Multidimensional associations of physical performance, balance, wellness and daily activities with frailty in older adults with coexisting frailty and diabetes.

BACKGROUND: The coexistence of frailty and type 2 diabetes mellitus in the older population heightens the risk of adverse events. However, research on functional and wellness factors associated with frailty in this population is limited. PURPOSE: To investigate the associations of physical performance, functional dependency, physical activity, nutritional status, sleep, self-perceived health and depression with frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. DESIGN: Cross-sectional. METHODS: The study included 123 community-dwelling older adults (73.7 ± 6.0 years) with pre-frailty/frailty and type 2 diabetes mellitus. Physical performance (Short Physical Performance Battery), functional dependency (Barthel Index and Lawton & Brody), physical activity and inactivity (GeneActiv wrist-worn accelerometer), malnutrition risk (Mini Nutritional Assessment), sleep (Pittsburgh Sleep Quality Index), self-perceived health (EuroQoL 5-Dimension 3-Level) and depression (Yesavage 15-item-Geriatric-Depression-Scale) were evaluated through personal interviews. Principal component analysis (PCA) was performed to categorize the variables into components, and logistic regressions were used to propose the best-fitted model for each component. RESULTS: The PCA identified four components: (i) physical performance, with gait speed and leg mean velocity as the main variables associated with frailty; (ii) balance, showing significant associations with monopodal balance; (iii) daily activities, with moderate to vigorous physical activity and the Lawton and Brody score as the main variables associated with frailty within this component; and (iv) wellness factors, with nutritional status, self-perceived health and depression score as the primary variables associated with frailty. CONCLUSIONS: This research underscores the significance of physical function and daily activities as protective factors against frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. The health dimension contributes both protective and risk factors, emphasizing the need for comprehensive assessments in managing frailty in this population. REPORTING METHOD: The study adhered to the STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Thermal resting pattern and acute skin temperature response to exercise in older adults: Role of cardiorespiratory fitness.

BACKGROUND: Infrared thermography is a growing area of interest in sports science due to the potential of skin temperature (Tsk) measurements to provide valuable information from rest to exercise. However, limited research exists on Tsk in older adults and the impact of factors such as sex and cardiorespiratory fitness (CRF) on Tsk. This study aims to investigate Tsk at rest and after acute exercise in older adults and assess whether sex or CRF influences Tsk. METHODS: Ninety-two participants (41 women, 68.48 ± 3.01 years) were examined with a thermographic camera in a conditioned room (23.02 ± 3.01 °C) at rest and after a graded protocol. The Tsk of 25 regions of interest (ROIs) were extracted and analysed. RESULTS: Men had higher overall Tsk at rest in 76% of ROIs, showing significant differences (p < 0.010) in six specific ROIs, independent of CRF. Both sexes had similar Tsk responses after graded exercise, with increases in distal parts (1.06 ± 0.50 °C), decreases in proximal parts (-0.62 ± 0.42 °C), and stable central Tsk (0.23 ± 0.59 °C). Increases in lower limb Tsk were significantly associated with CRF in men and women (ß = 0.438, p = 0.001, and ß = 0.535, p < 0.001, respectively), explaining 17% and 27% of the variance, respectively. CONCLUSIONS: This study demonstrates a sex-specific effect on resting Tsk in older adults, suggesting that sex-specific Tsk patterns should be considered when analysing Tsk in this population. Additionally, the association between increases in lower limb Tsk and CRF suggests that Tsk could be a promising predictor of CRF in older adults.

Changes in Muscle Deoxygenation During Squat Exercise After 6-Week Resistance Training With Different Percentages of Velocity Loss.

ABSTRACT: Costilla, M, Casals, C, Marín-Galindo, A, Sánchez-Sixto, A, Muñoz-López, A, Sañudo, B, Corral-Pérez, J, and Ponce-González, JG. Changes in muscle deoxygenation during squat exercise after 6-week resistance training with different percentages of velocity loss. J Strength Cond Res 37(8): 1573-1580, 2023-The present study compared, for the first time, the effects of 6 weeks of 20% (20VL) vs. 40% (40VL) velocity loss (VL) resistance training (RT) programs on muscle oxygen dynamics during the squat exercise. Twenty-three young men (21.4 ± 2.4 years) were randomly allocated into the 20VL group ( n = 8), 40VL group ( n = 7), or control group (CG; n = 8). The RT program consisted of 3 sets of Smith machine back squat exercise at 20VL or 40VL with a 3-minute rest between sets, twice per week for 6 weeks. Tissue oxygenation index (TOI) was measured using near-infrared spectroscopy in the vastus medialis and vastus lateralis during a squat test (8-repetition 1 m·s -1 load test), and the maximum (maxTOI) and minimum (minTOI) TOIs were measured during a 3-min recovery period. After the 6-week RT program, TOI increased significantly at the beginning of the test in both muscles (during the first 4 repetitions in the vastus lateralis and 5 repetitions in the vastus medialis) in the 20VL group ( p < 0.05), with nonsignificant changes in the 40VL group and CG. The maxTOI was significantly increased in the vastus medialis (+3.76%) and vastus lateralis (+3.97%) after the training only in the 20VL group ( p < 0.05). The minTOI in the vastus medialis reached during the test remained unchanged postintervention for both training groups, with the CG showing significantly higher values compared with the 20VL group (+14.1%; p < 0.05). In conclusion, depending on the VL reached during a squat RT program, different changes in muscle oxygen dynamics can be expected. Training at 20% of VL improves metabolic efficiency and the reoxygenation peak after the set.

Preclinical Pharmacokinetic and Pharmacodynamic Investigation of 5'-Methoxynobiletin from Ageratum conyzoides: In vivo and In silico Approaches.

PURPOSE: 5'-methoxynobiletin (5'-MeONB), a polymethoxyflavone isolated from A. conyzoides, has shown anti-inflammatory property. Nevertheless, the antinociceptive activity and pre-clinical pharmacokinetics (PK) characteristics of 5'-MeONB remain unknown. Considering the anti-inflammatory potential of the 5'-MeONB, this study aimed to investigate the pre-clinical PK behavior of 5'-MeONB, as well as its time course antinociceptive activity. METHODS: 5'-MeONB plasma concentrations were determined in Wistar rats after intravenous (i.v.) (10 mg/kg) and oral (50 mg/kg) administration, and in Swiss mice after oral administration (100 mg/kg). Plasma samples were deproteinization and 5'-MeONB quantified by a validated UPLC-MS method. Additionally, the antinociceptive activity of 5'-MeONB was evaluated after 15, 30, 60, 180 and 360 min following oral administration on the acute nocifensive behavior of mice induced by formalin. RESULTS: 5'-MeONB rats and mice plasma concentration-time profiles were best one-compartment model. After i.v. administration to rats, a short half-life, a high clearance and moderate volume of distribution at steady state were observed. Similar results were obtained after oral administration. The oral bioavailability ranged from 8 to 11%. Additionally, 5'-MeONB exhibited antinociceptive activity in both formalin phases, especially in the inflammatory phase of the model, inhibiting 68% and 91% of neurogenic and inflammatory responses, respectively, after 30 min of oral administration. CONCLUSIONS: The results described here provide novel insights on 5'-MeONB pharmacokinetics and pharmacodynamic effect, serving as support for future studies to confirm this compound as anti-nociceptive and anti-inflammatory effective agent.

Feasibility and performance of a combined extracorporeal assisted cardiac resuscitation and an organ donation program after uncontrolled cardiocirculatory death (Maastricht II).

INTRODUCTION: Approximately 500.000 people in Europe sustain cardiac arrest (CA) every year, being myocardial infarction the main etiology. Interest has been raised in a new approach to refractory cardiac arrest (rCA) using extra-corporeal oxygenation (ECMO). In settings where it can be rapidly implemented, ECMO assisted resuscitation (ECPR) may be considered. Additionally, donation after circulatory death, which seeks to obtain solid organs donation from patients suffering rCA, has increased its role effectively increasing the pool of donors. Combined programs with integration of ECPR and uncontrolled donation after circulatory determination of death (uDCDD) are worldwide limited and experience integrating these two techniques is lacking. METHODS: We report a 24 months experience of ECPR and uDCDD kidney transplantation based on a management protocol in a university teaching hospital in the urban area of Lisbon. RESULTS: Over a period of 24 months, 58 patients were admitted to our ICU with rCA, 6 (10%) in the ECPR program and 52 (90%) in the uDCDD. Seventy-eight percent of patients were male, with an average age of 49 year-old. CA was witnessed in 83% of cases and initial rhythm was ventricular fibrillation in 20 cases (35%). 13 (25%) patients were effective organ donors. Refusal for effective donation was mainly due to prior comorbidities. DISCUSSION: The development of an integrated program for ECPR and uDCDD is feasible and requires a well-established and efficient activation program. In an era of significant organ shortage, it provides a viable option for increasing the organ donation pool, with promising results.

Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle.

The study aimed to determine the levels of skeletal muscle angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age: 19-65 years, weight: 56-137 kg, BMI: 23-44) and 69 women (age: 18-55 years, weight: 41-126 kg, BMI: 22-39) was analyzed in duplicate by western blot. VO2 max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p = 0.001, n = 239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2 max per kg of legs lean mass (VO2 max-LLM) and age (p = 0.47). Multiple regression analysis showed that the fat % (ß = 0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2% of the variance. VO2 max-LLM had also predictive value (ß = 0.09). There was a significant fat % by VO2 max-LLM interaction, such that for subjects with low fat %, VO2 max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2 max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.

Optimization of Mouse Growth Hormone Plasmid DNA Electrotransfer into Tibialis Cranialis Muscle of "Little" Mice.

Previous non-viral gene therapy was directed towards two animal models of dwarfism: Immunodeficient (lit/scid) and immunocompetent (lit/lit) dwarf mice. The former, based on hGH DNA administration into muscle, performed better, while the latter, a homologous model based on mGH DNA, was less efficient, though recommended as useful for pre-clinical assays. We have now improved the growth parameters aiming at a complete recovery of the lit/lit phenotype. Electrotransfer was based on three pulses of 375 V/cm of 25 ms each, after mGH-DNA administration into two sites of each non-exposed tibialis cranialis muscle. A 36-day bioassay, performed using 60-day old lit/lit mice, provided the highest GH circulatory levels we have ever obtained for GH non-viral gene therapy: 14.7 ± 3.7 ng mGH/mL. These levels, at the end of the experiment, were 8.5 ± 2.3 ng/mL, i.e., significantly higher than those of the positive control (4.5 ± 1.5 ng/mL). The catch-up growth reached 40.9% for body weight, 38.2% for body length and 82.6%-76.9% for femur length. The catch-up in terms of the mIGF-1 levels remained low, increasing from the previous value of 5.9% to the actual 8.5%. Although a complete phenotypic recovery was not obtained, it should be possible starting with much younger animals and/or increasing the number of injection sites.

Protein synthesis signaling in skeletal muscle is refractory to whey protein ingestion during a severe energy deficit evoked by prolonged exercise and caloric restriction.

BACKGROUND: Exercise and protein ingestion preserve muscle mass during moderate energy deficits. OBJECTIVE: To determine the molecular mechanisms by which exercise and protein ingestion may spare muscle mass during severe energy deficit (5500 kcal/day). DESIGN: Fifteen overweight, but otherwise healthy men, underwent a pre-test (PRE), caloric restriction (3.2 kcals/kg body weight/day) + exercise (45 min one-arm cranking + 8 h walking) for 4 days (CRE), followed by a control diet (CD) for 3 days, with a caloric content similar to pre-intervention while exercise was reduced to less than 10,000 steps per day. During CRE, participants ingested either whey protein (PRO, n = 8) or sucrose (SU, n = 7) (0.8 g/kg body weight/day). Muscle biopsies were obtained from the trained and untrained deltoid, and vastus lateralis. RESULTS: Following CRE and CD, serum concentrations of leptin, insulin, and testosterone were reduced, whereas cortisol and the catabolic index (cortisol/total testosterone) increased. The Akt/mTor/p70S6K pathway and total eIF2α were unchanged, while total 4E-BP1 and Thr37/464E-BP1 were higher. After CRE, plasma BCAA and EAA were elevated, with a greater response in PRO group, and total GSK3ß, pSer9GSK3ß, pSer51eIF2α, and pSer51eIF2α/total eIF2α were reduced, with a greater response of pSer9GSK3ß in the PRO group. The changes in signaling were associated with the changes in leptin, insulin, amino acids, cortisol, cortisol/total testosterone, and lean mass. CONCLUSIONS: During severe energy deficit, pSer9GSK3ß levels are reduced and human skeletal muscle becomes refractory to the anabolic effects of whey protein ingestion, regardless of contractile activity. These effects are associated with the changes in lean mass and serum insulin, testosterone, and cortisol concentrations.

Impact of data averaging strategies on V̇O2max assessment: Mathematical modeling and reliability.

BACKGROUND: No consensus exists on how to average data to optimize V ˙ O2max assessment. Although the V ˙ O2max value is reduced with larger averaging blocks, no mathematical procedure is available to account for the effect of the length of the averaging block on V ˙ O2max. AIMS: To determine the effect that the number of breaths or seconds included in the averaging block has on the V ˙ O2max value and its reproducibility and to develop correction equations to standardize V ˙ O2max values obtained with different averaging strategies. METHODS: Eighty-four subjects performed duplicate incremental tests to exhaustion (IE) in the cycle ergometer and/or treadmill using two metabolic carts (Vyntus and Vmax N29). Rolling breath averages and fixed time averages were calculated from breath-by-breath data from 6 to 60 breaths or seconds. RESULTS: V ˙ O2max decayed from 6 to 60 breath averages by 10% in low fit ( V ˙ O2max  < 40 mL kg-1  min-1 ) and 6.7% in trained subjects. The V ˙ O2max averaged from a similar number of breaths or seconds was highly concordant (CCC > 0.97). There was a linear-log relationship between the number of breaths or seconds in the averaging block and V ˙ O2max (R2  > 0.99, P < 0.001), and specific equations were developed to standardize V ˙ O2max values to a fixed number of breaths or seconds. Reproducibility was higher in trained than low-fit subjects and not influenced by the averaging strategy, exercise mode, maximal respiratory rate, or IE protocol. CONCLUSIONS: The V ˙ O2max decreases following a linear-log function with the number of breaths or seconds included in the averaging block and can be corrected with specific equations as those developed here.

Fitness and academic performance in adolescents. The mediating role of leptin: DADOS study.

We tested the mediating effect of leptin on the association between physical fitness (PF) components and academic performance indicators in healthy adolescents. A total of 263 adolescents (13.9 ± 0.3 years, 47.5% girls, 12.5% overweight) from the DADOS (Deporte, ADOlescencia y Salud) Study were included in the analysis. PF components were assessed by the handgrip test for upper-limb muscular strength, standing long jump test for lower-limb muscular strength, 4 × 10-m shuttle run test for speed-agility, and 20-m shuttle run test for cardiorespiratory fitness. Plasma leptin concentration was assessed from antecubital vein blood after an overnight fast using a sensitive ELISA kit. Academic performance indicators were assessed through final school grades and through the Spanish version of the SRA Test of Educational Ability. Body composition was assessed by body mass index and skinfold thicknesses. Boot-strapped mediation procedures were performed and indirect effects with confidence intervals not including zero were interpreted as statistically significant. Our findings suggest that the positive associations observed between cardiorespiratory fitness and lower-limb muscular strength with academic performance indicators were mediated by leptin concentration after adjusting for sex, pubertal stage, socioeconomic status, and adiposity (percentage of mediation ranging from 54.61 to 82.02%). CONCLUSIONS: Improvements on PF components, particularly in cardiorespiratory fitness and lower-limb muscular strength, might reduce leptin concentration with potential benefits on academic performance in adolescents, independently of adiposity. What is Known: • Academic performance is associated with physical fitness and leptin concentration in children and adolescents. • Fitness modulates leptin concentration levels, regardless of physical activity and adiposity. What is New: • Leptin concentration mediates the association of cardiorespiratory fitness and muscular strength with academic performance in adolescents. • Improvements in cardiorespiratory fitness and muscular strength might reduce leptin concentration levels enhancing academic performance.

Effect of regional muscle location but not adiposity on mitochondrial biogenesis-regulating proteins.

PURPOSE: The aim of this study was to determine if the expression of the mitochondrial biogenesis-regulating proteins SIRT1, SIRT3 and PGC-1alpha in human skeletal muscle is influenced by adiposity. METHOD: Twenty-nine male subjects were recruited into three groups: control (n = 10), obese (n = 10) and post-obese (n = 9). Intentionally, groups were matched by age, aerobic capacity and in addition the control and post-obese groups also by BMI. Muscle biopsies were obtained from the m. deltoid and vastus lateralis. PGC-1alpha, SIRT1 and SIRT3 protein expression was analyzed by Western blot. RESULT: PGC-1alpha, SIRT1 and SIRT3 protein expression was similar regardless of the level of adiposity. Only a main effect of group on SIRT1 protein showed a trend toward higher expression in post-obese than control and obese (P = 0.09). Despite similar muscle fiber-type composition (previously reported), PGC-1alpha, SIRT1 and SIRT3 protein expression was higher in leg compared to arm muscle in all groups (P < 0.05). CONCLUSION: This study shows that PGC-1alpha, SIRT1 and SIRT3 protein expression in basal conditions was not altered in humans with different levels of adiposity but similar aerobic capacity. The expression of PGC-1alpha, SIRT1 and SIRT3 was higher in vastus lateralis than in deltoid muscle, indicating that local rather than systemic factors prevail in regulating the level of expression of these proteins.

What limits performance during whole-body incremental exercise to exhaustion in humans?

To determine the mechanisms causing task failure during incremental exercise to exhaustion (IE), sprint performance (10 s all-out isokinetic) and muscle metabolites were measured before (control) and immediately after IE in normoxia (P(IO2) 143 mmHg) and hypoxia (P(IO2): 73 mmHg) in 22 men (22 ± 3 years). After IE, subjects recovered for either 10 or 60 s, with open circulation or bilateral leg occlusion (300 mmHg) in random order. This was followed by a 10 s sprint with open circulation. Post-IE peak power output (W(peak)) was higher than the power output reached at exhaustion during IE (P < 0.05). After 10 and 60 s recovery in normoxia, W(peak) was reduced by 38 ± 9 and 22 ± 10% without occlusion, and 61 ± 8 and 47 ± 10% with occlusion (P < 0.05). Following 10 s occlusion, W(peak) was 20% higher in hypoxia than normoxia (P < 0.05), despite similar muscle lactate accumulation ([La]) and phosphocreatine and ATP reduction. Sprint performance and anaerobic ATP resynthesis were greater after 60 s compared with 10 s occlusions, despite the higher [La] and [H(+)] after 60 s compared with 10 s occlusion recovery (P < 0.05). The mean rate of ATP turnover during the 60 s occlusion was 0.180 ± 0.133 mmol (kg wet wt)(-1) s(-1), i.e. equivalent to 32% of leg peak O2 uptake (the energy expended by the ion pumps). A greater degree of recovery is achieved, however, without occlusion. In conclusion, during incremental exercise task failure is not due to metabolite accumulation or lack of energy resources. Anaerobic metabolism, despite the accumulation of lactate and H(+), facilitates early recovery even in anoxia. This points to central mechanisms as the principal determinants of task failure both in normoxia and hypoxia, with lower peripheral contribution in hypoxia.

Limitations to oxygen transport and utilization during sprint exercise in humans: evidence for a functional reserve in muscle O2 diffusing capacity.

To determine the contribution of convective and diffusive limitations to V̇(O2peak) during exercise in humans, oxygen transport and haemodynamics were measured in 11 men (22 ± 2 years) during incremental (IE) and 30 s all-out cycling sprints (Wingate test, WgT), in normoxia (Nx, P(IO2): 143 mmHg) and hypoxia (Hyp, P(IO2): 73 mmHg). Carboxyhaemoglobin (COHb) was increased to 6-7% before both WgTs to left-shift the oxyhaemoglobin dissociation curve. Leg V̇(O2) was measured by the Fick method and leg blood flow (BF) with thermodilution, and muscle O2 diffusing capacity (D(MO2)) was calculated. In the WgT mean power output, leg BF, leg O2 delivery and leg V̇(O2) were 7, 5, 28 and 23% lower in Hyp than Nx (P < 0.05); however, peak WgT D(MO2) was higher in Hyp (51.5 ± 9.7) than Nx (20.5 ± 3.0 ml min(-1) mmHg(-1), P < 0.05). Despite a similar P(aO2) (33.3 ± 2.4 and 34.1 ± 3.3 mmHg), mean capillary P(O2) (16.7 ± 1.2 and 17.1 ± 1.6 mmHg), and peak perfusion during IE and WgT in Hyp, D(MO2) and leg V̇(O2) were 12 and 14% higher, respectively, during WgT than IE in Hyp (both P < 0.05). D(MO2) was insensitive to COHb (COHb: 0.7 vs. 7%, in IE Hyp and WgT Hyp). At exhaustion, the Y equilibration index was well above 1.0 in both conditions, reflecting greater convective than diffusive limitation to the O2 transfer in both Nx and Hyp. In conclusion, muscle V̇(O2) during sprint exercise is not limited by O2 delivery, O2 offloading from haemoglobin or structure-dependent diffusion constraints in the skeletal muscle. These findings reveal a remarkable functional reserve in muscle O2 diffusing capacity.

Reliability and validity of the Portuguese version of the Generalized Anxiety Disorder (GAD-7) scale.

BACKGROUND: Generalized anxiety disorder has a strong impact on health-related quality of life. For this reason, it seems relevant to develop strategies allowing early diagnoses in order to promote appropriate treatments. The objective of this study was to culturally adapt and validate the GAD-7 for the Portuguese patients with generalized anxiety disorder. METHODS: For the cultural adaptation of the Portuguese version of the GAD-7 scale we started with a previous translation made by Mapi Institute and decided to perform a clinical review followed by a cognitive debriefing with patients. Once piloted, this version was then tested in a larger sample for feasibility and reliability (1-week test-retest). Construct validity was assessed by the relationship between GAD-7 and socio-demographic and clinical variables. Its unidimensionality was tested by principal component factor analysis. Criterion validity was assessed by comparing GAD-7 scores with those obtained by HADS, and EQ-5D. STAI was mainly used as a screening indicator for patient inclusion. RESULTS: GAD-7 was considered feasible with a mean completion time of 2.3 minutes and no major floor or ceiling effects. We found an excellent Cronbach's alpha internal consistency score (0.880) and the test-retest and interclass correlation coefficients were also very good. Regarding the construct validity, younger patients, those with higher education, employed and without anxiety symptoms revealed lower GAD-7 scores, meaning better health. The unidimensionality of GAD-7 index was also confirmed by principal component factor analysis. At last, GAD-7 was significantly correlated with other health outcome indices and the classification levels created by it and by HADS showed to be dependent. CONCLUSION: The excellent metric properties confirmed the cultural adaptation and validity of GAD-7 into Portuguese population, allowing the clinicians an early detection and treatment of these patients.

Leptin signaling in skeletal muscle after bed rest in healthy humans.

PURPOSE: This study aimed at determining the effects of bed rest on the skeletal muscle leptin signaling system. METHODS: Deltoid and vastus lateralis muscle biopsies and blood samples were obtained from 12 healthy young men (mean ± SD, BMI 22.8 ± 2.7 kg/m(2)) before and after 7 days of bed rest. Leptin receptor isoforms (OB-Rs), suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) protein expression and signal transducer and activator of transcription 3 (STAT3) phosphorylation were analyzed by Western blot. RESULTS: After bed rest basal insulin concentration was increased by 53% (P < 0.05), the homeostasis model assessment (HOMA) by 40% (P < 0.05), and serum leptin concentration by 35% (P < 0.05) with no changes in body fat mass. Although the soluble isoform of the leptin receptor (s-OBR) remained unchanged, the molar excess of leptin over sOB-R was increased by 1.4-fold after bed rest (P < 0.05). OB-Rs and SOCS3 protein expression, and STAT3 phosphorylation level remained unaffected in deltoid and vastus lateralis by bed rest, as PTP1B in the deltoid. PTP1B was increased by 90% with bed rest in the vastus lateralis (P < 0.05). There was a linear relationship between the increase in vastus lateralis PTP1B and the increase in both basal insulin concentrations (r = 0.66, P < 0.05) and HOMA (r = 0.68, P < 0.05) with bed rest. CONCLUSIONS: One week of bed rest is associated with increased leptin levels without augmenting STAT3 phosphorylation indicating some degree of leptin resistance in skeletal muscle, which can be explained, at least in part, by an elevation of PTP1B protein content in the vastus lateralis muscle.

Anti-tumor activity of grape juice concentrate in the rat tongue two-stage initiation-promotion protocol induced by 4-nitroquinoline 1-oxide.

The aim of this study was to evaluate the anti-tumor activity of grape juice concentrate following medium-term oral carcinogenesis assay induced by 4-nitroquinoline 1-oxide (4NQO). A total of 30 male Wistar rats were distributed into five groups, as follows (n = 6 per group): Group 1 - negative control group (non-treated group); Group 2 - received grape juice concentrate at 1% dose by gavage for eight consecutive weeks; Group 3 - received 4NQO for 8 weeks at 20 ppm dose in drinking water daily; Group 4 - received 4NQO at 20 ppm dose during 8 weeks in drinking water and treated with grape juice concentrate at 1% dose orally by gavage for first 4 weeks after 4-NQO administration; Group 5 - received 4NQO at 20 ppm dose for 8 weeks in drinking water and treated with grape juice concentrate at 1% dose orally by gavage between the 5th and 8th weeks daily. Histopathological analysis revealed a decrease in hyperplasic and dysplastic lesions in Group 4. Groups 4 and 5 showed decreased COX-2 and TNF-alpha and eNOS gene expression. Grape juice concentrate also increased SOD Cu/Zn and catalase expression. However, Ki-67 immunoexpression was reduced at the promotion step of oral carcinogenesis (G5). Taken together, our results demonstrate that grape juice concentrate modulates rat tongue carcinogenesis as a result of anti-inflammatory activity, antioxidant activity and down-regulation of oral cells proliferation.

Anticoagulation Management in V-V ECMO Patients: A Multidisciplinary Pragmatic Protocol.

(1) Background: Extracorporeal membrane oxygenation (ECMO) is a complex procedure affecting both the risk of thrombosis and bleeding. High-quality data to personalize anticoagulation management in ECMO are lacking, resulting in a high variability in practice among centers. For this reason, we review coagulation methods and monitoring and share a pragmatic proposal of coagulation management, as performed in our high-volume ECMO Referral Centre; (2) Methods: We revised the anticoagulation options and monitoring methods available for coagulation management in ECMO through PubMed search based on words including "anticoagulation," "coagulation assays," "ECMO," "ELSO," and "ISTH"; (3) Results: Actual revision of the literature was described as our routine practice regarding ECMO anticoagulation and monitoring; (4) Conclusions: No coagulation test is exclusively predictive of bleeding or thrombotic risk in patients undergoing ECMO support. An approach that allows for a tailored regimen of anticoagulation (regardless of agent used) and monitoring is mandatory. To accomplish this, we propose that the titration of anticoagulation therapies should include multiple laboratory tests, including anti-Xa, aPTT, ACT, viscoelastic tests, AT levels, platelet count, fibrinogen, and FXIII levels. Anticoagulation regimens should be tailored to a specific patient and personalized based on this complex array of essays.

Major determinants of primary non function from kidney donation after Maastricht II circulatory death: A single center experience.

PURPOSE: Organ shortage greatly limits treatment of patients with end-stage chronic kidney. Maastricht type 2 donation after circulatory death (DCD) has been shown to have similar results in long term outcomes in kidney transplantation, when compared with brain dead donation. Our main goal was to assess Maastricht type 2 DCD and evaluate factors that impact on early graft function. METHODS: A retrospective study was conducted in an ECMO Referral Centre. All patients who received a kidney transplant from Maastricht type 2 DCD were included in study. Early graft function and short term outcomes were assessed. RESULTS: From October 2017 to December 2022, 47 renal grafts were collected from 24 uDCD donors. Median warm ischemia time was 106 min (94-115), cannulation time was 10 min (8; 20) and duration of extracorporeal reperfusion (ANOR) was 180 min (126-214). Regarding early graft function, 25% had immediate graft function, 63.6% had delayed graft function and 11.4% had primary non-function (PNF). There was a correlation between cannulation time (p = 0.006) and ANOR with PNF (p = 0.016). CONCLUSIONS: Cannulation time and ANOR were the main factors that correlated with PNF. Better understanding of underlying mechanisms should be sought in future studies to reduce the incidence of PNF.

Limb compression induces multi-system genetic damage in rats.

Muscle crush injury is a common trauma in the modern society after as a result of mass disasters after penetration into muscle by high-velocity projectiles, blunt external trauma, or by gravity during prolonged immobilization in comatose patients after head trauma, alcoholic or drug overdose. However, the underlying mechanisms linking these alterations are still not fully understood, especially in acute phase. The aim of this study was to analyze genomic instability in multiple organs of rats after acute muscle injury by means of single cell gel (comet) assay. Rats were randomly distributed into three groups (n=6 each group): control group and experimental groups: sacrificed 6h as 12h after muscle compression. These results indicate genetic damage in peripheral blood cells as depicted by tail moment results. DNA breakage was also detected in liver, lung and kidney cells after acute muscle injury for two times evaluated. Heart cells showed genetic damage after 12h following muscle compression. Taken together, our results suggest that acute muscle injury induces genomic damage in multiple organs of Wistar rats. This novel finding offers new insights into the underlying mechanisms of the relationship between acute crush muscle injury and clinical manifestations that can occur during limb compression.