Mechanisms of pelvic floor muscle function and the effect on the urethra during a cough

Background: Current measurement tools have difficulty identifying the automaticphysiologic processes maintaining continence, and many questions still remainabout pelvic floor muscle (PFM) function during automatic events.Objective: To perform a feasibility study to characterise the displacement, velocity,and acceleration of the PFM and the urethra during a cough.Design, setting, and participants: A volunteer convenience sample of 23 continentwomen and 9 women with stress urinary incontinence (SUI) from the generalcommunity of San Francisco Bay Area was studied.Measurements: Methods included perineal ultrasound imaging, motion trackingof the urogenital structures, and digital vaginal examination. Statistical analysisused one-tailed unpaired student t tests, and Welch’s correction was applied whenvariances were unequal.Results and limitations: The cough reflex activated the PFM of continent women tocompress the urogenital structures towards the pubic symphysis, which wasabsent in women with SUI. The maximum accelerations that acted on the PFMduring a cough were generally more similar than the velocities and displacements.The urethras of women with SUI were exposed to uncontrolled transverse accelerationand were displaced more than twice as far ( p = 0.0002), with almost twicethe velocity ( p = 0.0015) of the urethras of continent women. Caution regardingthe generalisability of this study is warranted due to the small number of women inthe SUI group and the significant difference in parity between groups.Conclusions: During a cough, normal PFM function produces timely compressionof the pelvic floor and additional external support to the urethra, reducing displacement,velocity, and acceleration. In women with SUI, who have weakerurethral attachments, this shortening contraction does not occur; consequently,the urethras of women with SUI move further and faster for a longer duratio

Role of Genetic Testing in Kidney Stone Disease: A Narrative Review

\ua9 The Author(s) 2024.Purpose of Review: Kidney stone disease (KSD) is a common and potentially life-threatening condition, and half of patients experience a repeat kidney stone episode within 5–10 years. Despite the ~50% estimate heritability of KSD, international guidelines have not kept up with the pace of discovery of genetic causes of KSD. The European Association of Urology guidelines lists 7 genetic causes of KSD as ‘high risk’. Recent Findings: There are currently 46 known monogenic (single gene) causes of kidney stone disease, with evidence of association in a further 23 genes. There is also evidence for polygenic risk of developing KSD. Evidence is lacking for recurrent disease, and only one genome wide association study has investigated this phenomenon, identifying two associated genes (SLC34A1 and TRPV5). However, in the absence of other evidence, patients with genetic predisposition to KSD should be treated as ‘high risk’. Further studies are needed to characterize both monogenic and polygenic associations with recurrent disease, to allow for appropriate risk stratification. Durability of test result must be balanced against cost. This would enable retrospective analysis if no genetic cause was found initially. Summary: We recommend genetic testing using a gene panel for all children, adults < 25 years, and older patients who have factors associated with high risk disease within the context of a wider metabolic evaluation. Those with a genetic predisposition should be managed via a multi-disciplinary team approach including urologists, radiologists, nephrologists, clinical geneticists and chemical pathologists. This will enable appropriate follow-up, counselling and potentially prophylaxis

Improving starch and fibre in wheat grain for human health

Reducing the prevalence of diet- related diseases, including obesity and type 2 diabetes, is a major challenge for health professionals, food manufacturers and governments in both developed and developing countries. Cereals are key targets in meeting this challenge as they are staple foods throughout the world and major sources of energy (derived principally from starch) and dietary fibre. Wheat is the staple cereal in the UK and Europe, and the UK Biotechnology and Biological Sciences Research Council (BBSRC)- supported Designing Future Wheat programme is focused on manipulating the content and composition of starch and fibre to improve health impacts, including reducing the glycaemic response and improving fermentation in the colon. This work is contributing to the development of improved cultivars by breeders and foods by processors. It is also increasing our understanding of the behaviour of these components in the human gastrointestinal (GI) tract and will contribute to the establishment of targets and recommendations for regulatory authorities

Reformulation initiative for partial replacement of saturated with unsaturated fats in dairy foods attenuates the increase in LDL cholesterol and improves flow-mediated dilatation compared with conventional dairy: the randomized, controlled REplacement of SaturatEd fat in dairy on Total cholesterol (RESET) study

Background Modifying dairy fat composition by increasing the MUFA content is a potential strategy to reduce dietary SFA intake for cardiovascular disease (CVD) prevention in the population. Objectives To determine the effects of consuming SFA-reduced, MUFA-enriched (modified) dairy products, compared with conventional dairy products (control), on the fasting cholesterol profile (primary outcome), endothelial function assessed by flow-mediated dilatation (FMD; key secondary outcome), and other cardiometabolic risk markers. Methods A double-blind, randomized, controlled crossover 12-wk intervention was conducted. Participants with a 1.5-fold higher (moderate) CVD risk than the population mean replaced habitual dairy products with study products (milk, cheese, and butter) to achieve a high-fat, high-dairy isoenergetic daily dietary exchange [38% of total energy intake (%TE) from fat: control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA) diet]. Results Fifty-four participants (57.4% men; mean ± SEM age: 52 ± 3 y; BMI: 25.8 ± 0.5 kg/m2) completed the study. The modified diet attenuated the rise in fasting LDL cholesterol observed with the control diet (0.03 ± 0.06 mmol/L and 0.19 ± 0.05 mmol/L, respectively; P = 0.03). Relative to baseline, the %FMD response increased after the modified diet (0.35% ± 0.15%), whereas a decrease was observed after the control diet (−0.51% ± 0.15%; P< 0.0001). In addition, fasting plasma nitrite concentrations increased after the modified diet, yet decreased after the control diet (0.02 ± 0.01 μmol/L and −0.03 ± 0.02 μmol/L, respectively; P = 0.01). Conclusions In adults at moderate CVD risk, consumption of a high-fat diet containing SFA-reduced, MUFA-enriched dairy products for 12 wk showed beneficial effects on fasting LDL cholesterol and endothelial function compared with conventional dairy products. Our findings indicate that fatty acid modification of dairy products may have potential as a public health strategy aimed at CVD risk reduction. This trial was registered at clinicaltrials.gov as NCT02089035

Short-communication: a comparison of the in vitro angiotensin-1-converting enzyme inhibitory capacity of dairy and plant protein supplements

The consumption of supplements based on dairy or plant proteins may be associated with bioactive potential, including angiotensin-1-converting enzyme inhibitory (ACE-1i) activity, which is linked with blood pressure reduction in vivo. To gain insight into this proposed mechanism, the ACE-1i potential of protein-based supplements, including a selection of dairy (n = 10) and plant (n = 5) proteins were in vitro digested. The total digest was filtered and permeate and retentate were obtained. ACE-1i activity was measured as the ability of proteins (pre-digestion, 'gastric', permeate, and retentate) to decrease the hydrolysis of furanacroloyl-Phe-Glu-Glu (FAPGG) substrate for the ACE-1 enzyme. Permeate and retentate of dairy proteins exerted a significantly higher ACE-1i activity (mean of 10 proteins: 27.05 ± 0.2% and 20.7 ± 0.2%, respectively) compared with pre-digestion dairy proteins (16.7 ± 0.3%). Plant protein exhibited high ACE-1i in 'gastric' and retentate fractions (mean of five proteins: 54.9 ± 0.6% and 35.7 ± 0.6%, respectively). The comparison of the in vitro ACE-1i activity of dairy and plant proteins could provide valuable knowledge regarding their specific bioactivities, which could inform their use in the formulation of specific functional supplements that would require testing for blood pressure control in human randomly-controlled studies

Extractability and characteristics of proteins deriving from wheat DDGS

Wheat Distillers’ Dried Grains with Solubles (DDGS) and in-process samples were used for protein extraction. Prolamins were the predominant protein components in the samples. The absence of extractable α- and γ-gliadins in DDGS indicated protein aggregation during the drum drying processing stage. Prolamin extraction was performed using 70% (v/v) ethanol or alkaline-ethanol solution in the presence of reducing agent. DDGS extracts had relatively low protein contents (14-44.9%, w/w), regardless of the condition applied. The wet solids were the most suitable raw material for protein extraction, with recovery yields of ~ 55% (w/w) and protein content of ~58% (w/w) in 70% (v/v) ethanol. Protein extracts from wet solids were significantly rich in glutamic acid and proline. Mass balance calculations demonstrated the high carbohydrate content (~ 50%, w/w) of solid residues. Overall, the feasibility of utilising in-process samples of DDGS for protein extraction with commercial potential was demonstrated

Vitamin D intake and risk of CVD and all-cause mortality: evidence from the Caerphilly Prospective Cohort Study

OBJECTIVE: Prospective data on the associations between vitamin D intake and risk of CVD and all-cause mortality are limited and inconclusive. The aim of the present study was to investigate the associations between vitamin D intake and CVD risk and all-cause mortality in the Caerphilly Prospective Cohort Study. DESIGN: The associations of vitamin D intake with CVD risk markers were examined cross-sectionally at baseline and longitudinally at 5-year, 10-year and >20-year follow-ups. In addition, the predictive value of vitamin D intake for CVD events and all-cause mortality after >20 years of follow-up was examined. Logistic regression and general linear regression were used for data analysis. SETTING: Participants in the UK. SUBJECTS: Men (n 452) who were free from CVD and type 2 diabetes at recruitment. RESULTS: Higher vitamin D intake was associated with increased HDL cholesterol (P=0·003) and pulse pressure (P=0·04) and decreased total cholesterol:HDL cholesterol (P=0·008) cross-sectionally at baseline, but the associations were lost during follow-up. Furthermore, higher vitamin D intake was associated with decreased concentration of plasma TAG at baseline (P=0·01) and at the 5-year (P=0·01), but not the 10-year examination. After >20 years of follow-up, vitamin D was not associated with stroke (n 72), myocardial infarctions (n 142), heart failure (n 43) or all-cause mortality (n 281), but was positively associated with increased diastolic blood pressure (P=0·03). CONCLUSIONS: The study supports associations of higher vitamin D intake with lower fasting plasma TAG and higher diastolic blood pressure

Simultaneous host and parasite expression profiling identifies tissue-specific transcriptional programs associated with susceptibility or resistance to experimental cerebral malaria

BACKGROUND: The development and outcome of cerebral malaria (CM) reflects a complex interplay between parasite-expressed virulence factors and host response to infection. The murine CM model, Plasmodium berghei ANKA (PbA), which simulates many of the features of human CM, provides an excellent system to study this host/parasite interface. We designed "combination" microarrays that concurrently detect genome-wide transcripts of both PbA and mouse, and examined parasite and host transcriptional programs during infection of CM-susceptible (C57BL/6) and CM-resistant (BALB/c) mice. RESULTS: Analysis of expression data from brain, lung, liver, and spleen of PbA infected mice showed that both host and parasite gene expression can be examined using a single microarray, and parasite transcripts can be detected within whole organs at a time when peripheral blood parasitemia is low. Parasites display a unique transcriptional signature in each tissue, and lung appears to be a large reservoir for metabolically active parasites. In comparisons of susceptible versus resistant animals, both host and parasite display distinct, organ-specific transcriptional profiles. Differentially expressed mouse genes were related to humoral immune response, complement activation, or cell-cell interactions. PbA displayed differential expression of genes related to biosynthetic activities. CONCLUSION: These data show that host and parasite gene expression profiles can be simultaneously analysed using a single "combination" microarray, and that both the mouse and malaria parasite display distinct tissue- and strain-specific responses during infection. This technology facilitates the dissection of host-pathogen interactions in experimental cerebral malaria and could be extended to other disease models

Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria

<p>Abstract</p> <p>Background</p> <p>Severe and cerebral malaria are associated with endothelial activation. Angiopoietin-1 (ANG-1) and angiopoietin-2 (ANG-2) are major regulators of endothelial activation and integrity. The aim of this study was to investigate the clinical utility of whole blood angiopoietin (ANG) levels as biomarkers of disease severity in <it>Plasmodium falciparum </it>malaria.</p> <p>Methods</p> <p>The utility of whole blood ANG levels was examined in Thai patients to distinguish cerebral (CM; n = 87) and severe (non-cerebral) malaria (SM; n = 36) from uncomplicated malaria (UM; n = 70). Comparative statistics are reported using a non-parametric univariate analysis (Kruskal-Wallis test or Chi-squared test, as appropriate). Multivariate binary logistic regression was used to examine differences in whole blood protein levels between groups (UM, SM, CM), adjusting for differences due to ethnicity, age, parasitaemia and sex. Receiver operating characteristic curve analysis was used to assess the diagnostic accuracy of the ANGs in their ability to distinguish between UM, SM and CM. Cumulative organ injury scores were obtained for patients with severe disease based on the presence of acute renal failure, jaundice, severe anaemia, circulatory collapse or coma.</p> <p>Results</p> <p>ANG-1 and ANG-2 were readily detectable in whole blood. Compared to UM there were significant decreases in ANG-1 (p < 0.001) and significant increases in ANG-2 (p < 0.001) levels and the ratio of ANG-2: ANG-1 (p < 0.001) observed in patients with SM and CM. This effect was independent of covariates (ethnicity, age, parasitaemia, sex). Further, there was a significant decrease in ANG-1 levels in patients with SM (non-cerebral) versus CM (p < 0.001). In participants with severe disease, ANG-2, but not ANG-1, levels correlated with cumulative organ injury scores; however, ANG-1 correlated with the presence of renal dysfunction and coma. Receiver operating characteristic curve analysis demonstrated that the level of ANG-1, the level of ANG-2 or the ratio of ANG-2: ANG-1 discriminated between individuals with UM and SM (area under the curve, p-value: ANG-2, 0.763, p < 0.001; ANG-1, 0.884, p < 0.001; Ratio, 0.857, p < 0.001) or UM and CM (area under the curve, p-value: ANG-2, 0.772, p < 0.001; ANG-1, 0.778, p < 0.001; Ratio, 0.820, p < 0.001).</p> <p>Conclusions</p> <p>These results suggest that whole blood ANG-1/2 levels are promising clinically informative biomarkers of disease severity in malarial syndromes.</p

Improving wheat as a source of iron and zinc for global nutrition

Wheat is the staple food crop in temperate countries and increasingly consumed in developing countries, displacing traditional foods. However, wheat products are typically low in bioavailable iron and zinc, contributing to deficiencies in these micronutrients in countries where wheat is consumed as a staple food. Two factors contribute to the low contents of bioavailable iron and zinc in wheat: the low concentrations of these minerals in white flour, which is most widely consumed, and the presence of phytates in mineral-rich bran fractions. Although high zinc types of wheat have been developed by conventional plant breeding (biofortification), this approach has failed for iron. However, studies in wheat and other cereals have shown that transgenic (also known as genetically modified; GM) strategies can be used to increase the contents of iron and zinc in white flour, by converting the starchy endosperm tissue into a ‘sink’ for minerals. Although such strategies currently have low acceptability, greater understanding of the mechanisms which control the transport and deposition of iron and zinc in the developing grain should allow similar effects to be achieved by exploiting naturally induced genetic variation. When combined with conventional biofortification and innovative processing, this approach should provide increased mineral bioavailability in a range of wheat products, from white flour to wholemeal