Feasibility and preliminary efficacy of different intensities of functional training in elderly type 2 diabetes patients with cognitive impairment: a pilot randomised controlled trial.

BACKGROUND: Aging and type-2 diabetes (T2D) are the most important risk factors for cognitive impairment and Alzheimer's disease. Exercise training is an effective, safe, and practical intervention in improving glucose metabolism, physical function, and cognitive disorders. This pilot study investigated the feasibility and preliminary efficacy of high-intensity low-volume (HIFT) vs. low-intensity high-volume (LIFT) functional training in elderly T2D patients with cognitive impairment. METHODS: Forty-eight elderly T2D patients (31 female, 17 male, age 67.5 ± 5.8 years, MMSE score 18.8 ± 2.6, FBG 209.5 ± 37.9) were randomly assigned to HIFT, LIFT and control groups. Cognitive impairment was diagnosed with MMSE ≤ 23 based Iranian society. The SDMT, CVLT-II, BVMT-R, and Stroop tests were used to evaluated processing speed, learning, memory and attention respectively. Physical fitness tests include: tandem stance and walk test; TUG; 6MWT, 10MWT; SSST; 5TSTS; and hand grip was used to evaluated static and dynamic balance, agility, walking endurance, gait speed, lower limb function and lower and upper body strength respectively. As well as, Biochemical (FBG, insulin, HOMA-IR, HbA1c) and physiological outcomes (SBP, and DBP) were assessed. The HIFT group performed six weeks of functional training (three sessions per week) with 120-125% of the lactate threshold. The LIFT group performed six weeks of functional training (five sessions per week) with a 70-75% lactate threshold. Feasibility, safety, and acceptability of exercise programs were assessed at the end of the study. RESULT: HIFT showed a higher adherence rate (91% vs. 87.5%), safety, and acceptability compared to LIFT. MMSE and Stroop scores, 6MWT, FBG, insulin, HOMA-IR, HbA1c, SBP, and DBP significantly improved in HIFT (all, P ≤ 0.004) and LIFT (all, P ≤ 0.023). Changes in 6MWT, FBG, insulin, HOMA-IR, and HbA1c in HIFT (all, P ≤ 0.001) and LIFT (all, P ≤ 0.008) were significant compared to the control group. Changes in Stroop scores were significant only in the HIFT group compared to the control group (P = 0.013). SDMT, CVLT-II, BVMT-R, balance test, 10MWT, SSST, TUG and hang grip significantly improved only in HIFT (all, P ≤ 0.038). CONCLUSION: HIFT vs. LIFT is a safe, feasible, and effective approach for improving some aspects of physical, biochemical, and cognitive function in elderly T2D patients with cognitive impairment. This pilot study provides initial proof-of-concept data for the design and implementation of an appropriately powered randomised controlled trial (RCT) of HIFT vs. LIFT in a larger sample of elderly T2D patients with cognitive impairment. TRIAL REGISTRATION: Randomized controlled trial (RCT) (Iranian Registry of Clinical Trials, trial registration number: IRCT20230502058055N1. Date of registration: 11/06/2023.

Resistance Band Exercise: An Effective Strategy to Reverse Cardiometabolic Disorders in Women With Osteosarcopenic Obesity.

We designed to evaluate the effects of resistance elastic band exercises (REBEs) on cardiometabolic/obesity-related biomarkers in older females with osteosarcopenic obesity. Sixty-three patients (aged 65-80 years) with osteosarcopenic obesity and a body mass index exceeding 30 kg/m2 were enrolled in the study. The participants were randomly assigned to either an experimental group (REBE, n = 32) or a usual care group (n = 31). The experimental group completed a 12-week REBE program, three times a week and 60 min per session. There were decreases in lipid accumulation product (p = .033), visceral adipose index (p = .001), triglyceride-glucose-body mass index (p = .034), and atherogenic index of plasma (p = .028) in the experimental group compared with the usual care group. Our findings highlight the importance of an REBE program in improving combined cardiometabolic/obesity-related indices in older women with osteosarcopenic obesity. The incorporation of an REBE program may benefit individuals who are unable to tolerate or participate in more strenuous exercise programs.

Bone-muscle crosstalk following exercise plus Ursolic acid by myomiR-133a/Cx43-Runx2 axis in aged type 2 diabetes rat models.

Natural bioactive compound, Ursolic acid (UA), plus different types of exercise may exert the action on glycemic control, leading to clinical benefits in the prevention and treatment of aging/diabetes-associated complications. So, this study examined the effects of eight weeks combination of 250 mg of UA per day per kilogram of body weight of rat as well as resistance/endurance training on miR-133a expression across serum, bone marrow, skeletal muscle, and Connexin 43 (Cx43)-Runt-related transcription factor 2 (Runx2) signaling axis in high-fat diet and low-dose streptozotocin-induced T2D (here, HFD/STZ-induced T2D). The study was conducted on 56 male Wistar rats (427 ± 44 g, 21 months old), having HFD/STZ-induced T2D randomly assigned into 7 groups of 8 including (1) sedentary non-diabetic old rats (C); (2) sedentary type 2 diabetes animal model (D); (3) sedentary type 2 diabetes animal model + UA (DU); (4) endurance-trained type 2 diabetes animal model (DE); (5) resistance-trained type 2 diabetes animal model (DR); (6) endurance-trained type 2 diabetes animal model + UA (DEU); and (7) resistance-trained type 2 diabetes animal model + UA (DRU). Resistance training included a model of eight weeks of ladder resistance training at 60-80% maximal voluntary carrying capacity (MVCC) for five days/week. Treadmill endurance exercise protocol included eight weeks of repetitive bouts of low-/high-intensity training with 30%-40% and 60%-75% maximal running speed for five days/week, respectively. UA Supplementary groups were treated with 500 mg of UA per kg of high-fat diet per day. The results revealed significant supplement and exercise interaction effects for the BM miR-133a (p = 0.001), the bone marrow Runx2 (p = 0.002), but not the serum miR-133a (p = 0.517), the skeletal muscle miR-133a (p = 0.097) and the Cx43 (p = 0.632). In conclusion, only eight weeks of resistance-type exercise could affect miR-133a profile in muscles and osteoblast differentiation biomarker RUNX2 in aged T2D model of rats. 250 mg of UA per kilogram of body weight rat per day was administered orally, less than the sufficient dose for biological and physiological impacts on osteoblast differentiation biomarkers in aged T2D model of rats following eight weeks.

Rapid photodegradation and detection of zolpidem over ß-SnWO4 and α-SnWO4 nanoparticles: optimization and mechanism.

We reported the tin (II) tungstate nanoparticles as the photocatalyst and sensor modifier that were synthesized via chemical precipitation reaction and optimized thru the Taguchi design method. The method predicted the best synthesis conditions that led to smaller particles and desired morphologies. Different techniques were used to characterize the chemical structure, morphology, and purity of the nanoparticles. The photocatalytic behavior of different crystalline forms of the SnWO4 nanoparticles (α and ß) was considered by photodegradation of methylene orange and zolpidem under UV light irradiation, while the average size of ß-SnWO4 and α-SnWO4 nanoparticles prepared in optimum conditions is about 17 nm and 20 nm, respectively. Efficiencies of degradation of methyl orange and zolpidem on ß-SnWO4, in the presence of UV irradiation, were 93% and 98% and in the presence of α-SnWO4 were 73% and 82% after 2100 s, respectively. Voltammetric sensing of zolpidem was designed by modification of carbon paste electrode via ß-SnWO4 nanoparticles and investigated for determination of the drug in aqueous solution.

Potent cyclometallated Pd(II) antitumor complexes bearing α-amino acids: synthesis, structural characterization, DNA/BSA binding, cytotoxicity and molecular dynamics simulation.

A rational approach was adopted to design high-potential metal-based antitumor agents. A series of organometallic Pd(ii) complexes with a general formula of [Pd{κ2(C,C)-[(C6H4-2)PPh2]CH(CO)C6H4Ph-4}{κ2(N,O)}] (N,O = alanine (Pd-A), valine (Pd-V), leucine (Pd-L), l-isoleucine (Pd-I) and phenylalanine (Pd-F)) were prepared by cyclopalladation of the phosphorus ylide, bridge cleavage reaction and subsequent chelation of natural α-amino acids. The complexes were fully identified using IR and multinuclear 1H, 13C, 31P NMR spectroscopic methods. X-ray crystallography exhibited that the Pd(ii) atom is located in a slightly distorted square-planar environment surrounded by C,C-orthometallated phosphorus ylide as well as NO-pendant amino acid functionality. In vitro cytotoxicity evaluation of new cyclometallated Pd(ii) complexes toward a human leukemia (K562) cancer cell line indicated promising results. The highest cytotoxic activity was discovered in the case of phenylalanine (CH2C6H5). IC50 values of this complex on a panel of human tumor cell lines representative of liver (HepG2), breast (SKBR-3), and ovarian (A2780-Resistance/Sensitive) cancers also indicated promising antitumor effects in comparison with standard cisplatin. The binding interaction ability of the phenylalanine-containing orthopalladated complex, as the most efficient compound, with calf-thymus deoxyribonucleic acid (CT-DNA) and bovine serum albumin (BSA) was investigated. UV-Vis spectroscopy, competitive emission titration, and circular dichroism (CD) techniques demonstrated the intercalative binding of the Pd(ii) complex with DNA. Molecular docking studies also fully agreed with the experimental data. Examination of the reactivity towards the protein BSA revealed that the static quenching mechanism of BSA intrinsic fluorescence by the Pd(ii) complex with a binding constant (Kb) of ∼105 is indicative of the high affinity of the complex. The competitive binding experiment using site markers with definite binding sites demonstrated that the hydrophobic cavities of site I (subdomain IIA) are responsible for the bimolecular interaction between protein BSA and the complex. Molecular docking studies effectively confirmed the significance of hydrophobic interactions in Pd(ii)-BSA binding. The results of this study could greatly contribute to exploring new potent metal-based anticancer drugs.

Advanced weight-bearing mat exercises combined with functional electrical stimulation to improve the ability of wheelchair-dependent people with spinal cord injury to transfer and attain independence in activities of daily living: a randomized controlled trial.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To determine the effects of advanced weight-bearing mat exercises (AWMEs) with/without functional electrical stimulation (FES) of the quadriceps and gastrocnemius muscles on the ability of wheelchair-dependent people with spinal cord injury (SCI) to transfer and attain independence in activities of daily living (ADLs). SETTING: An outpatient clinic, Iran. METHODS: People with traumatic chronic paraplegia (N = 16) were randomly allocated to three groups. The exercise group (EX; N = 5) performed AWMEs of quadruped unilateral reaching and tall-kneeling for 24 weeks (3 days/week). Sessions were increased from 10 min to 54 min over the 24-week period. The exercise-FES group (EX + FES; N = 5) performed AWMEs simultaneously with FES of the quadriceps and gastrocnemius muscles. The control group performed no exercise and no FES (N = 6). The primary outcomes were the total Spinal Cord Independence Measure-III (SCIM-III) to reflect independence with ADL, and the sum of the four SCIM-III transfer items to reflect ability to transfer. There were six other outcomes. RESULTS: The mean (95% CI) between-group differences of the four transfer items of the SCIM-III for the EX vs. control group was 1.8 points (0.2-3.4), and for the EX + FES vs. control group was 2 points (0.4-3.6). The equivalent differences for the total SCIM-III scores were 2.7 points (-0.6-6.0) and 4.1 points (0.8-7.4), respectively. There were no significant between-group differences for any other outcomes. CONCLUSIONS: Advanced weight-bearing mat exercises improve the ability of wheelchair-dependent people with SCI to transfer and attain independence in ADL.

Oxytocin mediates the beneficial effects of the exercise training on breast cancer.

NEW FINDINGS: What is the central question of this study? We hypothesized that potential anti-tumour effects of exercise training might be mediated by oxytocin and explored the underlying mechanisms in a mouse model of breast cancer. What is the main finding and its importance? Interval exercise training, by inducing oxytocin secretion, may reduce the activity of the PI3K/Akt and ERK pathways, and consequently, results in a smaller tumour volume in a mouse model of breast cancer. Exercise training can affect the growth of breast tumours. We hypothesized that exercise training might reduce breast tumour growth by inducing oxytocin (OT) secretion and its related signalling pathways, such as PI3K/Akt and ERK. Therefore, 56 BALB/c mice were equally divided into seven groups to study the effects of OT and atosiban (an oxytocin receptor antagonist) together with interval exercise training on mammary tumour growth, as well as tumour-related signalling pathways, including PI3K/Akt and ERK. Animal weight, OT plasma concentration, tumour weight and volume were measured at the end of the study. PI3K/Akt and ERK were evaluated by Western blot and qPCR assays. The results showed that OT plasma concentration was significantly increased in trained animals. The volume and weight of tumours were decreased significantly after both exercise training and OT administration. The expression of genes involved in tumour cell proliferation, such as PI3KR2, Akt and mTOR, was notably lower in the exercise-trained and OT-treated groups. Furthermore, the expression of genes involved in cell apoptosis, such as caspase-3 and Bax, was significantly increased in the tumour tissues. In addition, Western blot results showed that phosphorylated Akt and ERK were significantly decreased in the exercise training and OT groups compared with the tumour group. Interestingly, atosiban reversed these effects. These results indicated that interval exercise training, acting via OT secretion, may reduce PI3K/Akt and ERK axis activities, and consequently, decrease tumour volume and weight in a mouse model of breast cancer.

Effects of whole body vibration training and mental training on mobility, neuromuscular performance, and muscle strength in older men.

This study was designed to evaluate the effects of whole body vibration (WBV) exercise, mental training (MT), and the concurrent effect of WBV and MT on lower body balance, neuromuscular performance, and leg muscle strength in elderly men. In a randomized control trial study with parallel group design, 42 older men (mean±standard deviation age, 68±5.78 years) were randomly divided into four groups: WBV (n=11), MT (n=12), WBV+MT (n=10), and control (n=9) groups. The protocol of training consisted of three sessions per week for 8 weeks and about 30 min for each session. The WBV exercise was performed on a vibration machine. In MT group, participants were asked to mentally visualize to do the Timed Up and Go and relaxation technics. postural stability, the Timed Up and Go test, 5-repetition chair-rising test, 6-m tandem gait test, 10-m walking, and leg isometric strength were measured in baseline and after 8-week intervention. Repeated measures-analysis of variance followed by post hoc was used to analyses the data. The results of this study showed that there were significant improvements (P<0.05) in postural stability, Timed Up and Go, 5-repetition chair-rising, 6-m tandem gait test, 10-m walking, and leg isometric strength in WBV, MT, and WBV+MT in comparison with baseline and in comparison with control group. It seems that older adults can take benefit from WBV and MT and WBV+MT exercise as a cost-effective and practical way without side effects to improve postural control, mobility, and functional performance.

Alteration in cardiac uncoupling proteins and eNOS gene expression following high-intensity interval training in favor of increasing mechanical efficiency.

OBJECTIVES: High-intensity interval training (HIIT) increases energy expenditure and mechanical energy efficiency. Although both uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS) affect the mechanical efficiency and antioxidant capacity, their effects are inverse. The aim of this study was to determine whether the alterations of cardiac UCP2, UCP3, and eNOS mRNA expression following HIIT are in favor of increased mechanical efficiency or decreased oxidative stress. MATERIALS AND METHODS: Wistar rats were divided into five groups: control group (n=12), HIIT for an acute bout (AT1), short term HIIT for 3 and 5 sessions (ST3 and ST5), long-term training for 8 weeks (LT) (6 in each group). The rats of the training groups were made to run on a treadmill for 60 min in three stages: 6 min running for warm-up, 7 intervals of 7 min running on treadmill with a slope of 5° to 20° (4 min with an intensity of 80-110% VO2max and 3 min at 50-60% VO2max), and 5-min running for cool-down. The control group did not participate in any exercise program. Rats were sacrificed and the hearts were extracted to analyze the levels of UCP2, UCP3 and eNOS mRNA by RT-PCR. RESULTS: UCP3 expression was increased significantly following an acute training bout. Repeated HIIT for 8 weeks resulted in a significant decrease in UCPs mRNA and a significant increase in eNOS expression in cardiac muscle. CONCLUSION: This study indicates that Long term HIIT through decreasing UCPs mRNA and increasing eNOS mRNA expression may enhance energy efficiency and physical performance.

Acute Cardiovascular and Hemodynamic Responses to Low Intensity Eccentric Resistance Exercise with Blood Flow Restriction.

BACKGROUND: Recently it has been suggested that low intensity (LI) resistance exercise (RE) alone or in combination with blood flow restriction (BFR) can be applied for cardiovascular function improvement or rehabilitation. OBJECTIVES: The aim of the present study was to investigate the acute effects of LI eccentric RE with and without BFR on heart rate (HR), rate pressure product (RPP), blood pressure (BP) parameters [systolic, diastolic, and mean arterial pressure (MAP)], oxygen saturation (SpO2) and rate of perceived exertion (RPE). METHODS: In a semi-experimental study 16 young adults (26.18 ± 3.67 years) volunteered and performed LI (30% maximum voluntary contraction) eccentric RE alone or combined with BFR. RESULTS: The results indicated that HR, RPP, and RPE increased significantly within both groups (P < 0.05); SBP and DBP increased significantly only with BFR (P < 0.05); MAP increased significantly during exercise without BFR (P < 0.05); and no change was observed in SpO2 in either groups (P > 0.05). Furthermore, studied parameters did not vary amongst different groups (P > 0.05). CONCLUSIONS: It is concluded that LI eccentric RE with BFR positively regulated the hemodynamic and cardiovascular responses. Therefore, the eccentric RE combined with BFR seems to be a good option for future studies with the aim of time efficacy, since it alters these parameters within normal values.

The effect of high intensity interval training on cardioprotection against ischemia-reperfusion injury in wistar rats.

The aims of the present study were to determine whether short term high intensity interval training (HIIT) could protect the heart against ischemia reperfusion (IR) injury; and if so, to evaluate how long the exercise-associated protection can be lasted. Sixty-three rats were randomly assigned into sedentary (n = 15), sham (n = 7), and exercise groups (n = 41). Rats in the exercise groups performed 5 consecutive days of HIIT on treadmill: 5 min warm up with 50 % VO2max, 6×2 min with 95-105 % VO2max (about 40 to 45 m/min), 5×2 min recovery with 65-75 % VO2max (about 28 to 32 m/min), and 3 min cool down with 50 % VO2max, all at 0 % grade. Animals exposed to an in vivo cardiac IR surgery, performed at days 1, 7, and 14 following the final exercise session. Ischemia-induced arrhythmias, myocardial infarct size (IS), plasma lactate dehydrogenase (LDH) and creatine kinase (CK) activities were measured in all animals. Compared to sedentary rats, exercised animals sustained less IR injury as evidenced by a lower size of infarction and lower levels of LDH and CK at day one and day 7 post exercise. In comparison of sedentary group, IS significantly decreased in EX-IR1 and EX-IR7 groups (50 and 35 %, respectively), but not in EX-IR14 group (19 %). The exercise-induced cardioprotection disappeared 14 days following exercise cessation. There were no significant changes in ischemia-induced arrhythmia between exercised and sedentary rats. The results clearly demonstrate that HIIT protects the heart against myocardial IR injury. This protective effect can be sustained for at least one week following the cessation of the training.

The effect of eight weeks endurance training and high-fat diet on appetite-regulating hormones in rat plasma.

OBJECTIVES: Consumption of high-fat foods is one of the major causes of obesity. Physical exercise is a strategy used to counteract obesity. The aim of this study was to investigate the effect of eight weeks endurance training and high-fat diet (HFD) on appetite-regulating hormones in rat plasma. MATERIALS AND METHODS: TWENTY EIGHT MALE WISTAR RATS WERE RANDOMLY DIVIDED INTO FOUR GROUPS: Control group with standard diet (CSD), endurance training with a standard diet (ESD), control group with high-fat diet (CHFD) and endurance training with high-fat diet (EHFD). Twenty-four hr after the last training session, the blood samples were obtained and analyzed for hormones levels. RESULTS: The significant increased weight gain and food intake and decreased plasma nesfatin-1 and PYY3-36 levels were observed in CHFD group, while exercise under the HFD antagonized these effects. There were no significant changes in ghrelin, insulin and leptin levels in different groups. CONCLUSION: These results suggest that exercise can prevent fattening effect of HFD. Probably, performing exercise makes a reduction of food intake and weight gain in rat via the increase in nesfatin-1 and PYY levels. However, further studies are necessary to understand the exact mechanisms involved in this field.

Surgically treatable pulmonary arteriovenous fistula.

Arteriovenous fistuli are congenital malformations. Usually symptoms depend on size of the lesion. Lesions smaller than 2 cm are often asymptomatic. The most common symptoms are dyspnea, palpitation and fatigue. Cyanosis is indicative of right to left shunt. Helical computed tomography (CT) scan is a helpful diagnostic tool in this case. Surgery is the treatment of choice in patients with isolated lesions. Embolization is a selective method in patients with multiple or bilateral lesions. The patient was a 13-year-old boy complaining of cyanosis of lips and nails as well as dyspnea for 5 years. Definite diagnosis of pulmonary arteriovenous malformation (PAVM) in the right middle lobe was based on CT angiography. The patient underwent a thoracotomy and lobectomy of the right middle lobe. After surgery cyanosis and dyspnea were completely resolved.