Heart Rate Variability as a Biomarker for Predicting Stroke, Post-stroke Complications and Functionality

© The Author(s) 2018. Background: Heart rate variability (HRV) is a non-invasive measure of the function of the autonomic nervous system, and its dynamic nature may provide a means through which stroke and its associated complications may be predicted, monitored, and managed. Objective: The objective of this review is to identify and provide a critique on the most recent uses of HRV in stroke diagnosis/management and highlight areas that warrant further research. Methods: The MEDLINE, CINAHL, and OVID MEDLINE databases were canvassed using a systematic search strategy, for articles investigating the use of HRV in stroke diagnosis and management. Initial paper selections were based on title alone, and final paper inclusion was informed by a full-text critical appraisal. Results: The systematic search returned 98 records, of which 51 were unique. Following screening, 22 records were included in the final systematic review. The included papers provided some information regarding predicting incident stroke, which largely seems to be best predicted by time- and frequency-domain HRV parameters. Furthermore, post-stroke complications and functionality are similarly predicted by time- and frequency-domain parameters, as well as non-linear parameters in some instances. Conclusions: Current research provides good evidence that HRV parameters may have utility as a biomarker for stroke and for post-stroke complications and/or functionality. Future research would benefit from the integration of non-linear, and novel parameters, the hybridisation of HRV parameters, and the expansion of the utilisation of predictive regression and hazard modelling

Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases

© The Author(s) 2018. Cardiovascular disease (CVD) is the leading cause of death in the world and our approach to the control and management of CVD mortality is limited. Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of Natto has been linked to a reduction in CVD mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, and lipid-lowering, antiplatelet, and neuroprotective effects. This review covers the major pharmacologic effects of NK with a focus on its clinical relevance to CVD. It outlines the advantages of NK and the outstanding issues pertaining to NK pharmacokinetics. Available evidence suggests that NK is a unique natural compound that possesses several key cardiovascular beneficial effects for patients with CVD and is therefore an ideal drug candidate for the prevention and treatment of CVD. Nattokinase is a promising alternative in the management of CVD

Vasodilation of rat skeletal muscle arteries by the novel BK channel opener GoSlo is mediated by the simultaneous activation of BK and Kv7 channels

BACKGROUND AND PURPOSE: BK channels play important roles in various physiological and pathophysiological processes and thus have been the target of several drug development programs focused on creating new efficacious BK channel openers, such as the GoSlo-SR compounds. However, the effect of GoSlo-SR compounds on vascular smooth muscle has not been studied. Therefore, we tested the hypothesis that GoSlo-SR compounds dilate arteries exclusively by activating BK channels. EXPERIMENTAL APPROACH: Experiments were performed on rat Gracilis muscle, saphenous, mesenteric and tail arteries using isobaric and isometric myography, sharp microelectrodes, digital droplet PCR and the patch-clamp technique. KEY RESULTS: GoSlo-SR compounds dilated isobaric and relaxed and hyperpolarized isometric vessel preparations and their effects were abolished after (i) functionally eliminating K channels by pre-constriction with 50 mM KCl or (ii) blocking all K channels known to be expressed in vascular smooth muscle. However, these effects were not blocked when BK channels were inhibited. Surprisingly, the K(V)7 channel inhibitor XE991 reduced their effects considerably, but neither K(V)1 nor K(V)2 channel blockers altered the inhibitory effects of GoSlo-SR. However, the combined blockade of BK and K(V)7 channels abolished the GoSlo-SR-induced relaxation. GoSlo-SR compounds also activated K(V)7.4 and K(V)7.5 channels expressed in HEK 293 cells. CONCLUSIONS AND IMPLICATIONS: This study shows that GoSlo-SR-compounds are effective relaxants in vascular smooth muscle and mediate their effects by a combined activation of BK and K(V)7.4/K(V)7.5 channels. Activation of K(V)1, K(V)2 or K(V)7.1 channels or other vasodilator pathways seem not to be involved

Mitigating the impact of COVID-19 on tuberculosis and HIV services: A cross-sectional survey of 669 health professionals in 64 low and middle-income countries.

OBJECTIVE: The experiences of frontline healthcare professionals are essential in identifying strategies to mitigate the disruption to healthcare services caused by the COVID-19 pandemic. METHODS: We conducted a cross-sectional study of TB and HIV professionals in low and middle-income countries (LMIC). Between May 12 and August 6, 2020, we collected qualitative and quantitative data using an online survey in 11 languages. We used descriptive statistics and thematic analysis to analyse responses. FINDINGS: 669 respondents from 64 countries completed the survey. Over 40% stated that it was either impossible or much harder for TB and HIV patients to reach healthcare facilities since COVID-19. The most common barriers reported to affect patients were: fear of getting infected with SARS-CoV-2, transport disruptions and movement restrictions. 37% and 28% of responses about TB and HIV stated that healthcare provider access to facilities was also severely impacted. Strategies to address reduced transport needs and costs-including proactive coordination between the health and transport sector and cards that facilitate lower cost or easier travel-were presented in qualitative responses. Access to non-medical support for patients, such as food supplementation or counselling, was severely disrupted according to 36% and 31% of HIV and TB respondents respectively; qualitative data suggested that the need for such services was exacerbated. CONCLUSION: Patients and healthcare providers across numerous LMIC faced substantial challenges in accessing healthcare facilities, and non-medical support for patients was particularly impacted. Synthesising recommendations of frontline professionals should be prioritised for informing policymakers and healthcare service delivery organisations

Free T3 as a Reliable Indicator of Thyroid Dysfunction in Cirrhosis

 Liver cirrhosis is a common ailment afflicting a significant proportion of Pakistani population of all ages. Quite often, these patients require multi-system intervention, owing to the nature of this disease. This study was specifically conceived to objectively assess the level of thyroid dysfunction in cirrhotics of the urban population of Karachi, together with its relationship to the severity of liver malfunction as gauged by the Childs classification. Liver and thyroid hormones are intricately correlated so thyroid hormone abnormalities are seen in patients of liver diseases, although they are clinically euthyroid. The aim of this study is to correlate the abnormalities in thyroid hormones with the clinical staging of hepatic encephalopathy and to examine the role of thyroid hormone as a reliable prognostic indicator of encephalopathy. We assessed 50 patients of cirrhosis for the thyroid hormone levels (including thyroxine, triiodothyronine and TSH) by Enzyme Linked Immuno sorbent Assay (ELISA) technique. Patients were also examined clinically for gradings of Cirrhosis by The Childs Pugh classification. All procedures on patients were done in accordance with the Helsinki Declaration. Triiodothyronine (FT3) was found to be a useful indicator of thyroid dysfunctions and it parallels the grading of Childs classification, whereas thyroxine and TSH were not found to be significantly correlated. We proposed that triiodothyronine could act as a prognostic marker to predict severity of cirrhosis and for assessing minimal hepatic encephalopathy. Keywords - Thyroid hormones, Cirrhosis, Childs classification, extra hepatic manifestations of liver disease.</jats:p

Assessing audit fees: Turnover, inflation & minimum stipend rate

Auditing firms rely on audit fees to generate revenue. The audit fee is generally agreed upon by auditee and auditor. For the calculation of audit fees, no standard formula exists. Pakistan's regulatory body for audit firms ‘ICAP' has imposed certain cost constraints on audit firms. As per the literature, stipend rates have been used rarely to determine audit fees. As a result, this paper examines audit fee determination using variables such as the company's assets, turnover, current ratio, inflation, and minimum stipend rate. These variables are especially influential in a developing country such as Pakistan. To determine audit fees, a panel regression model is being de-veloped. We used data from 40 publicly traded companies from 2014 to 2017 to regress on our model. After extensive testing with the Hausman and F-tests, the fixed effect model is finally applied. Empirically, it was discov-ered that the current ratio, the entity's turnover, and the stipend amount all have a significant positive effect on the calculation of audit fees. T The study's findings have significant implications not only for audit firms, but also for auditees in determining audit fees

Recent advances in molecular biomarkers for diabetes mellitus: a systematic review

© 2017 Informa UK Limited, trading as Taylor & Francis Group. Context: Diabetes is a growing global metabolic epidemic. Current research is focussing on exploring how the biological processes and clinical outcomes of diabetes are related and developing novel biomarkers to measure these relationships, as this can subsequently improve diagnostic, therapeutic and management capacity. Objective: The objective of this study is to identify the most recent advances in molecular biomarkers of diabetes and directions that warrant further research. Methods: Using a systematic search strategy, the MEDLINE, CINAHL and OVID MEDLINE databases were canvassed for articles that investigated molecular biomarkers for diabetes. Initial selections were made based on article title, whilst final inclusion was informed by a critical appraisal of the full text of each article. Results: The systematic search returned 246 records, of which 113 were unique. Following screening, 29 records were included in the final review. Three main research strategies (the development of novel technologies, broad biomarker panels, and targeted approaches) identified a number of potential biomarkers for diabetes including miR-126, C-reactive protein, 2-aminoadipic acid and betatrophin. Conclusion: The most promising research avenue identified is the detection and quantification of micro RNA. Further, the utilisation of functionalised electrodes as a means to detect biomarker compounds also warrants attention

Distance-quality trade-off and choice of family planning provider in urban Pakistan

Background: There is limited evidence between contraceptive use, availability of commodities and distance to the facility in developing countries. Distance to the facility is an essential determinant of contraceptive use. Still, women may not seek family planning services from the nearest facility and may be prepared to travel the farthest distance to receive quality family planning services. Methods: We analyzed women\u27s survey data linked to health facility data and applied an alternate specific conditional logit model to examine the distance a woman is prepared to travel and the quality of services offered by facilities in urban areas in Karachi, Pakistan. Results: This study analyzed data from 336 women and 28 facilities and identified that the mean distance to the nearest facility was 0.44 km; the chosen facility was, on average, 5 km away. Women preferred facilities that offered a range of contraceptive methods and additional services provided by female healthcare providers only. Furthermore, on average, women are willing to travel a further 1.7 km for a facility that offers more family planning methods, 1.4 km for a facility that offers additional health services and 11 km for a facility that offers services delivered by female healthcare providers. Conclusions: The findings highlight the quality measures women prioritize over distance and consider essential when choosing a family planning facilit

Isolation and antiproliferative activity of triterpenoids and fatty acids from the leaves and stem of <i>Turraea vogelii</i> Hook. f. ex benth

<p>Chloroform extract from the leaves of <i>Turraea vogelii</i> Hook f. ex Benth demonstrated cytotoxic activity against a chronic myelogenous leukemia cell, K-562 with IC₅₀ of 14.27 μg/mL, while chloroform, ethyl acetate and methanol extracts from the stem of the plant inhibited K-562 cells growth with IC₅₀ of 19.50, 24.10 and 85.40 μg/mL respectively. Bioactive chloroform extract of <i>Turraea vogelii</i> leaves affords two triterpenoids: oleana-12,15,20-trien-3β-ol <b>(1)</b>, and oleana-11,13-dien-3β,16α,28-triol <b>(2)</b>, with six fatty esters, ethyl hexaeicos-5-enoate <b>(3)</b>, 3-hydroxy-1,2,3-propanetriyltris(tetadecanoate) <b>(4)</b>, 1,2,3-propanetriyl(7Z,7′Z,7′′Z)tris(-7-hexadecenoate) <b>(5)</b>, 1,2,3-propanetriyl(5Z,5′Z,5′′Z)tris(-5-hexadecenoate) <b>(6)</b>, 1,2,3-propanetriyltris(octadecanoate) <b>(7)</b>, and 2β-hydroxymethyl tetraeicosanoate <b>(8).</b> Tetradecane (<b>9)</b>, four fatty acids: hexadecanoic acid (<b>10)</b>, tetradecanoic acid (<b>11)</b>, <b><i>(</i></b><i>Z)</i>-9-eicosenoic acid <b>(12)</b>, and ethyl tetradec-7-enoate <b>(13)</b> were isolated from chloroform extract of <i>Turraea vogelii</i> stem. 1,2,3-propanetriyltris(heptadecanoate) <b>(14)</b>, <i>(Z)</i>-9-octadecenoic acid <b>(15)</b> and <i>(Z)</i>-7-tetradecenoic acid <b>(16)</b> were isolated from ethyl acetate extract while <i>(Z)</i>-5-pentadecenoic acid <b>(17)</b> was obtained from methanol extract of the plant stem. Compounds <b>1</b>, <b>2</b>, <b>5</b>, <b>6</b>, <b>11</b>, <b>12</b>, <b>15</b>, <b>16</b> and <b>17</b> exhibited pronounced antiproliferative activity against K-562 cell lines.</p