Arterial stiffness in hypertensive and type 2 diabetes patients in Ghana: comparison of the cardio-ankle vascular index and central aortic techniques

Background

Diabetes and hypertension increase arterial stiffness and cardiovascular events in all societies studied so far; sub-Saharan African studies are sparse. We investigated factors affecting arterial function in Ghanaians with diabetes, hypertension, both or neither.

Method

Testing the hypothesis that arterial stiffness would progressively increase from controls to multiply affected patients, 270 participants were stratified into those with diabetes or hypertension only, with both, or without either. Cardio-ankle vascular index (CAVI), heart–ankle pulse wave velocity (haPWV), aortic PWV (PWVao) by Arteriograph, aortic and brachial blood pressures (BP), were measured.

Results

In patients with both diabetes and hypertension compared with either alone, values were higher of CAVI (mean?±?SD, 8.3?±?1.2 vs 7.5?±?1.1 and 7.4?±?1.1 units; p?<?0.05), PWVao (9.1?±?1.4 vs 8.7?±?1.9 and 8.1?±?0.9 m/s; p?<?0.05) and haPWV (8.5?±?1 vs 7.9?±?1 and 7.2?±?0.7 m/s; p?<?0.05) respectively. In multivariate analysis, age, having diabetes or hypertension and BMI were independently associated with CAVI in all participants (β?=?0.49, 0.2, 0.17 and -0.2 units; p?<?0.01, respectively). Independent determinants of PWVao were heart rate, systolic BP and age (β?=?0.42, 0.27 and 0.22; p?<?0.01), and for haPWV were systolic BP, age, BMI, diabetes and hypertension status (β?=?0.46, 0.32, -0.2, 0.2 and 0.11; p?<?0.01).

Conclusion

In this sub-Saharan setting with lesser atherosclerosis than the western world, arterial stiffness is significantly greater in patients with coexistent diabetes and hypertension but did not differ between those with either diabetes or hypertension only. Simple, reproducibly measured PWV/CAVI may offer effective and efficient targets for intervention.

     

Abscisic acid catabolism enhances dormancy release of grapevine buds

The molecular mechanism regulating dormancy release in grapevine buds is as yet unclear. It was formerly proposed that dormancy is maintained by abscisic acid (ABA)‐mediated repression of bud–meristem activity and that removal of this repression triggers dormancy release. It was also proposed that such removal of repression may be achieved via natural or artificial up‐regulation of VvA8H‐CYP707A4, which encodes ABA 8′‐hydroxylase, and is the most highly expressed paralog in grapevine buds. The current study further examines these assumptions, and its experiments reveal that (a) hypoxia and ethylene, stimuli of bud dormancy release, enhance expression of VvA8H‐CYP707A4 within grape buds, (b) the VvA8H‐CYP707A4 protein accumulates during the natural transition to the dormancy release stage, and (c) transgenic vines overexpressing VvA8H‐CYP707A4 exhibit increased ABA catabolism and significant enhancement of bud break in controlled and natural environments and longer basal summer laterals. The results suggest that VvA8H‐CYP707A4 functions as an ABA degrading enzyme, and are consistent with a model in which the VvA8H‐CYP707A4 level in the bud is up‐regulated by natural and artificial bud break stimuli, which leads to increased ABA degradation capacity, removal of endogenous ABA‐mediated repression, and enhanced regrowth. Interestingly, it also hints at sharing of regulatory steps between latent and lateral bud outgrowth.     

A fluorometric approach to local electric field measurements in a voltage-gated ion channel

Site-specific electrostatic measurements have been limited to soluble proteins purified for in vitro spectroscopic characterization or proteins of known structure; however, comparable measurements have not been made for functional membrane bound proteins. Here, using an electrochromic fluorophore, we describe a method to monitor localized electric field changes in a voltage-gated potassium channel. By coupling the novel probe Di-1-ANEPIA to cysteines in Shaker and tracking field-induced optical changes, in vivo electrostatic measurements were recorded with submillisecond resolution. This technique reports dynamic changes in the electric field during the gating process and elucidates the electric field profile within Shaker. The extension of this method to other membrane bound proteins, including transporters, will yield insight into the role of electrical forces on protein function.     

Substrate-favored lysosomal and proteasomal pathways participate in the normal balance control of insulin precursor maturation and disposal in β-cells

Our recent studies have uncovered that aggregation-prone proinsulin preserves a low relative folding rate and maintains a homeostatic balance of natively and non-natively folded states (i.e., proinsulin homeostasis, PIHO) in β-cells as a result of the integration of maturation and disposal processes. Control of precursor maturation and disposal is thus an early regulative mechanism in the insulin production of β-cells. Herein, we show pathways involved in the disposal of endogenous proinsulin at the early secretory pathway. We conducted metabolic-labeling, immunoblotting, and immunohistochemistry studies to examine the effects of selective proteasome and lysosome or autophagy inhibitors on the kinetics of proinsulin and control proteins in various post-translational courses. Our metabolic-labeling studies found that the main lysosomal and ancillary proteasomal pathways participate in the heavy clearance of insulin precursor in mouse islets/β-cells cultured at the mimic physiological glucose concentrations. Further immunoblotting and immunohistochemistry studies in cloned β-cells validated that among secretory proteins, insulin precursor is heavily and preferentially removed. The rapid disposal of a large amount of insulin precursor after translation is achieved mainly through lysosomal autophagy and the subsequent basal disposals are carried out by both lysosomal and proteasomal pathways within a 30 to 60-minute post-translational process. The findings provide the first clear demonstration that lysosomal and proteasomal pathways both play roles in the normal maintenance of PIHO for insulin production, and defined the physiological participation of lysosomal autophagy in the protein quality control at the early secretory pathway of pancreatic β-cells.     

Capturing cancer cells using aptamer-immobilized square capillary channels

We report a simple square capillary-based cell affinity chromatography device that utilizes a coating of aptamers for selective capture of target cancer cells from a flowing suspension. The device consists of a square capillary with an inner diameter of roughly five cell diameters, connected via Teflon tubing to a syringe. Aptamers are immobilized on the inner surface of the capillary through biotin-avidin chemistry, the extent of which can be controlled by adjusting the aptamer concentration. Introduction of different cell types into separate devices, as well as mixtures of target and non-target cells, demonstrated that aptamer-target cells can be captured in significantly higher concentrations compared to non-target cells. Once optimized, 91.1 ± 3.5% capture efficiency of target leukemia cells was reported, as well as 97.2 ± 2.8% and 83.6 ± 5.8% for two different colon cancer cell lines. In addition, cells captured in the device were imaged, and the square capillary exhibited better optical properties than standard cylindrical capillaries, leading to the detection of leukemia cells in blood samples. Compared to current microfluidic cell affinity devices, this capture device requires no complicated design or fabrication steps. By providing a simple means of detecting and imaging cancer cells in the blood, this work has potential to directly assist clinicians in determining disease prognosis and measuring therapeutic response.     

Health professionals' overestimation of knowledge on snakebite management,a threat to the survival of snakebite victims—A cross-sectional study in Ghana

BackgroundAccording to the World Health Organization, snakebites, a common occupational hazard in developing countries accounts for an annual loss of between 81,000 and 138, 000 lives following 5 million bites of which 2.7 million results in envenomation. Since snakebite-associated morbidity and mortality are more prevalent in agricultural economies such as Ghana, health professionals should be optimally knowledgeable on how to manage the incidence of snakebites. Lack of knowledge or overestimation of a professional''s knowledge can affect heath delivery especially for emergencies such as snakebites. The three rurally situated Tongu districts in South-Eastern Ghana with agriculture as the major source of livelihood for their inhabitants, are prone to snakebites. This study, therefore, brings up the need to assess whether the health professionals in these districts are well-equipped knowledge-wise to handle such emergencies and whether they can rightly estimate their knowledge with regards to snakebite management.Methodology/Principal findingsData was collected using a de novo semi-structured questionnaire administered through google form whose link was sent via WhatsApp to 186 health workers made up of nurses, midwives, physician assistants, medical doctors, pharmacists, and pharmacy technicians. This data was analyzed using Statistical Package for the Social Sciences (SPSS) Version 25. Association between variables was determined using the appropriate tools where necessary, using a confidence interval of 95% and significance assumed when p ≤ 0.05. This study found male health workers significantly more knowledgeable about snakebite management (11.53±5.67 vs 9.64±5.46; p = 0.022) but it was the females who overestimated their knowledge level (27.9% vs 24.1%). The medical doctors exhibited the best knowledge on snakebite management with the registered general nurses least knowledgeable. Although most professionals overestimated their knowledge, the registered general nurses were the worst at that (53.7%). Overall knowledge of health care professionals on snakebite management was below average [10.60±5.62/22 (48.2%)] but previous in-service training and involvement in the management of snakebite were associated with better knowledge. Respondents who had no previous training overestimated their knowledge level compared to those who had some post-qualification training on snakebite management (38.1% vs 7.5%). The greatest knowledge deficit of respondents was on the management of ASV associated adverse reactions.ConclusionHealth workers in rural Ghana overestimated their knowledge about snakebite management although their knowledge was low. Training schools, therefore, need to incorporate snakebite management in their curriculum and health authorities should also expose health workers to more in-service training on this neglected tropical disease.     

Effect of mine characteristics on life cycle impacts of US surface coal mining

Purpose  

This study’s aim was to understand the effect of mine characteristics on cradle-to-gate life cycle impacts of surface coal mining in the USA. Five bituminous coal strip mines were used as case studies. The study assessed the life cycle water use, land use, energy use, abiotic resource depletion, and climate change impacts.     

Dried Plasmodium falciparum-infected samples as positive controls for malaria rapid diagnostic tests

ABSTRACT: BACKGROUND: Rapid diagnostic tests (RDTs) are central to fulfilling the WHO's recommendation for parasitologic confirmation of all suspected cases of malaria. RDT performance may be compromised when exposed to the high temperature conditions typical of most malaria endemic regions. However, a systematic method to monitor RDT quality and performance in endemic countries is lacking at the present time. Current methods to monitor RDT performance in the field include comparing results from RDTs to diagnoses made by light microscopy and observing health workers perform tests. These methods are not substitutes for direct quality control. In this study, the suitability of dried Plasmodium falciparuminfected blood as quality control samples for malaria RDTs was evaluated. METHODS: Three cultured strains of P. falciparum at 200 and 2,000 parasites/mul were tested on 10 brands of RDT. After baseline testing to determine initial reactivity, aliquots of parasite-infected blood were air dried, stored at 35 degreesC, room temperature (~25 degreesC) or 4 degreesC for one, four and 12 weeks and were then tested on the 10 RDTs after rehydration. Extended stability testing of dried blood stored at 4 degreesC was done using P. falciparum strain 3D7 at 1,000 and 2,000 parasites/mul. RESULTS: All dried blood samples at 2,000 parasites/mul retained reactivity (100 % sensitivity) at all three temperatures and time points for all nine RDT brands that detect histidine-rich protein-2 (HRP2). The dried blood samples with 200 parasites/mul were detected by six of the nine HRP2-based RDTs at all storage temperatures and time points. The sensitivity for two of the three remaining HRP2-based RDTs was 100 % up to four weeks of storage at all temperatures but dropped to 87.5 % at week 12. Of the four RDTs that detect plasmodium lactate dehydrogenase (pLDH) in a pan-specific manner, alone or in combination with HRP2, the detection of pLDH in samples with 2,000 parasites/muL was 100 % for two RDTs and 80 % for the other two RDTs. The mean level for detection of pLDH at 200 parasites/mul was low (29 %), with a range of 0 % to100%, which was partly attributable to weak initial baseline reactivity. Reactivity of dried 3D7 at 1,000 and 2,000 parasites/mul stored at 4 degreesC was retained at 100 % for up to 52 weeks for both HRP2 and pLDH. CONCLUSIONS: In the absence of native or recombinant positive control antigens, well-standardized P. falciparum-infected dried blood samples can be used as positive control samples for monitoring RDT performance, particularly with HRP2-detecting tests.