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We performed a current study to examine the association between dietary inflammatory index (DII) score and older age-related muscle conditions, including sarcopenia, low muscle mass, low muscle strength, frailty, and/or disability. Systematic review and dose-response meta-analysis. A systematic literature search was performed using Scopus, PubMed/MEDLINE, and ISI Web of Science without limitation until October 04, 2022. Relative risk (RR) and 95% confidence interval (CI) were pooled by applying a random-effects model, while validated methods examined assess quality and publication bias via Newcastle-Ottawa Scale, Egger's regression asymmetry, and Begg's rank correlation tests respectively. A dose-response meta-analysis was conducted to estimate the RRs per 1-unit increment in DII scores. Adults (≥18 years) The risk of older age-related muscle conditions (sarcopenia, low muscle mass, low muscle strength, frailty, and/or disability) Data were available from 19 studies with 68079 participants. Results revealed that a higher DII score was significantly related to an increased risk of sarcopenia (RR=1.50; 95% CI: 1.26, 1.79; I2=53.3%; p<0.001; n=10; sample size =43097), low muscle strength (RR=1.47; 95% CI: 1.24, 1.74; I2=6.6%; p<0.001; n=4; sample size =9339), frailty (RR=1.61; 95% CI: 1.41, 1.84; I2=0.0%; p<0.001; study=5; participant=3882) and disability (RR=1.41; 95% CI: 1.16, 1.72; I2=58.4%; p=0.001; n=5; sample size =13760), but not low muscle mass (RR=1.24; 95% CI: 0.98, 1.56; I2=49.3%; p=0.069; n=4; sample size =11222). Additionally, results of the linear dose-response indicated that an increase of one point in the DII score was related to a 14% higher risk of sarcopenia, 6% higher risk of low muscle mass, 7% higher risk of low muscle strength, and a 7% higher risk of disability in adults. Non-linear dose-response relationships also revealed a positive linear association between the DII score and the risk of sarcopenia (Pnonlinearity = 0.097, Pdose-response <0.001), frailty (P nonlinearity = 0.844, Pdose-response=0.010) and disability (Pnonlinearity = 0.596, Pdose-response=0.007). Adherence to a pro-inflammatory diet was significantly associated with a higher risk of sarcopenia and other age-associated adverse effects such as low muscle strength, disability, and frailty. These results indicate a necessity to prioritize the reduction of pro-inflammatory diets to help promote overall older age-related muscle conditions.

High fat feeding impairs skeletal muscle metabolic flexibility and induces insulin resistance, whereas exercise training exerts positive effects on substrate handling and improves insulin sensitivity. To identify the genomic mechanisms by which exercise ameliorates some of the deleterious effects of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression and DNA methylation. HFD markedly induced expression of immune and inflammatory genes, which was not attenuated by Ex. Conversely, Ex markedly remodelled expression of genes associated with muscle growth and structure. We detected marked DNA methylation changes following HFD alone and in combination with Ex. Among the genes that showed a significant association between DNA methylation and gene expression changes were PYGM, which was epigenetically regulated in both groups, and ANGPTL4, which was regulated only following Ex. In conclusion, while short-term Ex did not prevent a HFD-induced inflammatory response, it provoked a genomic response that may protect skeletal muscle from atrophy. These epigenetic adaptations provide mechanistic insight into the gene-specific regulation of inflammatory and metabolic processes in human skeletal muscle.

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The culture in many team sports involves consumption of large amounts of alcohol after training/competition. The effect of such a practice on recovery processes underlying protein turnover in human skeletal muscle are unknown. We determined the effect of alcohol intake on rates of myofibrillar protein synthesis (MPS) following strenuous exercise with carbohydrate (CHO) or protein ingestion. In a randomized cross-over design, 8 physically active males completed three experimental trials comprising resistance exercise (8×5 reps leg extension, 80% 1 repetition maximum) followed by continuous (30 min, 63% peak power output (PPO)) and high intensity interval (10×30 s, 110% PPO) cycling. Immediately, and 4 h post-exercise, subjects consumed either 500 mL of whey protein (25 g; PRO), alcohol (1.5 g·kg body mass⁻¹), 12±2 standard drinks) co-ingested with protein (ALC-PRO), or an energy-matched quantity of carbohydrate also with alcohol (25 g maltodextrin; ALC-CHO). Subjects also consumed a CHO meal (1.5 g CHO·kg body mass⁻¹) 2 h post-exercise. Muscle biopsies were taken at rest, 2 and 8 h post-exercise. Blood alcohol concentration was elevated above baseline with ALC-CHO and ALC-PRO throughout recovery (P<0.05). Phosphorylation of mTOR(Ser2448) 2 h after exercise was higher with PRO compared to ALC-PRO and ALC-CHO (P<0.05), while p70S6K phosphorylation was higher 2 h post-exercise with ALC-PRO and PRO compared to ALC-CHO (P<0.05). Rates of MPS increased above rest for all conditions (∼29-109%, P<0.05). However, compared to PRO, there was a hierarchical reduction in MPS with ALC-PRO (24%, P<0.05) and with ALC-CHO (37%, P<0.05). We provide novel data demonstrating that alcohol consumption reduces rates of MPS following a bout of concurrent exercise, even when co-ingested with protein. We conclude that alcohol ingestion suppresses the anabolic response in skeletal muscle and may therefore impair recovery and adaptation to training and/or subsequent performance.

Background: The effects of combining resistance training (RT) and concurrent training (CT; resistance + endurance training) with varied protein doses on bone measures remain poorly understood. Hence, we conducted a comparison of the impacts of two high-protein diets (1.6 or 3.2 g kg−1 d−1) over 16 weeks in resistance-trained males, either with CT or RT alone. Methods: A total of forty-eight males, all of whom were resistance-trained, had the following demographics: 26.6 ± 6 years, body mass index: 25.6 ± 2.9 kg m−2 administered either 3.2 g kg−1 d−1 protein (CT2; n = 12; RT2; n = 12) or 1.6 g kg−1 d−1 protein (CT1; n = 12; RT1; n = 12) during 16 weeks (four sessions·w−1). Bone parameters were assessed pre- and post-intervention. Results: There was no significant interaction between the intervention group and time for the legs, arms, ribs, or pelvis area BMC and BMD (p > 0.05). For the BMD of the pelvis and the BMC of the right ribs, however, there were significant time effects noted (p < 0.05). Furthermore, there was a significant interaction between the intervention group and time in the lumbar and thoracic spines, with a particular time effect noted for the thoracic spine region (p < 0.05). The regional differences in skeletal responses to the intervention are highlighted by these data. Conclusion: Our findings show that the intake of two high-protein diets combined with RT and CT during 16 weeks had no adverse effects on bone tissue parameters. While these findings indicate that protein intake between 2 and 3 times the current RDI does not promote bone demineralization when consumed in conjunction with exercise, future studies investigating the long-term effects of chronic high protein intake on bone tissue health are warranted.

Background We implemented a high-protein diet (2 g·kg −1 ·d −1 ) throughout 12 weeks of concurrent exercise training to determine whether interferences to adaptation in muscle hypertrophy, strength and power could be attenuated compared to resistance training alone. Methods Thirty-two recreationally active males (age: 25 ± 5 years, body mass index: 24 ± 3 kg·m −2 ; mean ± SD) performed 12 weeks of either isolated resistance (RES; n  = 10) or endurance (END; n  = 10) training (three sessions·w −1 ), or concurrent resistance and endurance (CET; n  = 12) training (six sessions·w −1 ). Maximal strength (1RM), body composition and power were assessed pre- and post-intervention. Results Leg press 1RM increased ~ 24 ± 13% and ~ 33 ± 16% in CET and RES from PRE-to-POST ( P  < 0.001), with no difference between groups. Total lean mass increased ~ 4% in both CET and RES from PRE-to-POST ( P  < 0.001). Ultrasound estimated vastus lateralis volume increased ~ 15% in CET and ~ 11% in RES from PRE-to-POST ( P  < 0.001), with no difference between groups. Wingate peak power relative to body mass displayed a trend ( P  = 0.053) to be greater in RES (12.5 ± 1.6 W·kg BM −1 ) than both CET (10.8 ± 1.7 W·kg BM −1 ) and END (10.9 ± 1.8 W·kg BM −1 ) at POST. Absolute VO 2peak increased 6.9% in CET and 12% in END from PRE-to-POST ( P  < 0.05), with no difference between groups. Conclusion Despite high protein availability, select measures of anaerobic power-based adaptations, but not muscle strength or hypertrophy, appear susceptible to ‘interference effects’ with CET and should be closely monitored throughout training macro-cycles. T rials Registry : This trial was registered with the Australian-New Zealand Clinical Trials Registry (ACTRN12617001229369).

Purpose Autophagy is an intracellular degradative system sensitive to hypoxia and exercise-induced perturbations to cellular bioenergetics. We determined the effects of low-intensity endurance-based exercise performed with blood-flow restriction (BFR) on cell signaling adaptive responses regulating autophagy and substrate metabolism in human skeletal muscle. Methods In a randomized cross-over design, nine young, healthy but physically inactive males completed three experimental trials separated by 1 week of recovery consisting of either a resistance exercise bout (REX: 4 × 10 leg press repetitions, 70% 1-RM), endurance exercise (END: 30 min cycling, 70% V O 2peak ), or low-intensity cycling with BFR (15 min, 40% V O 2peak ). A resting muscle biopsy was obtained from the vastus lateralis 2 weeks prior to the first exercise trial and 3 h after each exercise bout. Results END increased ULK1 Ser757 phosphorylation above rest and BFR (~37 to 51%, P  < 0.05). Following REX, there were significant elevations compared to rest (~348%) and BFR (~973%) for p38γ MAPK Thr180/Tyr182 phosphorylation ( P  < 0.05). Parkin content was lower following BFR cycling compared to REX (~20%, P  < 0.05). There were no exercise-induced changes in select markers of autophagy following BFR. Genes implicated in substrate metabolism ( HK2 and PDK4) were increased above rest (~143 to 338%) and BFR cycling (~212 to 517%) with END ( P  < 0.001). Conclusion A single bout of low-intensity cycling with BFR is insufficient to induce intracellular “stress” responses (e.g., high rates of substrate turnover and local hypoxia) necessary to activate skeletal muscle autophagy signaling.

We developed an innovative and efficient, feeder-free culture method to genetically modify and expand peripheral blood-derived NK cells with high proliferative capacity, while preserving the responsiveness of their native activating receptors. Activated peripheral blood NK cells were efficiently transduced by a retroviral vector, carrying a second-generation CAR targeting CD19. CAR expression was demonstrated across the different NK-cell subsets. CAR.CD19-NK cells display higher antileukemic activity toward CD19+ cell lines and primary blasts obtained from patients with B-cell precursor ALL compared with unmodified NK cells. In vivo animal model data showed that the antileukemia activity of CAR.CD19-NK cell is superimposable to that of CAR-T cells, with a lower xenograft toxicity profile. These data support the feasibility of generating feeder-free expanded, genetically modified peripheral blood NK cells for effective “off-the-shelf” immuno-gene-therapy, while their innate alloreactivity can be safely harnessed to potentiate allogeneic cell therapy.

Purpose Endoscopic endonasal skull base surgery (EESBS) is a clean-contaminated procedure. Guidelines regarding the antibiotic prophylaxis in EESBS have not been developed yet, and today, there are no universally accepted protocols. In this article, we investigated the efficacy of our new ultra-short antibiotic prophylaxis protocol for EESBS guided by the cultural results of preoperative microbiological nasal swabs. Methods We defined as “nasal swab-related antibiotic protocol” the administration of a first-generation cephalosporin (cefazolin 2 g) in patients whose nasal swabs revealed the presence of normal nasal flora or methicillin-sensitive Staphylococcus aureus (MSSA), and the administration of vancomycin 1 g intravenously in patients whose nasal swabs revealed the presence of methicillin-resistant Staphylococcus aureus (MRSA) or with reported cephalosporin/penicillin allergy. This case-control study included 120 patients who underwent EESBS. The case group included 60 cases who received the “nasal swab-related antibiotic protocol,” while the control group included 60 cases who received the “standard hospital antibiotic protocol” used in neurosurgery (cefazolin 2 g plus metronidazole 500 mg at induction, and 2 g of cefazolin repeated after 180 min). Results The preoperative microbiological nasal swabs showed normal nasal flora in 42 patients (70%), MSSA in 17 patients (28.3%), and MRSA in 1 patient (1.6%). During the study period, no cases of meningitis or sinusitis occurred in the case group (“nasal swab-related antibiotic protocol” ) , while two infections (3.3%, 1 sinusitis and 1 meningitis) were reported in the control group (“standard hospital antibiotic protocol”). Mean length of hospitalization was 6.5 days for the case group and 8.5 days in the control group. “Standard hospital antibiotic protocol” is less expensive (range, 2.88–5.42 euros) compared with our new “nasal swab-related antibiotic protocol” (range, 10.02–32.56 euros), but in line with other antibiotic prophylaxis protocols reported in literature. Discussion The low complication rates of our case series (0%) is comparable to complication rates reported in literature (1.6% for meningitis and 8% for sinusitis). Compared with other perioperative antibiotic regimens reported in literature, the “nasal swab-related antibiotic protocol” is cheap and at least equally effective. We discuss the rationale on which we based the choice of chemoprophylaxis, the timing, and the length of our regimen. Conclusions Our study confirmed the safety and efficacy of our easily applicable and low-cost antibiotic prophylaxis protocol.