Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, Dioscorea polygonoides.

In this study, three steroidal sapogenins (Delta3 diosgenin, diosgenin, and pennogenin) and the phytosterols, stigmasterol and beta-sitosterol were isolated from Jamaican bitter yam, Dioscorea polygonoides. Their effects on fasting blood glucose and intestinal amylase and ATPases in streptozotocin-induced diabetic rats were studied. The diabetic rats (fed supplemented and unsupplemented diets) lost weight significantly compared to the normal group. There was a significant increase in the activity of alpha-amylase in the proximal region of the small intestinal mucosa of diabetic rats fed sapogenin extract or commercial diosgenin. However, this did not result in increased fasting blood glucose. Instead, supplementation of the diet with bitter yam sapogenin extract significantly decreased fasting blood glucose compared to the diabetic group. Supplementation of the diet with bitter yam sapogenin extract or commercial diosgenin significantly reduced Na+-K+-ATPase activity in all three regions compared to the diabetic control group. Commercial diosgenin supplementation resulted in a significant increase in Ca2+ ATPase activity in proximal region compared to the diabetic control and bitter yam sapogenin extract groups. The effect of bitter yam sapogenin extract or commercial diosgenin on intestinal Na+-K+-ATPase activity could account for their hypoglycemic properties. However, there was adverse effect on the body weight.     

Major limb amputation and mortality in patients with neuro‐ischaemic lower extremity wounds managed in a tertiary hospital: Focus on the differences among patients with diabetes,peripheral arterial disease and both

A majority of lower extremities neuro‐ischaemic wounds (NIU) are related to: (a) only diabetes (DM); (b) only peripheral artery disease (PAD); (c) co‐existing diabetes and peripheral artery disease (DM‐PAD). This study aims to characterise the major clinical outcomes of forementioned three groups of lower extremity wound patients in Singapore. Patients hospitalised for lower extremity NIU between January 2014 and October 2017 in a tertiary hospital in Singapore were analysed. Patients'' major limb amputation and mortality were assessed using Cox regression models. Cumulative survival and amputation‐free survival among the three classified groups were calculated using Kaplan‐Meier analysis. Compared with patients with only DM, those in the PAD group and the DM‐PAD group had higher risk of major limb amputation (adjusted hazard ratio: 2.47, 95% CI: 1.65‐3.70; adjusted hazard ratio: 2.01, 95% CI: 1.53‐2.65 respectively) and mortality (adjusted hazard ratio: 2.36, 95% CI: 1.57‐3.55; adjusted hazard ratio: 2.46, 95% CI: 1.86‐3.26 respectively). The 3‐year survival and amputation‐free survival were lowest in the DM‐PAD group (52.1% and 41.5% respectively), followed by the PAD group (53.3% and 44.6% respectively) and the DM group (74.2% and 68.5% respectively). Lower extremity NIU patients with PAD or DM‐PAD were found to have poorer clinical prognosis than those with DM only.     

Experiences of parents whose children participated in a longitudinal follow‐up study

BackgroundLong‐term follow‐up is necessary to understand the impact of perinatal interventions. Exploring parents'' motives and experiences in consenting to their children taking part in longitudinal studies and understanding what outcomes are important to families may enhance participation and mitigate the loss to follow‐up. As existing evidence is largely based on investigators'' perspectives using Western samples, the present pilot study explored parents'' perspectives in a multicultural New Zealand context.MethodsData were generated using semi‐structured interviews with parents whose children had participated in a longitudinal study after neonatal recruitment. Parents'' experiences of being part of the study were analysed thematically using an inductive approach.ResultsParents (n = 16) were generally happy with the outcomes measured. Additionally, parents were interested in lifelong goals such as the impact of parental diabetes. We identified three themes: (1) Facilitators: Research participation was aided by motives and parent and research characteristics such as wishing to help others and straightforward recruitment; (2) Barriers: A hesitancy to participate was due to technical and clinical research aspects, participation burden and cultural barriers, such as complex wording, time commitment and nonindigenous research and (3) Benefits: Children and parents experienced advantages such as the opportunity for education.ConclusionsParents reported positive experiences and described the unexpected benefit of increasing families'' health knowledge through participation. Improvements for current follow‐up studies were identified. Different ethnicities reported different experiences and perspectives, which warrants ongoing research, particularly with indigenous research participants.Patient or Public ContributionNo active partnership with parents of patients took place.     

GABA-related actions in isolated in vitro preparations of the rat small intestine

Longitudinal organ bath preparations of the rat duodenum, jejunum and ileum were tested for their responsiveness to GABA-receptor agonists. The GABAA-receptor agonists, GABA and 3APS, induced non-adrenergic, non-cholinergic relaxations and/or contractions, although the magnitude and type of response varied depending upon the region tested. All regions relaxed to applied GABA or 3APS, however the jejunum and ileum also responded with cholinergic contractions. These relaxant and contractile actions were neurogenic and sensitive to blockade by the GABA antagonists bicuculline or picrotoxinin, and desensitization to either agonist. The GABAB-receptor agonist baclofen, caused a reduction in electrically evoked cholinergic contractions. These inhibitory actions of baclofen were insensitive to bicuculline or picrotoxinin. Taken together, these results show that GABA-ergic actions in the rat small intestine are mediated by two pharmacologically distinct neural receptor populations, the GABAA and GABAB sites, the distribution and sensitivity of which differ along the length of the small intestine.     

The past,present, and future of sleep measurement in mild cognitive impairment and early dementia—towards a core outcome set: a scoping review

Study ObjectivesSleep abnormalities emerge early in dementia and may accelerate cognitive decline. Their accurate characterization may facilitate earlier clinical identification of dementia and allow for assessment of sleep intervention efficacy. This scoping review determines how sleep is currently measured and reported in Mild Cognitive Impairment (MCI) and early dementia, as a basis for future core outcome alignment.MethodsThis review follows the PRISMA Guidelines for Scoping Reviews. CINAHL, Embase, Medline, Psychinfo, and British Nursing Index databases were searched from inception—March 12, 2021. Included studies had participants diagnosed with MCI and early dementia and reported on sleep as a key objective/ outcome measure.ResultsNineteen thousand five hundred and ninety-six titles were returned following duplicate removal with 188 studies [N] included in final analysis. Sleep data was reported on 17 139 unique, diagnostically diverse participants (n). “Unspecified MCI” was the most common diagnosis amongst patients with MCI (n = 5003, 60.6%). Despite technological advances, sleep was measured most commonly by validated questionnaires (n = 12 586, N = 131). Fewer participants underwent polysomnography (PSG) (n = 3492, N = 88) and actigraphy (n = 3359, N = 38) with little adoption of non-PSG electroencephalograms (EEG) (n = 74, N = 3). Sleep outcome parameters were reported heterogeneously. 62/165 (37.6%) were described only once in the literature (33/60 (60%) in interventional studies). There was underrepresentation of circadian (n = 725, N = 25) and micro-architectural (n = 360, N = 12) sleep parameters.ConclusionsAlongside under-researched areas, there is a need for more detailed diagnostic characterization. Due to outcome heterogeneity, we advocate for international consensus on core sleep outcome parameters to support causal inference and comparison of therapeutic sleep interventions.     

The influence of sleeping sickness on mortality in two districts of Northern Nigeria

The object of this enquiry was to obtain some idea of the mortality of untreated sleeping sickness in two non-adjacent districts in Northern Nigeria. The method employed was to obtain data, by methodical questioning of every householder, from which the crude death and other rates could be calculated over a preceding period, and be correlated with the known incidence of sleeping sickness. The figures were worked out village by village, and the villages then combined into groups of sufficient size to make the numbers significant.In the first district, Igabi, a close correlation was obtained, the death rate rising from 71.4 per 1,000 with a sleeping sickness incidence of 18.6 per cent., to 104 per 1,000 with a sleeping sickness incidence of 28.6 per cent. In other words an additional death occurred for approximately every additional three people infected. The infantile mortality rate also showed a close correlation with the sleeping sickness incidence. As infants were not found to be infected, this result was unexpected. The reasons for it are discussed. The birth rate showed no definite correlation.In the second district, Kankara, no correlation was found to exist, and the conclusion is drawn that, during the period under review, sleeping sickness was not fatal; the patients must either have harboured a mild chronic infection carrying no threat to life, or have been undergoing spontaneous cure.The clinical types of the cases found are described. They are similar in the two districts, and would not have been suspected of having so different a prognosis.It is pointed out that Igabi lies in the middle of a sleeping sickness belt, and it is suggested that the virulence of the disease in this district may be accounted for by the very free means of communication which exist, and by the movement in the past of large gangs of labour, tending to disseminate many different strains of trypanosome imported from outside. The infection in Kankara, on the other hand, was probably of later, though not very recent, introduction; and as the district is situated on the very edge of the belt and is traversed by no main roads or railways, the possibility of a multiplicity of strains existing is very much less. If this conclusion is correct, it emphasizes the necessity of careful sleeping sickness control measures in areas which may be opened up in the future.The mean birth rate found in Igabi was 64.7 per 1,000; and the mean death rate 84.2. The corresponding figures for Kankara were 44.1 and 23.6. The reliability of these figures is discussed.     

SERCA2a gene therapy in heart failure: an anti-arrhythmic positive inotrope

Therapeutic options that directly enhance cardiomyocyte contractility in chronic heart failure (HF) therapy are currently limited and do not improve prognosis. In fact, most positive inotropic agents, such as β-adrenoreceptor agonists and PDE inhibitors, which have been assessed in HF patients, cause increased mortality as a result of arrhythmia and sudden cardiac death. Cardiac sarcoplasmic reticulum Ca²⁺-ATPase2a (SERCA2a) is a key protein involved in sequestration of Ca²⁺ into the sarcoplasmic reticulum (SR) during diastole. There is a reduction of SERCA2a protein level and function in HF, which has been successfully targeted via viral transfection of the SERCA2a gene into cardiac tissue in vivo. This has enhanced cardiac contractility and reduced mortality in several preclinical models of HF. Theoretical concerns have been raised regarding the possibility of arrhythmogenic adverse effects of SERCA2a gene therapy due to enhanced SR Ca²⁺ load and induction of SR Ca²⁺ leak as a result. Contrary to these concerns, SERCA2a gene therapy in a wide variety of preclinical models, including acute ischaemia/reperfusion, chronic pressure overload and chronic myocardial infarction, has resulted in a reduction in ventricular arrhythmias. The potential mechanisms for this unexpected beneficial effect, as well as mechanisms of enhancement of cardiac contractile function, are reviewed in this article.     

Can dietary fibre help provide safer food products for sufferers of gluten intolerance? A well-established biophysical probe may help towards providing an answer

ABSTRACT: Gluten intolerance is a condition which affects an increasing percentage of the world's population and for which the only current treatment is a restrictive gluten free diet. However could the inclusion of a particular polysaccharide, or blends of different types, help with the provision of 'safer' foods for those individuals who suffer from this condition. We review the current knowledge on the prevalence, clinical symptoms and treatment of gluten intolerance, and the use and properties of the allergens responsible. We consider the potential for dietary fibre polysaccharides to sequester peptides that are responsible for activation of the disease in susceptible individuals, and consider the potential of co-sedimentation in the analytical ultracentrifuge as a molecular probe for finding interactions strong enough to be considered as useful.