Growth hormone secretagogues exert differential effects on skeletal muscle calcium homeostasis in male rats depending on the peptidyl/non-peptidyl structure

TheorexigenicandanaboliceffectsinducedbyghrelinandthesyntheticGHsecretagogues(GHSs) are thought to positively contribute to therapeutic approaches and the adjunct treatment of a number of diseases associated with muscle wasting such as cachexia and sarcopenia. However, manyquestionsaboutthepotentialutilityandsafetyofGHSsinboththerapyandskeletalmuscle functionremainunanswered.Byusingfura-2cytofluorimetrictechnique,wedeterminedtheacute effectsofghrelin,aswellasofpeptidylandnonpeptidylsyntheticGHSsoncalciumhomeostasis, a critical biomarker of muscle function, in isolated tendon-to-tendon male rat skeletal muscle fibers.ThesyntheticnonpeptidylGHSs,butnotpeptidylghrelinandhexarelin,wereabletosignificantlyincreaserestingcytosoliccalcium[Ca2]i.ThenonpeptidylGHS-induced[Ca2] iincrease was independent of GHS-receptor 1a but was antagonized by both thapsigargin/caffeine and cyclosporineA,indicatingtheinvolvementofthesarcoplasmicreticulumandmitochondria.EvaluationoftheeffectsofapseudopeptidylGHSandanonpeptidylantagonistoftheGHS-receptor 1a together with a drug-modeling study suggest the conclusion that the lipophilic nonpeptidyl structureofthetestedcompoundsisthekeychemicalfeaturecrucialfortheGHS-inducedcalcium alterationsintheskeletalmuscle.Thus,syntheticGHSscanhavedifferenteffectsonskeletalmuscle fibersdependingontheirmolecularstructures.Thecalciumhomeostasisdysregulationspecifically induced by the nonpeptidyl GHSs used in this study could potentially counteract the beneficial effects associated with these drugs in the treatment of muscle wasting of cachexia- or other age-related disorders

Role of Colourcoded Doppler Ultrasonography in the Evaluation of Patients With Peyronie's Disease

From March 1995 to February 1996, sixteen consecutive patients with Peyronie's Disease (PD) were routinely submitted to penile dynamic colour-coded doppler ultrasonography (CCDU). The test yielded normal results in 6 patients who had no erectile problems and in other 4 patients who conversely complained of reduced erectile function. In the other 6 patients who complained of reduced erectile function, the test pointed out pure arteriogenic failure in 1 case, pure venogenic failure in 4, and mixed arteriogenic and venogenic failure in 1. CCDU enables a precise assessment of erectile function as well of the site, kind and entity of the penile curvature to be corrected. These data are very useful when planning the surgical approach for each patient

Assessment of Stress Levels using technological tools: A Review and Prospective Analysis of Heart Rate Variability and Sleep Quality Parameters

Abstract "Stress overload” (SO) represents an imbalance where psychosocial, work, environmental, or health-related burdens exceed an individual's adaptive capacity, engendering negative physical and mental health outcomes. This study reviews tech tools, focusing on Heart Rate Variability (HRV) and metrics for sleep quality analysis (SA) i.e. the number of nocturnal awakenings (NNA). Modern technologies for measuring HRV and NNA could enhance the traditional stress detection methods, respectively from the neuropsychologist by the “Stress Overload Scale” (SOS) and polysomnography (PSG) by the neurophysiology technician. Notably, they also allow continuous monitoring, and may curtail healthcare costs. Employing Machine Learning (ML) on smartwatches using photoplethysmography (PPG) HRV accuracy achieves 98.10-98.18%. Wearable devices also exhibit strong sensitivity and specificity for measuring NNA. In children distinct nocturnal movement patterns should be considered. While HRV correlates directly with stress levels, poor SA indicates only a 4.7 fold increased risk of SO. HRV's integration into allostatic load assessments is advocated. However clinical validation is necessary, while potential privacy concerns may arise, as electrocardiography (ECG) signals can potentially uniquely identify patients. Synthesizing HRV solely from photoplethysmography (PPG) data obtained from wearable devices offers an economical and practical approach, although it may be less accurate than HRV from ECG guided by Respiratory Rate (RR). The latter requires additional hardware, i.e. ECG sensor and either Respiratory Inductive Plethysmography or Respiratory Impedance Plethysmography. However, modern smartwatches possess sufficient computational power to perform ML inference, making them capable of improving PPG-based HRV estimation. By leveraging comprehensive datasets capturing signals like plethysmography, ECG, HRV, and RR, alongside sleep metrics, it will be possible to develop refined algorithms to increase the accuracy of stress risk prediction and its level. Continuous monitoring may support nursing diagnosis of SO, enhancing early intervention and its evaluation. © 2023 CEUR-WS. All rights reserved

A 1-year maintenance after early adjuvant intravesical chemotherapy has a limited efficacy in preventing recurrence of intermediate risk non-muscle-invasive bladder cancer

OBJECTIVE To evaluate the efficacy of 1-year maintenance after a 6-week cycle of early intravesical chemotherapy, as the role of maintenance in intravesical chemotherapy is debated. PATIENTS AND METHODS Between May 2002 and August 2003, 577 patients with non-muscle-invasive bladder cancer (NMI-BC) underwent transurethral resection (TUR) and early intravesical chemotherapy (epirubicin, 80 mg/50 mL). They were randomized between a 6-week induction cycle and the induction cycle plus maintenance with 10 monthly instillations. In all, 95 patients with T1G3, Tis or single and primary Ta-T1 G1-G2 tumours were excluded; 482 patients at intermediate risk of recurrence continued the study. All patients had cytology and cystoscopy at 3-monthly intervals for the first 2-years and 6-monthly thereafter. RESULTS The tumours' characteristics were equally distributed between the two arms. Treatment interruption for toxicity was required in 39 patients. One death due to toxicity of early instillation occurred. The median follow-up was 48 months. Ten patients (2.5%) progressed and 117 patients (29.6%) recurred. No statistically significant difference in the recurrence-free rate (RFS) was detected between the two arms (P = 0.43). An advantage in favour of the maintenance arm was evident only at 18 months after TUR (P = 0.03). A trend for a higher benefit from maintenance in primary and multiple tumours was detected. CONCLUSIONS In patients with intermediate risk NMI-BC treated by TUR and early adjuvant chemotherapy, adding a maintenance regimen with monthly instillations for 1 year is of limited efficacy in preventing recurrence

Chemically pure beta-tricalcium phosphate powders: Evidence of two crystal structures

The question whether beta-tricalcium phosphate (beta-TCP) can form a solid solution with beta-calcium pyrophosphate (beta-CPP) and/or hydroxyapatite (HA) has still not been solved. For this reason, wet-chemically synthesized beta-TCP powders with only 20 ppm Sr (among 43 tested elements) and with different HA and beta-CPP contents, or in other words Ca/P molar ratios, were used. The graphical relationship between these various Ca/P molar ratios determined by X-ray diffraction and by inductively-coupled plasma mass spectrometry showed no discontinuity, indicating the absence of a solid solution between beta-TCP and beta-CPP or HA. Analysis of the beta-TCP lattice parameters as a function of the Ca/P molar ratio revealed a discontinuity at a Ca/P molar ratio of 1.500 and a maximum microstrain. These results indicated that at least two beta-TCP structures co-existed, with variable mixing ratios depending on the Ca/P molar ratio, and with a distinct jump at a Ca/P molar ratio of 1.500