Effect of beetroot juice on lowering blood pressure in free-living, disease-free adults: a randomized, placebo-controlled trial

Extent: 6p.Background: The consumption of beetroot juice on a low nitrate diet may lower blood pressure (BP) and therefore reduce the risk of cardiovascular events. However, it is unknown if its inclusion as part of a normal diet has a similar effect on BP. The aim of the study was to conduct a randomized controlled trial with free-living adults to investigate if consuming beetroot juice in addition to a normal diet produces a measureable reduction in BP. Method: Fifteen women and fifteen men participated in a double-blind, randomized, placebo-controlled, crossover study. Volunteers were randomized to receive 500 g of beetroot and apple juice (BJ) or a placebo juice (PL). Volunteers had BP measured at baseline and at least hourly for 24-h following juice consumption using an ambulatory blood pressure monitor (ABPM). Volunteers remained at the clinic for 1-h before resuming normal non-strenuous daily activities. The identical procedure was repeated 2-wk later with the drink (BJ or PL) not consumed on the first visit. Results: Overall, there was a trend (P=0.064) to lower systolic blood pressure (SBP) at 6-h after drinking BJ relative to PL. Analysis in men only (n=13) after adjustment for baseline differences demonstrated a significant (P<0.05) reduction in SBP of 4 – 5 mmHg at 6-h after drinking BJ. Conclusions: Beetroot juice will lower BP in men when consumed as part of a normal diet in free-living healthy adults.Leah T Coles and Peter M Clifto

Patient freedom to choose a weight loss diet in the treatment of overweight and obesity: a randomized dietary intervention in type 2 diabetes and pre-diabetes

BackgroundOffering the overweight or obese patient the option of choosing from a selection of weight loss diets has not been investigated in type 2 diabetes. The aim of the study was to investigate if the option to choose from, and interchange between a selection of diets (&ldquo;Choice&rdquo;), as opposed to being prescribed one set diet (&ldquo;No Choice&rdquo;), improves drop out rates and leads to improved weight loss and cardio-metabolic outcomes.MethodsThe study was a 12 month, randomized parallel intervention. A total of 144 volunteers with type 2 diabetes or pre-diabetes and a BMI &gt;27 were randomized to &ldquo;No Choice&rdquo; or &ldquo;Choice&rdquo;. Those in the No Choice group were placed on a set weight loss diet (CSIRO) with no change permitted. Those in the Choice group could choose from, and interchange between, the CSIRO, South Beach or Mediterranean diets.ResultsThere were no differences in attrition rates or weight loss between the &ldquo;Choice&rdquo; and &ldquo;No Choice&rdquo;. In a secondary analysis of the intention-to-treat weight loss data with last measured weight carried forward gave a highly significant diet group by time by gender interaction (p&thinsp;=&thinsp;0.002) with men doing better in the No Choice group overall (maximum difference &ldquo;No Choice &ldquo;-2.9&thinsp;&plusmn;&thinsp;4.6 kg vs. &ldquo;Choice&rdquo;-6.2 kg&thinsp;&plusmn;&thinsp;5.3 kg at 6 months) and women doing better in the Choice group overall (maximum difference Choice -3.1&thinsp;&plusmn;&thinsp;3.7 kg vs. &ldquo;No Choice&rdquo; -2.0 kg&thinsp;&plusmn;&thinsp;2.6 kg at 6 months).ConclusionsMen prefer direction in their weight loss advice and do less well with choice. A gender-specific approach is recommended when prescribing weight loss diets.Trial registrationanzctr.org.au ACTRN12612000310864.<br /

Facial Curvature Detects and Explicates Ethnic Differences in Effects of Prenatal Alcohol Exposure

Background Our objective is to help clinicians detect the facial effects of prenatal alcohol exposure by developing computer-based tools for screening facial form. Methods All 415 individuals considered were evaluated by expert dysmorphologists and categorized as (i) healthy control (HC), (ii) fetal alcohol syndrome (FAS), or (iii) heavily prenatally alcohol exposed (HE) but not clinically diagnosable as FAS; 3D facial photographs were used to build models of facial form to support discrimination studies. Surface curvature-based delineations of facial form were introduced. Results (i) Facial growth in FAS, HE, and control subgroups is similar in both cohorts. (ii) Cohort consistency of agreement between clinical diagnosis and HC-FAS facial form classification is lower for midline facial regions and higher for nonmidline regions. (iii) Specific HC-FAS differences within and between the cohorts include: for HC, a smoother philtrum in Cape Coloured individuals; for FAS, a smoother philtrum in Caucasians; for control-FAS philtrum difference, greater homogeneity in Caucasians; for control-FAS face difference, greater homogeneity in Cape Coloured individuals. (iv) Curvature changes in facial profile induced by prenatal alcohol exposure are more homogeneous and greater in Cape Coloureds than in Caucasians. (v) The Caucasian HE subset divides into clusters with control-like and FAS-like facial dysmorphism. The Cape Coloured HE subset is similarly divided for nonmidline facial regions but not clearly for midline structures. (vi) The Cape Coloured HE subset with control-like facial dysmorphism shows orbital hypertelorism. Conclusions Facial curvature assists the recognition of the effects of prenatal alcohol exposure and helps explain why different facial regions result in inconsistent control-FAS discrimination rates in disparate ethnic groups. Heavy prenatal alcohol exposure can give rise to orbital hypertelorism, supporting a long-standing suggestion that prenatal alcohol exposure at a particular time causes increased separation of the brain hemispheres with a concomitant increase in orbital separation

GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop

The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.Peer reviewe

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Prediction of cellular ATP generation from foods in the adult human : application to developing specialist weight-loss foods : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Palmerston North, New Zealand

For the accurate prediction of the potential ‘available energy’ of a food at the cellular level (i.e. ATP generation from food) it is necessary to be able to predict both the quantity and location of uptake (upper-tract or colon) for each energy-yielding nutrient. The objective was to develop a valid model (‘Combined Model’) for predicting the (potential) ATP available to the body from absorbed nutrients across the total digestive tract. The model was intended for the adult human under conditions where energy intake ≤ energy expenditure and all absorbed nutrients are catabolised. The development of the model involved two parts: (i) the experimental development of a dual in vivo – in vitro digestibility assay (‘dual digestibility assay’) to predict human upper-tract nutrient digestibility, as modelled by the rat upper digestive tract, and colonic digestibility, as predicted by fermenting rat ileal digesta in an in vitro digestion system containing human faecal bacteria; and (ii) the development of a series of mathematical equations to predict the net ATP yielded during the post-absorptive catabolism of each absorbed nutrient at the cellular level. A strong correlation (r=0.953, P=0.047) was found between total tract organic matter digestibility (OMD), as predicted with the newly developed dual in vivo – in vitro digestibility assay and with that determined in a metabolic study with humans for four mixed diets ranging considerably in nutrient content. There were no statistically significant (P>0.05) differences for mean OMD between the predicted and determined values for any of the diets. The Combined Model (dual in vivo – in vitro digestibility assay + stoichiometric predictive equations) was applied to three meal replacement formulations and was successfully able to differentiate between the diets in terms of both energy digestibility and predicted ATP yields. When the energy content of each diet was compared to that of a baseline food (dextrin), some metabolisable energy (ME) models gave considerably different ratios compared to that predicted by the Combined Model. By way of example, for Diet C a ratio of 0.96 (Atwater and FDA models) was found ii versus 0.75 (Combined Model). Thus, the model has practical application for predicting dietary available energy content, particularly in the research and development of specialised weight-loss foods, where it may be more accurate than some current ME models. Uniquely, the Combined Model is able to define a food in terms of ATP content (mol ATP / g food) using recent estimates of cellular P/O ratios and therefore, directly relates dietary energy intake to the quantity and form (ATP) of energy ultimately delivered at the cellular level