The real-world outcomes from high intensity interval training, intermittent fasting and whole-food diets

Background: Given global epidemics of obesity and diabetes, it is clear that adherence to current nutrition and activity guidelines is insufficient. Novel lifestyle interventions such as high intensity interval training (HIIT), intermittent fasting and paleolithic (Paleo) diets may provide alternative options and have proven beneficial for health in controlled studies. However, outcomes from real-world implementation are uncertain. Although HIIT is effective in laboratory settings to improve cardiorespiratory fitness, body composition and measures of metabolic health, it is unknown whether overweight adults will choose to perform HIIT, or can do so safely and effectively while unsupervised. Similarly, although unconventional dietary approaches such as intermittent fasting and Paleo diets produce weight loss and metabolic improvements in controlled trials, there is minimal evidence of long-term efficacy under free-living conditions. The aim of this study was to examine the real-world outcomes from these alternative exercise and dietary approaches in overweight and obese participants after 12 months. Methods: Within a weight loss intervention evaluating the effect of different support strategies, 250 healthy adults who were overweight or obese chose to undertake unsupervised exercise programmes of HIIT or 30 minutes/day of moderate intensity exercise. Participants could also choose whether to follow intermittent fasting, modified Paleo, or a Mediterranean diet. Eligible participants underwent medical screening to identify health issues relevant to safety during vigorous exercise. HIIT participants received a medical assessment to identify any undiagnosed cardiovascular disease. Following a single supervised HIIT training session, they were advised to independently undertake HIIT three times a week for 12 months. A range of HIIT protocols were offered, with durations of intervals ranging from 30 seconds to 4 minutes, performed at an intensity of 8-10 on a 10-point scale of Rating of Perceived Exertion (RPE), with all HIIT protocols able to be completed within a 20-30 minute session. All participants also received dietary recommendations at baseline during a single education session, which included the exercise advice for those who chose daily moderate intensity exercise. Intermittent fasting participants were instructed to reduce caloric consumption to 25% of their recommended intake on two days each week, and Paleo participants were advised to reduce consumption of any grain-based foods and vegetable oils, and to eat a diet of mainly plant and animal based whole-foods. Those participants opting for the Mediterranean diet were encouraged to include wholegrains, fish, nuts and olive oil, while reducing red meat, sugar and saturated fat. Weight, body composition, blood pressure, aerobic fitness, physical activity, blood indices, dietary intake and psychological outcomes were assessed at 0, 6 and 12 months. Adherence to HIIT was assessed by heart rate monitoring of HIIT sessions over a one-week period every three months. Results: Up to 19% of HIIT participants had relevant medical issues that could increase health risk during vigorous exercise that were not identified by screening questionnaires. One hundred and four participants (42%) chose to try HIIT and these participants were not leaner, fitter, or more active (all P>0.05) at baseline than those choosing moderate intensity daily exercise (n=146). Most HIIT participants (84.6%) could perform adequately intense HIIT during the initial supervised training session, but adherence to at least twice weekly unsupervised sessions decreased over time to only 19.6% by 12 months. There were no differences between exercise groups in weight (adjusted difference; 95% CI: -0.44kg; -2.5, 1.6), visceral fat (-103cm3; -256, 49), or MVPA (1 minute; -6, 8) at 12 months. However, within the HIIT cohort, adherent participants (23%) showed greater reductions in weight (-2.7kg; -5.2 -0.2) and visceral fat (-292cm3; -483, -101) than non-adherent participants. Intermittent fasting was the most popular dietary intervention (54%), but dietary choice did not result in differences in weight or body composition at 12 months. However, those following intermittent fasting had poorer glycaemic control and a worse lipid profile than those following the Mediterranean diet at 12 months. Conclusions: Although HIIT was initially a popular choice, adherence declined rapidly over time, with less than one-quarter of participants undertaking regular unsupervised HIIT at 12 months. However, those who did adhere to HIIT experienced greater weight loss, visceral fat reduction and metabolic improvements than non-adherent participants, demonstrating that HIIT can be a useful alternative for some overweight people. Intermittent fasting was a popular diet choice, but when compared to a Mediterranean diet resulted in slightly worse metabolic outcomes after 12 months. These findings support current recommendations to consume diets rich in unprocessed whole-foods

Endocrine Disruptor Regulation of MicroRNA Expression in Breast Carcinoma Cells

Several environmental agents termed "endocrine disrupting compounds" or EDCs have been reported to bind and activate the estrogen receptor-α (ER). The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA levels in human blood and adipose tissue are detectable in most if not all women and men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs) and more recently non-coding RNAs (ncRNAs). Of the ncRNAs, microRNAs have emerged as a target of estrogen signaling. Given the important implications of EDC-regulated ER function, we sought to define the effects of BPA and DDT on microRNA regulation and expression levels in estrogen-responsive human breast cancer cells.To investigate the cellular effects of DDT and BPA, we used the human MCF-7 breast cancer cell line, which is ER (+) and hormone sensitive. Our results show that DDT and BPA potentiate ER transcriptional activity, resulting in an increased expression of receptor target genes, including progesterone receptor, bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the expression of multiple microRNAs in MCF-7 cells, including miR-21, differential patterns of microRNA expression were induced by DDT and BPA compared to estrogen.We have shown, for the first time, that BPA and DDT, two well known EDCs, alter the expression profiles of microRNA in MCF-7 breast cancer cells. A better understanding of the molecular mechanisms of these compounds could provide important insight into the role of EDCs in human disease, including breast cancer

Impact of AlphaFold on Structure Prediction of Protein Complexes: The CASP15-CAPRI Experiment

We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homo-dimers, 3 homo-trimers, 13 hetero-dimers including 3 antibody-antigen complexes, and 7 large assemblies. On average ~70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their 5 best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% for the targets compared to 8% two years earlier, a remarkable improvement resulting from the wide use of the AlphaFold2 and AlphaFold-Multimer software. Creative use was made of the deep learning inference engines affording the sampling of a much larger number of models and enriching the multiple sequence alignments with sequences from various sources. Wide use was also made of the AlphaFold confidence metrics to rank models, permitting top performing groups to exceed the results of the public AlphaFold-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem

Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment

We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average ~70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem

The real-world outcomes from high intensity interval training, intermittent fasting and whole-food diets

Background: Given global epidemics of obesity and diabetes, it is clear that adherence to current nutrition and activity guidelines is insufficient. Novel lifestyle interventions such as high intensity interval training (HIIT), intermittent fasting and paleolithic (Paleo) diets may provide alternative options and have proven beneficial for health in controlled studies. However, outcomes from real-world implementation are uncertain. Although HIIT is effective in laboratory settings to improve cardiorespiratory fitness, body composition and measures of metabolic health, it is unknown whether overweight adults will choose to perform HIIT, or can do so safely and effectively while unsupervised. Similarly, although unconventional dietary approaches such as intermittent fasting and Paleo diets produce weight loss and metabolic improvements in controlled trials, there is minimal evidence of long-term efficacy under free-living conditions. The aim of this study was to examine the real-world outcomes from these alternative exercise and dietary approaches in overweight and obese participants after 12 months. Methods: Within a weight loss intervention evaluating the effect of different support strategies, 250 healthy adults who were overweight or obese chose to undertake unsupervised exercise programmes of HIIT or 30 minutes/day of moderate intensity exercise. Participants could also choose whether to follow intermittent fasting, modified Paleo, or a Mediterranean diet. Eligible participants underwent medical screening to identify health issues relevant to safety during vigorous exercise. HIIT participants received a medical assessment to identify any undiagnosed cardiovascular disease. Following a single supervised HIIT training session, they were advised to independently undertake HIIT three times a week for 12 months. A range of HIIT protocols were offered, with durations of intervals ranging from 30 seconds to 4 minutes, performed at an intensity of 8-10 on a 10-point scale of Rating of Perceived Exertion (RPE), with all HIIT protocols able to be completed within a 20-30 minute session. All participants also received dietary recommendations at baseline during a single education session, which included the exercise advice for those who chose daily moderate intensity exercise. Intermittent fasting participants were instructed to reduce caloric consumption to 25% of their recommended intake on two days each week, and Paleo participants were advised to reduce consumption of any grain-based foods and vegetable oils, and to eat a diet of mainly plant and animal based whole-foods. Those participants opting for the Mediterranean diet were encouraged to include wholegrains, fish, nuts and olive oil, while reducing red meat, sugar and saturated fat. Weight, body composition, blood pressure, aerobic fitness, physical activity, blood indices, dietary intake and psychological outcomes were assessed at 0, 6 and 12 months. Adherence to HIIT was assessed by heart rate monitoring of HIIT sessions over a one-week period every three months. Results: Up to 19% of HIIT participants had relevant medical issues that could increase health risk during vigorous exercise that were not identified by screening questionnaires. One hundred and four participants (42%) chose to try HIIT and these participants were not leaner, fitter, or more active (all P>0.05) at baseline than those choosing moderate intensity daily exercise (n=146). Most HIIT participants (84.6%) could perform adequately intense HIIT during the initial supervised training session, but adherence to at least twice weekly unsupervised sessions decreased over time to only 19.6% by 12 months. There were no differences between exercise groups in weight (adjusted difference; 95% CI: -0.44kg; -2.5, 1.6), visceral fat (-103cm3; -256, 49), or MVPA (1 minute; -6, 8) at 12 months. However, within the HIIT cohort, adherent participants (23%) showed greater reductions in weight (-2.7kg; -5.2 -0.2) and visceral fat (-292cm3; -483, -101) than non-adherent participants. Intermittent fasting was the most popular dietary intervention (54%), but dietary choice did not result in differences in weight or body composition at 12 months. However, those following intermittent fasting had poorer glycaemic control and a worse lipid profile than those following the Mediterranean diet at 12 months. Conclusions: Although HIIT was initially a popular choice, adherence declined rapidly over time, with less than one-quarter of participants undertaking regular unsupervised HIIT at 12 months. However, those who did adhere to HIIT experienced greater weight loss, visceral fat reduction and metabolic improvements than non-adherent participants, demonstrating that HIIT can be a useful alternative for some overweight people. Intermittent fasting was a popular diet choice, but when compared to a Mediterranean diet resulted in slightly worse metabolic outcomes after 12 months. These findings support current recommendations to consume diets rich in unprocessed whole-foods

Validity of a Virtual Reality-Based Clinical Case for Assessment of Clinical Competence

Reliable and valid assessment of the clinical competence of medical students and doctors is essential for the safety of patients. Current modes of assessment are limited in their ability to evaluate some key aspects of competence, such as clinical reasoning ability and timely decision-making. The aims of this study were to assess the validity of a virtual reality-based clinical case as a method of assessment of clinical competence. In addition, this study intended to specifically examine the capacity of the virtual reality case format to assess clinical reasoning ability. The Otago Virtual Hospital is a virtual reality-based computer programme in which the performance of doctors and students can be assessed while managing a simulated clinical case in real time. As a pilot study, 12 participants, (consisting of three cohorts comprised of third-year medical students, fifth-year medical students and qualified doctors) from Otago Medical School participated in a simulated clinical case. Their performance was measured by scoring their achievement of set outcomes representing optimal management; these were developed from expert opinion. Qualitative thematic analysis of case transcripts was undertaken to compare clinical reasoning skills. Scores of performance from the virtual reality case showed qualified doctors achieved the highest scores, significantly higher than the third-year student group. Qualified doctors were also significantly better able to make correct full diagnoses and achieve safe clinical management compared with the student cohorts. These results showed some significant differences between groups at different stages of medical training, hence supporting the construct validity of the virtual-reality based clinical case. Thematic analysis to identify clinical reasoning themes indicated that compared to the student cohorts, the qualified doctor group was better able to transform information into key clinical concepts, generate more accurate diagnoses, and generate correct diagnoses more efficiently. With increasing clinical experience there was a superior ability to communicate clinical information succinctly and precisely, and to construct effective patient management plans. The virtual reality based clinical case provided an authentic clinical task. Within the programme, overall performance and clinical reasoning abilities could be assessed by analysis of a summary admission note at the conclusion of the case. These results suggest that simulated virtual cases may provide a valid and rapid means of assessing clinical competence, and can provide more comprehensive information about clinical reasoning ability than traditional means of assessment

Adherence to Hunger Training over 6 Months and the Effect on Weight and Eating Behaviour: Secondary Analysis of a Randomised Controlled Trial

Monitoring blood glucose prior to eating can teach individuals to eat only when truly hungry, but how adherence to ‘hunger training’ influences weight loss and eating behaviour is uncertain. This exploratory, secondary analysis from a larger randomized controlled trial examined five indices of adherence to ‘hunger training’, chosen a priori, to examine which adherence measure best predicted weight loss over 6 months. We subsequently explored how the best measure of adherence influenced eating behavior in terms of intuitive and emotional eating. Retention was 72% (n = 36/50) at 6 months. Frequency of hunger training booklet entry most strongly predicted weight loss, followed by frequency of blood glucose measurements. Participants who completed at least 60 days of booklet entry (of recommended 63 days) lost 6.8 kg (95% CI: 2.6, 11.0; p < 0.001) more weight than those who completed fewer days. They also had significantly higher intuitive eating scores than those who completed 30 days or less of booklet entry; a difference (95% CI) of 0.73 (0.12, 1.35) in body-food choice congruence and 0.79 (0.06, 1.51) for eating for physical rather than emotional reasons. Adherent participants also reported significantly lower scores for emotional eating of −0.70 (−1.13, −0.27). Following hunger training and focusing on simply recording ratings of hunger on a regular basis can produce clinically significant weight loss and clinically relevant improvements in eating behaviour

What monitoring strategies are most successful for promoting weight loss? A randomised controlled trial

Aim: To determine the effectiveness of 4 different monitoring strategies on weight and health markers in adults with overweight/obesity undertaking a 1-year weight loss programme.<div><br><div><div>Methods: 250 overweight or obese adults were randomised to track either a) their weight daily, b) dietary intake using MyFitnessPal, c) hunger (using a novel method called “hunger training”), d) progress via regular face-to-face meetings, or a control group for 12 months. All participants received diet and exercise advice and 171 participants completed the study. </div><div><br></div><div>Results: All groups lost weight over the course of the intervention (typically 3.9-6.8kg) with no difference between the intervention groups and the control (all p ≥ 0.084). However, participants who tracked hunger lost significantly more weight at 1-year than those who tracked dietary intake (3.2kg, 0.1-6.4kg, p=0.046), or who met regularly with a support person (2.9kg, 95% CI 0.8-5.1kg, p=0.008). Few significant differences were observed in eating behaviour (all p≥0.111), although the face-to-face and hunger tracking groups reported more favourable effects on depression and anxiety at 1-year than control participants. Adherence to the monitoring strategies (% recommended days) ranged from 29.6% for hunger training to 63.6% for attendance at the monthly face-to-face sessions. </div><div><br></div><div>Conclusions: Daily tracking of weight, food, or hunger, or regular face-to-face support did not result in significantly greater weight loss compared with diet and exercise advice alone. However tracking hunger may be a promising approach for encouraging weight loss. </div></div></div

Bedtime, body mass index and obesity risk in preschool-aged children

Background Although sleep duration is a risk factor for obesity in young children, less is known about other aspects of sleep health, including bedtime, on obesity risk.Objective To determine whether bedtime is associated with body mass index (BMI) z-score or obesity risk in children ages 2 to 5 years, and to determine if associations are independent of sleep duration.Methods Cohort analyses were undertaken using three early life obesity prevention trials (POI, INSIGHT, Healthy Beginnings) and a longitudinal cohort study (HOME). Bedtime was assessed by questionnaire and BMI through clinical measurement between 2 and 5 years in 1642 children. Adjusted regression models examined whether BMI z-score and obesity (BMI z-score >= 2) were associated with bedtime, nocturnal sleep time and 24-hour sleep time. A discrete mixture model categorized children into bedtime trajectory groups across time points.Results Bedtime was inconsistently associated with BMI z-score. Although each hour later of bedtime was associated with greater odds of obesity at ages 3 (OR; 95% CI: 1.05; 1.003, 1.10) and 5 (1.35; 1.08, 1.69) years, odds were attenuated after adjustment for nocturnal or 24-hour sleep time. Longer nocturnal sleep duration at 2 years was associated with lower odds of obesity (OR 0.90; 0.86, 0.94), as was longer 24-hour sleep duration at 3 years in girls (0.70; 0.62, 0.78). BMI z-score and odds of obesity were not significantly different between 'early to bed' and 'late to bed' trajectory groups.Conclusions Timing of bedtime appears inconsistently related to obesity in young children, possibly via influencing overall sleep duration