Lifestyle counseling in hypertension-related visits – analysis of video-taped general practice visits

<p>Abstract</p> <p>Background</p> <p>The general practitioner (GP) can play an important role in promoting a healthy lifestyle, which is especially relevant in people with an elevated risk of cardiovascular diseases due to hypertension. Therefore, the aim of this study was to determine the frequency and content of lifestyle counseling about weight loss, nutrition, physical activity, and smoking by GPs in hypertension-related visits. A distinction was made between the assessment of lifestyle (gathering information or measuring weight or waist circumference) and giving lifestyle advice (giving a specific advice to change the patient's behavior or referring the patient to other sources of information or other health professionals).</p> <p>Methods</p> <p>For this study, we observed 212 video recordings of hypertension-related visits collected within the Second Dutch National Survey of General Practice in 2000/2001.</p> <p>Results</p> <p>The mean duration of visits was 9.8 minutes (range 2.5 to 30 minutes). In 40% of the visits lifestyle was discussed (n = 84), but in 81% of these visits this discussion lasted shorter than a quarter of the visit. An assessment of lifestyle was made in 77 visits (36%), most commonly regarding body weight and nutrition. In most cases the patient initiated the discussion about nutrition and physical activity, whereas the assessment of weight and smoking status was mostly initiated by the GP. In 35 visits (17%) the GP gave lifestyle advice, but in only one fifth of these visits the patient's motivation or perceived barriers for changing behavior were assessed. Supporting factors were not discussed at all.</p> <p>Conclusion</p> <p>In 40% of the hypertension-related visits lifestyle topics were discussed. However, both the frequency and quality of lifestyle advice can be improved.</p

Extensive DRB region diversity in cynomolgus macaques: recombination as a driving force

The DR region of primate species is generally complex and displays diversity concerning the number and combination of distinct types of DRB genes present per region configuration. A highly variable short tandem repeat (STR) present in intron 2 of nearly all primate DRB genes can be utilized as a quick and accurate high through-put typing procedure. This approach resulted previously in the description of unique and haplotype-specific DRB-STR length patterns in humans, chimpanzees, and rhesus macaques. For the present study, a cohort of 230 cynomolgus monkeys, including self-sustaining breeding groups, has been examined. MtDNA analysis showed that most animals originated from the Indonesian islands, but some are derived from the mainland, south and north of the Isthmus of Kra. Haplotyping and subsequent sequencing resulted in the detection of 118 alleles, including 28 unreported ones. A total of 49 Mafa-DRB region configurations were detected, of which 28 have not yet been described. Humans and chimpanzees possess a low number of different DRB region configurations in concert with a high degree of allelic variation. In contrast, however, allelic heterogeneity within a given Mafa-DRB configuration is even less frequently observed than in rhesus macaques. Several of these region configurations appear to have been generated by recombination-like events, most probably propagated by a retroviral element mapping within DRB6 pseudogenes, which are present on the majority of haplotypes. This undocumented high level of DRB region configuration-associated diversity most likely represents a species-specific strategy to cope with various pathogens

In silico assessment of potential druggable pockets on the surface of α1-Antitrypsin conformers

The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α1-antitrypsin (A1AT). Pathological mutations disturb the conformational landscape of A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens for small molecule inhibitors of polymerisation have generally focused on one major druggable site visible in all crystal structures of native A1AT. In an alternative approach, we scan all surface clefts observed in crystal structures of A1AT and in 100 computationally produced conformers, mimicking the native solution ensemble. We assess the persistence, variability and druggability of these pockets. Finally, we employ molecular docking using publicly available libraries of small molecules to explore scaffold preferences for each site. Our approach identifies a number of novel target sites for drug design. In particular one transient site shows favourable characteristics for druggability due to high enclosure and hydrophobicity. Hits against this and other druggable sites achieve docking scores corresponding to a Kd in the µM–nM range, comparing favourably with a recently identified promising lead. Preliminary ThermoFluor studies support the docking predictions. In conclusion, our strategy shows considerable promise compared with the conventional single pocket/single conformer approach to in silico screening. Our best-scoring ligands warrant further experimental investigation

MHC class I A region diversity and polymorphism in macaque species

The HLA-A locus represents a single copy gene that displays abundant allelic polymorphism in the human population, whereas, in contrast, a nonhuman primate species such as the rhesus macaque (Macaca mulatta) possesses multiple HLA-A-like (Mamu-A) genes, which parade varying degrees of polymorphism. The number and combination of transcribed Mamu-A genes present per chromosome display diversity in a population of Indian animals. At present, it is not clearly understood whether these different A region configurations are evolutionarily stable entities. To shed light on this issue, rhesus macaques from a Chinese population and a panel of cynomolgus monkeys (Macaca fascicularis) were screened for various A region-linked variations. Comparisons demonstrated that most A region configurations are old entities predating macaque speciation, whereas most allelic variation (>95%) is of more recent origin. The latter situation contrasts the observations of the major histocompatibility complex class II genes in rhesus and cynomolgus macaques, which share a high number of identical alleles (>30%) as defined by exon 2 sequencing

Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy

BACKGROUND : The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients. METHODS : In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency. RESULTS : Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman’s rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR = 1.96, 95 % CI: 0.99 to 3.88, P = 0.053). CONCLUSIONS : Close to third of metformin-treated T2DM patients had vitamin B12 deficiency. The deficiency was not associated with peripheral neuropathy. Black race was a protective factor for vitamin B12 deficiency.The Department of Pharmacology, University of Pretoriahttp://bmcpharmacoltoxicol.biomedcentral.comam2017Internal MedicinePharmacolog

Sex-biased parental care and sexual size dimorphism in a provisioning arthropod

The diverse selection pressures driving the evolution of sexual size dimorphism (SSD) have long been debated. While the balance between fecundity selection and sexual selection has received much attention, explanations based on sex-specific ecology have proven harder to test. In ectotherms, females are typically larger than males, and this is frequently thought to be because size constrains female fecundity more than it constrains male mating success. However, SSD could additionally reflect maternal care strategies. Under this hypothesis, females are relatively larger where reproduction requires greater maximum maternal effort – for example where mothers transport heavy provisions to nests. To test this hypothesis we focussed on digger wasps (Hymenoptera: Ammophilini), a relatively homogeneous group in which only females provision offspring. In some species, a single large prey item, up to 10 times the mother’s weight, must be carried to each burrow on foot; other species provide many small prey, each flown individually to the nest. We found more pronounced female-biased SSD in species where females carry single, heavy prey. More generally, SSD was negatively correlated with numbers of prey provided per offspring. Females provisioning multiple small items had longer wings and thoraxes, probably because smaller prey are carried in flight. Despite much theorising, few empirical studies have tested how sex-biased parental care can affect SSD. Our study reveals that such costs can be associated with the evolution of dimorphism, and this should be investigated in other clades where parental care costs differ between sexes and species