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By definition, heart failure (HF) is a pathological condition affecting the structure and function of all organs in the body, and the brain is not an exception to that. Failure of the heart to pump enough blood centrally and peripherally is at the foundation of HF patients' inability to attend even the most ordinary daily activities and progressive deterioration of their cognitive capacity. What is more, between heart and brain exists a bidirectional relationship that goes well beyond hemodynamics and concerns bioelectric and endocrine signaling. This increasingly consolidated evidence makes the scenario even more complex. Studies have mainly chased how HF impairs cognition without focusing much on preventive measures, notably cardio-cerebral health proxies. Here, we aim to provide a brief account of known and hypothetical factors that may explain how exercise can help obviate cognitive dysfunction associated with HF in its different forms. As we shall see, there is a stringent need for a deeper grasp of such mechanisms. Indeed, gaining this new knowledge will automatically shed new light on the inner workings of HF itself, thus resulting in more effective prevention and treatment of this escalating syndrome., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fatemeh Safari reports financial support was provided by Shahid Sadoughi University of Medical Sciences and Health Services. Jacopo Agrimi reports financial support was provided by Department of Biomedical Sciences, University of Padua., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Total hip arthroplasty (THA) after rotational acetabular osteotomy (RAO) is technically demanding because of the characteristic acetabular morphology after RAO. The present study aimed to investigate the differences in the three-dimensional cup position between THA after RAO and primary THA., Materials and Methods: We analysed the pre-operative and post-operative computed tomography (CT) data of 120 patients (20 patients after RAO and 100 patients without a history of RAO) who underwent THA between January 2017 and June 2018. We evaluated radiographic parameters, including acetabular anteversion, antero-posterior distance at the level of the femoral head centre, the presence of anterior acetabular osteophyte and/or rotated fragment during RAO from the CT data. Additionally, operative data and clinical scores were also evaluated., Results: Although we found no significant differences in any clinical parameters, there were significant differences in radiographic parameters and operative data. The morphology of the acetabulum was significantly retroverted, and the antero-posterior distance was longer in patients after RAO, compared to the implanted cup. Additionally, longer operative time was necessary for such patients. These results reflect the atypical acetabular morphology after RAO, and emphasize that care should be taken to avoid anterior bony impingement and post-operative dislocation., Conclusion: For cup implantation during THA after RAO, surgeons should acknowledge the atypical morphology of the acetabulum and not be misled by its visual shape., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Obesity remains a serious relevant public health concern throughout the world despite related countermeasures being well understood (i.e. mainly physical activity and an adjusted diet). Among different nutritional approaches, there is a growing interest in ketogenic diets (KD) to manipulate body mass (BM) and to enhance fat mass loss. KD reduce the daily amount of carbohydrate intake drastically. This results in increased fatty acid utilisation, leading to an increase in blood ketone bodies (acetoacetate, 3- β -hydroxybutyrate and acetone) and therefore metabolic ketosis. For many years, nutritional intervention studies have focused on reducing dietary fat with little or conflicting positive results over the long term. Moreover, current nutritional guidelines for athletes propose carbohydrate-based diets to augment muscular adaptations. This review discusses the physiological basis of KD and their effects on BM reduction and body composition improvements in sedentary individuals combined with different types of exercise (resistance training or endurance training) in individuals with obesity and athletes. Ultimately, we discuss the strengths and the weaknesses of these nutritional interventions together with precautionary measures that should be observed in both individuals with obesity and athletic populations. A literature search from 1921 to April 2021 using Medline, Google Scholar, PubMed, Web of Science, Scopus and Sportdiscus Databases was used to identify relevant studies. In summary, based on the current evidence, KD are an efficient method to reduce BM and body fat in both individuals with obesity and athletes. However, these positive impacts are mainly because of the appetite suppressive effects of KD, which can decrease daily energy intake. Therefore, KD do not have any superior benefits to non-KD in BM and body fat loss in individuals with obesity and athletic populations in an isoenergetic situation. In sedentary individuals with obesity, it seems that fat-free mass (FFM) changes appear to be as great, if not greater, than decreases following a low-fat diet. In terms of lean mass, it seems that following a KD can cause FFM loss in resistance-trained individuals. In contrast, the FFM-preserving effects of KD are more efficient in endurance-trained compared with resistance-trained individuals.

Introduction: A disintegrin and metalloproteinase 17 (Adam17), also known as TNFα-converting enzyme (Tace), is a membrane-anchored protein involved in shedding of TNF, IL-6 receptor, ligands of epidermal growth factor receptor (EGFR), and Notch receptor. This study aimed to examine the role of Adam17 in adult articular cartilage and osteoarthritis (OA) pathophysiology., Materials and Methods: Adam17 expression was examined in mouse knee joints during OA development. We analyzed OA development in tamoxifen-inducible chondrocyte-specific Adam17 knockout mice of a resection of the medial meniscus and medial collateral ligament (medial) model, destabilization of the medial meniscus (DMM) model, and aging model. We analyzed downstream pathways by in vitro experiments, and further performed intra-articular administration of an Adam17 inhibitor TAPI-0 for surgically induced mouse OA., Results: Adam17 expression in mouse articular cartilage was increased by OA progression. In all models, Adam17 knockout mice showed ameliorated progression of articular cartilage degradation. Adam17 knockout decreased matrix metallopeptidase 13 (Mmp13) expression in both in vivo and in vitro experiments, whereas Adam17 activation by phorbol-12-myristate-13-acetate (PMA) increased Mmp13 and decreased aggrecan in mouse primary chondrocytes. Adam17 activation enhanced release of soluble TNF and transforming growth factor alpha, a representative EGF ligand, from mouse primary chondrocytes, while it did not change release of soluble IL-6 receptor or nuclear translocation of Notch1 intercellular domain. Intra-articular administration of the Adam17 inhibitor ameliorated OA progression., Conclusions: This study demonstrates regulation of OA development by Adam17, involvement of EGFR and TNF pathways, and the possibility of Adam17 as a therapeutic target for OA., (© 2021. The Japanese Society Bone and Mineral Research.)

Measurements of wear resistance and metal ion release are important for designing bearing couples or interfaces in total hip arthroplasty (THA). In this study, we investigated wear resistance and metal ion release of surface-modified metal-free all-polymer hip bearings, such as poly(ether-ether-ketone), (PEEK) on cross-linked polyethylene (PEEK-on-CLPE), with a hydrated gel-like surface layer, to propose an improved alternative to the conventional materials used to design THA bearings. The PEEK surface resulted in less metal ion release than the cobalt-chromium-molybdenum (Co-Cr-Mo) alloy surface owing to the lack of metal. The PEEK-on-CLPE bearing (6.33 mg/10 6  cycles) had lower wear (rate) than the bearing with Co-Cr-Mo alloy-on-CLPE (10.47 mg/10 6  cycles) under controlled laboratory conditions; the wear performance of the all-polymer hip bearings was further improved with hemi- or both-surface modified with a hydrated poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer (3.74 and 3.06 mg/10 6  cycles, respectively). The PMPC-grafted interface of PEEK-on-CLPE will be especially suitable for THA candidates. This study is of key importance for the design of lifelong THA and a better understanding of the limitations resulting from using PEEK. Further studies are necessary to evaluate the possibility of using this material in artificial hips., (© 2021 Wiley Periodicals LLC.)

Introduction: Recently, a modified intermittent fasting protocol was demonstrated to be able to maintain muscle mass and strength, decrease fat mass, and improve some inflammation and cardiovascular risk factors in healthy resistance-trained males after 2 months. The present study sought to investigate the long-term effects on these parameters., Methods: The experiment was a single-blind randomized study. Twenty healthy subjects were enrolled and underwent 12 months of either a time-restricted eating (TRE) diet or a normal diet (ND) protocol, along with resistance training. In the TRE protocol, subjects consumed their energy needs in three meals during an 8-h period of time each day (1 pm, 4 pm, and 8 pm). Subjects in the ND group also had three meals, which were consumed at 8 am, 1 pm, and 8 pm. Groups were matched for kilocalories consumed and macronutrient distribution at baseline., Results: After 12 months of TRE, body mass, fat mass, insulin-like growth factor 1, and testosterone were significantly lower compared with ND. Moreover, inflammatory markers (interleukin 6, interleukin 1β, and tumor necrosis factor α), insulin sensitivity (fasting glucose, insulin, and homeostatic model assessment for insulin resistance index), and lipid profile (cholesterol, HDL, and LDL) significantly improved after TRE compared with ND. Finally, subjects in TRE spontaneously decreased their daily energy intake, whereas those in ND maintained their starting kilocalories per day. No adverse events were reported., Conclusions: Our results suggest that long-term TRE combined with a resistance training program is feasible, safe, and effective in reducing inflammatory markers and risk factors related to cardiovascular and metabolic diseases., (Copyright © 2021 by the American College of Sports Medicine.)

Background: The COVID-19 pandemic forced most Italian athletes to cease their regular training activities, with possible consequences on both mental and physical health. The present study aimed at assessing changes in Physical Activity (PA) from pre- to lockdown, and examining the relationships among lockdown PA, quality of life (mental and physical health), motivation to exercise, psychological distress, intolerance of uncertainty, and body dissatisfaction. Methods: A total of 204 athletes of different sports (91 elite; 110 females; mean age = 22.55, SD = 5.76) answered an online survey investigating demographics, sport-related questions, PA (IPAQ-S), quality of life (SF-12), and psychological variables (BREQ-2, DASS-21, IUS-R, and EDI-3-Body dissatisfaction subscale). Results: Both elite and non-elite athletes significantly reduced their PA intensity and volume ( p < 0.001). Elite athletes did not differ from non-elite in terms of total PA intensity and hours of training during lockdown ( p > 0.05). Elite and individual athletes showed higher intrinsic motivation to exercise compared to non-elite and team sports ( p < 0.01). Female athletes displayed higher distress, worse mental health, and higher body dissatisfaction than males ( p < 0.05). Mediation models showed that vigorous PA positively affected both mental ( p < 0.05) and physical ( p < 0.001) health during lockdown, independently of distress and intolerance of uncertainty. Conclusion: The COVID-19 lockdown was taxing for athletes, particularly professionals; those who were able to practice PA at high intensity during lockdown reported better mental and physical health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Casali, Cerea, Moro, Paoli and Ghisi.)

Aging and menopause are associated with morphological and functional changes which may lead to loss of muscle mass and therefore quality of life. Resistance training (RT) is an effective training mode to increase muscle mass. We reviewed the existing literature to identify studies implementing RT protocols and evaluating muscle hypertrophy exclusively in healthy, postmenopausal and elderly women. Participants' age range was comprised between 50 and 80 years. The primary outcome observed was muscle hypertrophy. Fat mass was also evaluated, if available. PubMed and Web of Science were the screened database, and original articles written in English and published from 2000 up to 2020 were included. 26 articles were considered eligible and included. Quality assessment revealed a "moderate quality" of the included studies, however the majority of studies was able to reach level 4 of evidence and on overall grade of recommendation C. In total, data from 745 female participants subjected to different forms of resistance training were considered. Heterogeneity across studies was present regarding study design, intervention length (mean 16 weeks), training frequency (3 d/w), no. of exercises (n = 7.4) and participants' age (65.8 ± 4.9 years). Small-to-moderate significant increases (k = 43; SMD = 0.44; 95% CI 0.28; 0.60; p < 0.0001) of lean body mass were observed in post-menopausal and elderly women, regardless of age, intervention period, weekly training frequency and no. of exercises. No effects were noted for fat mass (k = 17; SMD = 0.27; 95% CI - 0.02; 0.55; p = 0.07). Studies need to concentrate on providing information regarding training parameters to more effectively counteract the effects of aging and menopause on skeletal muscle mass., (© 2021. The Author(s).)

Exercise generates reactive oxygen species (ROS), creating a redox imbalance towards oxidation when inadequately intense. Normobaric and hyperbaric oxygen (HBO) breathed while not exercising induces antioxidant enzymes expression, but literature is still poor. Twenty-two athletes were assigned to five groups: controls; 30%, or 50% O 2 ; 100% O 2 (HBO) at 1.5 or 2.5 atmosphere absolute (ATA). Twenty treatments were administered on non-training days. Biological samples were collected at T0 (baseline), T1 (end of treatments), and T2 (1 month after) to assess ROS, antioxidant capacity (TAC), lipid peroxidation, redox (amino-thiols) and inflammatory (IL-6, 10, TNF-α) status, renal function (i.e., neopterin), miRNA, and hemoglobin. At T1, O 2 mixtures and HBO induced an increase of ROS, lipid peroxidation and decreased TAC, counterbalanced at T2. Furthermore, 50% O 2 and HBO treatments determined a reduced state in T2. Neopterin concentration increased at T1 breathing 50% O 2 and HBO at 2.5 ATA. The results suggest that 50% O 2 treatment determined a reduced state in T2; HBO at 1.5 and 2.5 ATA similarly induced protective mechanisms against ROS, despite the latter could expose the body to higher ROS levels and neopterin concentrations. HBO resulted in increased Hb levels and contributed to immunomodulation by regulating interleukin and miRNA expression.

This systematic review and meta-analysis evaluated the influence of intermittent fasting (IF) in combination with resistance training (RT) on body composition outcomes. Studies examining IF vs. non-IF diets in individuals performing RT, published up to February 2021, were identified through PubMed, the Cochrane Library, Web of Science, Embase, and SCOPUS databases. Eight studies, including 221 participants were analyzed using a random-effects model to calculate weighted mean differences (WMDs) with 95% confidence intervals (CIs). Results indicated that IF had a significant effect on body mass (WMD = -2.08 kg; 95% CI: -3.04, -1.13), fat mass (WMD = -1.36 kg; 95% CI: -1.94, -0.78), body mass index (WMD = -0.52 kg/m 2 ; 95% CI: -0.85, -0.19), and body fat percentage (WMD = -1.49%; 95% CI: -2.24, -0.74) relative to non-IF diets, without a significant effect for fat-free mass (WMD = -0.27 kg; 95% CI: -0.82, 0.28). The present systematic review and meta-analysis demonstrates potentially beneficial effects of IF in combination with RT for reducing body mass and body fat relative to non-IF control diets, with similar preservation of fat-free mass., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Accumulation of adipose tissue in specific body areas is related to many physiological and hormonal variables. Spot reduction (SR) is a training protocol aimed to stimulate lipolysis locally, even though this training protocol has not been extensively studied in recent years. Thus, the present study sought to investigate the effect of a circuit-training SR on subcutaneous adipose tissue in healthy adults., Methods: Fourteen volunteers were randomly assigned to spot reduction (SR) or to a traditional resistance training (RT) protocol. Body composition via bioimpedance analysis (BIA) and subcutaneous adipose tissue via skinfold and ultrasound were measured before and after eight weeks of training., Results: SR significantly reduced body mass ( p < 0.05) and subcutaneous abdominal adipose tissue ( p < 0.05)., Conclusions: circuit-training SR may be an efficient strategy to reduce in a localized manner abdominal subcutaneous fat tissue depot.

Typing methods are needed for epidemiological tracking of new emerging and hypervirulent strains because of the growing incidence, severity and mortality of Clostridioides difficile infections (CDI). The aim of this study was the evaluation of a typing Matrix-Assisted Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS (T-MALDI)) method for the rapid classification of the circulating C. difficile strains in comparison with polymerase chain reaction (PCR)-ribotyping results. Among 95 C. difficile strains, 10 ribotypes (PR1-PR10) were identified by PCR-ribotyping. In particular, 93.7% of the isolates (89/95) were grouped in five ribotypes (PR1-PR5). For T-MALDI, two classifying algorithm models (CAM) were tested: the first CAM involved all 10 ribotypes whereas the second one only the PR1-PR5 ribotypes. Better performance was obtained using the second CAM: recognition capability of 100%, cross-validation of 96.6% and agreement of 98.4% (60 correctly typed strains, limited to PR1-PR5 classification, out of 61 examined strains) with PCR-ribotyping results. T-MALDI seems to represent an alternative to PCR-ribotyping in terms of reproducibility, set up time and costs, as well as a useful tool in epidemiological investigation for the detection of C. difficile clusters (either among CAM included ribotypes or out-of-CAM ribotypes) involved in outbreaks.

Background: Rotational acetabular osteotomy (RAO) is a type of pelvic osteotomy performed to improve the acetabular bony coverage against the femoral head for patients with acetabular dysplasia. The acetabular bony coverage is ideally evaluated three-dimensionally; however, there is a paucity of published data regarding three-dimensional morphology in patients with long-term excellent outcome after RAO. The present study investigated the characteristics of three-dimensional acetabular morphology with long-term excellent outcome after RAO in comparison to patients with normal hip joints and those converted to total hip arthroplasty (THA) after RAO because of osteoarthritis (OA) progression., Methods: Anteroposterior plain radiograph and computed tomography data of 57 hip joints (17 joints with excellent outcome 20 years or more after RAO, 16 normal joints, and 20 joints converted to THA after RAO) were analyzed. The two-dimensional lateral center-edge (CE) angle from plain radiographs and acetabular anteversion, anterior acetabular sector angle, and posterior sector angle from computed tomography (CT) images were calculated., Results: Compared with patients converted to THA, all parameters in patients with long-term excellent outcome after RAO were similar to those in patients with normal hip joints, particularly in the three-dimensional analyses. The anterior bony coverage was excessive, whereas the posterior bony coverage was deficient in patients converted to THA after RAO. Anterior bony impingement and posterior instability may be the cause of OA progression after RAO., Conclusion: Caution must be taken to avoid rotating the separated fragment excessively to the anterior direction during RAO to prevent OA progression and achieve long-term excellent outcome.

Background: Although there is substantial interest in intermittent fasting as a dietary approach in active individuals, information regarding its effects in elite endurance athletes is currently unavailable. The present parallel randomized trial investigated the effects of a particular intermittent fasting approach, called time-restricted eating (TRE), during 4 weeks of high-level endurance training., Methods: Sixteen elite under-23 cyclists were randomly assigned either to a TRE group or a control group (ND). The TRE group consumed 100% of its estimated daily energy needs in an 8-h time window (from 10:00 a.m. to 6:00 p.m.) whilst energy intake in the ND group was distributed in 3 meals consumed between 7:00 a.m. and 9:00 p.m. Fat and fat-free mass were estimated by bioelectrical impedance analysis and VO 2max and basal metabolism by indirect gas analyzer. In addition, blood counts, anabolic hormones (i.e. free testosterone, IGF-1) and inflammatory markers (i.e. IL-6, TNF-α) were assessed., Results: TRE reduced body weight (- 2%; p = 0.04) and fat mass percentage (- 1.1%; p = 0.01) with no change in fat-free mass. Performance tests showed no significant differences between groups, however the peak power output/body weight ratio (PPO/BW) improved in TRE group due to weight loss (p = 0.02). Free testosterone and IGF-1 decreased significantly (p = 0.01 and p = 0.03 respectively) in TRE group. Leucocyte count decreased in ND group (p = 0.02) whilst the neutrophils-to-lymphocytes ratio (NLR) decreased significantly (p = 0.03) in TRE group., Conclusions: Our results suggest that a TRE program with an 8-h feeding window elicits weight loss, improves body composition and increases PPO/BW in elite cyclists. TRE could also be beneficial for reducing inflammation and may have a protective effect on some components of the immune system. Overall, TRE could be considered as a component of a periodized nutrition plan in endurance athletes., Trial Registration: This trial was retrospectively registered at clinicaltrials.gov as NCT04320784 on 25 March 2020.

Background: The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are reported to influence erythropoiesis and the human iron status. Large study cohorts encompassing biomarkers of iron metabolism and BCAAs are still lacking., Methods: We investigated potential interactions between blood concentrations of all three BCAAs valine, leucine and isoleucine and biomarkers of iron metabolism [i.e., hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), iron, transferrin, ferritin, transferrin saturation, soluble transferrin receptor (sTfR)] in 430 outpatients referred for a medical health check-up. Linear regression models were performed to assess possible associations between variables., Results: All three BCAAs were positively correlated with Hb, ferritin and the sTfR (r-values: 0.145-0.382; P values: <0.001-0.003). The strongest correlation was observed between valine and Hb (r=0.382; P value <0.001). Linear regression models showed a statistically significant influence of all three BCAAs on Hb and ferritin (β-coefficients: 0.173-0.351; all P values: <0.001). Seventeen patients with anemia (4%) were found with significantly lower serum BCAA concentrations compared to 413 non-anemic individuals (P<0.05)., Conclusions: These data indicate a pathophysiological link between the three BCAAs valine, leucine and isoleucine and the human iron indicators Hb and ferritin. Further studies are needed to clarify the exact causal mechanisms of these findings., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (Available at http://dx.doi.org/10.21037/atm-20-624a). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Initial bacterial adhesion to medical devices and subsequent biofilm formation are known as the leading causes of surgical site infection (SSI). Therefore, inhibition of bacterial adhesion and biofilm formation on the surface of medical devices can reduce the risk of SSIs. In this study, a highly hydrophilic, antibiofouling surface was prepared by coating the bioabsorbable suture surface with poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate) (PMB). The PMB-coated and noncoated sutures exhibited similar mechanical strength and surface morphology. The effectiveness of the PMB coating on the suture to suppress adhesion and biofilm formation of methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus was investigated both in vitro and in vivo . The bacterial adhesion test revealed that PMB coating significantly reduced the number of adherent bacteria, with no difference in the number of planktonic bacteria. Moreover, fluorescence microscopy and scanning electron microscopy observations of adherent bacteria on the suture surface after contact with bacterial suspension confirmed PMB coating-mediated inhibition of biofilm formation. Additionally, we found that the PMB-coated sutures exhibited significant antibiofouling effects in vivo . In conclusion, PMB-coated sutures demonstrated bacteriostatic effects associated with a highly hydrophilic, antibiofouling surface and inhibited bacterial adhesion and biofilm formation. Therefore, PMB-coated sutures could be a new alternative to reduce the risk of SSIs., Competing Interests: Co-author (M.J.) is employed by KEISEI Medical Industrial Corporation Limited., (Copyright © 2020 Taizo Kaneko et al.)

Purpose: The results of reamed bipolar hemiarthroplasty (BHA) in patients with hip osteoarthritis (OA) are reported to be unfavorable. Acetabular reaming for sufficient bony coverage caused bipolar head migration into the superomedial direction, and most patients required revision surgeries. Several methods are applicable to treat decreased bone stock. This study aimed to investigate the midterm results of revision surgeries using the cementless cup with the rim-fit technique., Methods: Between 1996 and 2014, acetabular revision surgeries using the cementless cup with the rim-fit technique were performed in 86 hips (74 patients). We evaluated radiographic outcomes, including positional change of the rotation center of the artificial femoral head, presence of implant loosening, and filling of the initial gap. We also evaluated clinical outcomes, including the Harris hip score (HHS), and postoperative complications., Results: The average positional changes from BHA to prerevision surgeries were 8.0 mm superiorly and 4.1 mm medially. The average changes from prerevision to postrevision surgeries were 3.7 mm inferiorly and 2.4 mm laterally. No implant loosening was found in all cases; the initial gap between the acetabular host bone and the acetabular cup was filled in 53 (93%) among 57 hips. The average HHS improved from 65.9 before revision surgeries to 83.8 in the latest follow-up. Dislocation and postoperative periprosthetic fracture occurred in two and five hips, respectively; no cases required rerevision surgeries., Conclusion: There were favorable midterm results of the revision total hip arthroplasty for migrated BHA in patients with hip OA using cementless cup with the rim-fit technique.

At the beginning of 2020 a respiratory diseased named COVID-19 rapidly spread worldwide. Due to the presence of comorbidities and a greater susceptibility to infections, older adults are the population most affected by this pandemic. An efficient pharmacological treatment for COVID-19 is not ready yet; in the meanwhile, a general quarantine has been initiated as a preventive action against the spread of the disease. If on one side this countermeasure is slowing the spread of the virus, on the other side is also reducing the amount of physical activity. Sedentariness is associated with numerous negative health outcomes and increase risk of fall, fractures and disabilities in older adults. Models of physical inactivity have been widely studied in the past decades, and most studies agreed that is necessary to implement physical exercise (such as walking, low load resistance or in bed exercise) during periods of disuse to protect muscle mass and function from catabolic crisis. Moreover, older adults have a blunted response to physical rehabilitation, and a combination of intense resistance training and nutrition are necessary to overcome the loss of in skeletal muscle due to disuse., Competing Interests: We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Consistent practice of physical activity has well known positive effects on general health; however, time for exercise remains one major barrier for many. An acute bout of high intensity interval resistance training (HIIRT) increases acute resting energy expenditure (REE) and decreases respiratory ratio (RR), suggesting its potential role on weight loss and increased fatty acid oxidation. The aim of this study was to test the long-term effect of HIIRT on body composition, lipid profile and muscle strength using a randomized parallel trial. Twenty healthy young adults (22.15 1.95 years) were randomized to perform either a HIIRT ( N = 11) protocol, consisting of three sets of 6 repetitions at 6 repetition maximum (RM) and then 20 seconds of rest between repetitions until exhaustion repeated for 3 times with 2'30″ rest between sets or a traditional training (TRT, N = 9) protocol of 3 sets of 15 reps with 75 sec of rest between sets. Body composition, resting energy metabolism, aerobic capacity, muscle strength and blood measurements were taken before and after 8 weeks of training. Both protocols enhanced muscle strength, but only HIIRT improved endurance strength performance (+22.07%, p < 0.05) and lean body mass (+2.82%, p < 0.05). REE and RR were unaltered as lipid profile. HIIRT represents a valid training method to improve muscle strength and mass, but its role on body weight control was not confirmed., Competing Interests: The authors declare no conflict of interest.

We aim to investigate the effect of 6 weeks of betaine supplementation on body composition and muscle performance during CrossFit© training. Twenty-nine subjects matched for training status (4.16 0.95 day/week) and body fat mass (12.66 4.08%) were randomly assigned to a betaine (BET; N = 14) or placebo group (PLA; N = 15). Body composition and cellular hydration were estimated with skinfolds measurement and bioelectrical impendence before and after 6 weeks of training. Muscle performance was assessed using three different tests: 3-RM back-squat for muscle strength, 2 km rowing test for aerobic capacity and Bergeron Beep Test for anaerobic capacity. Muscle strength assessed during back squat significantly increased in BET (p = 0.04) but not in the PLA group, however, there were no statistical differences between groups. Although not significant, fat mass was reduced in BET compared to PLA. Overall, body composition and cell hydration measurements did not change in response to training or betaine supplementation. Short-term (6 weeks) betaine supplementation supports muscle strength but was not ergogenic for trained subjects to aerobic and anaerobic performance in the CrossFit©-specific test., Competing Interests: The authors declare no conflict of interest.

Aging induces physiological decline in human skeletal muscle function and morphology, including type II fiber atrophy and an increase in type I fiber frequency. Resistance exercise training (RET) is an effective strategy to overcome muscle mass loss and improve strength, with a stronger effect on type II fibers. In the present study, we sought to determine the effect of a 12-wk progressive RET program on the fiber type-specific skeletal muscle hypertrophic response in older adults. Nineteen subjects [10 men and 9 women (71.1 ± 4.3 yr)] were studied before and after the 12-wk program. Immunohistochemical analysis was used to quantify myosin heavy chain (MyHC) isoform expression, cross-sectional area (CSA), satellite cell abundance, myonuclear content, and lipid droplet density. RET induced an increase in MyHC type II fiber frequency and a concomitant decrease in MyHC type I fiber frequency. Mean CSA increased significantly only in MyHC type II fibers (+23.3%, P < 0.05), but myonuclear content increased only in MyHC type I fibers ( P < 0.05), with no change in MyHC type II fibers. Satellite cell content increased ~40% in both fiber types ( P > 0.05). RET induced adaptations to the capillary supply to satellite cells, with the distance between satellite cells and the nearest capillary increasing in type I fibers and decreasing in type II fibers. Both fiber types showed similar decrements in intramuscular lipid density with training ( P < 0.05). Our data provide intriguing evidence for a fiber type-specific response to RET in older adults and suggest flexibility in the myonuclear domain of type II fibers during a hypertrophic stimulus. NEW & NOTEWORTHY In older adults, progressive resistance exercise training (RET) increased skeletal muscle fiber volume and cross-sectional area independently of myonuclear accretion, leading to an expansion of the myonuclear domain. Fiber type-specific analyses illuminated differential adaptation; type II fibers underwent hypertrophy and exhibited myonuclear domain plasticity, whereas myonuclear accretion occurred in type I fibers in the absence of a robust hypertrophic response. RET also augmented satellite cell-capillary interaction and reduced intramyocellular lipid density to improve muscle quality.

Objectives: Adequate muscle perfusion supports the transport of nutrients, oxygen and hormones into muscle fibers. Aging is associated with a substantial decrease in skeletal muscle capillarization, fiber size and oxidative capacity, which may be improved with regular physical activity. The aim of this study was to investigate the relationship between muscle capillarization and indices of muscle hypertrophy (i.e. lean mass; fiber cross sectional area (CSA)) in older adults before and after 12 weeks of progressive resistance exercise training (RET)., Design: Interventional study SETTING AND PARTICIPANTS: 19 subjects (10 male and 9 female; 71.1 ± 4.3 years; 27.6 ± 3.2 BMI) were enrolled in the study and performed a whole body RET program for 12 weeks. Subjects where then retrospectively divided into a LOW or HIGH group, based on their pre-RET capillary-to-fiber perimeter exchange index (CFPE). Physical activity level, indices of capillarization (capillaries-to-fiber ratio, C:Fi; CFPE index and capillary-to-fiber interface, LC-PF index), muscle hypertrophy, muscle protein turnover and mitochondrial function were assessed before and after RET., Results: Basal capillarization (C:Fi; CFPE and LP-CF index) correlates with daily physical activity level (C:Fi, r = 0.57, p = 0.019; CFPE index, r = 0.55, p = 0.024; LC-PF index, r = 0.56, p = 0.022) and CFPE and LC-PF indices were also positively associated with oxidative capacity (respectively r = 0.45, p = 0.06; r = 0.67, p = 0.004). Following RET, subjects in the HIGH group underwent hypertrophy with significant improvements in muscle protein synthesis and muscle fiber CSA (p < 0.05). However, RET did not promote muscle hypertrophy in the LOW group, but RET significantly increased muscle capillary density (p < 0.05)., Conclusion/implications: Muscle fiber capillarization before starting an exercise training program may be predictive of the muscle hypertrophic response to RET in older adults. Increases in muscle fiber size following RET appear to be blunted when muscle capillarization is low, suggesting that an adequate initial capillarization is critical to achieve a meaningful degree of muscle adaptation to RET., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives:  Primary aim of this study was to evaluate survival rate of lithium disilicate veneers in upper and lower anterior teeth. Secondary aims were to evaluate changing in proportions of teeth before and after restorations and to assess mean thickness of the veneers., Materials and Methods:  Seventy-nine upper and lower lithium disilicate veneers were made in 13 patients with worn teeth. Mean follow-up was 3 years. To perform anterior definitive rehabilitations, malocclusions and loss of vertical dimension were treated by full mouth rehabilitations to obtain proper occlusal conditions. Veneers were made of lithium disilicate core and fluorapatite-based ceramic stratification. Survival rate was calculated by Kaplan-Meier analysis. Changing in teeth proportion before and after restorations was analyzed by a paired t -test. Descriptive statistics of thickness values were also performed., Results:  One case of detachment was observed with a 98.7% survival rate. Teeth's proportions were preserved although the first upper right incisor and canine changed in dimension., Conclusions:  Lithium disilicate veneers in esthetical rehabilitations of worn teeth proved to be an effective way of treatment in a medium follow-up of 3 years. Proportions seemed to be maintained with a minimum dental removal., Competing Interests: The authors do not have any financial interest in the companies whose materials are included in this article.None declared., (Dental Investigation Society.)

Ketogenic diet (KD) is a nutritional regimen characterized by a high-fat and an adequate protein content and a very low carbohydrate level (less than 20 g per day or 5% of total daily energy intake). The insufficient level of carbohydrates forces the body to primarily use fat instead of sugar as a fuel source. Due to its characteristic, KD has often been used to treat metabolic disorders, obesity, cardiovascular disease, and type 2 diabetes. Skeletal muscle constitutes 40% of total body mass and is one of the major sites of glucose disposal. KD is a well-defined approach to induce weight loss, with its role in muscle adaptation and muscle hypertrophy less understood. Considering this lack of knowledge, the aim of this review was to examine the scientific evidence about the effects of KD on muscle hypertrophy. We first described the mechanisms of muscle hypertrophy per se, and secondly, we discussed the characteristics and the metabolic function of KD. Ultimately, we provided the potential mechanism that could explain the influence of KD on skeletal muscle hypertrophy.

Background: Muscle protein synthesis (MPS) can be stimulated by ingestion of protein sources, such as whey, casein, or soy. Protein supplementation can enhance muscle protein synthesis after exercise and may preserve skeletal muscle mass and function in aging adults. Therefore, identifying protein sources with higher anabolic potency is of high significance., Objective: The aim of this study was to determine the anabolic potency and efficacy of a novel whey protein hydrolysate mixture (WPH) on mechanistic target of rapamycin complex 1 (mTORC1) signaling and skeletal MPS in healthy young subjects., Methods: Ten young men (aged 28.7 ± 3.6 y, 25.2 ± 2.9 kg/m2 body mass index [BMI]) were recruited into a double-blind two-way crossover trial. Subjects were randomized to receive either 0.08 g/kg of body weight (BW) of WPH or an intact whey protein (WHEY) mixture during stable isotope infusion experiments. Fractional synthetic rate, leucine and phenylalanine kinetics, and markers of amino acid sensing were assessed as primary outcomes before and 1-3 h after protein ingestion using a repeated measures mixed model., Results: Blood leucine concentration, delivery of leucine to muscle, transport of leucine from blood into muscle and intracellular muscle leucine concentration significantly increased to a similar extent 1 h after ingestion of both mixtures (P < 0.05). Phosphorylation of S6K1 (i.e. a marker of mTORC1 activation) increased equally by ∼20% 1-h postingestion (P < 0.05). Ingestion of WPH and WHEY increased mixed MPS similarly in both groups by ∼43% (P < 0.05); however, phenylalanine utilization for synthesis increased in both treatments 1-h postingestion but remained elevated 3-h postingestion only in the WPH group (P < 0.05)., Conclusions: We conclude that a small dose of WPH effectively increases leucine transport into muscle, activating mTORC1 and stimulating MPS in young men. WPH anabolic potency and efficacy for promoting overall muscle protein anabolism is similar to WHEY, an intact protein source. This trial was registered at clinicaltrials.gov as NCT03313830., (Copyright © American Society for Nutrition 2019.)

Sarcopenia, age-associated involuntary loss of muscle and strength, can progress to clinically relevant functional decline. Resistance exercise attenuates muscle and strength loss but may not be feasible for some older adults. Aerobic exercise training (AET) improves cardiopulmonary health; however, effects on protein turnover, muscle mass, and strength are less clear. We aimed to determine whether AET improves basal myofibrillar protein synthesis (MPS) and capillarization, promoting hypertrophy and strength. We hypothesized that AET improves strength with increased MPS and capillarization. Older adults were randomized to non-exercise (NON; n = 11, 71.4 ± 4.18 years) or exercise (EX; n = 12, 73.7 ± 4.05 years). EX completed 24 weeks of AET (walking 3×/week, 45 minutes, 70% heart rate reserve); NON remained sedentary. A stable isotope tracer was infused. MPS and capillarization were analyzed from vastus lateralis muscle biopsies. Strength was measured via isokinetic dynamometry. Lean mass was determined with dual-energy X-ray absorptiometry. Basal MPS increased in EX (+50.7%, P  =   0.01) along with capillary density (+66.4%, P  =   0.03), peak oxygen consumption (+15.8%, P  =   0.01), quadriceps strength (+15.1%, P  =   0.01), and muscle quality (peak torque divided by leg lean mass, +15.5%, P  =   0.01). Lean mass did not change ( P  >   0.05). AET increases muscle protein turnover and capillarization in older adults, improving muscle quality., Competing Interests: The authors have no conflicts of interests to disclose.

The influence of meal frequency and timing on health and disease has been a topic of interest for many years. While epidemiological evidence indicates an association between higher meal frequencies and lower disease risk, experimental trials have shown conflicting results. Furthermore, recent prospective research has demonstrated a significant increase in disease risk with a high meal frequency (≥6 meals/day) as compared to a low meal frequency (1⁻2 meals/day). Apart from meal frequency and timing we also have to consider breakfast consumption and the distribution of daily energy intake, caloric restriction, and night-time eating. A central role in this complex scenario is played by the fasting period length between two meals. The physiological underpinning of these interconnected variables may be through internal circadian clocks, and food consumption that is asynchronous with natural circadian rhythms may exert adverse health effects and increase disease risk. Additionally, alterations in meal frequency and meal timing have the potential to influence energy and macronutrient intake.A regular meal pattern including breakfast consumption, consuming a higher proportion of energy early in the day, reduced meal frequency (i.e., 2⁻3 meals/day), and regular fasting periods may provide physiological benefits such as reduced inflammation, improved circadian rhythmicity, increased autophagy and stress resistance, and modulation of the gut microbiota.

mTORC1 regulates protein synthesis and in turn is regulated by growth factors, energy status, and amino acid availability. In kidney cell (HEK293-T) culture, the GAP activity toward RAG (GATOR1) protein complex suppresses activation of the RAG A/B-RAG C/D heterodimer when amino acids are insufficient. During amino acid sufficiency, the RAG heterodimer recruits mTORC1 to the lysosomal membrane where its interaction with Ras homolog enriched in brain (Rheb) stimulates mTORC1's kinase activity. The DEP domain containing 5 (DEPDC5) protein, a GATOR1 subunit, causes familial focal epilepsy when mutated, and global knockout of the Depdc5 gene is embryonically lethal. To study the function of DEPDC5 in skeletal muscle, we generated a muscle-specific inducible Depdc5 knockout mouse, hypothesizing that knocking out Depdc5 in muscle would make mTORC1 constitutively active, causing hypertrophy and improving muscle function. Examining mTORC1 signaling, morphology, mitochondrial respiratory capacity, contractile function, and applied physical function ( e.g. rotarod, treadmill, grip test, and wheel running), we observed that mTORC1 activity was significantly higher in knockout (KO) mice, indicated by the increased phosphorylation of mTOR and its downstream effectors (by 118% for p-mTOR/mTOR, 114% for p-S6K1/S6K1, and 35% for p-4E-BP1/4E-BP1). The KO animals also exhibited soleus muscle cell hypertrophy and a 2.5-fold increase in mitochondrial respiratory capacity. However, contrary to our hypothesis, neither physical nor contractile function improved. In conclusion, DEPDC5 depletion in adult skeletal muscle removes GATOR1 inhibition of mTORC1, resulting in muscle hypertrophy and increased mitochondrial respiration, but does not improve overall muscle quality and function., (© 2019 Graber et al.)

Older adults undergoing age-related decrements in muscle health can benefit substantially from resistance exercise training, a potent stimulus for whole muscle and myofiber hypertrophy, neuromuscular performance gains, and improved functional mobility. With the use of advancing technologies, research continues to elucidate the mechanisms of and heterogeneity in adaptations to resistance exercise training beyond differences in exercise prescription. This review highlights the current knowledge in these areas and emphasizes knowledge gaps that require future attention of the field.

Although laboratory tests and mid-term clinical outcomes show the clinical safety and remarkable wear resistance of the highly cross-linked polyethylene (HXLPE) acetabular liner with a nanometer-scaled graft layer of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), the wear resistance of the layer under severe abrasive conditions is concerning. We evaluated the effects of a roughened femoral head and the grafting locus on the wear resistance of the PMPC-grafted HXLPE liner and the effect of PMPC grafting on wear resistance of the HXLPE substrate by removing the PMPC-grafted layer using a severely roughened femoral head. Against a moderately roughened femoral head, the PMPC-grafted HXLPE liner showed negative wear, although an untreated HXLPE liner increased the wear by 154.1% compared with wear against a polished femoral head, confirming that PMPC grafts were unaffected. Against a severely roughened femoral head, the PMPC-grafted layer of the head contact area might be removed under severe conditions. However, the wear rate was reduced by 52.5% compared to that of untreated HXLPE liners. Moreover, the head non-contact area-modified PMPC-grafted HXLPE liner against a polished femoral head reduced the wear by 76.8% compared with untreated HXLPE liner; thus, this area may be also important in the development of fluid-film lubrication. STATEMENT OF SIGNIFICANCE: Here we describe effects of a roughened femoral head and the locus of grafting on the wear-resistance of the phospholipid polymer grafted highly cross-linked polyethylene (PMPC-HXLPE) liner. Against a moderately roughened femoral head, the PMPC-HXLPE liner showed negative wear, confirming that PMPC grafts were unaffected. After removing the PMPC layer of the head contact area using a severely roughened femoral head, the wear rate not only exceeded that of untreated HXLPE liners, but was reduced by 52.5%, confirming that PMPC grafting does not affect the wear-resistance of the HXLPE substrate. In addition, the head non-contact area-modified PMPC-HXLPE liner reduced the wear by 76.8%. Thus, this area may also may be important in the development of fluid-film lubrication., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Recently, traditional strategies for manipulating orthopedic bearing substrates have attempted to improve their wear resistance by adjusting polyethylene substrate through cross-linking and antioxidant blending. However, further research is required on the substrate, as well as the surface focused on the structure and role of articular cartilage. We therefore develop an orthopedic bearing surface comprising a nanometer-scale hydrated gel-like layer by grafting highly hydrophilic poly(2-methacryloyloxyethyl phosphorylcholine), with the aim of mimicking the lubrication mechanism of articular cartilage, and investigate its surface characteristics, bulk characteristics, and behavior under load bearing conditions upon accelerated aging. Neither the hydrophilicity nor lubricity of the gel-like surface was influenced by accelerated aging; instead, high stability was revealed, even under strong oxidation conditions. The characteristics of the hydrated gel-like surface potentiated the wear resistance of the cross-linked polyethylene liner, irrespective of accelerated aging. These results suggest that the hydrated gel-like surface enhances the longevity of cross-linked polyethylene bearings even under load-bearing conditions. Furthermore, the inflection point on the time series of wear can be a suitable indicator of the durability of the life-long protectant. In conclusion, the hydrated gel-like surface can positively increase orthopedic implant durability.

To overcome clinical issues caused by large bone defects and subsequent nonunion, various approaches to bone regeneration have been researched, including tissue engineering, biomaterials, stem cells and drug screening. Previously, we developed a free-standing biodegradable polymer nanosheet composed of poly(L-lactic acid) (PLLA) using a simple fabrication process consisting of spin-coating and peeling techniques. We reported that sandwich-type PLLA nanosheets loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) displayed long-lasting, sustained release of rhBMP-2, and markedly enhanced bone regeneration in mouse calvarial bone defects. Here, we fabricated multi-layered nanosheets loaded with fibroblast growth factor-2 (FGF-2), and investigated their application for long bone regeneration. Subcutaneously implanted tri-layered PLLA nanosheets displayed sustained release of loaded rhFGF-2 for about 2 weeks. Next, we prepared critical-sized mouse femoral defects and implanted mono- or tri-layered nanosheets, or a gelatin hydrogel with rhFGF-2. Amongst these conditions, the tri-layered nanosheet most efficiently induced bone regeneration. Indeed, bone regeneration was enhanced even after 4 weeks in the tri-layered nanosheet group, and was accompanied by FGFR1 activation and subsequent osteoblast differentiation. Multi-layered PLLA nanosheets loaded with rhFGF-2 may be useful for bone regenerative medicine. Furthermore, the multi-layered PLLA nanosheet structure may potentially be applied as a potent sustained-release carrier. STATEMENTS OF SIGNIFICANCE: Here, we describe multi-layered poly(L-lactic acid) (PLLA) nanosheets loaded with recombinant human fibroblast growth factor-2 (rhFGF-2) as a modified sustained-release carrier for bone regeneration. In vivo imaging system analysis revealed that subcutaneously implanted tri-layered PLLA nanosheets displayed sustained release of loaded rhFGF-2 for 2 weeks. In critical-sized mouse femoral defects, tri-layered nanosheets loaded with rhFGF-2 most efficiently induced bone regeneration. Notably, bone regeneration was enhanced even after 4 weeks in the tri-layered nanosheet group, and was accompanied by FGFR1 activation and subsequent osteoblast differentiation. Multi-layered PLLA nanosheets loaded with rhFGF-2 may be useful for bone regenerative medicine. Furthermore, the multi-layered PLLA nanosheet structure may potentially be applied as a potent sustained-release carrier., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: Rotational acetabular osteotomy is a type of pelvic osteotomy that involves rotation of the acetabular bone to improve the bony coverage of the femoral head for patients with acetabular dysplasia. Favourable post-operative long-term outcomes have been reported in previous studies. However, there is a paucity of published data regarding three-dimensional bony coverage. The present study investigated the three-dimensional bony coverage of the acetabulum covering the femoral head in hips before and after rotational acetabular osteotomy and in normal hips., Methods: The computed tomography data of 40 hip joints (12 joints before and after rotational acetabular osteotomy; 16 normal joints) were analyzed. The three-dimensional bony coverage of each joint was evaluated using original software., Results: The post-operative bony coverage improved significantly compared with pre-operative values. In particular, the anterolateral aspect of the acetabulum tended to be dysplastic in patients with acetabular dysplasia compared to those with normal hip joints. However, greater bony coverage at the anterolateral aspect was obtained after rotational acetabular osteotomy. Meanwhile, the results of the present study may indicate that the bony coverage in the anterior aspect may be excessive., Conclusion: Three-dimensional analysis indicated that rotational acetabular osteotomy achieved favorable bony coverage. Further investigations are necessary to determine the ideal bony coverage after rotational acetabular osteotomy.

Taper fretting corrosion is considered a potentially limiting factor for total hip arthroplasty longevity. Recently, attention has been focused on new materials for ceramic femoral heads, for example, zirconia-toughened alumina (ZTA), since they have an alternative bearing surface that can improve the wear resistance. Moreover, ceramics have high chemical stability and corrosion resistance. In this study, we evaluated the effects of ZTA and Co-Cr-Mo alloy femoral heads on their taper fretting and/or corrosion characteristics under a controlled hip simulator test. After the test, less fretting and corrosion were observed in the taper surface of the trunnion against the ZTA femoral head than for that against the Co-Cr-Mo alloy femoral head. In addition, corrosion damages were only observed in the lateral-distal taper surface (noncontact area) of the trunnion in the Co-Cr-Mo alloy femoral head group. The ZTA femoral head group also eliminated the potential for Co ion release into the lubricants from taper corrosion, reducing the possibility of adverse local tissue inflammatory responses. In conclusion, ZTA femoral heads showed markedly less fretting corrosion compared to Co-Cr-Mo alloy femoral heads and have a lower potential for metal ion release. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2815-2826, 2018., (© 2017 Wiley Periodicals, Inc.)

Purpose: This study aimed to (1) investigate the success of posterior implants tilted >45° when 4 immediately loaded implants were used to support full-arch prostheses, eliminating any distal cantilever and (2) examine the effect on marginal bone loss (MBL) of different combinations of anterior multi-unit abutment (MUA) angles and posterior implant tilting angles., Materials and Methods: Records of patients rehabilitated according to the Columbus Bridge Protocol were analyzed. Peri-implant bone levels (PBLs) and MBL were measured for each implant. The influence of posterior implant tilting angle on PBL, MBL, and implant and prosthetic success rate was investigated. The impact on the same endpoints of different anterior MUA angles, and different combinations of anterior MUA and tilted posterior implant angles was also examined., Results: Records of 41 patients were analyzed, for a total of 46 complete rehabilitations, and 142 implants (52 anterior, 63 posterior tilted ≤45° [group 1], and 27 posterior tilted >45° [group 2]). No implants were lost during the follow-up (25.9 months), and no prosthetic complications were reported. Success rate for posterior implants was 100% in group 1 and 96.3% in group 2. Mean MBL differed significantly between the 2 groups (0.45 mm in group 1, 0.66 in group 2 [P = .04]), but not when the analysis was limited to implants in the same jaw. Implant tilting angle did not correlate with MBL and the MUA angle had no effect on bone resorption around posterior implants, neither in the sample as a whole nor in individual patients., Conclusions: Posterior implants tilted >45° to eliminate distal cantilever may be as safe as those tilted less in severely atrophic jaws rehabilitated with immediately loaded, full-arch prostheses supported on 4 implants. Further prospective studies on larger samples of patients and implants and with longer follow-up are needed to confirm these findings., (© 2018 Wiley Periodicals, Inc.)

Aggressive/challenging behaviors (A/CB) are a major public health problem for individuals with intellectual disabilities (ID). A leading reason for psychiatric hospitalizations and incarcerations, such behaviors are costly to the health care system, agencies, and families. Social problem-solving (SPS) training programs for individuals with ID have had positive behavioral results, but most were conducted in clinical or forensic settings. None was a community-based preventive intervention, none examined whether the behaviors decreased in residential and work settings, and none addressed cost-effectiveness. In preliminary work, we modified an effective SPS training program (ADAPT: Attitude, Define, Alternatives, Predict, and Try out), using input from individuals with ID and residential staff, as a community-based preventive intervention that we delivered in group homes (STEPS: Steps to Effective Problem-solving). Individuals with ID have high rates of obesity, and our attention-control condition is a nutrition intervention: Food for Life. We describe the protocol for a randomized clinical trial to: (1) test the efficacy of the STEPS intervention for improving SPS skills and reducing A/CB compared to an attention-control nutrition intervention in group homes; (2) assess the mediating effect of residential staff SPS skills, group-home level SPS skills, and group cohesiveness on the improvement of SPS skills and reductions in A/CB; and (3) evaluate the cost-effectiveness of STEPS. We expect to show that STEPS is a preventive strategy to reduce A/CBs among individuals with ID and improve the cost-effectiveness of their care., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Dumbbell curl (DC) and barbell curl in its two variants, straight (BC) or undulated bar (EZ) are typical exercises to train the elbow flexors. The aim of the study was to verify if the execution of these three variants could induce a selective electromyographic (EMG) activity of the biceps brachii (BB) and brachioradialis (BR)., Methods: Twelve participants performed one set of ten repetitions at 65% of their 1-RM for each variant of curl. Pre-gelled electrodes were applied with an inter-electrode distance of 24 mm on BB and BR. An electrical goniometer was synchronously recorded with EMG signals to determine the concentric and eccentric phases of each variant of curl., Results: We detected higher activation profile of both BB ( P  < 0.05) and BR ( P  < 0.01) during the EZ compared to the DC. Higher levels of activation was found during the concentric phase for only the BR performed with an EZ compared to DC ( P  < 0.001) and performing BC compared to DC ( P  < 0.05). The eccentric phase showed a higher activation of the BB muscle in EZ compared to DC ( P  < 0.01) and in BC compared to DC ( P  < 0.05). The BR muscle showed a higher activation performing EZ compared to DC ( P  < 0.01)., Discussion: The EZ variant may be preferred over the DC variant as it enhances BB and BR EMG activity during the whole range of motion and only in the eccentric phase. The small difference between BC and EZ variants of the BB and BR EMG activity makes the choice between these two exercises a matter of subjective comfort., Competing Interests: The authors declare there are no competing interests.

Background: The muscle protein anabolic response to contraction and feeding may be blunted in older adults. Acute bouts of exercise can improve the ability of amino acids to stimulate muscle protein synthesis (MPS) by activating mechanistic target of rapamycin complex 1 (mTORC1) signaling, but it is not known whether exercise training may improve muscle sensitivity to amino acid availability., Objective: The aim of this study was to determine if muscle protein anabolism is resistant to essential amino acids (EAAs) and whether resistance exercise training (RET) improves muscle sensitivity to EAA in healthy older adults., Methods: In a longitudinal study, 19 healthy older adults [mean ± SD age: 71 ± 4 y body mass index (kg/m2): 28 ± 3] were trained for 12 wk with a whole-body program of progressive RET (60-75% 1-repetition maximum). Body composition, strength, and metabolic health were measured pre- and posttraining. We also performed stable isotope infusion experiments with muscle biopsies pre- and posttraining to measure MPS and markers of amino acid sensing in the basal state and in response to 6.8 g of EAA ingestion., Results: RET increased muscle strength by 16%, lean mass by 2%, and muscle cross-sectional area by 27% in healthy older adults (P < 0.05). MPS and mTORC1 signaling (i.e., phosphorylation status of protein kinase B, 4E binding protein 1, 70-kDa S6 protein kinase, and ribosomal protein S6) increased after EAA ingestion (P < 0.05) pre- and posttraining. RET increased basal MPS by 36% (P < 0.05); however, RET did not affect the response of MPS and mTORC1 signaling to EAA ingestion., Conclusion: RET increases strength and basal MPS, promoting hypertrophy in healthy older adults. In these subjects, a small dose of EAAs stimulates muscle mTORC1 signaling and MPS, and this response to EAAs does not improve after RET. Our data indicate that anabolic resistance to amino acids may not be a problem in healthy older adults. This trial was registered at www.clinicaltrials.gov as NCT02999802.

Younger, active patients who undergo total hip arthroplasty (THA) have increasing needs for wider range of motion and improved stability of the joint. Therefore, bearing materials having not only higher wear resistance but also mechanical strength are required. Carbon fiber-reinforced poly(ether ether ketone) (CFR-PEEK) is known as a super engineering plastic that has great mechanical strength. In this study, we focused on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-grafted CFR-PEEK and investigated the effects of PMPC grafting and the femoral heads materials on the wear properties of CFR-PEEK liners. Compared with untreated CFR-PEEK, the PMPC-grafted CFR-PEEK surface revealed higher wettability and lower friction properties under aqueous circumstances. In the hip simulator wear test, wear particles generated from the PMPC-grafted CFR-PEEK liners were fewer than those of the untreated CFR-PEEK liners. There were no significant differences in the size and the morphology of the wear particles between the differences of PMPC-grafting and the counter femoral heads. Zirconia-toughened alumina (ZTA) femoral heads had significantly smoother surfaces compared to cobalt-chromium-molybdenum alloy femoral heads after the hip simulator test. Thus, we conclude that the bearing combination of the PMPC-grafted CFR-PEEK liner and ZTA head is expected to be a lifelong bearing interface in THA. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1028-1037, 2018., (© 2017 Wiley Periodicals, Inc.)

Manipulating the surface and substrate of cross-linked polyethylene (CLPE) is an essential approach for obtaining life-long orthopedic bearings. We therefore proposed a bearing material comprised of an antioxidative substrate generated by vitamin E blending (HD-CLPE[VE]) with a poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-grafted surface, and investigated its wear resistance and oxidative stability under accelerated aging and load bearing conditions. Neither the hydration nor friction kinetics of the molecular network structure of the PMPC-grafted surface or the HD-CLPE(VE) substrate were influenced by accelerated aging but rather exhibited high stability even under high oxidation conditions. The characteristics of the PMPC-grafted surface improved the wear and impact fatigue resistance of the HD-CLPE(VE) liner regardless of accelerated aging. Notably, the PMPC-grafted surface was found to affect the potential oxidative stability at the rim part of the acetabular liner. PMPC chains serve several important functions on the surface regardless of load bearing, such as high lubricity or low lipophilicity attributed to phosphorylcholine groups and/or surrounding water-fluid film, and suppression of lipid diffusion attributed to methacrylate main chains on the surface. Together, these results provide preliminary evidence that the PMPC graft layer and vitamin E-blended substrate might positively affect the extent of orthopedic implant durability., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

One of the important factors in determining the success of joint replacement is the wear performance of polyethylene. Although highly crosslinked polyethylene (CLPE) is presently used, it is still not adequate. We have developed a surface modification technology using poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) in an attempt to improve wear performance. In this study, we evaluated the wear and creep deformation resistances of 3-mm and 6-mm thick PMPC-grafted CLPE disks, set on a metal back-plate, with and without a sham screw hole. The gravimetric wear and volumetric change of the disks were examined using a multidirectional pin-on-disk tester. PMPC grafting decreased the gravimetric wear of CLPE regardless of the presence of a screw hole, and did not affect the volumetric change. The volumetric change in the bearing and backside surfaces of the 3-mm thick disk with a screw hole was much larger than that of those without a screw hole or those of the 6-mm thick disk, which was caused by creep deformation. PMPC grafting on the bearing surface can be a material engineering approach to reduce the wear without changing the creep deformation resistance, and is a promising surface modification technology that can be used to increase the longevity of various artificial joints. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 610-618, 2018., (© 2017 Wiley Periodicals, Inc.)

The present study aimed to compare the effects of equal-volume resistance training performed with single-joint (SJ) or multi-joint exercises (MJ) on VO 2 max, muscle strength and body composition in physically active males. Thirty-six participants were divided in two groups: SJ group ( n = 18, 182.1 ± 5.2, 80.03 ± 2.78 kg, 23.5 ± 2.7 years) exercised with only SJ exercises (e.g., dumbbell fly, knee extension, etc.) and MJ group ( n = 18, 185.3 ± 3.6 cm, 80.69 ± 2.98 kg, 25.5 ± 3.8 years) with only MJ exercises (e.g., bench press, squat, etc.). The total work volume (repetitions × sets × load) was equated between groups. Training was performed three times a week for 8 weeks. Before and after the training period, participants were tested for VO 2 max, body composition, 1 RM on the bench press, knee extension and squat. Analysis of covariance (ANCOVA) was used to compare post training values between groups, using baseline values as covariates. According to the results, both groups decreased body fat and increased fat free mass with no difference between them. Whilst both groups significantly increased cardiorespiratory fitness and maximal strength, the improvements in MJ group were higher than for SJ in VO 2 max (5.1 and 12.5% for SJ and MJ), bench press 1 RM (8.1 and 10.9% for SJ and MJ), knee extension 1 RM (12.4 and 18.9% for SJ and MJ) and squat 1 RM (8.3 and 13.8% for SJ and MJ). In conclusion, when total work volume was equated, RT programs involving MJ exercises appear to be more efficient for improving muscle strength and maximal oxygen consumption than programs involving SJ exercises, but no differences were found for body composition.

Background: We evaluated the clinical and radiographic outcomes, including femoral head penetration, of total hip arthroplasty performed using a specific polyethylene (PE) liner in small Asian patients at 10 years after the index surgery. In addition, we investigated whether femoral head penetration was affected by patient-related, implant-related, and surgical factors., Methods: Between August 2002 and June 2005, for cementless primary total hip arthroplasty, we used acetabular PE liners that were manufactured from GUR 1050 resin, machined from isostatic compression-molded bar stock, and sterilized with a gamma ray irradiation in argon gas. We assessed 82 hips in 78 patients who received these liners., Results: The mean Harris hip score improved from 41.0 preoperatively to 84.5 at 10 years postoperatively. Periprosthetic osteolysis was observed in 7 hips (9.8%). No acetabular component migration was detected, and no revision surgery was performed 10 years postoperatively. The mean steady-state wear rate was 0.031 mm/y, which was lower than the wear rate for other conventional PE liners of the previous studies. Among the patient-related, implant-related, and surgical factors, sex was significantly associated with the mean steady-state wear rate, with a higher rate in male patients than in female patients., Conclusion: PE acetabular liners used in small Asian patients show similar clinical outcomes and reduced wear compared with those of other liners. In addition, sex is significantly associated with the mean steady-state wear rate, and the steady-state wear rate is higher in male patients than in female patients., (Copyright © 2017. Published by Elsevier Inc.)

To overcome serious clinical problems caused by large bone defects, various approaches to bone regeneration have been researched, including tissue engineering, biomaterials, stem cells and drug screening. Previously, we developed a free-standing biodegradable polymer nanosheet composed of poly(L-lactic acid) (PLLA) using a simple fabrication process consisting of spin-coating and peeling techniques. Here, we loaded recombinant human bone morphogenetic protein-2 (rhBMP-2) between two 60-nm-thick PLLA nanosheets, and investigated these sandwich-type nanosheets in bone regeneration applications. The PLLA nanosheets displayed constant and sustained release of the loaded rhBMP-2 for over 2months in vitro. Moreover, we implanted the sandwich-type nanosheets with or without rhBMP-2 into critical-sized defects in mouse calvariae. Bone regeneration was evident 4weeks after implantation, and the size and robustness of the regenerated bone had increased by 8weeks after implantation in mice implanted with the rhBMP-2-loaded nanosheets, whereas no significant bone formation occurred over a period of 20weeks in mice implanted with blank nanosheets. The PLLA nanosheets loaded with rhBMP-2 may be useful in bone regenerative medicine; furthermore, the sandwich-type PLLA nanosheet structure may potentially be applied as a potent prolonged sustained-release carrier of other molecules or drugs., Statements of Significance: Here we describe sandwich-type poly(L-lactic acid) (PLLA) nanosheets loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a novel method for bone regeneration. Biodegradable 60-nm-thick PLLA nanosheets display strong adhesion without any adhesive agent. The sandwich-type PLLA nanosheets displayed constant and sustained release of the loaded rhBMP-2 for over 2months in vitro. The nanosheets with rhBMP-2 markedly enhanced bone regeneration when they were implanted into critical-sized defects in mouse calvariae. In addition to their application for bone regeneration, PLLA nanosheets may be useful for various purposes in combination with various drugs or molecules, because they displays excellent capacity as a sustained-release carrier., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

To reduce the production of wear particles and subsequent aseptic loosening, we created a human articular cartilage-mimicked surface for a highly cross-linked polyethylene liner, whose surface grafted layer consisted of a biocompatible phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine). Although our previous in vitro findings showed that poly(2-methacryloyloxyethyl phosphorylcholine)-grafted particles were biologically inert and caused no subsequent bone resorptive responses, and poly(2-methacryloyloxyethyl phosphorylcholine) grafting markedly decreased wear in hip joint simulator tests, the clinical safety, and in vivo wear resistance of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners remained open to question. Therefore, in the present study, we evaluated clinical and radiographic outcomes of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners 5 years subsequent to total hip replacement in 68 consecutive patients. No reoperation was required for any reason, and no adverse events were associated with the implanted liners. The average Harris Hip Score increased from 38.6 preoperatively to 96.5 5 years postoperatively, and health-related quality of life, as indicated by the Short Form 36 Health Survey, improved. Radiographic analyses showed no periprosthetic osteolysis or implant migration. Between 1 and 5 years postoperatively, the mean steady-state wear rate was 0.002 mm/year, which represented a marked reduction relative to other highly cross-linked polyethylene liners, and appeared to be unaffected by patient-related or surgical factors. Although longer follow up is required, poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners improved mid-term clinical outcomes. The clinical safety and wear-resistance results are encouraging with respect to the improvement of long-term clinical outcomes with poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2007-2016, 2017., (© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The liver is well known to possess high regenerative capacity in response to partial resection or tissue injury. However, liver regeneration is often impaired in the case of advanced liver fibrosis/cirrhosis when mature hepatocytes can hardly self-proliferate. Hepatic progenitor cells have been implicated as a source of hepatocytes in regeneration of the fibrotic liver. Although alpha-fetoprotein (AFP) is known as a clinical marker of progenitor cell induction in injured/fibrotic adult liver, the origin and features of such AFP-producing cells are not fully understood. Here, we demonstrate a unique and distinct AFP-expressing cell population that is induced by the Jagged1/Notch2 signal in murine fibrotic liver. Following repeated carbon tetrachloride injections, a significant number of AFP-positive cells with high proliferative ability were observed along the fibrous septa depending on the extent of liver fibrosis. These AFP-positive cells exhibited features of immature hepatocytes that were stained positively for hepatocyte-lineage markers, such as albumin and hepatocyte nuclear factor 4 alpha, and a stem/progenitor cell marker Sox9. A combination of immunohistological examination of fibrotic liver tissues and coculture experiments with primary hepatocytes and hepatic stellate cells indicated that increased Jagged1 expression in activated hepatic stellate cells stimulated Notch2 signaling and up-regulated AFP expression in adjacent hepatocytes. The mobilization and proliferation of AFP-positive cells in fibrotic liver were further enhanced after partial hepatectomy, which was significantly suppressed in Jagged1-conditional knockout mice. Finally, forced expression of the intracellular domain of Notch2 in normal liver induced a small number of AFP-expressing hepatocytes in vivo. Conclusion : Insight is provided into a novel pathophysiological role of Jagged1/Notch2 signaling in the induction of AFP-positive cells in fibrotic liver through the interaction between hepatocytes and activated hepatic stellate cells. ( Hepatology Communications 2017;1:215-229).

The surface and substrate of a cross-linked polyethylene (CLPE) liner are designed to achieve resistance against oxidative degradation in the construction of hip joint replacements. In this study, we aimed to evaluate the oxidative degradation caused by lipid absorption of a highly hydrophilic nanometer-scaled thickness layer prepared by grafting a poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer and a high-dose gamma-ray irradiated CLPE with vitamin E blending (HD-CLPE[VE]). The HD-CLPE(VE) and PMPC-grafted HD-CLPE(VE) exhibited extremely high oxidation resistance regardless of lipid absorption, even though residual-free radical levels were detectable. The water wettability of the PMPC-grafted CLPE and PMPC-grafted HD-CLPE(VE) surfaces was considerably greater than that of untreated surfaces. The hydrated PMPC-grafted layer also exhibited extremely low solubility for squalene. Lipids such as squalene and cholesterol esters diminished the oxidation resistance of CLPE despite the vitamin E improvement. Notably, the PMPC-grafted surface was resistant to lipid absorption and diffusion as well as subsequent lipid-related oxidative degradation, likely because of the presence of the hydrated PMPC-grafted layer. Together, these results provide preliminary evidence that the resistance against lipid absorption and diffusion of a hydrated PMPC-grafted layer might positively affect the extent of resistance to the in vivo oxidation of orthopedic implants., (Copyright © 2016 Elsevier Ltd. All rights reserved.)