Cocoa Flavanols Adjuvant to an Oral Nutritional Supplement Acutely Enhances Nutritive Flow in Skeletal Muscle without Altering Leg Glucose Uptake Kinetics in Older Adults

Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05; 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p < 0.05). In addition, there was a trend (p = 0.058) for MBV in m. tibialis anterior to increase in response to ONS in the cocoa condition only. Leg blood flow and vascular conductance increased, and vascular resistance decreased in response to ONS (p < 0.05), but these responses were not different between conditions (p > 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p < 0.05) comparably between conditions (p > 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.     

Influence of Material Deprivation on Clinical Outcomes Among People Living with HIV in High-Income Countries: A Systematic Review and Meta-analysis

AIDS and Behavior - Despite developments in HIV treatment and care, disparities persist with some not fully benefiting from improvements in the HIV care continuum. We conducted a systematic review...     

Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia,even in patients with early stage disease

Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high‐resolution single telomere length analysis (STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia (CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere ‘fusogenic’ range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival (P < 0·0001; Hazard ratio [HR] = 13·2, 95% confidence interval [CI] = 11·6–106·4) and this was preserved in early‐stage disease patients (P < 0·0001, HR=19·3, 95% CI = 17·8–802·5). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10 years) and those with poor prognosis (13% survival at 10 years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high‐resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL.     

UK guidelines on the management of iron deficiency in pregnancy

Iron deficiency is the most common deficiency state in the world, affecting more than 2 billion people globally. Although it is particularly prevalent in less-developed countries, it remains a significant problem in the developed world, even where other forms of malnutrition have already been almost eliminated. Effective management is needed to prevent adverse maternal and pregnancy outcomes, including the need for red cell transfusion. The objective of this guideline is to provide healthcare professionals with clear and simple recommendations for the diagnosis, treatment and prevention of iron deficiency in pregnancy and the postpartum period. This is the first such guideline in the UK and may be applicable to other developed countries. Public health measures, such as helminth control and iron fortification of foods, which can be important to developing countries, are not considered here. The guidance may not be appropriate to all patients and individual patient circumstances may dictate an alternative approach.     

The use of intermittent pneumatic compression of the thigh to affect arterial and venous blood flow proximal to a chronic wound site

Intermittent pneumatic compression of the lower limbs has been shown to have beneficial effects in patients with chronic ulceration. However, the intermittent compression cuff will normally be applied over the wound, which may produce discomfort or interfere with other treatments. Thigh‐only approaches to intermittent pneumatic compression could solve this problem. This study aimed to demonstrate if such a system would have positive effects on venous and arterial blood flow distal to the compression site, but proximal to wound sites. The distal venous and arterial effects of a prototype thigh‐only 3‐chamber sequential intermittent pneumatic compression system were tested in 20 healthy volunteers, and 13 patients with ulcers of various aetiologies using Doppler ultrasound. The system produced hyperaemic responses in the arterial flow of both test groups. The peak venous velocity on deflation of the first and second chambers of the cuff was also greater in the patients with ulceration than in the healthy volunteers (11.6 cm/s vs 8.3 cm/s, P = .1). This work demonstrates that compression of the thigh alone can produce positive haemodynamic effects in the calves of patients with chronic wounds, and that this approach should be investigated as a therapy to improve blood flow to wound sites.     

Human autoantibodies specific for the α1A calcium channel subunit reduce both P-type and Q-type calcium currents in cerebellar neurons

The pharmacological properties of voltage-dependent calcium channel (VDCC) subtypes appear mainly to be determined by the α₁ pore-forming subunit but, whether P-and Q-type VDCCs are encoded by the same α₁ gene presently is unresolved. To investigate this, we used IgG antibodies to presynaptic VDCCs at motor nerve terminals that underlie muscle weakness in the autoimmune Lambert–Eaton myasthenic syndrome (LEMS). We first studied their action on changes in intracellular free Ca²⁺ concentration [Ca²⁺]_i in human embryonic kidney (HEK293) cell lines expressing different combinations of human recombinant VDCC subunits. Incubation for 18 h with LEMS IgG (2 mg/ml) caused a significant dose-dependent reduction in the K⁺-stimulated [Ca²⁺]_i increase in the α_1A cell line but not in the α_1B, α_1C, α_1D, and α_1E cell lines, establishing the α_1A subunit as the target for these autoantibodies. Exploiting this specificity, we incubated cultured rat cerebellar neurones with LEMS IgG and observed a reduction in P-type current in Purkinje cells and both P- and Q-type currents in granule cells. These data are consistent with the hypothesis that the α_1A gene encodes for the pore-forming subunit of both P-type and Q-type VDCCs.