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1.
PLoS One ; 19(5): e0302596, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38748742

RESUMO

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.


Assuntos
Desempenho Atlético , Basquetebol , Tutoria , Cadeiras de Rodas , Humanos , Tutoria/métodos , Masculino , Adulto
2.
Cancers (Basel) ; 16(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38672629

RESUMO

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.

3.
Pediatr Pulmonol ; 59(5): 1339-1345, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38376005

RESUMO

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.


Assuntos
Altitude , Asma , Nariz Eletrônico , Compostos Orgânicos Voláteis , Humanos , Asma/fisiopatologia , Masculino , Feminino , Projetos Piloto , Adolescente , Criança , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/urina , Espirometria , Itália , Biomarcadores/urina , Biomarcadores/análise , Inflamação/fisiopatologia , Óxido Nítrico/análise , Teste da Fração de Óxido Nítrico Exalado
4.
Asian J Urol ; 11(1): 19-25, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38312822

RESUMO

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.

5.
Eur Urol Focus ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38290859

RESUMO

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.

6.
Int Braz J Urol ; 50(1): 65-79, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38166224

RESUMO

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.


Assuntos
Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Teorema de Bayes , Detecção Precoce de Câncer , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Resultado do Tratamento
7.
Cell Rep Med ; 4(12): 101306, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38052214

RESUMO

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.


Assuntos
Caquexia , Neoplasias , Humanos , Camundongos , Animais , Caquexia/tratamento farmacológico , Caquexia/etiologia , Caquexia/metabolismo , Tacrolimo/metabolismo , Tacrolimo/farmacologia , Músculo Esquelético/metabolismo , Proteína 1A de Ligação a Tacrolimo/genética , Proteína 1A de Ligação a Tacrolimo/metabolismo , Proteína 1A de Ligação a Tacrolimo/farmacologia , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Neoplasias/patologia
8.
Hortic Res ; 10(5): uhad048, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37786435

RESUMO

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.

9.
Nutrients ; 15(18)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37764858

RESUMO

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.


Assuntos
Sarcopenia , Humanos , Idoso , Músculo Esquelético , Estado Nutricional , Exercício Físico , Insulina
10.
PeerJ ; 11: e15785, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719122

RESUMO

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.


Assuntos
Basquetebol , Cadeiras de Rodas , Humanos , Objetivos , Estações do Ano , Atletas
11.
iScience ; 26(8): 107475, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37588163

RESUMO

Septic patients frequently develop skeletal muscle wasting and weakness, resulting in severe clinical consequences and adverse outcomes. Sepsis triggers sustained induction of autophagy, a key cellular degradative pathway, in skeletal muscles. However, the impact of enhanced autophagy on sepsis-induced muscle dysfunction remains unclear. Using an inducible and muscle-specific Atg7 knockout mouse model (Atg7iSkM-KO), we investigated the functional importance of skeletal muscle autophagy in sepsis using the cecal ligation and puncture model. Atg7iSkM-KO mice exhibited a more severe phenotype in response to sepsis, marked by severe muscle wasting, hypoglycemia, higher ketone levels, and a decreased in survival as compared to mice with intact Atg7. Sepsis and Atg7 deletion resulted in the accumulation of mitochondrial dysfunction, although sepsis did not further worsen mitochondrial dysfunction in Atg7iSkM-KO mice. Overall, our study demonstrates that autophagy inactivation in skeletal muscles triggers significant worsening of sepsis-induced muscle and metabolic dysfunctions and negatively impacts survival.

12.
JCI Insight ; 8(15)2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37551712

RESUMO

Age-associated sarcopenia, characterized by a progressive loss in muscle mass and strength, is the largest cause of frailty and disability in the elderly worldwide. Current treatments involve nonpharmacological guidelines that few subjects can abide by, highlighting the need for effective drugs. Preclinical models were employed to test the benefits of RJx-01, a combination drug composed of metformin and galantamine, on sarcopenia. In worms, RJx-01 treatment improved lifespan, locomotion, pharyngeal pumping, and muscle fiber organization. The synergistic effects of RJx-01 were recapitulated in a transgenic mouse model that displays an exacerbated aging phenotype (Opa1-/-). In these mice, RJx-01 ameliorated physical performance, muscle mass and force, neuromuscular junction stability, and systemic inflammation. RJx-01 also improved physical performance and muscle strength in 22-month-old WT mice and also improved skeletal muscle ultrastructure, mitochondrial morphology, autophagy, lysosomal function, and satellite cell content. Denervation and myofiber damage were decreased in RJx-01-treated animals compared with controls. RJx-01 improved muscle quality rather than quantity, indicating that the improvement in quality underlies the beneficial effects of the combination drug. The studies herein indicate synergistic beneficial effects of RJx-01 in the treatment of sarcopenia and support the pursuit of RJx-01 in a human clinical trial as a therapeutic intervention for sarcopenia.


Assuntos
Metformina , Sarcopenia , Humanos , Camundongos , Animais , Idoso , Lactente , Sarcopenia/tratamento farmacológico , Galantamina/farmacologia , Metformina/farmacologia , Envelhecimento/fisiologia , Músculo Esquelético/patologia , Camundongos Transgênicos
14.
Autophagy ; : 1-3, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37309183

RESUMO

Skeletal muscles play key roles in movement, posture, thermogenesis, and whole-body metabolism. Autophagy plays essential roles in the regulation of muscle mass, function and integrity. However, the molecular machinery that regulates autophagy is still incompletely understood. In our recent study, we identified and characterized a novel Forkhead Box O (FoxO)-dependent gene, PHAF1/MYTHO (phagophore assembly factor 1/macro-autophagy and youth optimizer), as a novel autophagy regulator that controls muscle integrity. MYTHO/PHAF1 is upregulated in multiple conditions leading to muscle atrophy, and downregulation of its expression spares muscle atrophy triggered by fasting, denervation, cachexia and sepsis. Overexpression of PHAF1/MYTHO is sufficient to induce muscle atrophy. Prolonged downregulation of PHAF1/MYTHO causes a severe myopathic phenotype, which is characterized by impaired autophagy, muscle weakness, myofiber degeneration, mammalian target of rapamycin complex 1 (mTORC1) hyperactivation and extensive ultrastructural defects, such as accumulation of proteinaceous and membranous structures and tubular aggregates. This myopathic phenotype is attenuated upon administration of the mTORC1 inhibitor rapamycin. These findings position PHAF1/MYTHO as a novel regulator of skeletal muscle autophagy and tissue integrity.

15.
Hortic Res ; 10(5): uhad056, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37213682

RESUMO

Grapevine embodies a fascinating species as regards phenotypic plasticity and genotype-per-environment interactions. The terroir, namely the set of agri-environmental factors to which a variety is subjected, can influence the phenotype at the physiological, molecular, and biochemical level, representing an important phenomenon connected to the typicality of productions. We investigated the determinants of plasticity by conducting a field-experiment where all terroir variables, except soil, were kept as constant as possible. We isolated the effect of soils collected from different areas, on phenology, physiology, and transcriptional responses of skin and flesh of a red and a white variety of great economic value: Corvina and Glera. Molecular results, together with physio-phenological parameters, suggest a specific effect of soil on grapevine plastic response, highlighting a higher transcriptional plasticity of Glera in respect to Corvina and a marked response of skin compared to flesh. Using a novel statistical approach, we identified clusters of plastic genes subjected to the specific influence of soil. These findings could represent an issue of applicative value, posing the basis for targeted agricultural practices to enhance the desired characteristics for any soil/cultivar combination, to improve vineyards management for a better resource usage and to valorize vineyards uniqueness maximizing the terroir-effect.

16.
Int J Sports Med ; 44(8): 576-583, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37207661

RESUMO

This study explored the performance of the Sitting Volleyball serve by investigating the causal factors associated with ball velocity. Thirty-seven athletes underwent anthropometry and strength assessment and performed ten successful maximal effort serves. Ball velocity was measured using a sports radar gun. The hip, shoulder, elbow and wrist angles at the instant of ball impact as well as the height of ball impact were estimated through two-dimensional motion analysis. The causal relationships between variables were described through a linear Structural Equation Model and a Directed Acyclic Graph. Results showed that a smaller hip angle determines a greater shoulder angle, which in turn causes a greater elbow angle. A more open elbow angle together with a greater vertical reach allowed for a greater height of ball impact. Finally, increased height of ball impact along with greater abdominal strength are beneficial for higher ball velocity. These results underlined that the Sitting Volleyball serve is a multifactorial stroke involving anthropometric, technical and strength factors and suggest that athletes should improve their abdominal strength and master the technique necessary to perform the serve with the shoulder and the elbow joints fully extended in order to produce the greatest possible impact on the ball.


Assuntos
Voleibol , Humanos , Postura Sentada , Ombro , Cotovelo , Punho , Fenômenos Biomecânicos
17.
Nat Commun ; 14(1): 1849, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37012289

RESUMO

Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD+ repletion therapy in cachectic mice reveals that NAD+ precursor, vitamin B3 niacin, efficiently corrects tissue NAD+ levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose NAD+ metabolism as a therapy target for cachectic cancer patients.


Assuntos
Neoplasias , Niacina , Humanos , Camundongos , Animais , Niacina/farmacologia , Niacina/uso terapêutico , Niacina/metabolismo , NAD/metabolismo , Caquexia/tratamento farmacológico , Caquexia/etiologia , Caquexia/metabolismo , Niacinamida/metabolismo , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Músculo Esquelético/metabolismo
18.
World J Urol ; 41(5): 1337-1344, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37085644

RESUMO

PURPOSE: To evaluate the relationship between warm ischemia time (WIT) duration and renal function after robot-assisted partial nephrectomy (RAPN). METHODS: The CLOCK trial is a phase 3 randomized controlled trial comparing on- vs off-clamp RAPN. All patients underwent pre- and postoperative renal scintigraphy. Six-month absolute variation of eGFR (AV-GFR), rate of relative variation in eGFR over 25% (RV-GFR > 25), absolute variation of split renal function (SRF) at scintigraphy (AV-SRF). The relationships WIT/outcomes were assessed by correlation graphs and then modeled by uni- and multivariable regression. RESULTS: 324 patients were included (206 on-clamp, 118 off-clamp RAPN). Correlation graphs showed a threshold on WIT equal to 10 min. The differences in outcome measures between cases with WIT < vs ≥ 10 min were: AV-GFR - 3.7 vs - 7.5 ml/min (p < 0.001); AV-SRF - 1% vs - 3.6% (p < 0.001); RV-GFR > 25 9.3% vs 17.8% (p = 0.008). Multivariable models found that AV-GFR was related to WIT ≥ 10 min (regression coefficient [RC] - 0.52, p = 0.019), age (RC - 0.35, p = 0.001) and baseline eGFR (RC - 0.30, p < 0.001); RV-GFR > 25 to WIT ≥ 10 min (odds ratio [OR] 1.11, p = 0.007) and acute kidney injury defined as > 50% increase in serum creatinine (OR 19.7, p = 0.009); AV-SRF to WIT ≥ 10 min (RC - 0.30, p = 0.018), baseline SRF (RC - 0.76, p < 0.001) and RENAL score (RC - 0.60. p = 0.028). The main limitation was that the CLOCK trial was designed on a different endpoint and therefore the present analysis could be underpowered. CONCLUSIONS: Up to 10 min WIT had no consequences on functional outcomes. Above the 10-min threshold, a statistically significant, but clinically negligible impact was found.


Assuntos
Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Isquemia Quente , Neoplasias Renais/cirurgia , Taxa de Filtração Glomerular , Resultado do Tratamento , Nefrectomia , Cintilografia , Radioisótopos , Estudos Retrospectivos
19.
Nat Commun ; 14(1): 1199, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36864049

RESUMO

Autophagy is a critical process in the regulation of muscle mass, function and integrity. The molecular mechanisms regulating autophagy are complex and still partly understood. Here, we identify and characterize a novel FoxO-dependent gene, d230025d16rik which we named Mytho (Macroautophagy and YouTH Optimizer), as a regulator of autophagy and skeletal muscle integrity in vivo. Mytho is significantly up-regulated in various mouse models of skeletal muscle atrophy. Short term depletion of MYTHO in mice attenuates muscle atrophy caused by fasting, denervation, cancer cachexia and sepsis. While MYTHO overexpression is sufficient to trigger muscle atrophy, MYTHO knockdown results in a progressive increase in muscle mass associated with a sustained activation of the mTORC1 signaling pathway. Prolonged MYTHO knockdown is associated with severe myopathic features, including impaired autophagy, muscle weakness, myofiber degeneration, and extensive ultrastructural defects, such as accumulation of autophagic vacuoles and tubular aggregates. Inhibition of the mTORC1 signaling pathway in mice using rapamycin treatment attenuates the myopathic phenotype triggered by MYTHO knockdown. Skeletal muscles from human patients diagnosed with myotonic dystrophy type 1 (DM1) display reduced Mytho expression, activation of the mTORC1 signaling pathway and impaired autophagy, raising the possibility that low Mytho expression might contribute to the progression of the disease. We conclude that MYTHO is a key regulator of muscle autophagy and integrity.


Assuntos
Músculo Esquelético , Distrofia Miotônica , Adolescente , Humanos , Animais , Camundongos , Autofagia/genética , Atrofia Muscular/genética , Macroautofagia , Alvo Mecanístico do Complexo 1 de Rapamicina/genética
20.
Biology (Basel) ; 12(3)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36979073

RESUMO

Olfactory areas in mammalian brains are linked to centers that modulate behavior. During aging, sensitivity to odors decreases and structural changes are described in olfactory areas. We explored, in two groups of male mice (young and elderly, 6 and 19 months old, respectively), the link between the changes in olfactory bulb structure, detected with magnetic resonance imaging, and behavioral changes in a battery of tests on motor, olfactory, cognitive performance, and emotional reactivity. The behavioral pattern of elderly mice appears less anxious, being less scared by new situations. Additionally, the olfactory bulb of young and elderly mice differed in two variables derived from magnetic resonance imaging (fractional anisotropy and T2 maps). A random forest approach allowed to select the variables most predictive of the differences between young and elderly mice, and correlations were found between three behavioral variables indicative of anxious behavior and the two magnetic resonance variables mentioned above. These data suggest that in the living mouse, it is possible to describe co-occurring age-related behavioral and structural changes in the olfactory bulb. These data serve as a basis for studies on normal and pathological aging in the mouse, but also open new opportunities for in vivo human aging studies.

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