Revising LH cut-off for the diagnosis of central precocious puberty via triptorelin stimulation assay.

INTRODUCTION: Precocious puberty (PP) in girls is defined by thelarche before age 8. The diagnostic gold standard is an increased LH level following gonadotropin-releasing hormone (GnRH) stimulation. Alternatively, GnRH analogues like triptorelin can be used, though their interpretation varies. Since 2000, we have used a triptorelin-induced LH cut-off of 15 IU/L, 4 h post-stimulus. However, many girls showed LH values below this threshold despite evident pubertal progression. PURPOSE: To establish a new LH threshold post-triptorelin stimulation for earlier diagnosis of central precocious puberty (CPP) in girls showing pubertal progression and to evaluate additional parameters for diagnostic accuracy. METHODS: We enrolled 186 girls with thelarche onset between ages 1-8 and a GnRH analogue assay performed between 2015-2019 without signs of axis activation. Within this cohort, 62 patients repeated the triptorelin test due to rapid pubertal progression. The assay involved administering 100 mcg/m² of triptorelin and measuring LH, FSH, and estradiol levels before and four hours post-injection. RESULTS: Patients with axis activation at the second test had significantly higher post-stimulus LH levels at the first test compared to those below 15 IU/L. They also had higher basal LH levels, elevated LH/FSH ratio, and increased growth velocity. Statistical analysis identified a new post-stimulus LH threshold of 5 IU/L. CONCLUSION: We propose a LH value of 5 IU/L after triptorelin administration as a new threshold for early CPP diagnosis. While the LH/FSH ratio and growth velocity are associated with axis activation, they did not significantly enhance diagnostic accuracy when combined with the LH value.

Robotic-Assisted Radical Cystectomy: Single-Center Analysis of Factors Impacting Clavien ≥ II Complications.

Despite the advent of robotics and the decreasing rate of complications after radical cystectomy, several factors are renowned to impair the early outcomes of this procedure. The aim of this paper is to provide a multivariate analysis (MVA) of patient and surgical procedure-related variables likely to affect postoperative course and 30-day complication rate. Fifty-five robotic-assisted radical cystectomies (RARCs) performed at a single center from July 2021 to March 2023 were enrolled. Baseline demographics, comorbidities, and intraoperative and postoperative data were collected. Uni- and multivariate analyses were performed to evaluate the relationship with Clavien ≥ II complications arising within 30 days of surgery. A postoperative Clavien ≥ II complication was evident in 15 patients (28%), whereas Clavien ≥ III occurred only in 5 (9%). At MVA, the only independent predictor of Clavien ≥ II complications was a prior neoadjuvant chemotherapy (OR 5.6; 95% CI 1.22-25.3, p = 0.026). Recognized the small sample size, patients who received a prior NAC should deserve special care within the postoperative course.

Assessing the Muscle-Bone Unit in Girls Exposed to Different Amounts of Impact-Loading Physical Activity-A Cross-Sectional Association Study.

BACKGROUND/OBJECTIVES: In children, an association exists between muscle and bone, as well as between physical activity and osteogenesis. Impact loading is a factor in increasing bone accrual during growth. In this work, we explored the muscle-bone association in girls exposed to long-term physical activity at different levels of impact loading. METHODS: Four groups of girls aged 7-16 were considered. The curricular (C; n = 22) group only had curricular physical activity at school (2 h/w). In addition to curricular physical activity, the girls in the dance (D; n = 21), gymnastics at lower training (GL; n = 14), and gymnastics at higher training (GH; n = 20) groups had 2 h/w, 4 h/w, and 4 h/w < training ≤ 12 h/w additional physical activity, respectively, for at least one year. A visual analysis estimated the respective amounts of impact-loading activity. The bone mineral content (BMC), areal bone mineral density (aBMD), and fat-free soft tissue mass (FFSTM) were assessed with dual-energy X-ray absorptiometry. RESULTS: The results showed that, after adjusting for several confounders, statistically significant correlations were present between muscle mass and several bone mineral variables. A regression analysis confirmed the correlation in the data, and showed the marginal role of other body composition variables and physical activity for predicting BMC and BMD. CONCLUSION: Skeletal muscle mass is a major determinant of the BMC and BMD of the TBLH, as well as of the Appendicular level, in girls exposed to different amounts of long-term impact-loading physical activity.

Autophagy in Skeletal Muscle.

Skeletal muscle fibers possess, like all cells of our body, an evolutionary conserved autophagy machinery, which allows them to segregate unfolded proteins and damaged organelles within autophagosomes, and to induce fusion of autophagosomes with lysosomes, leading to degradation of those altered cell constituents. This process may be selective for specific cell components, as in the case of glycogen (glycophagy) or organelles, as with mitochondria (mitophagy). The autophagic flux is activated by fasting, and contributes with the proteasome to provide the organism with amino acids required for survival. Autophagy is also essential for the normal turnover of muscle proteins and organelles, as shown by the degenerative changes induced by genetic block of the autophagic mechanism, and in several myopathies. Autophagy is enhanced in muscle by exercise and impaired during aging, suggesting that aging-dependent muscle dysfunction could be delayed by boosting autophagy.

Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice.

Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16LUC reporter mice. We profiled the constituent components of HK by mass spectrometry, and identified luteolin-the most concentrated flavonoid in HK-as a senomorphic compound. Mechanistically, by performing surface plasmon resonance and in situ proximity ligation assay, we found that luteolin disrupted the p16-CDK6 interaction. This work demonstrates that administration of HK promotes longevity in mice, possibly by modulating cellular senescence and by disrupting the p16-CDK6 interaction.

Impact on Glycemia Risk Index and other metrics in type 1 adult patients switching to Advanced Hybrid Closed-Loop systems: a one-year real-life experience.

BACKGROUND: Advanced Hybrid Closed-Loop system (AHCL) has profoundly changed type 1 diabetes therapy. This study primarily aimed to assess the impact on Glycemia Risk Index (GRI) and other continuous glucose monitoring (CGM) metrics when switching from one of four insulin strategies to AHCL in type 1 adult patients. METHODS: A single-center, retrospective pre/post observational study; 198 patients (age 44.4 ± 12.7 years, 115 females/83 males, diabetes duration 24.7 ± 11.6 years, HbA1c 7.4 ± 1%), treated with different insulin therapies (MDI, CSII, SAP with PLGS, HCL) were assessed before and after switching to an AHCL (MiniMed 780G, Diabeloop Roche, Tandem Control-IQ) at 1, 3, 6, and 12 months. Mixed-effects multivariable regression models were used to estimate the mean pre/post variations at different time points, adjusted for potential confounders. RESULTS: A month after the switch, there was an improvement in CGM metrics and HbA1c for all patients: GRI -10.7, GMI -0.27%, CV -2.1%, TAR>250 -3.7%, TAR180-250 -5.6%, TIR + 9.7%, HbA1c -0.54% (all p < 0.001). This improvement was maintained throughout the observational period (at 3, 6, and 12 months, with all p-values < 0.001). When improvements across the 780, Diabeloop, and Tandem CIQ devices were compared: Diabeloop demonstrated significantly better performance in terms of GRI, GMI, CV, TAR>250 at T1 (for all p < 0.01); 780 recorded highest average decrease in TAR180-250 (p = 0.020), while Tandem achieved the most significant reduction in TBR54-69 (p = 0.004). CONCLUSIONS: Adopting an AHCL leads to a rapid and sustained improvement in GRI and other parameters of metabolic control for up to a year, regardless of prior insulin therapies, baseline conditions or brands.

C16ORF70/MYTHO promotes healthy aging in C.elegans and prevents cellular senescence in mammals.

The identification of genes that confer either extension of life span or accelerate age-related decline was a step forward in understanding the mechanisms of aging and revealed that it is partially controlled by genetics and transcriptional programs. Here, we discovered that the human DNA sequence C16ORF70 encodes a protein, named MYTHO (macroautophagy and youth optimizer), which controls life span and health span. MYTHO protein is conserved from Caenorhabditis elegans to humans and its mRNA was upregulated in aged mice and elderly people. Deletion of the orthologous myt-1 gene in C. elegans dramatically shortened life span and decreased animal survival upon exposure to oxidative stress. Mechanistically, MYTHO is required for autophagy likely because it acts as a scaffold that binds WIPI2 and BCAS3 to recruit and assemble the conjugation system at the phagophore, the nascent autophagosome. We conclude that MYTHO is a transcriptionally regulated initiator of autophagy that is central in promoting stress resistance and healthy aging.

Does previous transurethral resection of the prostate affect the outcomes in robotic assisted radical prostatectomy?

PURPOSE: Transurethral resection of the prostate (TURP) is one of the surgical options for treating enlarged prostates with lower urinary symptoms (LUTS). In this older group of patients, concomitant prostate cancer is not uncommon. However, the fibrosis and distortion of the prostate anatomy by prior TURP can potentially hinder surgical efficacy at robotic-assisted radical prostatectomy (RARP). We aim to evaluate functional, and oncologic outcomes of RARP in patients with and without previous TURP. METHODS: 231 men with previous TURP underwent RARP (TURP group). These men were propensity score matched using clinicopathological characteristics to men without previous TURP who underwent RARP (Control group). Perioperative and postoperative variables were analysed for significant differences in outcomes between groups. Variables analysed included estimated blood loss (EBL), operative time, catheter time, hospitalization time, postoperative complications, positive surgical margins (PSM) rates, cancer status, biochemical recurrence (BCR), potency, and continence rates. RESULTS: Patients in the TURP group showed no statistically significant differences in operative safety measures including median EBL, operative time, catheter time, hospitalization time or postoperative complications. No significant difference between the groups in terms of potency rates and continence rates. Furthermore, there were no statistically significant differences in oncological outcomes, including PSM rates (15% vs 18%, P = 0.3) and BCR. CONCLUSION: In RARP after TURP there is often noticeable distortion of the surgical anatomy. For an experienced team the procedure is safe and provides similar oncologic control and functional outcomes to RARP in patients without previous TURP.

Cost analysis of new robotic competitors: a comparison of direct costs for initial hospital stay between Da Vinci and Hugo RAS for radical prostatectomy.

Robotic surgery with Da Vinci has revolutionized the treatment of several diseases, including prostate cancer; nevertheless, costs remain the major drawback. Recently, new robotic platforms entered the market aiming to reduce costs and improve the access to robotic surgery. The aim of the study is to compare direct cost for initial hospital stay of radical prostatectomy performed with two different robotic systems, the Da Vinci and the new Hugo RAS system. This is a projection study that applies cost of robotic surgery, derived from a local tender, to the clinical course of robotic radical prostatectomy (RALP) performed with Da Vinci and Hugo RAS. The study was performed in a public referral center for robotic surgery equipped with both systems. The cost of robotic surgery from a local tender were considered and included rent, annual maintenance, and a per-procedure fee covering the setup of four robotic instruments. Those costs were applied to patients who underwent RALP with both systems since November 2022. The primary endpoint is to evaluate direct costs of initial hospital stay for Da Vinci and Hugo RAS, by considering equipment costs (as derived from the tender), and costs of theater and of hospitalization. The direct per-procedure cost is €2,246.31 for a Da Vinci procedure and €1995 for a Hugo RALP. In the local setting, Hugo RAS provides 11% of cost saving for RALP. By applying this per-procedure cost to our clinical data, the expenditure for the entire index hospitalization is € 6.7755,1 for Da Vinci and € 6.637,15 for Hugo RALP. The new Hugo RAS system is willing to reduce direct expenditures of robotic surgery for RALP; furthermore, it provides similar peri-operative outcomes compared to the Da Vinci. However, other drivers of costs should be taken into account, such as the duration of OR use-that is more than just console time and may depend on the facility's background and organization. Further variations in direct costs of robotic systems are related to caseload, local agreements and negotiations. Thus, cost comparison of new robotic platform still remains an ongoing issue.

Optimizing wheelchair basketball lineups: A statistical approach to coaching strategies.

This study was designed to support the tactical decisions of wheelchair basketball (WB) coaches in identifying the best players to form winning lineups. Data related to a complete regular season of a top-level WB Championship were examined. By analyzing game-related statistics from the first round, two clusters were identified that accounted for approximately 35% of the total variance. Cluster 1 was composed of low-performing athletes, while Cluster 2 was composed of high-performing athletes. Based on data related to the second round of the Championship, we conducted a two-fold evaluation of the clusters identified in the first round with the team's net performance as the outcome variable. The results showed that teams where players belonging to Cluster 2 had played more time during the second round of the championship were also those with the better team performance (R-squared = 0.48, p = 0.035), while increasing the playing time for players from Classes III and IV does not necessarily improve team performance (r2 = -0.14, p = 0.59). These results of the present study suggest that a collaborative approach between coaches and data scientists would significantly advance this Paralympic sport.

Peritoneal Flap Following Lymph Node Dissection in Robotic Radical Prostatectomy: A Novel "Bunching" Technique.

BACKGROUND: Pelvic lymph node dissection (PLND) is recommended while performing robot-assisted radical prostatectomy (RARP) for patients with localized intermediate or high-risk prostate cancer. However, symptomatic lymphoceles can occur after surgery, adding significant morbidity to patients. Our objective is to describe a novel Peritoneal Bladder Flap Bunching technique (PBFB) to reduce the risk of clinically significant lymphoceles in patients undergoing RARP and PLND. METHODS: We evaluated 2267 patients who underwent RARP with PLND, dividing them into two groups: Group 1, comprising 567 patients who had the peritoneal flap (PBFB), and Group 2, comprising 1700 patients without the flap; propensity score matching carried out at a 1:3 ratio. Variables analyzed included estimated blood loss (EBL), operative time, postoperative complications, lymphocele formation, and the development of symptomatic lymphocele. RESULTS: The two groups exhibited similar preoperative characteristics after matching. There was no statistically significant difference in the occurrence of lymphoceles between the flap group and the non-flap group, with rates of 24% and 20.9%, respectively (p = 0.14). However, none of the patients in the flap group (0%) developed symptomatic lymphoceles, whereas 2.2% of patients in the non-flap group experienced symptomatic lymphoceles (p = 0.01). CONCLUSION: We have demonstrated a modified technique for a peritoneal flap (PBFB) with the initial elimination of postoperative symptomatic lymphoceles and promising short-term outcomes.

Association between individual sensor behavior of an electronic nose and airways inflammation in children with asthma: a pilot study at alpine altitude climate.

BACKGROUND: Markers of airway inflammation can be helpful in the management of childhood asthma. Residential activities, such as intensive asthma camps at alpine altitude climate (AAC), can help reduce bronchial inflammation in patients who fail to achieve optimal control of the disease. Analysis of volatile organic compounds (VOCs) can be obtained using electronic devices such as e-Noses. We aimed to identify alterations in urinary e-Nose sensors among children with asthma participating in an intensive camp at AAC and to investigate associations between urinary e-Nose analysis and airway inflammation. METHODS: We analyzed data collected in children with asthma recruited between July and September 2020. All children were born and resided at altitudes below 600 m asl. Urinary VOCs (measured using the Cyranose 320® VOC analyzer), Fractional exhaled Nitric Oxide (FeNO) and spirometry were evaluated upon children's arrival at the Istituto Pio XII, Misurina (BL), Italy, at 1756 m asl (T0), and after 7 (T1) and 15 days (T2) of stay. RESULTS: Twenty-two patients (68.2% males; median age: 14.5 years) were enrolled. From T0 to T1 and T2, the negative trend for FeNO was significant (p < .001). Significant associations were observed between e-Nose sensors S7 (p = .002), S12 (p = .013), S16 (p = .027), S17 (p = .017), S22 (p = .029), S29 (p = .021), S31 (p = .009) and ΔFeNO at T0-T1. ΔFeNO at T0-T2 was significantly associated with S17 (p = .015), S19 (p = .004), S21 (p = .020), S24 (p = .012), S25 (p = .018), S26 (p = .008), S27 (p = .002), S29 (p = .007), S30 (p = .013). CONCLUSIONS: We showed that a decrease in FeNO levels after a short sojourn at AAC is associated with behaviors of individual urinary e-Nose sensors in children with asthma.

Oncologic outcomes with and without amniotic membranes in robotic-assisted radical prostatectomy: A propensity score matched analysis.

Objective: Placement of human placenta derived grafts during robotic-assisted radical prostatectomy (RARP) hastens the return of continence and potency. The long-term impact on the oncologic outcomes remains to be investigated. Our objective was to determine the oncologic outcomes of patients with dehydrated human amnion chorion membrane (dHACM) at RARP compared to a matched cohort. Methods: In a referral centre, from August 2013 to October 2019, 599 patients used dHACM in bilateral nerve-sparing RARP. We excluded patients with less than 12 months follow-up, simple prostatectomy, and unilateral nerve-sparing. Patients with dHACM (amnio group) were 529, and were propensity score matched 1:1 to 2465 patients without dHACM (non-amnio group) and a minimum follow-up of 36 months. At the time of RARP, dHACM was placed around the neurovascular bundle in the amnio group. Continuous and categorical variables in matched groups was tested by two-sample Kolmogorov-Smirnov test and Fisher's exact test respectively. Outcomes measured were biochemical recurrence (BCR), adjuvant and salvage therapy rates. Results: Propensity score matching resulted in two groups of 444 patients. Cumulative incidence functions for BCR did not show a difference between the groups (p=0.3). Patients in the non-amnio group required salvage therapy more frequently than the amnio group, particularly after partial nerve-sparing RARP (6.3% vs. 2.3%, p=0.001). Limitations are the absence of prospective randomization. Conclusion: The data suggest that using dHACM does not have a negative impact on BCR in patients. Outcomes of cancer specific and overall survival will require follow-up study to increase our understanding of these grafts' impact on prostate cancer biology.

Impacts on functional and oncological outcomes of Robotic-assisted Radical Prostatectomy 10 years after the US Preventive Service Taskforce recommendations against PSA screening

ABSTRACT Objective: In the following years after the United States Preventive Service Task Force (USPSTF) recommendation against prostate cancer screening with PSA in 2012, several authors worldwide described an increase in higher grades and aggressive prostate tumors. In this scenario, we aim to evaluate the potential impacts of USPSTF recommendations on the functional and oncological outcomes in patients undergoing robotic-assisted radical prostatectomy (RARP) in a referral center. Material and Methods: We included 11396 patients who underwent RARP between 2008 and 2021. Each patient had at least a 12-month follow-up. The cohort was divided into two groups based on an inflection point in the outcomes at the end of 2012 and the beginning of 2013. The inflection point period was detected by Bayesian regression with multiple change points and regression with unknown breakpoints. We reported continuous variables as median and interquartile range (IQR) and categorical variables as absolute and relative percent frequencies. Results: Group 1 had 4760 patients, and Group 2 had 6636 patients, with a median follow-up of 109 and 38 months, respectively. In the final pathology, Group 2 had 9.5% increase in tumor volume, 24% increase on Gleason ≥ 4+3 (ISUP 3), and 18% increase on ≥ pT3. This translated to a 6% increase in positive surgical margins and 24% reduction in full nerve sparing in response to the worsening pathology. There was a significant decline in post-operative outcomes in Group 2, including a 12-month continence reduction of 9%, reduction in potency by 27%, and reduction of trifecta by 22%. Conclusions: The increasing number of high-risk patients has led to worse functional and oncologic outcomes. The initial rapid rise in PSM was leveled by the move towards more partial nerve sparing. Among some historical changes in prostate cancer diagnosis and management in the period of our study, the USPSTF recommendation coincided with worse outcomes of prostate cancer treatment in a population who could benefit from PSA screening at the appropriate time.

Impact of Prostate Size on the Functional and Oncological Outcomes of Robot-assisted Radical Prostatectomy.

BACKGROUND AND OBJECTIVE: Robot-assisted radical prostatectomy (RARP) is the main surgical approach for treatment of prostate cancer in the USA. Prostate size is always depicted as a factor affecting the outcomes of RARP as shown by many studies, but these studies are limited to a small number of patients. Our aim was to evaluate functional and oncologic outcomes of RARP across varying prostate size measured as prostate specimen weight. METHODS: A cohort of 14 481 patients who underwent RARP in a single center was divided into four groups according to prostate specimen weight: group 1, <50 g; group 2, 50-100 g; group 3, 100-150 g; and group 4, >150 g. Perioperative and postoperative variables and pathological and functional outcomes were compared among the four groups. Cumulative incidence functions were plotted to visualize the distribution of event-time variables among the groups, and differences were evaluated using the log-rank test. KEY FINDINGS AND LIMITATIONS: Patients with larger prostates (groups 3 and 4) were more likely to have higher prostate-specific antigen (PSA), lower biopsy grade group, and worse baseline urinary and sexual characteristics. Group 4 had lower rates of full nerve-sparing surgery (13.7% vs 38.3%) and lymph node dissection (51.3% vs 71.4%), more pT2 disease (69.8% vs 60.3%), less pT3 disease (30.2% vs 39.7%), and lower rates of positive surgical margins (12.8% vs 19.3%) and biochemical recurrence (5.9% vs 7.5%) than group 1. Finally, we observed differences in functional outcomes among the groups for greater prostate size, and patients in group 4 had worse rates of urinary continence (77.8% vs 89.5%) and recovery of sexual function (70.0% vs 84.1%) than group 1. Our study is limited by its retrospective design. CONCLUSIONS AND CLINICAL IMPLICATIONS: The results demonstrate that in this large cohort of patients, greater prostate size affects multiple outcomes, including the rate of nerve-sparing surgery, potency and continence recovery, and oncological and pathological outcomes. These data will be valuable when counseling patients regarding possible RARP outcomes and the timeline for recovery. PATIENT SUMMARY: Our study shows that prostate size can affect the outcomes of robot-assisted removal of the prostate for patients with prostate cancer. Larger prostate size can be associated with worse functional outcomes after surgery.

Impacts on functional and oncological outcomes of Robotic-assisted Radical Prostatectomy 10 years after the US Preventive Service Taskforce recommendations against PSA screening.

OBJECTIVE: In the following years after the United States Preventive Service Task Force (USPSTF) recommendation against prostate cancer screening with PSA in 2012, several authors worldwide described an increase in higher grades and aggressive prostate tumors. In this scenario, we aim to evaluate the potential impacts of USPSTF recommendations on the functional and oncological outcomes in patients undergoing robotic-assisted radical prostatectomy (RARP) in a referral center. MATERIAL AND METHODS: We included 11396 patients who underwent RARP between 2008 and 2021. Each patient had at least a 12-month follow-up. The cohort was divided into two groups based on an inflection point in the outcomes at the end of 2012 and the beginning of 2013. The inflection point period was detected by Bayesian regression with multiple change points and regression with unknown breakpoints. We reported continuous variables as median and interquartile range (IQR) and categorical variables as absolute and relative percent frequencies. RESULTS: Group 1 had 4760 patients, and Group 2 had 6636 patients, with a median follow-up of 109 and 38 months, respectively. In the final pathology, Group 2 had 9.5% increase in tumor volume, 24% increase on Gleason ≥ 4+3 (ISUP 3) , and 18% increase on ≥ pT3. This translated to a 6% increase in positive surgical margins and 24% reduction in full nerve sparing in response to the worsening pathology. There was a significant decline in post-operative outcomes in Group 2, including a 12-month continence reduction of 9%, reduction in potency by 27%, and reduction of trifecta by 22%. CONCLUSIONS: The increasing number of high-risk patients has led to worse functional and oncologic outcomes. The initial rapid rise in PSM was leveled by the move towards more partial nerve sparing. Among some historical changes in prostate cancer diagnosis and management in the period of our study, the USPSTF recommendation coincided with worse outcomes of prostate cancer treatment in a population who could benefit from PSA screening at the appropriate time.

FK506 bypasses the effect of erythroferrone in cancer cachexia skeletal muscle atrophy.

Skeletal muscle atrophy is a hallmark of cachexia, a wasting condition typical of chronic pathologies, that still represents an unmet medical need. Bone morphogenetic protein (BMP)-Smad1/5/8 signaling alterations are emerging drivers of muscle catabolism, hence, characterizing these perturbations is pivotal to develop therapeutic approaches. We identified two promoters of "BMP resistance" in cancer cachexia, specifically the BMP scavenger erythroferrone (ERFE) and the intracellular inhibitor FKBP12. ERFE is upregulated in cachectic cancer patients' muscle biopsies and in murine cachexia models, where its expression is driven by STAT3. Moreover, the knock down of Erfe or Fkbp12 reduces muscle wasting in cachectic mice. To bypass the BMP resistance mediated by ERFE and release the brake on the signaling, we targeted FKBP12 with low-dose FK506. FK506 restores BMP-Smad1/5/8 signaling, rescuing myotube atrophy by inducing protein synthesis. In cachectic tumor-bearing mice, FK506 prevents muscle and body weight loss and protects from neuromuscular junction alteration, suggesting therapeutic potential for targeting the ERFE-FKBP12 axis.

A molecular phenology scale of grape berry development.

Fruit growth and development consist of a continuous succession of physical, biochemical, and physiological changes driven by a genetic program that dynamically responds to environmental cues. Establishing recognizable stages over the whole fruit lifetime represents a fundamental requirement for research and fruit crop cultivation. This is especially relevant in perennial crops like grapevine (Vitis vinifera L.) to scale the development of its fruit across genotypes and growing conditions. In this work, molecular-based information from several grape berry transcriptomic datasets was exploited to build a molecular phenology scale (MPhS) and to map the ontogenic development of the fruit. The proposed statistical pipeline consisted of an unsupervised learning procedure yielding an innovative combination of semiparametric, smoothing, and dimensionality reduction tools. The transcriptomic distance between fruit samples was precisely quantified by means of the MPhS that also enabled to highlight the complex dynamics of the transcriptional program over berry development through the calculation of the rate of variation of MPhS stages by time. The MPhS allowed the alignment of time-series fruit samples proving to be a complementary method for mapping the progression of grape berry development with higher detail compared to classic time- or phenotype-based approaches.

Anabolic Resistance in the Pathogenesis of Sarcopenia in the Elderly: Role of Nutrition and Exercise in Young and Old People.

The development of sarcopenia in the elderly is associated with many potential factors and/or processes that impair the renovation and maintenance of skeletal muscle mass and strength as ageing progresses. Among them, a defect by skeletal muscle to respond to anabolic stimuli is to be considered. Common anabolic stimuli/signals in skeletal muscle are hormones (insulin, growth hormones, IGF-1, androgens, and ß-agonists such epinephrine), substrates (amino acids such as protein precursors on top, but also glucose and fat, as source of energy), metabolites (such as ß-agonists and HMB), various biochemical/intracellular mediators), physical exercise, neurogenic and immune-modulating factors, etc. Each of them may exhibit a reduced effect upon skeletal muscle in ageing. In this article, we overview the role of anabolic signals on muscle metabolism, as well as currently available evidence of resistance, at the skeletal muscle level, to anabolic factors, from both in vitro and in vivo studies. Some indications on how to augment the effects of anabolic signals on skeletal muscle are provided.

Evaluating field-goal shooting effectiveness in wheelchair basketball players across a competitive season: a preliminary study.

Background: Information about non-elite wheelchair basketball (WB) players across national competitive seasons are still missing. This study aimed at identifying which situational-related variables were associated with shooting effectiveness in non-elite WB players. Methods: All the matches played by one WB team across one national competitive season were video-recorded and analysed; 333 shooting attempts from high-point players and several situational-related variables were considered. Results: Pearson's Chi-square test showed that increased shooting effectiveness under the following conditions: playing on home ground, during won matches, while taking shots with the wheelchair in motion, and when no opposing player raised their arm in defence. Results of the multivariable logistic regression analysis showed a statistically significant influence of match location (p-value = 0.001), shot-clock remaining (p-value = 0.015) and modality of press (p-value < 0.001). The highest attack effectiveness was achieved when teams played at home (odds ratio [OR] = 2.49), while the shooting effectiveness decreased when the shot occurred during the last seconds of the action (OR = 0.36), or the opponents defended with the arm raised (OR = 0.19). These results suggest that coaches should include exercises aimed at shooting under conditions of increased pressure in their programmes in order to create specific situations during the training sessions to prepare their high-point athletes for shots under specific match constraints.