The effect of high-intensity interval training on cognitive function in patients with substance use disorder: Study protocol for a two-armed randomized controlled trial.

Introduction: Substance use disorder (SUD) is characterized by cognitive impairment, especially executive dysfunction. Executive function is recognized as an important determinant of treatment outcome as it is associated with dropout rate, attendance to therapy and potential relapse after treatment termination. Physical activity can have beneficial effects on cognitive function, but there is still a lack of knowledge regarding potential benefits of aerobic exercise for executive function in SUD treatment. The aim of this study is to examine the effect of aerobic high-intensity interval training (HIIT) on cognitive function and the subsequent effect on treatment outcome in patients with SUD. Methods and analysis: This study is a randomized controlled trial, including men and women ≥18 years with diagnosed SUD by ICD-10. The patients will be recruited from the department for inpatient treatment at Blue Cross - Lade Addiction Treatment Center, Trondheim, Norway. Participants will be randomized 1:1 into either HIIT (3x/week) + treatment as usual (TAU), or TAU alone. Study outcomes will be assessed at baseline, after eight weeks of intervention, and at 3- and 12-months follow-up. The primary outcome is to compare the change in executive function (via altered BRIEF-A score, Behavior Rating Inventory of Executive Function-Adult) measured between the two study groups after eight weeks. Secondary outcomes include mapping of cognitive function in different subgroups (e.g. type of substance, age, fitness level), collecting self-reported information about quality of life, craving, sleep quality, etc., as well as assessing compliance to TAU and long-term treatment outcome. Ethics and dissemination: The project was approved by the Regional Ethical Committee and will be performed in accordance with this protocol and the Declaration of Helsinki. Written informed consent will be obtained from all participants prior to inclusion. This project will explore a novel approach to how exercise can be applied in SUD treatment, beyond the well-known effects on physical health. We expect to achieve new knowledge in regard to what extent HIIT can improve cognitive abilities and subsequent treatment outcome in SUD. Trial registration number: https://www.clinicaltrials.gov/NCT05324085.

Cardiopulmonary and muscular effects of different doses of high-intensity physical training in substance use disorder patients: study protocol for a block allocated controlled endurance and strength training trial in an inpatient setting.

INTRODUCTION: Patients with substance use disorder (SUD) have high prevalence of lifestyle-related comorbidities. Physical exercise is known to yield substantial prophylactic impact on disease and premature mortality, and there seems to be an inverse association between physical fitness and adverse health outcomes. High-intensity training is regarded as most effective for improving physical fitness, but less is known concerning the ideal training dose necessary to achieve clinically relevant effects in these patients. The aim of this study is to compare the effect of low-dose and high-dose, high-intensity training, on physical fitness in patients diagnosed with SUD. METHODS AND ANALYSIS: This study will recruit 40 in-patients of mixed genders, aged 18-70 years. Participants will be block allocated to low-dose or high-dose training, encompassing 24 high-intensity interval and maximal strength training sessions (3/week × 8 weeks). After a 10 min warm-up, the low-dose group will perform 1×4 min intervals at ⁓90% of maximal heart rate and 2×4 repetitions strength training at ⁓90% of 1 repetition maximum. The high-dose group will perform 4×4 min intervals at ⁓90% of maximal heart rate and 4×4 repetitions strength training at ⁓90% of 1 repetition maximum. Clinical measurements and physical tests will be conducted at baseline, midway and on completion and a questionnaire on physical activity will be administered at baseline. ETHICS AND DISSEMINATION: This protocol is in accordance with the Standard Protocol Items: Recommendations for Interventional Trials statement. All participants will sign a written informed consent. The Regional Committee of Medical Research Ethics, Norway has approved the study. A study of this kind is warranted, and the results will be published in an open access journal to ensure public access, and presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04065334.

Acute Effects of Strength and Endurance Training on Bone Turnover Markers in Young Adults and Elderly Men.

Context: Exercise is recognized as an important strategy to prevent bone loss, but its acute effects on bone turnover markers (BTMs) and related markers remain uncertain. Objective: To assess the acute effects of two different exercise modes on BTMs and related markers in young adults of both sexes and elderly men. Design Setting Participants: This was a three-group crossover within-subjects design study with a total of 53 participants-19 young women (aged 22-30), 20 young men (aged 21-30 years), and 14 elderly men (aged 63-74 years)-performing two different exercise sessions [strength training (ST) and high-intensity interval training (HIIT)] separated by 2 weeks, in a supervised laboratory setting. Main Outcome Measures: Plasma volume-corrected serum measurements of the BTMs C-terminal telopeptide of type 1 collagen (CTX-I) and procollagen of type 1 N-terminal propeptide (P1NP), total osteocalcin (OC), sclerostin, and lipocalin-2 (LCN2) at baseline, immediately after, and 3 and 24 h after each of the two exercise modes were performed. Results and Conclusion: Analyses revealed sex- and age-dependent differences in BTMs and related bone markers at baseline and time-, sex-, and age-dependent differences in response to exercise. No differences between exercise modes were observed for BTM response except for sclerostin in young men and LCN2 in elderly men. An acute, transient, and uniform increase in P1NP/CTX-1 ratio was found in young participants, demonstrating that beneficial skeletal effects on bone metabolism can be attained through both aerobic endurance and resistance exercise, although this effect seems to be attenuated with age. The acute effects of exercise on bone-related biomarkers were generally blunted after 24 h, suggesting that persistent alterations following prolonged exercise interventions should be assessed at later time points.

Diabetes Prevalence and Associated Risk Factors among Women in a Rural District of Nepal Using HbA1c as a Diagnostic Tool: A Population-Based Study.

Given the scarcity of data on diabetes prevalence and associated risk factors among women in rural Nepal, we aimed to examine this, using glycated hemoglobin (HbA1c) as a diagnostic tool. A cross-sectional survey addressing reproductive health and non-communicable diseases was conducted in 2012-2013 among non-pregnant, married women in Bolde, a rural district of Nepal. HbA1c ≥ 6.5% (48 mmol/mol) was used as diagnostic criterion for diabetes, a cut-off of 7.0% (53 mmol/mol) was used to increase the specificity. HbA1c was measured in 757 women (17-86 years). The prevalence of diabetes and prediabetes was 13.5% and 38.5%, respectively. When using 7.0% as a cut-off, the prevalence of diabetes was 5.8%. Aging, intake of instant noodles and milk and vegetarian food (ns) were associated with increased risk for diabetes. Waist circumference was higher among women with diabetes, although not significant. The women were uneducated (87.6%), and only 12% had heard about diabetes. In conclusion, we observed a higher prevalence of diabetes and prediabetes than anticipated among rural, Nepalese women. The increased risk was mainly attributed to dietary factors. In contrast to most previous studies in Nepal, we used HbA1c as diagnostic criterion.

Maximal strength training-induced increase in efferent neural drive is not reflected in relative protein expression of SERCA.

INTRODUCTION: Maximal strength training (MST), performed with heavy loads (~ 90% of one repetition maximum; 1RM) and few repetitions, yields large improvements in efferent neural drive, skeletal muscle force production, and skeletal muscle efficiency. However, it is elusive whether neural adaptations following such high intensity strength training may be accompanied by alterations in energy-demanding muscular factors. METHODS: Sixteen healthy young males (24 ± 4 years) were randomized to MST 3 times per week for 8 weeks (n = 8), or a control group (CG; n = 8). Measurements included 1RM and rate of force development (RFD), and evoked potentials recordings (V-wave and H-reflex normalized to M-wave (M) in the soleus muscle) applied to assess efferent neural drive to maximally contracting skeletal muscle. Biopsies were obtained from vastus lateralis and analyzed by western blots and real-time PCR to investigate the relative protein expression and mRNA expression of Sarcoplasmic Reticulum Ca2+ ATPase (SERCA) 1 and SERCA2. RESULTS: Significant improvements in 1RM (17 ± 9%; p < 0.001) and early (0-100 ms), late (0-200 ms) and maximal RFD (31-53%; p < 0.01) were observed after MST, accompanied by increased maximal Vmax/Msup-ratio (9 ± 14%; p = 0.046), with no change in H-reflex to M-wave ratio. No changes were observed in the CG. No pre- to post-training differences were found in mRNA or protein expressions of SERCA1 and SERCA2 in either group. CONCLUSION: MST increased efferent neural drive to maximally contracting skeletal muscle, causing improved force production. No change was observed in SERCA expression, indicating that responses to high intensity strength training may predominantly be governed by neural adaptations.

Evidence of impaired bone quality in men with type 1 diabetes: a cross-sectional study.

OBJECTIVE: Type 1 diabetes (T1D) is associated with substantial fracture risk. Bone mineral density (BMD) is, however, only modestly reduced, suggesting impaired bone microarchitecture and/or bone material properties. Yet, the skeletal abnormalities have not been uncovered. Men with T1D seem to experience a more pronounced bone loss than their female counterparts. Hence, we aimed to examine different aspects of bone quality in men with T1D. DESIGN AND METHODS: In this cross-sectional study, men with T1D and healthy male controls were enrolled. BMD (femoral neck, total hip, lumbar spine, whole body) and spine trabecular bone score (TBS) were measured by dual x-ray absorptiometry, and bone material strength index (BMSi) was measured by in vivo impact microindentation. HbA1c and bone turnover markers were analyzed. RESULTS: Altogether, 33 men with T1D (43 ± 12 years) and 28 healthy male controls (42 ± 12 years) were included. Subjects with T1D exhibited lower whole-body BMD than controls (P = 0.04). TBS and BMSi were attenuated in men with T1D vs controls (P = 0.016 and P = 0.004, respectively), and T1D subjects also had a lower bone turnover. The bone parameters did not differ between subjects with or without diabetic complications. Duration of disease correlated negatively with femoral neck BMD but not with TBS or BMSi. CONCLUSIONS: This study revealed compromised bone material strength and microarchitecture in men with T1D. Moreover, our data confirm previous studies which found a modest decrease in BMD and low bone turnover in subjects with T1D. Accordingly, bone should be recognized as a target of diabetic complications.

The effect of an exercise program in pregnancy on vitamin D status among healthy, pregnant Norwegian women: a randomized controlled trial.

BACKGROUND: Vitamin D insufficiency is common in pregnant women worldwide. Regular prenatal exercise is considered beneficial for maternal and fetal health. There is a knowledge gap regarding the impact of prenatal exercise on maternal vitamin D levels. The objective of this study was to investigate whether a prenatal exercise program influenced serum levels of total, free and bioavailable 25-hydroxyvitamin D (25(OH)D) and related parameters. This is a post hoc analysis of a randomized controlled trial with gestational diabetes as the primary outcome. METHODS: Healthy, pregnant women from two Norwegian cities (Trondheim and Stavanger) were randomly assigned to a 12-week moderate-intensity exercise program (Borg perceived rating scale 13-14) or standard prenatal care. The intervention group (n = 429) underwent exercise at least three times weekly; one supervised group training and two home based sessions. The controls (n = 426) received standard prenatal care, and exercising was not denied. Training diaries and group training was used to promote compliance and evaluate adherence. Serum levels of 25(OH)D, parathyroid hormone, calcium, phosphate, magnesium and vitamin D-binding protein were measured before (18-22 weeks' gestation) and after the intervention (32-36 weeks' gestation). Free and bioavailable 25(OH)D concentrations were calculated. Regression analysis of covariance (ANCOVA) was applied to assess the effect of the training regime on each substance with pre-intervention levels as covariates. In a second model, we also adjusted for study site and sampling month. Intention-to-treat principle was used. RESULTS: A total of 724 women completed the study. No between-group difference in serum 25(OH)D and related parameters was identified by ANCOVA using baseline serum levels as covariates. The second model revealed a between-group difference in levels of 25(OH)D (1.9, 95% CI 0.0 to 3.8 nmol/L; p = 0.048), free 25(OH)D (0.55, 95% CI 0.10 to 0.99 pmol/L; p = 0.017) and bioavailable 25(OH)D (0.15 95% CI 0.01 to 0.29 nmol/L; p = 0.036). No serious adverse events related to regular exercise were seen. CONCLUSION: This study, a post hoc analysis, indicates that exercise may affect vitamin D status positively, and emphasizes that women with uncomplicated pregnancies should be encouraged to perform regular exercise. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00476567 , registered May 22, 2007.

Adiponectin prevents orthodontic tooth movement in rats.

OBJECTIVE: The objective was to examine the effects of repetitive local administration of adiponectin on experimental tooth movement in rats. MATERIALS AND METHODS: The maxillary right first molar of male Wistar rats (n=24) was moved mesially for 14days, with local adiponectin injections (0.2 or 2µg) every third day. Micro-computed tomography was performed at days 0, 6 and 14 and molar movement, bone density and bone volume fraction were calculated from the scans. Changes in extracellular matrix collagen and cell numbers in the periodontal ligament were analyzed histologically, and levels of circulating cytokines were measured by Luminex and ELISA. RESULTS: Adiponectin injections induced a reduction in tooth movement after 12 and 14days compared to controls. No tooth movement was observed between days 3 and 14 in the group receiving the highest dosage (2µg) of adiponectin. Differences in bone density and bone volume fractions between treatment and control groups were not identified. Relative size and morphology of collagen fibrils, and cell number in the periodontal region after adiponectin injections were unchanged compared to controls. Levels of circulating adiponectin or other selected factors in plasma were not influenced by the adiponectin injections. CONCLUSIONS: Submucosal injections of adiponectin prevented experimental tooth movement in rats. The effect was dosage-dependent and local. Adiponectin injections caused no detectable changes in bone density, periodontal cell number or collagen content.

High doses of vitamin C plus E reduce strength training-induced improvements in areal bone mineral density in elderly men.

PURPOSE: Resistance training is beneficial for maintaining bone mass. We aimed to investigate the skeletal effects of high doses of antioxidants [vitamin C + E (α-tocopherol)] supplementation during 12-week supervised strength training in healthy, elderly men METHODS: Design: double-blinded randomized placebo-controlled study. Participants followed a supervised, undulating periodic exercise program with weekly adjusted load: 3 sessions/week and 3-15 repetitions maximum (RM) sets/exercise. The control group (CG, n = 17, 67 ± 5 years) received placebo and the antioxidant group (AO, n = 16, 70 ± 7 years) 1000 mg vitamin C + 235 mg vitamin E, daily. Areal bone mineral density (aBMD) at whole body, lumbar spine (L1-L4), total hip, and femoral neck were measured by dual energy X-ray absorptiometry and muscle strength by 1RM. Serum analyses of bone-related factors and adipokines were performed. RESULTS: In the CG, total hip aBMD increased by 1.0% (CI: 0.3-1.7) versus pretest and lumbar spine aBMD increased by 0.9% (CI: -0.2 to 2.0) compared to the AO. In the CG, there was an increase in serum concentrations of insulin-like growth factor 1 [+27.3% (CI: -0.3 to 54.9)] and leptin [+31.2% (CI: 9.8-52.6)) versus pretest, and a decrease in sclerostin [-9.9% (CI: 4.4-15.3)] versus pretest and versus AO. Serum bone formation markers P1NP and osteocalcin increased in both groups, while the bone resorption marker CTX-1 remained unchanged. CONCLUSION: High doses of antioxidant supplementations may constrain the favorable skeletal benefits of 12 weeks of resistance exercise in healthy elderly men.

The PPARα Agonist Fenofibrate Improves the Musculoskeletal Effects of Exercise in Ovariectomized Rats.

The musculoskeletal effects of exercise are attenuated by estrogen deficiency. The peroxisome proliferator-activated receptor-α agonist fenofibrate exerts beneficial effects in bone and muscle. We therefore examined whether fenofibrate could enhance the musculoskeletal training response during estrogen deficiency. We investigated the combined effects of 8 weeks of fenofibrate and jumping exercise in ovariectomized (OVX) Sprague Dawley rats. Female rats were allocated to a sham-operated group and four OVX groups; fenofibrate (OVX-Fen), exercise (OVX-Ex), combined fenofibrate and exercise (OVX-FenEx), and a control group (OVX-Ctr) (n = 12/group). Fenofibrate (90 mg/kg/d) or methylcellulose was given by gavage. The combination of exercise and fenofibrate resulted in enhanced femoral bone mineral density (BMD) and improved bone microarchitecture compared with fenofibrate alone as well as increased trabecular BMD compared with OVX-Ctr. These effects were not seen in the OVX-Ex group. Femoral BMD was normalized in both exercise groups relative to sham and increased more in all intervention groups compared with OVX-Ctr. A higher plasma level of the bone formation marker type 1 collagen amino propeptide was observed in the OVX-Fen and OVX-FenEx groups compared with controls. Lean mass and soleus muscle weight were higher in the OVX-FenEx group than in the OVX-Ctr group, which coincided with lower mRNA levels of Atrogin1. These results suggest that peroxisome proliferator-activated receptor-α activation improves the musculoskeletal effects of exercise during estrogen deficiency.

Impaired skeletal health in patients with chronic atrophic gastritis.

OBJECTIVE: In chronic atrophic gastritis (CAG), destruction of gastric parietal cells causes anacidity and hypergastrinemia. Use of proton pump inhibitors, which also induces gastric anacidity, is associated with increased fracture rates. Our objectives were to study possible differences in bone mineral density (BMD) and bone quality in patients with CAG compared to controls. MATERIAL AND METHODS: We performed a cross-sectional study on 17 CAG patients aged 54 ± 13 years and 41 sex- and age-matched controls. Lumbar and femoral BMD and bone quality assessed by lumbar trabecular bone score (TBS) were measured by DXA, and bone material strength (BMS) by microindentation of the tibia. Serum bone markers (CTX, P1NP, sclerostin, osteocalcin, OPG, RANKL) were analyzed. RESULTS: We found lower lumbar BMD Z-score (-0.324 ± 1.096 versus 0.456 ± 1.262, p = 0.030), as well as a higher frequency of osteoporosis at the lumbar spine (p = 0.046) and osteopenia at total hip (p = 0.019) in patients compared to controls. In a post hoc subgroup analysis, we observed that the differences were confined to the male patients. TBS also tended to be lower in male patients (p = 0.059), while BMS did not differ between the groups. Osteocalcin, sclerostin, OPG, and OPG/RANKL ratio were lower in patients compared to controls, while CTX and P1NP did not differ between the groups. CONCLUSIONS: We observed lower lumbar BMD, increased frequency of osteopenia and osteoporosis in male, but not female patients with CAG. Bone markers suggest a decrease in bone formation and increased bone resorption in CAG patients compared to controls.

Strength training-induced responses in older adults: attenuation of descending neural drive with age.

Although reductions in resting H-reflex responses and maximal firing frequency suggest that reduced efferent drive may limit muscle strength in elderly, there are currently no reports of V-wave measurements in elderly, reflecting the magnitude of efferent output to the muscle during maximal contraction. Furthermore, it is uncertain whether potential age-related neural deficiencies can be restored by resistance training. We assessed evoked reflex recordings in the triceps surae muscles during rest and maximal voluntary contraction (MVC), rate of force development (RFD), and muscle mass in seven elderly (74 ± 6 years) males before and after 8 weeks of heavy resistance training, contrasted by seven young (24 ± 4 years) male controls. At baseline, m. soleus (SOL) V/M ratio (0.124 ± 0.082 vs. 0.465 ± 0.197, p < 0.05) and H/M ratio (0.379 ± 0.044 vs. 0.486 ± 0.101 p = 0.07) were attenuated in elderly compared to young. Also, SOL H-reflex latency (33.29 ± 2.41 vs. 30.29 ± 0.67 ms, p < 0.05) was longer in elderly. The reduced neural drive was, despite similar leg muscle mass (10.7 ± 1.2 vs. 11.5 ± 1.4 kg), mirrored by lower MVC (158 ± 48 vs. 240 ± 54 Nm, p < 0.05) and RFD (294 ± 126 vs. 533 ± 123 Nm s(-1), p < 0.05) in elderly. In response to training SOL V/M ratio (0.184 ± 0.092, p < 0.05) increased in the elderly, yet only to a level ~40 % of the young. This was accompanied by increased MVC (190 ± 70 Nm, p < 0.05) and RFD (401 ± 147 Nm[Symbol: see text]s(-1), p < 0.05) to levels of ~80 % and ~75 % of the young. H/M ratio remained unchanged. These findings suggest that changes in supraspinal activation play a significant role in the age-related changes in muscle strength. Furthermore, this motor system impairment can to some extent be improved by heavy resistance training.

Plantar flexion training primes peripheral arterial disease patients for improvements in cardiac function.

This study investigated if initial calf muscle training immediately followed by whole body training improved aerobic power and cardiovascular function in peripheral arterial disease (PAD) patients. The training group (n = 10) pursued 8 weeks of high aerobic intensity plantar flexion interval training continued by 8 weeks of high aerobic intensity treadmill training. The control group (n = 11) received advice according to exercise guidelines. Treadmill VO2peak and time to exhaustion increased significantly with 16.8 and 23.4% during the plantar flexion training period while no changes occurred in heart stroke volume (SV). Following treadmill training, SV increased with 25.1% while treadmill VO2peak and time to exhaustion increased 9.9 and 16.1%. Plantar flexion training was effective for increasing treadmill VO2peak and time to exhaustion in PAD patients and amplified the effects of the additional treadmill training, as SV increased and treadmill VO2peak and time to exhaustion improved further. This study suggests that calf muscle training prime PAD patients for cardiovascular adaptations when applying whole body exercise.