Acute effects of whole-body vibration on unilateral isometric knee extensors maximal torque and fatigability during an intermittent endurance task in adult males.

Whole-body vibration (WBV) has been employed for performance-enhancing purposes. WBV may positively affect muscular endurance and its underlying neural mechanisms due to an enhanced muscular blood circulation and oxygen uptake. However, the effects of WBV on endurance-related torque signal complexity have been understudied. This study aims to investigate the acute effects of WBV on i) maximal isometric torque production; ii) isometric knee extensors fatigability and iii) torque signal complexity during an isometric endurance task. Thirty adult males performed an isometric intermittent endurance protocol on their dominant lower limb after performing: static half squat with WBV (WBV), static half squat without WBV (HS), and no exercise protocol (CC). For each repetition the maximal torque was identified. The maximal torque of the first repetition was identified as the PeakT. The Mean torque (MTorque) and fatigue index (pFatigue) were calculated as the mean and the percentage decay in torque across the entire set of eighteen repetitions (MTorque0-100 %, pFatigue0-100 %), and across shorter blocks of six repetitions (MTorque0-33 %, pFatigue0-33 %; MTorque34-66 %, pFatigue34-66 %, and MTorque67-100 %, pFatigue67-100 %). Torque fluctuations were analysed computing Sample Entropy (SampEn) and the coefficient of variation (CV). PeakT was significantly higher in CC than in WBV (p < 0.01) and in HS (p < 0.01). PeakT was significantly higher in HS than in WB (p < 0.05). MTorque0-100 %, MTorque0-33 %, MTorque34-66 %, and MTorque67-100 % were significantly higher in CC than in WBV (all p-values <0.01) and in HS (p < 0.01). MTorque67-100 % was significantly higher in HS than in WB (p = 0.049). pFatigue34-66 % was significantly higher in WBV than in CC (p < 0.05) whereas pFatigue67-100 % was significantly higher in CC than in WB (p < 0.01) and in HS (p < 0.01). No effect of condition was observed for SampEn and CV. Acute WBV does not lead to beneficial effects on maximal torque production and isometric knee extensors fatigability. These acute detrimental effects may be related to long-term WBV-related adaptations.

The Accordion Zebrafish tq206 Mutant in the Assessment of a Novel Pharmaceutical Approach to Brody Myopathy.

Brody disease (BD) is an "ultra-rare" human genetic disorder of skeletal muscle function due to defects in the atp2a1 gene causing deficiency of the SERCA protein, isoform1. The main clinical signs are exercise-induced stiffness and delayed muscular relaxation after physical exercises, even mild ones. No mouse model nor specific therapies exist for Brody myopathy, which is therefore considered an orphan disease. Bovine congenital pseudomyotonia (PMT) is a muscular disorder characterized by an impairment of muscle relaxation and is the only mammalian model of human BD. The pathogenetic mechanism underlying bovine PMT has been recently clarified. These findings prompted us to purpose a potential pharmacological approach addressing a specific population of BD patients who exhibit reduced expression but still exhibit activity of the SERCA1 pump. Preclinical research involving in vivo studies is essential and necessary before clinical trials can be pursued and SERCA protein shows a high degree of conservation among species. So far, the only animal models available to study BD in vivo are a group of zebrafish mutant lines known as accordion zebrafish (acc). In this paper, we focused on a comprehensive characterization of the "acctq206" zebrafish variant. Our aim was to use this mutant line as an experimental animal model for testing the novel therapeutic approach for BD.

Sunitinib for the treatment of patients with advanced pheochromocytomas or paragangliomas: The phase 2 non-randomized SUTNET clinical trial.

BACKGROUND: Metastatic Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors characterized by high morbidity and limited systemic treatment options, mainly based on radiometabolic treatments or chemotherapy. Based on the preclinical rationale that PGGLs carcinogenesis relies on angiogenesis, treatment with tyrosine kinase inhibitors (TKI) may represent another viable therapeutic option. METHODS: We conducted a prospective phase II study in patients with metastatic or unresectable PGGLs. Patients received sunitinib (50 mg daily for 4 weeks, followed by a 2-week rest period) until progressive disease (PD), unacceptable toxicity or consent withdrawal. The primary endpoint was 12-month progression-free survival (PFS) rate; secondary endpoints were safety overall response rate (ORR) according to RECIST 1.1 criteria and overall survival (OS). EudraCT Number: 2011-002632-99. RESULTS: Fifty patients were included. At a median follow-up of 71.7 months (IQR 35.4-100.1), the 1 year-PFS rate was 53.4 % (95 %CI 41.1-69.3) and median PFS was 14.1 months (95 % CI 8.9-25.7). ORR was 15.6 %, the median OS was 49.4 months (95 %CI 21.2-NA), and grade 3 or higher treatment-related adverse events were reported in 34 % patients. No significant correlation was found between specific genetic alterations or genomic clusters and sunitinib efficacy. CONCLUSION: Sunitinib is an active drug in patients with advanced PGGLs, capable of inducing prolonged disease control with a manageable toxicity profile.

Effects of magnesium supplementation on muscle soreness in different type of physical activities: a systematic review.

BACKGROUND: Magnesium is a micronutrient and an intracellular cation responsible for different biochemical reactions involved in energy production and storage, control of neuronal and vasomotor activity, cardiac excitability, and muscle contraction. Magnesium deficiency may result in impaired physical performance. Moreover, magnesium plays an important role on delayed onset muscle soreness after training. Thus, physically active individuals and sport specialists have to pay attention to magnesium supplementation (MgS). However, the type, timing and dosage of magnesium intake are not well elucidated yet. Hence, we aimed to systematically review the literature regarding the effects of MgS on muscle soreness in physically active individuals. We focused exclusively on MgS, excluding those studies in which magnesium was administered together with other substances. METHODS: Three electronic databases and literature sources (PUBMED, SCOPUS and Web of Sciences-Core Collection) were searched, in accordance with PRISMA guidelines. After the database search, 1254 articles were identified, and after excluding duplicates, 960 articles remained. Among these, 955 were excluded following the title and abstract screening. The remaining 5 articles were screened in full text and 4 study met the eligibility criteria. RESULTS: These studies showed that MgS reduced muscle soreness, improved performance, recovery and induced a protective effect on muscle damage. CONCLUSION: To reach these positive effects, individuals engaged in intense exercise should have a Mg requirement 10-20% higher than sedentary people, to be taken in capsules and 2 h before training. Moreover, it is suggested to maintain magnesium levels in the recommended range during the off-season. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42024501822.

The Effect of Physical Activity/Exercise on miRNA Expression and Function in Non-Communicable Diseases-A Systematic Review.

Exercise may differently affect the expression of key molecular markers, including skeletal muscle and circulating miRNAs, involved in cellular and metabolic pathways' regulation in healthy individuals and in patients suffering from non-communicable diseases (NCDs). Epigenetic factors are emerging as potential therapeutic biomarkers in the prognosis and treatment of NCDs and important epigenetic factors, miRNAs, play a crucial role in cellular pathways. This systematic review aims to underline the potential link between changes in miRNA expression after different types of physical activity/exercise in some populations affected by NCDs. In June 2023, we systematically investigated the following databases: PubMed, MEDLINE, Scopus, and Web of Science, on the basis of our previously established research questions and following the PRISMA guidelines. The risk of bias and quality assessment were, respectively, covered by ROB2 and the Newcastle Ottawa scale. Of the 1047 records extracted from the initial search, only 29 studies were found to be eligible. In these studies, the authors discuss the association between exercise-modulated miRNAs and NCDs. The NCDs included in the review are cancer, cardiovascular diseases (CVDs), chronic obstructive pulmonary disease (COPD), and type 2 diabetes mellitus (T2DM). We evidenced that miR-146, miR-181, miR-133, miR-21, and miRNA-1 are the most reported miRNAs that are modulated by exercise. Their expression is associated with an improvement in health markers and they may be a potential target in terms of the development of future therapeutic tools.

Influence of living settings on physical activity levels and volition in exercise in male and female university students.

This study explored the influence of living settings on physical activity (PA) levels and volition in exercise and their correlation, considering sex differences. Five hundred and sixty-six university students (261 rural and 305 urban) from Calabria region (Italy) attending universities courses filled an online survey where Global Physical Activity Questionnaire and Volition in Exercise Questionnaire were administered. Rural females (RF) showed lower PA levels and self-confidence than rural males (RM) (p<0.01). Postponing training and unrelated thoughts were higher in RF than RM (p<0.01 and p<0.05 respectively). PA levels, self-confidence and coping with failure were lower in urban females (UF) than urban males (UM) (p<0.01), Postponing training and unrelated thoughts were higher in UF than UM (p<0.01 and p<0.05). In RF and UF, PA levels positively correlated with self-confidence (Rho = 0.397) and coping with failure (Rho = 0.330), whereas negatively correlated with postponing training (Rho = -0.487) and unrelated thoughts (Rho = -0.283). In RM and UM, PA levels positively correlated with self-confidence (Rho = 0.270) and coping with failure (Rho = 0.258), whereas it negatively correlated with postponing training (Rho = -0.285). PA levels positively correlated with reasons (Rho = 0.260) only in UM. We showed for the first time the relationship between PA and volition factors considering the living setting in university students. Sex differences were observed in some volition facilitators and PA levels independently by the living context.

Effects of school-based physical activity on volition in exercise, sleep quality and internet addiction in Italian adolescents.

School-settings represent ideal context to promote healthy habits as in adolescence most risk factors may occur or intensify leading to the adoption of unhealthy lifestyles. Thus, a deeper understanding of the factors promoting healthy lifestyles in adolescents is of utmost importance. This observational study aims to investigate: 1) gender-related differences in physical activity (Physical Activity Questionnaire for Adolescets - PAQ-A), sleep quality (Pittsburgh Sleep Quality Index - PSQI) and internet addiction (Internet Addiction Test - IAT) levels and Volition in Exercise (VE); 2) the relationship between PAQ-A and VE, PSQI and IAT; 3) the effects of a five-month (T0; T5) school-based physical activity (PA) intervention on the above-mentioned factors. PAQ-A,VE, PSQI and IAT were assessed before (T0) and after (T5) a school-based PA intervention. The PA intervention consisted of coordinative exercises and team sports performed for 1 h twice a week. At T0, girls showed lower PAQ-A, PSQI scores, lower volition facilitators ("self-confidence" and "coping with failure") and higher volition inhibitor ("postponing training") than boys. Significant correlations were observed for volition factors an IAT in males and volition and PSQI and IAT in females. After the PA intervention (T5), "postponing training" and "self-confidence" factors were reduced compared to T0. Exercise specialists should consider gender differences in volition in exercise factors during a school-based PA to plan and realize PA protocols aiming at maximizing exercise adherence to tackle sedentary behaviors in adolescents.

Yoga as an alternative to cycling in type 1 diabetes: A preliminary study of acute effects on glucose levels.

We evaluated the acute effects of yoga compared to cycling on glucose change and variability, and the occurrence of hypoglycemia in adults with type 1 diabetes. Fifteen participants performed 50 min of cycling or yoga. Glucose values were collected before and after exercise. Coefficient of variation (CV) and hypoglycemic episodes were evaluated from the start up to 12 h after exercise. Cycling and yoga significantly reduced glucose values during exercise, and CV was lower after yoga. One hypoglycemic episode occurred with yoga and seven with cycling. Yoga is a safe exercise that acutely reduces glucose values, but with lower risk of hypoglycemia compared to cycling.

Atlastin-1 regulates endosomal tubulation and lysosomal proteolysis in human cortical neurons.

Mutation of the ATL1 gene is one of the most common causes of hereditary spastic paraplegia (HSP), a group of genetic neurodegenerative conditions characterised by distal axonal degeneration of the corticospinal tract axons. Atlastin-1, the protein encoded by ATL1, is one of three mammalian atlastins, which are homologous dynamin-like GTPases that control endoplasmic reticulum (ER) morphology by fusing tubules to form the three-way junctions that characterise ER networks. However, it is not clear whether atlastin-1 is required for correct ER morphology in human neurons and if so what the functional consequences of lack of atlastin-1 are. Using CRISPR-inhibition we generated human cortical neurons lacking atlastin-1. We demonstrate that ER morphology was altered in these neurons, with a reduced number of three-way junctions. Neurons lacking atlastin-1 had longer endosomal tubules, suggestive of defective tubule fission. This was accompanied by reduced lysosomal proteolytic capacity. As well as demonstrating that atlastin-1 is required for correct ER morphology in human neurons, our results indicate that lack of a classical ER-shaping protein such as atlastin-1 may cause altered endosomal tubulation and lysosomal proteolytic dysfunction. Furthermore, they strengthen the idea that defective lysosome function contributes to the pathogenesis of a broad group of HSPs, including those where the primary localisation of the protein involved is not at the endolysosomal system.

Epidemiology and Clinical impact of single and multi-viral respiratory infections in post-pandemic era.

Acute respiratory tract infections (ARI) are common diseases in children and adults and could cause severe infections in high-risk patients, like the immunocompromised and elderly, and are the leading cause of morbidity, hospitalization and mortality. This study aimed to explore the prevalence of respiratory viruses and the clinical impact of single- and multi-infection among hospitalized patients in various age groups. 3578 nasopharyngeal swabs (NPS) were analyzed for pathogen detection of acute respiratory tract infections. 930 out of 3578 NPS were diagnosed positive for at least one respiratory virus. The distribution of viral infections, prevalence and pathogen, differed significantly among age groups. Most RTI are observed in the age group over 65 years (50.6%) with a high SARS-CoV2 prevalence, following by group <5 years (25.6%), where the most frequently detected viruses were RSV, Rhinovirus, FluA-H3, MPV, and AdV. The co-infection rate also varies according to age and, in some cases, especially in older adults, could have severe clinical impact. This study emphasizes that it is important to know and analyze, in all age groups of hospitalized patients, the epidemiology of respiratory viruses, the prevalence of coinfections, and the clinical impact of various pathogens. Furthermore, in a clinical setting, the rapid diagnosis of respiratory infections by means of molecular tests is crucial not only to avoid hospital outbreaks, but also to allow early and optimal treatment to reduce morbidity and mortality.

Higher-order G-quadruplex structures and porphyrin ligands: Towards a non-ambiguous relationship.

Herein, we evaluated the interaction of the tetracationic porphyrin H2TCPPSpm4 with three distinct DNA G-quadruplex (G4) models, i.e., the tetramolecular G4 d(TGGGGT)4 (Q1), the 5'-5' stacked G4-dimer [d(CGGAGGT)4]2 (Q2), and a mixture of 5'-5' stacked G-wires [d(5'-CGGT-3'-3'-GGC-5')4]n (Qn). The combined data obtained from UV-Vis, CD, fluorescence, PAGE, RLS, AFM, NMR, and HPLC-SEC experiments allowed us to shed light on the binding mode of H2TCPPSpm4 with the three G4 models differing for the type and the number of available G4 ending faces, the length of the G4 units, and the number of stacked G4 building blocks. Specifically, we found that H2TCPPSpm4 interacted with the shortest Q1 as an end-stacking ligand, whereas the groove binding mode was ascertained in the case of the Q2 and Qn G4 models. In the case of the interaction with Q1 and Qn, we found that H2TCPPSpm4 induces the formation of supramolecular aggregates at porphyrin/G4 ratios higher than 2:1, whereas no significant aggregation was observed for the interaction with Q2 up to the 5:1 ratio. These results unambiguously demonstrated the suitability of porphyrins for the development of specific G4 ligands or G4-targeting diagnostic probes, being H2TCPPSpm4 capable to distinguish between different G4s.

Selective activation of prodrugs in breast cancer using metabolic glycoengineering and the tetrazine ligation bioorthogonal reaction.

Increasing the selectivity of chemotherapies by converting them into prodrugs that can be activated at the tumour site decreases their side effects and allows discrimination between cancerous and non-cancerous cells. Herein, the use of metabolic glycoengineering (MGE) to selectively label MCF-7 breast cancer cells with tetrazine (Tz) activators for subsequent activation of prodrugs containing the trans-cyclooctene (TCO) moiety by a bioorthogonal reaction is demonstrated. Three novel Tz-modified monosaccharides, Ac4ManNTz 7, Ac4GalNTz 8, and Ac4SiaTz 16, were used for expression of the Tz activator within sialic-acid rich breast cancer cells' surface glycans through MGE. Tz expression on breast cancer cells (MCF-7) was evaluated versus the non-cancerous L929 fibroblasts showing a concentration-dependant effect and excellent selectivity with ≥35-fold Tz expression on the MCF-7 cells versus the non-cancerous L929 fibroblasts. Next, a novel TCO-N-mustard prodrug and a TCO-doxorubicin prodrug were analyzed in vitro on the Tz-bioengineered cells to probe our hypothesis that these could be activated via a bioorthogonal reaction. Selective prodrug activation and restoration of cytotoxicity were demonstrated for the MCF-7 breast cancer cells versus the non-cancerous L929 cells. Restoration of the parent drug's cytotoxicity was shown to be dependent on the level of Tz expression where the Ac4ManNTz 7 and Ac4GalNTz 8 derivatives (20 µM) lead to the highest Tz expression and full restoration of the parent drug's cytotoxicity. This work suggests the feasibility of combining MGE and tetrazine ligation for selective prodrug activation in breast cancer.

The Effects of Online Home-Based Pilates Combined with Diet on Body Composition in Women Affected by Obesity: A Preliminary Study.

Diet and exercise intervention are the first strategies to counteract obesity. An online home-based exercise program may be a feasible approach in an obese population. Therefore, this study aimed to investigate the effects of twelve weeks of online Pilates plus diet on body composition in individuals affected by obesity. Thirty-five females were randomly assigned to a home-based Pilates group (PG, n = 18) or a group without intervention (control group, CG, n = 17). All participants followed a Mediterranean diet. The PG followed a twelve-week online Pilates Matwork program (three times/week; 180 min/week), while the CG was not involved in any structured physical exercise program. Body composition and handgrip strength were evaluated at baseline (T0) and after the intervention (T1). A significant group × time interaction (p < 0.05) was found for the fat mass percentage (pFM). Specifically, the pFM was significantly lower at T1 than at T0 in the PG. Significant group × time interactions for fat-free mass (p < 0.05), appendicular skeletal muscle mass (p < 0.05), and skeletal muscle mass (p < 0.01) were found. All these variables were significantly higher at T1 than at T0 in the PG (p < 0.05). Home-based Pilates combined with diet intervention may represent an effective strategy to improve body composition in terms of fat mass reduction and muscle mass gain in adults affected by obesity.

Human Campylobacter spp. infections in Italy.

PURPOSE: Campylobacter is a frequent cause of enteric infections with common antimicrobial resistance issues. The most recent reports of campylobacteriosis in Italy include data from 2013 to 2016. We aimed to provide national epidemiological and microbiological data on human Campylobacter infections in Italy during the period 2017-2021. METHODS: Data was collected from 19 Hospitals in 13 Italian Regions. Bacterial identification was performed by mass spectrometry. Antibiograms were determined with Etest or Kirby-Bauer (EUCAST criteria). RESULTS: In total, 5419 isolations of Campylobacter spp. were performed. The most common species were C. jejuni (n = 4535, 83.7%), followed by C. coli (n = 732, 13.5%) and C. fetus (n = 34, 0.6%). The mean age of patients was 34.61 years and 57.1% were males. Outpatients accounted for 54% of the cases detected. Campylobacter were isolated from faeces in 97.3% of cases and in 2.7% from blood. C. fetus was mostly isolated from blood (88.2% of cases). We tested for antimicrobial susceptibility 4627 isolates (85.4%). Resistance to ciprofloxacin and tetracyclines was 75.5% and 54.8%, respectively; resistance to erythromycin was 4.8%; clarithromycin 2% and azithromycin 2%. 50% of C. jejuni and C. coli were resistant to ≥ 2 antibiotics. Over the study period, resistance to ciprofloxacin and tetracyclines significantly decreased (p < 0.005), while resistance to macrolides remained stable. CONCLUSION: Campylobacter resistance to fluoroquinolones and tetracyclines in Italy is decreasing but is still high, while macrolides retain good activity.

COL1A1::PDGFB fusion-associated uterine fibrosarcoma: A case report and review of the literature.

BACKGROUND: Mesenchymal neoplasms of the uterus encompass a diverse group of tumors, with varying characteristics and origins, collectively accounting for 8% of uterine malignancies. The most common variants include uterine leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, adenosarcoma, and undifferentiated sarcoma. Clinical presentation is often nonspecific and can lead to delayed diagnosis. Uterine sarcomas are generally aggressive, resulting in poorer prognosis compared to carcinomas. Recent advances in molecular techniques, such as next-generation sequencing (NGS), have led to the identification of new subtypes of uterine sarcomas, including COL1A1::PDGFB fusion-associated fibrosarcoma, which has a specific chromosomal translocation t(17;22)(q22;q13). Imatinib, a tyrosine kinase inhibitor (TKI), is an effective treatment for dermatofibrosarcoma protuberans (DFSP), marked by this translocation. CASE: We present the case of a 42-year-old woman diagnosed with COL1A1::PDGFB fusion-associated uterine fibrosarcoma. The patient underwent total hysterectomy and excision of the tumor, initially misdiagnosed as a low-grade leiomyosarcoma. Subsequent histological examination, immunohistochemistry, and fluorescence in situ hybridization (FISH) confirmed the diagnosis. After 10 months, disease recurrence was detected, and Imatinib therapy was initiated at a dose of 400 mg daily. An allergic reaction led to a temporary discontinuation, but upon resumption with appropriate medication, a positive radiological response was observed. The patient achieved a complete remission after 2 years and is still on Imatinib treatment. CONCLUSIONS: COL1A1::PDGFB fusion-associated uterine fibrosarcoma is an extremely rare mesenchymal neoplasm. In a case we present herein, we treated a patient with imatinib as first-line medical therapy. The patient is currently in complete remission after 37 months from treatment start. To the best of our knowledge, this represents a unique observation. We also provide a detailed literature review of the published cases so far. Prospective case series are needed to further understand the natural history of these tumors and optimize treatment strategies.

The effects of pre-task music on choice visual reaction time in elite taekwondo athletes.

OBJECTIVES: The effects of music on sport performance mainly involved endurance or resistance exercises overlooking possible effects on reaction time, which is deemed essential in martial arts for a proficient performance. Therefore, the aim of this study was to investigate the effects of the exposure to pre-task music on choice visual reaction time in elite taekwondo athletes. DESIGN: Repeated measure study design. METHODS: Reaction time and mean Heart Rate (HRmean) were recorded in twenty young taekwondo athletes (17.5 ±â€¯2.5 years old) while performing a roundhouse kick in response to different visual stimuli after three warmup conditions: listening to self-selected music (SM), research-selected music (RM) or no music (CC). Moreover, Feeling Scale (FS), Felt Arousal Scale (FAS) were recorded before (T0) and after warmup (T1) in each testing session. RESULTS: SM and RM elicited significantly faster reaction times compared to CC (-3.3 % and -5.2 %, respectively). No significant difference in reaction time was observed between SM and RM. The FS and FAS scores were significantly higher at T1 compared to T0 in the SM and RM conditions, whereas no difference between T0 and T1 was observed in the CC condition. No difference was observed for HRmean between SM, RM and CC conditions. CONCLUSIONS: Listening to SM and RM during the warmup improved choice visual reaction times in elite taekwondo athletes. These results suggest the use of music as a performance-enhancing strategy prior to combat competition or training in martial arts.

Shoulder brace has no detrimental effect on basic spatio-temporal gait parameters and functional mobility after arthroscopic rotator cuff repair.

BACKGROUND: The risk of falls in patients undergoing orthopedic procedures is significant in terms of health and socioeconomic effects. RESEARCH QUESTION: Is there an influence of the shoulder abduction brace (SAB) on gait parameters in patients undergoing arthroscopic rotator cuff repair (ARCR)? METHODS: Thirty-five patients undergoing ARCR, who used a 15° SAB in the postoperative period, were included in a prospective study. Participants underwent gait analysis preoperatively (T0), 24 h after surgery (T1), 1 week (T2), and 4 weeks after surgery (1 week after SAB removal) (T3) by using a wearable inertial sensor (BTS G-Walk sensor). Gait Parameters (cadence, speed, right (R) and left (L) step length, gait and propulsion-R and L symmetry indices) and functional mobility (agility and balance) were assessed using the 10-meter test (10MWT) and the Timed Up and Go (TUG) test, respectively. RESULTS: There were 22 men and 13 women with a median age of 56 (IQR 48.0-61.0) years. The right upper limb was involved in 83% of cases. Regarding the 10MWT, speed was significantly higher at T0 than at T1 (p < 0.01) and significantly lower at T1 than at T3 (p < 0.05). Cadence was significantly lower at T1 than at T3 (p < 0.05). Propulsion-R was significantly higher at T3 than at T1 (p < 0.01), whereas propulsion-L was significantly lower at T1 than at T0 (p < 0.05) and significantly higher at T2 and T3 than T1 (p < 0.01 for all). No significant differences were found for R and L step lengths as well as for symmetry index (p > 0.05). Regarding TUG test, the final turning phase was significantly higher at T2 than at T3 (p < 0.01). SIGNIFICANCE: The results demonstrated that the use of the SAB affected gait speed and propulsion only 24 h after ARCR, but no effects were reported at long-term observations.

Study of metabolism and potential toxicity of nine synthetic opioid analogs using the zebrafish larvae model.

The use of novel psychoactive substances (NPSs) has dramatically increased worldwide, and among them, synthetic opioids are one of the fastest growing groups, where cinnamylpiperazines and 2-benzylbenzimidazoles represent two of the most relevant subclasses. However, the data on their toxicity and metabolism are still limited. The aim of the present study was to evaluate the toxicity and metabolic pathways of some compounds belonging to these families, namely, AP-237, 2-methyl AP-237, isotonitazene, flunitazene, etodesnitazene, metonitazene, metodesnitazene, N-pyrrolidino etonitazene, and butonitazene. The study was performed using a zebrafish early life stages model. In fact, zebrafish (Danio rerio) embryos and larvae have recently been recognized as a suitable animal model in alternative to mammals, because they require less time and resources and do not need complex procedures for ethics approval. The cellular toxicity after a single administration was assessed at the fourth day post-fertilization with acridine orange staining. Possible morphological defects were evaluated with a light microscope after 24 h of exposure to 1 µmol/L concentration of each drug. Subsequently, the larvae were euthanized and underwent analysis of drug metabolites using UPLC coupled to an Orbitrap high-resolution mass spectrometer. High rates of morphological defects, as well as of cellular death, were detected, but no significant difference in mortality between treatment and control groups was observed. In addition, several metabolites, mainly produced through monohydroxylation, N-dealkylation, and O-dealkylation, were identified in the larvae extracts.