High intensity interval training as a novel treatment for impaired awareness of hypoglycaemia in people with type 1 diabetes (HIT4HYPOS): a randomised parallel-group study.

AIMS/HYPOTHESIS: Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes may develop through a process referred to as habituation. Consistent with this, a single bout of high intensity interval exercise as a novel stress stimulus improves counterregulatory responses (CRR) to next-day hypoglycaemia, referred to as dishabituation. This longitudinal pilot study investigated whether 4 weeks of high intensity interval training (HIIT) has sustained effects on counterregulatory and symptom responses to hypoglycaemia in adults with type 1 diabetes and IAH. METHODS: HIT4HYPOS was a single-centre, randomised, parallel-group study. Participants were identified using the Scottish Diabetes Research Network (SDRN) and from diabetes outpatient clinics in NHS Tayside, UK. The study took place at the Clinical Research Centre, Ninewells Hospital and Medical School, Dundee, UK. Participants were aged 18-55 years with type 1 diabetes of at least 5 years' duration and HbA1c levels <75 mmol/mol (<9%). They had IAH confirmed by a Gold score ≥4, modified Clarke score ≥4 or Dose Adjustment For Normal Eating [DAFNE] hypoglycaemia awareness rating of 2 or 3, and/or evidence of recurrent hypoglycaemia on flash glucose monitoring. Participants were randomly allocated using a web-based system to either 4 weeks of real-time continuous glucose monitoring (RT-CGM) or RT-CGM+HIIT. Participants and investigators were not masked to group assignment. The HIIT programme was performed for 20 min on a stationary exercise bike three times a week. Hyperinsulinaemic-hypoglycaemic (2.5 mmol/l) clamp studies with assessment of symptoms, hormones and cognitive function were performed at baseline and after 4 weeks of the study intervention. The predefined primary outcome was the difference in hypoglycaemia-induced adrenaline (epinephrine) responses from baseline following RT-CGM or RT-CGM+HIIT. RESULTS: Eighteen participants (nine men and nine women) with type 1 diabetes (median [IQR] duration 27 [18.75-32] years) and IAH were included, with nine participants randomised to each group. Data from all study participants were included in the analysis. During the 4 week intervention there were no significant mean (SEM) differences between RT-CGM and RT-CGM+HIIT in exposure to level 1 (28 [7] vs 22 [4] episodes, p=0.45) or level 2 (9 [3] vs 4 [1] episodes, p=0.29) hypoglycaemia. The CGM-derived mean glucose level, SD of glucose and glucose management indicator (GMI) did not differ between groups. During the hyperinsulinaemic-hypoglycaemic clamp studies, mean (SEM) change from baseline was greater for the noradrenergic responses (RT-CGM vs RT-CGM+HIIT: -988 [447] vs 514 [732] pmol/l, p=0.02) but not the adrenergic responses (-298 [687] vs 1130 [747] pmol/l, p=0.11) in those participants who had undergone RT-CGM+HIIT. There was a benefit of RT-CGM+HIIT for mean (SEM) change from baseline in the glucagon CRR to hypoglycaemia (RT-CGM vs RT-CGM+HIIT: 1 [4] vs 16 [6] ng/l, p=0.01). Consistent with the hormone response, the mean (SEM) symptomatic response to hypoglycaemia (adjusted for baseline) was greater following RT-CGM+HIIT (RT-CGM vs RT-CGM+HIIT: -4 [2] vs 0 [2], p<0.05). CONCLUSIONS/INTERPRETATION: In this pilot clinical trial in people with type 1 diabetes and IAH, we found continuing benefits of HIIT for overall hormonal and symptomatic CRR to subsequent hypoglycaemia. Our findings also suggest that HIIT may improve the glucagon response to insulin-induced hypoglycaemia. TRIAL REGISTRATION: ISRCTN15373978. FUNDING: Sir George Alberti Fellowship from Diabetes UK (CMF) and the Juvenile Diabetes Research Foundation.

The metabolome as a diagnostic for maximal aerobic capacity during exercise in type 1 diabetes.

AIMS/HYPOTHESIS: Our aim was to characterise the in-depth metabolic response to aerobic exercise and the impact of residual pancreatic beta cell function in type 1 diabetes. We also aimed to use the metabolome to distinguish individuals with type 1 diabetes with reduced maximal aerobic capacity in exercise defined by V ˙ O 2peak . METHODS: Thirty participants with type 1 diabetes (≥3 years duration) and 30 control participants were recruited. Groups did not differ in age or sex. After quantification of peak stimulated C-peptide, participants were categorised into those with undetectable (<3 pmol/l), low (3-200 pmol/l) or high (>200 pmol/l) residual beta cell function. Maximal aerobic capacity was assessed by V ˙ O 2peak test and did not differ between control and type 1 diabetes groups. All participants completed 45 min of incline treadmill walking (60% V ˙ O 2peak ) with venous blood taken prior to exercise, immediately post exercise and after 60 min recovery. Serum was analysed using targeted metabolomics. Metabolomic data were analysed by multivariate statistics to define the metabolic phenotype of exercise in type 1 diabetes. Receiver operating characteristic (ROC) curves were used to identify circulating metabolomic markers of maximal aerobic capacity ( V ˙ O 2peak ) during exercise in health and type 1 diabetes. RESULTS: Maximal aerobic capacity ( V ˙ O 2peak ) inversely correlated with HbA1c in the type 1 diabetes group (r2=0.17, p=0.024). Higher resting serum tricarboxylic acid cycle metabolites malic acid (fold change 1.4, p=0.001) and lactate (fold change 1.22, p=1.23×10-5) differentiated people with type 1 diabetes. Higher serum acylcarnitines (AC) (AC C14:1, F value=12.25, p=0.001345; AC C12, F value=11.055, p=0.0018) were unique to the metabolic response to exercise in people with type 1 diabetes. C-peptide status differentially affected metabolic responses in serum ACs during exercise (AC C18:1, leverage 0.066; squared prediction error 3.07). The malic acid/pyruvate ratio in rested serum was diagnostic for maximal aerobic capacity ( V ˙ O 2peak ) in people with type 1 diabetes (ROC curve AUC 0.867 [95% CI 0.716, 0.956]). CONCLUSIONS/INTERPRETATION: The serum metabolome distinguishes high and low maximal aerobic capacity and has diagnostic potential for facilitating personalised medicine approaches to manage aerobic exercise and fitness in type 1 diabetes.

Adapting to compromised routines: Parental perspectives on physical activity and health for children and adolescents with type 1 diabetes in the UK during COVID-19 lockdown.

PURPOSE: To determine how COVID-19 lockdown impacted physical activity (PA) levels, wellbeing, and diabetes management in children (aged 0-17 years) with type 1 diabetes (T1D), from the perspectives of their parent/guardian. DESIGN AND METHODS: This qualitative descriptive study is part of a larger, parallel mixed-methods design study, which incorporated a cross-sectional survey and semi-structured one-to-one interviews. Interviewees were recruited from the survey, which was distributed to parents of children/adolescents with T1D in the UK. Interviews explored diabetes management, mental and physical wellbeing, changes in PA levels, sleep quality before/during lockdown, and the effects of lockdown on the individual and their family. The interviews were transcribed and the data were analysed thematically. RESULTS: 14 interviews were conducted with parents. Thematic analysis generated a central theme of routine disruption, with four further themes on diabetes management routines, harnessing the opportunities of lockdown, weighing up risk, and variable impact on wellbeing. CONCLUSIONS: Maintaining or increasing PA during COVID-19 lockdown was associated with better diabetes management, sleep, and wellbeing for children/adolescents with T1D, despite significant disruption to established routines. Use of technology during the pandemic contributed positively to wellbeing. PRACTICE IMPLICATIONS: It is crucial to emphasize the significance of maintaining a well-structured routine when treating patients with type 1 diabetes. A consistent routine, incorporating regular physical exercise and good sleep hygiene, will help with managing overall diabetes control.

Underpinning the Food Matrix Regulation of Postexercise Myofibrillar Protein Synthesis by Comparing Salmon Ingestion With the Sum of Its Isolated Nutrients in Healthy Young Adults.

BACKGROUND: Protein is most commonly consumed as whole foods as opposed to single nutrients. However, the food matrix regulation of the postprandial muscle protein synthetic response has received little attention. OBJECTIVES: The purpose of this study was to assess the effects of eating salmon (SAL) and of ingesting the same nutrients as an isolated mixture of crystalline amino acids and fish oil (ISO) on the stimulation of postexercise myofibrillar protein synthesis (MPS) and whole-body leucine oxidation rates in healthy young adults. METHODS: Ten recreationally active adults (24 ± 4 y; 5 men, 5 women) performed an acute bout of resistance exercise, followed by the ingestion of SAL or ISO in a crossover fashion. Blood, breath, and muscle biopsies were collected at rest and after exercise during primed continuous infusions of L-[ring-2H5]phenylalanine and L-[1-13C]leucine. All data are presented as means ± SD and/or mean differences (95% CIs). RESULTS: Postprandial essential amino acid (EAA) concentrations peaked earlier (P = 0.024) in the ISO group than those in the SAL group. Postprandial leucine oxidation rates increased over time (P < 0.001) and peaked earlier in the ISO group (1.239 ± 0.321 nmol/kg/min; 63 ± 25 min) than those in the SAL group (1.230 ± 0.561 nmol/kg/min; 105 ± 20 min; P = 0.003). MPS rates for SAL (0.056 ± 0.022 %/h; P = 0.001) and ISO (0.046 ± 0.025 %/h; P = 0.025) were greater than the basal rates (0.020 ± 0.011 %/h) during the 0- to 5-h recovery period, with no differences between conditions (P = 0.308). CONCLUSION: We showed that the postexercise ingestion of SAL or ISO stimulate postexercise MPS rates with no differences between the conditions. Thus, our results indicate that ingesting protein from SAL as a whole-food matrix is similarly anabolic to ISO in healthy young adults. This trial was registered at www. CLINICALTRIALS: gov as NCT03870165.

Recommendations from Diabetes UK's 2022 diabetes and physical activity workshop.

AIMS: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of diabetes and physical activity and provide recommendations to researchers and research funders on how best to address them. METHODS: A 1-day research workshop was conducted, bringing together researchers, people living with diabetes, healthcare professionals, and members of staff from Diabetes UK to identify and prioritise recommendations for future research into physical activity and diabetes. RESULTS: Workshop attendees prioritised four key themes for further research: (i) better understanding of the physiology of exercise in all groups of people: in particular, what patient metabolic characteristics influence or predict the physiological response to physical activity, and the potential role of physical activity in beta cell preservation; (ii) designing physical activity interventions for maximum impact; (iii) promoting sustained physical activity across the life course; (iv) designing physical activity studies for groups with multiple long-term conditions. CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to diabetes and physical activity and calls on the research community to develop applications in these areas and funders to consider how to stimulate research in these areas.

Identifying behavioural barriers and facilitators to engaging men in a community-based lifestyle intervention to improve physical and mental health and well-being.

BACKGROUND: There are few community-based lifestyle interventions designed to target physical and mental health of men. We conducted a qualitative focus group study with men to explore their perceived barriers and facilitators to uptake and engagement with interventions designed to improve their physical and mental health and wellbeing. METHODS: A volunteer sampling approach (advertisements posted on a premier league football club's social media) was used to recruit men aged 28 to 65 years who were interested in improving their physical and/or mental health and wellbeing. Focus group discussions were conducted at a local premier league football club to 1) explore men's perceived barriers and facilitators to uptake of community-based interventions; 2) identify health issues considered important to address; 3) obtain participant views on how to best engage men in community-based interventions; and 4) use the findings to inform the development of a multibehavioural complex community-based intervention (called 'The 12th Man'). RESULTS: Six focus group discussions were conducted (duration 27 to 57 min) involving 25 participants (median age 41 years, IQR = 21 years). Thematic analyses generated seven themes: 'Lifestyle behaviours for both mental health and physical health'; 'work pressures are barriers to engaging with lifestyle behaviour change'; previous injuries are barriers to engagement in physical activity and exercise'; personal and peer group relationships impact on lifestyle behaviour change'; relationships between body image and self-confidence on mastery of skills for physical activity and exercise'; building motivation and personalised goal setting'; and 'credible individuals increase uptake and continued engagement with lifestyle behaviour change'. CONCLUSIONS: Findings suggest that a multibehavioural community-based lifestyle intervention designed for men should promote parity of esteem between physical and mental health. It should also acknowledge individual needs and preferences, emotions in the context of goal setting and planning, and be delivered by a knowledgeable and credible professional. The findings will inform the development of a multibehavioural complex community-based intervention ('The 12th Man').

Ageing modifies acute resting blood pressure responses to incremental consumption of dietary nitrate: a randomised, cross-over clinical trial.

Beetroot (BR) is a rich source of nitrate (NO3-) that has been shown to reduce blood pressure (BP). Yet, no studies have examined the vascular benefits of BR in whole-food form and whether the effects are modified by age. This study was a four-arm, randomised, open-label, cross-over design in twenty-four healthy adults (young n 12, age 27 ± 4 years, old n 12, age 64 ± 5 years). Participants consumed whole-cooked BR at portions of (NO3- content in brackets) 100 g (272 mg), 200 g (544 mg) and 300 g (816 mg) and a 200-ml solution containing 1000 mg of potassium nitrate (KNO3) on four separate occasions over a 4-week period (≥7-d washout period). BP, plasma NO3- and nitrite (NO2-) concentrations, and post-occlusion reactive hyperaemia via laser Doppler, were measured pre- and up to 5-h post-intervention. Data were analysed by repeated-measures ANOVA. Plasma NO2- concentrations were higher in the young v. old at baseline and post-intervention (P < 0·05). All NO3- interventions decreased systolic and diastolic BP in young participants (P < 0·05), whereas only KNO3 (at 240-300 min post-intake) significantly decreased systolic (-4·8 mmHg, -3·5 %, P = 0·024) and diastolic (-5·4 mmHg, -6·5 %, P = 0·007) BP in older participants. In conclusion, incremental doses of dietary NO3- reduced systolic and diastolic BP in healthy young adults whereas in the older group a significant decrease was only observed with the highest dose. The lower plasma NO2- concentrations in older participants suggest that there may be mechanistic differences in the production of NO from dietary NO3- in young and older populations.

Dietary fat intake is associated with insulin resistance and an adverse vascular profile in patients with T1D: a pooled analysis.

BACKGROUND: Insulin resistance (IR) increases vascular risk in individuals with Type 1 Diabetes (T1D). We aimed to investigate the relationship between dietary intake and IR, as well as vascular biomarkers in T1D. METHODS: Baseline data from three randomised controlled trials were pooled. Estimated glucose disposal rate (eGDR) was used as an IR marker. Employing multivariate nutrient density substitution models, we examined the association between macronutrient composition and IR/vascular biomarkers (tumour necrosis factor-α, fibrinogen, tissue factor activity, and plasminogen activator inhibitor-1). RESULTS: Of the 107 patients, 50.5% were male with mean age of 29 ± 6 years. Those with lower eGDR were older with a longer diabetes duration, higher insulin requirements, and an adverse vascular profile (p < 0.05). Patients with higher degrees of IR had higher total energy intake (3192 ± 566 vs. 2772 ± 268 vs. 2626 ± 395 kcal/d for eGDR < 5.1 vs. 5.1-8.6 vs. ≥ 8.7 mg/kg/min, p < 0.001) and consumed a higher absolute and proportional amount of fat (47.6 ± 18.6 vs. 30.4 ± 8.1 vs. 25.8 ± 10.4%, p < 0.001). After adjusting for total energy intake, age, sex, and diabetes duration, increased carbohydrate intake offset by an isoenergetic decrease in fat was associated with higher eGDR (ß = 0.103, 95% CI 0.044-0.163). In contrast, increased dietary fat at the expense of dietary protein intake was associated with lower eGDR (ß = - 0.119, 95% CI - 0.199 to - 0.040). Replacing fat with 5% isoenergetic amount of carbohydrate resulted in decreased vascular biomarkers (p < 0.05). CONCLUSION: Higher fat, but not carbohydrate, intake is associated with increased IR and an adverse vascular profile in patients with T1D.

COVID-19 epidemic modelling for policy decision support in Victoria, Australia 2020-2021.

BACKGROUND: Policy responses to COVID-19 in Victoria, Australia over 2020-2021 have been supported by evidence generated through mathematical modelling. This study describes the design, key findings, and process for policy translation of a series of modelling studies conducted for the Victorian Department of Health COVID-19 response team during this period. METHODS: An agent-based model, Covasim, was used to simulate the impact of policy interventions on COVID-19 outbreaks and epidemic waves. The model was continually adapted to enable scenario analysis of settings or policies being considered at the time (e.g. elimination of community transmission versus disease control). Model scenarios were co-designed with government, to fill evidence gaps prior to key decisions. RESULTS: Understanding outbreak risk following incursions was critical to eliminating community COVID-19 transmission. Analyses showed risk depended on whether the first detected case was the index case, a primary contact of the index case, or a 'mystery case'. There were benefits of early lockdown on first case detection and gradual easing of restrictions to minimise resurgence risk from undetected cases. As vaccination coverage increased and the focus shifted to controlling rather than eliminating community transmission, understanding health system demand was critical. Analyses showed that vaccines alone could not protect health systems and need to be complemented with other public health measures. CONCLUSIONS: Model evidence offered the greatest value when decisions needed to be made pre-emptively, or for questions that could not be answered with empiric data and data analysis alone. Co-designing scenarios with policy-makers ensured relevance and increased policy translation.

An MR fingerprinting approach for quantitative inhomogeneous magnetization transfer imaging.

PURPOSE: Magnetization transfer (MT) and inhomogeneous MT (ihMT) contrasts are used in MRI to provide information about macromolecular tissue content. In particular, MT is sensitive to macromolecules, and ihMT appears to be specific to myelinated tissue. This study proposes a technique to characterize MT and ihMT properties from a single acquisition, producing both semiquantitative contrast ratios and quantitative parameter maps. THEORY AND METHODS: Building on previous work that uses multiband RF pulses to efficiently generate ihMT contrast, we propose a cyclic steady-state approach that cycles between multiband and single-band pulses to boost the achieved contrast. Resultant time-variable signals are reminiscent of an MR fingerprinting acquisition, except that the signal fluctuations are entirely mediated by MT effects. A dictionary-based low-rank inversion method is used to reconstruct the resulting images and to produce both semiquantitative MT ratio and ihMT ratio maps, as well as quantitative parameter estimates corresponding to an ihMT tissue model. RESULTS: Phantom and in vivo brain data acquired at 1.5 Tesla demonstrate the expected contrast trends, with ihMT ratio maps showing contrast more specific to white matter, as has been reported by others. Quantitative estimation of semisolid fraction and dipolar T1 was also possible and yielded measurements consistent with literature values in the brain. CONCLUSION: By cycling between multiband and single-band pulses, an entirely MT-mediated fingerprinting method was demonstrated. This proof-of-concept approach can be used to generate semiquantitative maps and quantitatively estimate some macromolecular-specific tissue parameters.

Pharmacokinetic Profile of Incremental Oral Doses of Dietary Nitrate in Young and Older Adults: A Crossover Randomized Clinical Trial.

BACKGROUND: Dietary nitrate consumption can increase concentrations of nitrate and nitrite in blood, saliva, and urine. Whether the change in concentrations is influenced by age is currently unknown. OBJECTIVES: We aimed to measure changes in nitrate and nitrite concentrations in plasma, urine, and saliva and exhaled NO concentrations after single incremental doses of dietary nitrate in young and older healthy adults. METHODS: Twelve young (18-35 y old) and 12 older (60-75 y old) healthy, nonsmoking participants consumed single doses of 100 g, 200 g, 300 g whole beetroot (BR) and 1000 mg potassium nitrate (positive control) ≥7 d apart in a crossover, randomized clinical trial. Plasma nitrate and nitrite concentrations and exhaled NO concentrations were measured over a 5-h period. Salivary nitrate and nitrite concentrations were measured over a 12-h period and urinary nitrate over a 24-h period. Time, intervention, age, and interaction effects were measured with repeated-measures ANOVAs. RESULTS: Dose-dependent increases were seen in plasma, salivary, and urinary nitrate after BR ingestion (all P ≤ 0.002) but there were no differences between age groups at baseline (all P ≥ 0.56) or postintervention (all P ≥ 0.12). Plasma nitrite concentrations were higher in young than older participants at baseline (P = 0.04) and after consumption of 200 g (P = 0.04; +25.7 nmol/L; 95% CI: 0.97, 50.3 nmol/L) and 300 g BR (P = 0.02; +50.3 nmol/L; 95% CI: 8.57, 92.1 nmol/L). Baseline fractional exhaled NO (FeNO) concentrations were higher in the younger group [P = 0.03; +8.60 parts per billion (ppb); 95% CI: 0.80, 16.3 ppb], and rose significantly over the 5-h period, peaking 5 h after KNO3 consumption (39.4 ± 4.5 ppb; P < 0.001); however, changes in FeNO were not influenced by age (P = 0.276). CONCLUSIONS: BR is a source of bioavailable dietary nitrate in both young and older adults and can effectively raise nitrite and nitrate concentrations. Lower plasma nitrite and FeNO concentrations were found in older subjects, confirming the impact of ageing on NO bioavailability across different systems.This trial was registered at www.isrctn.com as ISRCTN86706442.

Capturing the real-world benefit of residual ß-cell function during clinically important time-periods in established Type 1 diabetes.

AIMS: Many individuals with type 1 diabetes retain residual ß-cell function, with increased endogenous insulin secretion associated with reduced hyperglycaemia, hypoglycaemia and glycaemic variability. However, it is unknown when these improvements occur during the day. Dysglycaemia is common in overnight and postprandial periods and associated with diabetes complications. Therefore, this study aimed to determine the influence of residual ß-cell function upon nocturnal and postprandial glycaemic control in established type 1 diabetes. METHODS: Under free-living conditions, 66 participants wore a blinded continuous glucose monitor (CGM), kept a food diary, and completed a stimulated urine C-peptide creatinine (UCPCR) test. Nocturnal, and postprandial CGM outcomes (participant means and discrete event analysis) were compared between UCPCR groups: undetectable (Cpepund ), low (Cpeplow : 0.001-0.19 nmol/mmol) and high (Cpephigh : ≥0.2 nmol/mmol). RESULTS: Greater ß-cell function was associated with incremental improvements in glycaemia. Cpephigh spent significantly greater time in normoglycaemia than Cpepund overnight (76 ± 20% vs. 58 ± 20%, p = 0.005) and 0-300 mins postprandially (68 ± 22% vs. 51 ± 22%, p = 0.045), while also having reducing nocturnal variability (SD 1.12 ± 0.41 vs. 1.52 ± 0.43 mmol/L, p = 0.010). Analysis of individual events, controlling for diabetes duration, BMI, basal insulin, use of a continuous or flash glucose monitor and (for postprandial) meal type, carbohydrate and bolus insulin intake, replicated the group findings, additionally demonstrating Cpepund had increased hyperglycaemia versus Cpeplow overnight and increased postprandial hypoglycaemic events compared with Cpephigh . For all participants, breakfast had a significantly higher incremental area under the curve than lunch and dinner. CONCLUSIONS: Residual ß-cell function is associated with improved nocturnal and postprandial glycaemic control. These data may be of clinical importance for identifying specific periods and individuals where further glycaemic management strategies would be beneficial.

Relative protein intake and associations with markers of physical function in those with type 2 diabetes.

AIMS: To examine the independent associations between relative protein intake (g kg-1  day 1 ) and markers of physical function in those with type 2 diabetes, while also comparing with current guidelines for protein intake. METHODS: This analysis reports data from the ongoing Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) study. Functional assessments included: Short Physical Performance Battery (SPPB), 60 s sit-to-stand (STS-60), 4-m gait speed, time to rise from a chair (×5) and handgrip strength. Participants also completed a self-reported 4 day diet diary. Regression analyses assessed whether relative protein intake was associated with markers of physical function. Interaction terms assessed whether the associations were modified by sex, age, HbA1c or body mass index (BMI). RESULTS: 413 participants were included (mean ± SD:age = 65.0 ± 7.7 years, 33% female, BMI = 30.6 ± 5.1 kg/m2 ). The average total protein intake was 0.88 ± 0.31 g kg-1  day-1 . 33% of individuals failed to meet the reference nutrient intake for the United Kingdom (≥0.75 g kg-1  day-1 ), and 87% for European recommendations (≥1.2 g kg-1  day-1 ). After adjustment, each 0.5 g/kg of protein intake was associated with an 18.9% (95% CI: 2.3, 35.5) higher SPPB score, 22.7% (1.1, 44.3) more repetitions in STS-60, 21.1% (4.5, 37.7) faster gait speed and 33.2% (16.9, 49.5) lower chair rise time. There were no associations with handgrip strength or any interactions. CONCLUSIONS: Relative protein intake was positively associated with physical function outcomes, even after consideration of total energy intake. As a number of individuals were below the current guidelines, protein intake may be a modifiable factor of importance for people with type 2 diabetes.

External support factors utilized by patients in coping with cancer: a European perspective.

PURPOSE: The article presents the results of research on psychosocial aspects of living with cancer in the Slovak Republic focusing on hospitalized and outpatient cancer patients in treatment during the curative stage of the disease. Assessing cancer patient's interest in receiving help from individual members of a multidisciplinary team was a part of the research. METHODS: The research was done through a questionnaire designed to focus on individual psychosocial aspects of cancer treatment. The research sample included 67 hospitalized patients and 61 outpatients. Execution of research was conducted in the individual clinical workplaces. RESULTS: When calculating the interest of cancer patients in spiritual counseling during oncological treatment, hospitalized patients indicated significant interest (p = .014). Similarly, hospitalized patients indicated more interest in using psychological counseling (p = .040) as well as in consultation with the social worker with a significant difference of (p = .017). Interest in the aid of a physical therapist was exhibited more significantly with hospitalized patients (p = .000). Significant interest in hospitalized patients using additional members of the multidisciplinary team was statistically significant (p = .017). Outpatient cancer patients indicated significant interest in finding information about medical conditions on the Internet (p = .000). For items addressing an interest in meeting people with cancer in self-help groups, there was no significant difference between outpatient and hospital patients (p = .298) as with talking to other patients who had cancer (p = .207). CONCLUSION: External support factors are important in helping patients cope with cancer. Health professionals can help patients mitigate the various difficulties associated with cancer.

Enhancing epidemiological surveillance of the emergence of the SARS-CoV-2 Omicron variant using spike gene target failure data, England, 15 November to 31 December 2021.

When SARS-CoV-2 Omicron emerged in 2021, S gene target failure enabled differentiation between Omicron and the dominant Delta variant. In England, where S gene target surveillance (SGTS) was already established, this led to rapid identification (within ca 3 days of sample collection) of possible Omicron cases, alongside real-time surveillance and modelling of Omicron growth. SGTS was key to public health action (including case identification and incident management), and we share applied insights on how and when to use SGTS.

Replace, amplify, transform: a qualitative study of how postgraduate trainees and supervisors experience and use telehealth for instruction in ambulatory patient care.

BACKGROUND: Little is known about using telehealth patient visits as an educational mode. Therefore, rapid implementation of telehealth during the COVID-19 pandemic had to be done without understanding how to optimize telehealth for education. With the likely sustained/post-pandemic use of telehealth in ambulatory patient care, filling gaps in our understanding of how telehealth can be used for instruction in this context is critical. This study sought to understand perceptions of pediatric postgraduate trainees and supervisors on the use of telehealth for instruction in ambulatory settings with the goal of identifying effective ways to enhance learning during telehealth visits. METHODS: In May-June of 2020, the authors purposefully sampled first- and third-year postgraduate trainees and supervising attendings from pediatric fellowship programs at one institution that implemented telehealth for instructional activities. They conducted semi-structured interviews; interviews lasted a median of 51 min (trainees) and 41 min (supervisors). They conducted interviews and data analysis iteratively until reaching saturation. Using thematic analysis, they created codes and constructed themes from coded data. They organized themes using the Replace-Amplify-Transform (RAT) model, which proposes that technology can replace in-person learning and/or amplify and transform learning. RESULTS: First-year trainees (n = 6), third-year trainees (n = 5) and supervisors (n = 6) initially used telehealth to replace in-person learning. However, skills that could be practiced in telehealth visits differed from in-person visits and instructional activities felt rushed or awkward. Trainees and supervisors adapted and used telehealth to amplify learning by enhancing observation and autonomy. They also transformed learning, using telehealth to develop novel skills. CONCLUSIONS: To harness telehealth for instructional activities, our findings indicated that trainees and supervisors should shift from using it as a direct replacement for in-person education to taking advantage of novel opportunities to amplify and transform education in PGME. The authors provide data-driven recommendations to help PGME trainees, supervisors and educators capitalize on the educational advantages of telehealth.

Effects of Distinct Force Magnitude of Spinal Manipulative Therapy on Blood Biomarkers of Inflammation: A Proof of Principle Study in Healthy Young Adults.

OBJECTIVES: The purpose of this preliminary study was to determine the influence of thoracic spinal manipulation therapy (SMT) of different force magnitudes on blood biomarkers of inflammation in healthy adults. METHODS: Nineteen healthy young adults (10 female, age: 25.6 ± 1.2 years) were randomized into the following 3 groups: (1) control (preload only), (2) single thoracic SMT with a total peak force of 400N, and (3) single thoracic SMT with a total peak force of 800N. SMT was performed by an experienced chiropractor, and a force-plate embedded treatment table (Force Sensing Table Technology) was used to determine the SMT force magnitudes applied. Blood samples were collected at pre intervention (baseline), immediately post intervention, and 20 minutes post intervention. A laboratory panel of 14 different inflammatory biomarkers (pro, anti, dual role, chemokine, and growth factor) was assessed by multiplex array. Change scores from baseline of each biomarker was used for statistical analysis. Two-way repeated-measures analysis of variance was used to investigate the interaction and main effects of intervention and time on cytokines, followed by Tukey's multiple comparison test (P ≤ .05). RESULTS: A between-group (800N vs 400N) difference was observed on interferon-gamma, interleukin (IL)-5, and IL-6, while a within-group difference (800N: immediately vs 20 minutes post-intervention) was observed on IL-6 only. CONCLUSION: In this study, we measured short-term changes in plasma cytokines in healthy young adults and found that select plasma pro-inflammatory and dual-role cytokines were elevated by higher compared to lower SMT force. Our findings aid to advance our understanding of the potential relationship between SMT force magnitude and blood cytokines and provide a healthy baseline group with which to compare similar studies in clinical populations in the future.

Incorporation of Dietary Amino Acids Into Myofibrillar and Sarcoplasmic Proteins in Free-Living Adults Is Influenced by Sex, Resistance Exercise, and Training Status.

BACKGROUND: Acute exercise increases the incorporation of dietary amino acids into de novo myofibrillar proteins after a single meal in controlled laboratory studies in males. It is unclear whether this extends to free-living settings or is influenced by training or sex. OBJECTIVES: We determined the effects of exercise, training status, and sex on 24-hour free-living dietary phenylalanine incorporation into skeletal muscle proteins. METHODS: In a parallel group design, recreationally active males (mean ± SD age, 23 ± 3 years;  BMI. 23.4 ± 2.9 kg/m2; n = 10) and females (age 24 ± 5 years;  BMI, 23.1 ± 3.9 kg/m2; n = 9) underwent 8 weeks of whole-body resistance exercise 3 times a week. Controlled diets containing 1.6 g/kg-1/d-1 (amino acids modelled after egg), enriched to 10% with [13C6] or [2H5]phenylalanine, were consumed before and after an acute bout of resistance exercise. Fasted muscle biopsies were obtained before [untrained, pre-exercise condition (REST ] and 24 hours after an acute bout of resistance exercise in untrained (UT) and trained (T) states to determine dietary phenylalanine incorporation into myofibrillar (ΔMyo) and sarcoplasmic (ΔSarc) proteins, intracellular mechanistic target of rapamycin (mTOR) colocalization with ulex europaeus agglutinin-1 (UEA-1; capillary marker; immunofluorescence), and amino acid transporter expression (Western blotting). RESULTS: The ΔMyo values were ∼62% greater (P < 0.01) in females than males at REST. The ΔMyo values increased above REST by ∼51% during UT and ∼30% in T (both P < 0.01) in males, remained unchanged in females during UT, and were ∼33% lower at T when compared to UT (P = 0.013). Irrespective of sex, ΔMyo and ΔSarc were decreased at T compared to UT (P ≤ 0.026). Resistance training increased mTOR colocalization with UEA-1 (P = 0.004), while L amino acid transporter 1, which was greater in males (P < 0.01), and sodium-coupled neutral amino acid transporter 2 protein expression were not affected by acute exercise (P ≥ 0.33) or training (P ≥ 0.45). CONCLUSIONS: The exercise-induced incorporation of dietary phenylalanine into myofibrillar and sarcoplasmic proteins is attenuated after training regardless of sex, suggesting a reduced reliance on dietary amino acids for postexercise skeletal muscle remodeling in the T state.

Low responders to endurance training exhibit impaired hypertrophy and divergent biological process responses in rat skeletal muscle.

NEW FINDINGS: What is the central question of this study? The extent to which genetics determines adaptation to endurance versus resistance exercise is unclear. Previously, a divergent selective breeding rat model showed that genetic factors play a major role in the response to aerobic training. Here, we asked: do genetic factors that underpin poor adaptation to endurance training affect adaptation to functional overload? What is the main finding and its importance? Our data show that heritable factors in low responders to endurance training generated differential gene expression that was associated with impaired skeletal muscle hypertrophy. A maladaptive genotype to endurance exercise appears to dysregulate biological processes responsible for mediating exercise adaptation, irrespective of the mode of contraction stimulus. ABSTRACT: Divergent skeletal muscle phenotypes result from chronic resistance-type versus endurance-type contraction, reflecting the principle of training specificity. Our aim was to determine whether there is a common set of genetic factors that influence skeletal muscle adaptation to divergent contractile stimuli. Female rats were obtained from a genetically heterogeneous rat population and were selectively bred from high responders to endurance training (HRT) or low responders to endurance training (LRT; n = 6/group; generation 19). Both groups underwent 14 days of synergist ablation to induce functional overload of the plantaris muscle before comparison to non-overloaded controls of the same phenotype. RNA sequencing was performed to identify Gene Ontology biological processes with differential (LRT vs. HRT) gene set enrichment. We found that running distance, determined in advance of synergist ablation, increased in response to aerobic training in HRT but not LRT (65 ± 26 vs. -6 ± 18%, mean ± SD, P < 0.0001). The hypertrophy response to functional overload was attenuated in LRT versus HRT (20.1 ± 5.6 vs. 41.6 ± 16.1%, P = 0.015). Between-group differences were observed in the magnitude of response of 96 upregulated and 101 downregulated pathways. A further 27 pathways showed contrasting upregulation or downregulation in LRT versus HRT in response to functional overload. In conclusion, low responders to aerobic endurance training were also low responders for compensatory hypertrophy, and attenuated hypertrophy was associated with differential gene set regulation. Our findings suggest that genetic factors that underpin aerobic training maladaptation might also dysregulate the transcriptional regulation of biological processes that contribute to adaptation to mechanical overload.

Re-Examining Myofascial Pain Syndrome: Toward Biomarker Development and Mechanism-Based Diagnostic Criteria.

PURPOSE OF REVIEW: We discuss the need for a mechanism-based diagnostic framework with a focus on the development of objective measures (e.g., biomarkers) that can potentially be added to the diagnostic criteria of the syndrome. Potential biomarkers are discussed in relation to current knowledge on the pathophysiology of myofascial pain syndrome (MPS), including alterations in redox status, inflammation, and the myofascial trigger point (MTrP) biochemical milieu, as well as imaging and neurophysiological outcomes. Finally, we discuss the long-term goal of conducting a Delphi survey, to assess the influence of putative MPS biomarkers on clinician opinion, in order to ultimately develop new criteria for the diagnosis of MPS. RECENT FINDINGS: Myofascial pain syndrome (MPS) is a prevalent healthcare condition associated with muscle weakness, impaired mood, and reduced quality of life. MPS is characterized by the presence of myofascial trigger points (MTrPs): stiff and discrete nodules located within taut bands of skeletal muscle that are painful upon palpation. However, physical examination of MTrPs often yields inconsistent results, and there is no gold standard by which to diagnose MPS. The current MPS diagnostic paradigm has an inherent subjectivity and the absence of correlation with the underlying pathophysiology. Recent advancements in ultrasound imaging, systemic biomarkers, MTrP-specific biomarkers, and the assessment of dysfunction in the somatosensorial system may all contribute to improved diagnostic effectiveness of MPS.