve integrity. In fact, the stress-phenotype could identify persons at high risk of neurodegeneration to indicate a neurodegenerative condition.

Chronic depression symptoms and salivary NOx are associated with retinal vascular dysregulation: The SABPA study.

BACKGROUND: Depression has been associated with impaired nitric oxide (NO)-mediated vasodilation and vascular dysregulation (VD). Whether depression and NO levels will disturb retinal haemodynamics is not clear. OBJECTIVES AND METHODS: Associations between the retinal vasculature, diastolic ocular perfusion pressure (DOPP) as measure of hypoperfusion, NO metabolites (NOx) and depression symptoms were assessed. Chronic VD risk markers [depression symptoms (Patient Health Questionnaire/PHQ-9 ≥ 10) and 24 h pulse pressure] were determined in a bi-ethnic cohort (n = 313; 48.6 ± 9 years; 53.9% men). At 3 year follow-up, retinal vessel calibre and retinopathy signs were quantified from digital images. Salivary NOx was obtained pre- and post-flicker light-induced provocation (FLIP). DOPP was defined as diastolic blood pressure minus intraocular pressure. RESULTS: Chronic VD risk was evident in Blacks opposed to acute risk in Whites (P < 0.05). At follow-up, retinopathy (Blacks 60.4%/Whites 39.6%), lower pre-FLIP (µM) and higher post-FLIP NOx (changes from baseline, %), arteriolar narrowing and wider venular calibre values were evident in Blacks compared to Whites, independent of confounders. A wider venular calibre, an index of stroke risk, was associated with chronic depression symptoms [cut point 248 MU: Area under the curve 0.61 (95% CI: 0.51, 0.72); 71% sensitivity; 55% specificity] as well as with hypoperfusion in the Blacks. In this group, arteriolar narrowing was associated with hypoperfusion; and attenuated arteriolar dilation with increased post-FLIP NOx responses. CONCLUSIONS: Chronic depression symptoms may alter NO regulation and facilitate VD. NO-mediated vasoconstriction presumably impeded perfusion, retinal haemodynamics and -remodelling; potentiating stroke risk in Blacks.

Baroreceptor sensitivity, cardiovascular responses and ECG left ventricular hypertrophy in men: the SABPA study.

AIM. Research has shown a significant relationship between hypertension and attenuated baroreceptor sensitivity (BRS), which in turn reflects alterations of autonomic control of the cardiovascular system. The objective of this study was to compare the BRS of African and Caucasian men and determine possible associations with blood pressure and left ventricular hypertrophy. MATERIALS AND METHODS. Participants included African (n = 82) and Caucasian (n = 100) male teachers, aged between 20 and 65 years, recruited in the North-West Province, South Africa. Ambulatory blood pressure monitoring was conducted for a 22-23-h period and, thereafter, cardiovascular parameters were recorded with a Finometer and 12-lead ECG during rest and while challenging the cardiovascular system with the cold pressor and Stroop color?word conflict tests. Spontaneous BRS was calculated as well as the Cornell product [marker of left ventricular hypertrophy (LVH)]. RESULTS. The African men had significantly lower BRS stress responses. Attenuated BRS coupled to an ?-adrenergic response pattern predicted elevation of blood pressure in the African men. BRS reduction did not prove to be a significant predictor of LVH. CONCLUSION. Lower BRS, especially during stress, may pose a significant health threat for African men regarding earlier development or promotion of α -adrenergic-driven hypertension and greater risk for cardiovascular disease.

Coping facilitated troponin T increases and hypo-responsivity in the copeptin-HPA-axis during acute mental stress in a black cohort: The SABPA study.

BACKGROUND: Defensive coping (DefS) was associated with a vulnerable cardiovascular profile in blacks. The copeptin/vasopressin system is a manifestation of hypothalamic-pituitary-adrenal-axis activity and may act as an acute compensatory mechanism when there is a disruption in volume-loading homeostasis, i.e. when cardiac stress is evident. Whether DefS will influence associations between copeptin and cardiac stress markers, remains unclear. Here we aimed to determine associations between acute mental stress responses of copeptin, vascular responsiveness and biomarkers of cardiomyocyte injury [cardiac troponin T (cTnT)] and cardiac wall-stress [N-terminal pro-brain natriuretic peptide (NT-proBNP)] in DefS race groups. METHODS: South African black and white teachers (n = 378) of both sexes, participated in this target population study. Cases with a history of myocardial infarction, stroke and atrial fibrillation were excluded. We obtained coping scores (Coping Strategy Indicator), beat-to-beat blood pressure and fasting blood samples at rest and after 1-min exposure to the Stroop-Colour-Word-Conflict-test. RESULTS: Interaction effects (p < .05) for copeptin percentage change (%) during the Stroop-Colour-Word-Conflict-test determined stratification of participants into race and DefS (≥26, above-median score) groups. In DefS blacks, Stroop-Colour-Word-Conflict-test exposure elicited increases in cTnT%, NT-proBNP% and diastolic-blood pressure%. Again, in these individuals, multiple regression analyses showed positive associations between copeptin% and total peripheral resistance%; with inverse associations between copeptin% and cTnT% (p < .05). None of these associations were found in DefS whites. CONCLUSIONS: Utilisation of DefS in blacks provoked vascular hyper-responsiveness and cardiac wall stress (elevated cTnT and NT-proBNP); possibly mediated via the copeptin/vasopressin system. However, a presumably hypo-responsive hypothalamic-pituitary-adrenal-axis during stress exposure could not counteract coronary perfusion deficits via additional copeptin/vasopressin release. The presence of defensiveness may have clinical implications in preventive cardiology.

The use of nonparametric effect sizes in single study musculoskeletal physiotherapy research: A practical primer.

There is a strong push for the inclusion of effect size indexes alongside the reporting of statistical analysis in academic journals. Nonparametric methods of analysis have generally been developed less than their parametric counterparts have, and are also generally less well known. Too often researchers use parametric statistics where nonparametric measures would be more appropriate. This holds true for nonparametric measures of effect size, where even when researchers use nonparametric statistics, some use parametric effect size measures to interpret the result. This paper attempts to provide a practical overview and illustration of the correct usage and interpretation of effect size measures for nonparametric statistics for single study designs using real-world physiotherapy data in the worked examples. This primer covers a range of different formulae based on categorical measures of effect size, as well as between- and within-group designs using ranked data. While this primer does use examples focusing on physiotherapy research, the applications of the information can be used in any field of research.

The use of parametric effect sizes in single study musculoskeletal physiotherapy research: A practical primer.

Many researchers often do not report effect sizes at all, and, if they do report them, often do not report the correct measure for the design that has been used in the research. With the increased level of attention being given to the reporting of effect sizes and their corresponding confidence intervals, it is important that there is field-specific literature pertaining to the calculation and reporting of these measures. This paper acts as a practical primer for the calculation and reporting of effect size measures aimed at, but not limited to, the field of musculoskeletal physiotherapy research. This primer involves a discussion on which effect sizes are appropriate for within and between-subject single study research, illustrating, through examples based on musculoskeletal research data, how these measures are calculated, interpreted, and reported.

Development and evaluation of a rapid multiplex-PCR based system for Mycobacterium tuberculosis diagnosis using sputum samples.

Global tuberculosis (TB) control and eradication is hampered by the unavailability of simple, rapid and affordable diagnostic tests deployable at low infrastructure microscopy centers. We have developed and evaluated the performance of a nucleic acid amplification test for detection of Mycobacterium tuberculosis (MTB), the NWU-TB test, in clinical sputum specimens from 306 patients with suspected pulmonary tuberculosis. The test involves sputum sample processing using a Lyser device within 7 min, followed by rapid multiplex-PCR on a fast thermal cycler within 25 min, and amplicon resolution on agarose gel electrophoresis. Samples were also examined for presence of MTB using smear microscopy, GeneXpert and MGIT culture. Results were assessed in comparison to a MGIT culture as gold standard. Of the 306 patients, 174 had a previous TB history or already on treatment, and 132 were TB naïve cases. The NWU-TB system was found to have an overall sensitivity and specificity of 80.8% (95% CI: 75-85.7) and 75.6% (95% CI: 64.9-84.4) respectively, in comparison to 85.3% (95% CI: 79.9-89.6) and 73.2% (95% CI: 62.2-82.4) respectively for GeneXpert; and 62.1% (95% CI: 55.3-68.4) and 56.1% (95% CI: 44.7-67) respectively for smear microscopy. The study has shown that the NWU-TB system allows detection of TB in less than two hours and can be utilized at low infrastructure sites to provide quick and accurate diagnosis at a very low cost.

Defensive coping, urbanization, and neuroendocrine function in Black Africans: the THUSA study.

Dissociation between ß-adrenergic behavioral and physiological defensive active coping (AC) responses was associated with cardiometabolic risk in urban but not rural African males. Whether this is partly driven by underlying neuroendocrine dysfunction is not certain. We aimed to assess the association between coping style, urbanization, and neuroendocrine function. Blood pressure (BP) and serum stress hormones were assessed across levels of urbanization (rural vs. urban) and coping style (active vs. passive) in 178 Black African men. Urban men demonstrated increased hypertension prevalence, α-adrenergic hemodynamic pattern, lower testosterone levels, and a larger cortisol:testosterone ratio (Cort:Test) compared to their rural counterparts. This was particularly evident in urban AC men where cortisol and Cort:Test explained 36-40% of the variance in BP. Dissociation between behavioral and physiological ß-adrenergic neuroendocrine responses in urban AC African men was shown. A stressful urban environment might induce an apparent loss of physiological control, thereby facilitating disturbed neuroendocrine AC responses, which could increase cardiovascular disease risk.