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There is increasing evidence of the use of wastewater-based epidemiology to integrate conventional monitoring assessing disease symptoms and signs of viruses in a specific territory. We present the results of SARS-CoV-2 environmental surveillance activity in wastewater samples collected between September 2020 and July 2021 in 9 wastewater treatment plants (WTPs) located in central and western Sicily, serving over 570,000 residents. The presence of SARS-CoV-2, determined in 206 wastewater samples using RT-qPCR assays, was correlated with the notified and geo-referenced cases on the areas served by the WTPs in the same study period. Overall, 51% of wastewater samples were positive. Samples were correlated with 33,807 SARS-CoV-2 cases, reported in 4 epidemic waves, with a cumulative prevalence of 5.9% among Sicilian residents. The results suggest that the daily prevalence of SARS-CoV-2 active cases was statistically significant and higher in areas with SARS-CoV-2 positive wastewater samples. According to these findings, the proposed method achieves a good sensitivity profile (78.3%) in areas with moderate or high viral circulation (≥133 cases/100,000 residents) and may represent a useful tool in the management of epidemics based on an environmental approach, although it is necessary to improve the accuracy of the process.

Purpose Hepatic encephalopathy (HE) is a potential complication of cirrhosis. Magnetic resonance imaging (MRI) may demonstrate hyperintense T1 signal in the globi pallidi. The purpose of this study was to evaluate the performance of MRI-based radiomic features for diagnosing and grading chronic HE in adult patients affected by cirrhosis. Methods Adult patients with and without cirrhosis underwent brain MRI with identical imaging protocol on a 3T scanner. Patients without history of chronic liver disease were the control population. HE grading was based on underlying liver disease, severity of clinical manifestation, and number of encephalopathic episodes. Texture analysis was performed on axial T1-weighted images on bilateral lentiform nuclei at the level of the foramina of Monro. Diagnostic performance of texture analysis for the diagnosis and grading of HE was assessed by calculating the area under the receiver operating characteristics (AUROC) with 95% confidence interval (CI). Results The final study population consisted of 124 patients, 70 cirrhotic patients, and 54 non-cirrhotic controls. Thirty-eight patients had history of HE with 22 having an HE grade > 1. The radiomic features predicted the presence of HE with an AUROC of 0.82 (95% CI: 0.73, 0.90; P P P Conclusion In cirrhotic patients, MR radiomic is effective in predicting the presence of chronic HE and in grading its severity.

BACKGROUND In soccer, a better understanding of the bioimpedance parameters with physical performance may be useful to efficiently monitor and interpret players' performance variation throughout a certain period of the season. Therefore, this study aimed to examine the association between phase angle (PhA) and arms and legs lean soft tissue (ALST and LLST) with physical performance in young elite soccer players. METHODS Fifteen young male elite soccer players (age = 14.2±1.2 years, BMI = 20.51±1.38 kg/m2) participated in this investigation. Raw bioimpedance parameters (reactance, resistance, and phase angle) were obtained by a bioelectrical impedance analysis (BIA) device. Then, ALST and LLST were estimated. All players underwent a physical testing battery including countermovement jump (CMJ), 10-m and 20-m sprint, and Yo-Yo Intermittent Recovery Test level 1 (YoYo IRTL1) in the domains of anaerobic and aerobic performance, respectively. RESULTS The results showed that LST (total, arms and legs) positively correlated with CMJ (0.64 < r < 0.69; p < 0.001) and negatively correlated with 10-m (-0.59 < r < -0.63; p < 0.05) and 20-m sprint (-0.67 < r < -0.73; p < 0.001), while PhA positively correlated with CMJ (r = 0.57; p < 0.05) and negatively correlated (r = -0.54; p < 0.05) only with 20-m sprint. No significant association was found between the BIA-related parameters (PhA and LST) and Yo- Yo IRT level 1. CONCLUSIONS The present findings highlight the existing association of PhA and LST with jumping and sprinting performance in young elite soccer players. This result supports the use of BIA-related measures as a simple and practical approach to monitoring anaerobic performance changes, rather than aerobic, over time throughout the season.

Purpose: To investigate the relationship between the training load (TL = rate of perceived exertion × training time) and wellness index (WI) in soccer. Methods: The WI and TL data were recorded from 28 subelite players (age = 20.9 [2.4] y; height = 181.0 [5.8] cm; body mass = 72.0 [4.4] kg) throughout the 2017/2018 season. Predictive models were constructed using a supervised machine learning method that predicts the WI according to the planned TL. The validity of our predictive model was assessed by comparing the classification’s accuracy with the one computed from a baseline that randomly assigns a class to an example by respecting the distribution of classes (B1). Results: A higher TL was reported after the games and during match day (MD)-5 and MD-4, while a higher WI was recorded on the following days (MD-6, MD-4, and MD-3, respectively). A significant correlation was reported between daily TL (TLMDi) and WI measured the day after (WIMDi+1) (r = .72, P

Aims To evaluate prospectively whether an intravenous gadolinium injection could improve the detection of the central vein sign on susceptibility-weighted imaging sequences obtained with a 1.5 T magnetic resonance scanner in patients with multiple sclerosis compared to unenhanced susceptibility-weighted images. Materials and methods This prospective, institution review board-approved study included 19 patients affected by multiple sclerosis (six men; 13 women; mean age 40.8 years, range 20–74 years). Patients had the relapsing–remitting clinical subtype in 95% of cases, and only one (5%) patient had the primary progressive clinical subtype of multiple sclerosis. T2-weighted images, fluid-attenuated inversion recovery images, unenhanced and contrast-enhanced susceptibility-weighted images were evaluated in consensus by two neuroradiologists for the presence of the central vein sign. The readers were blinded to magnetic resonance imaging reports, clinical information, the presence and the localisation of focal hyperintense white matter lesions. Any discordance between readers was resolved through a joint review of the recorded images with an additional neuroradiologist. Results A total of 317 multiple sclerosis lesions were analysed. The central vein sign had a higher prevalence detection rate on gadolinium-enhanced susceptibility-weighted images (272 of 317 lesions, 86%) compared to unenhanced susceptibility-weighted images (172 of 317 lesions, 54%). Conclusion Gadolinium-enhanced susceptibility-weighted imaging improves the detection rate of the central vein sign in multiple sclerosis lesions.

Background Optimal pulmonary vein (PV) occlusion, usually verified with selective contrast injection, is mandatory to obtain an effective PV isolation during cryoballoon (CB) ablation. Aim of the study The purpose of this study was to verify the feasibility and the accuracy of a new dielectric sensing system in assessing PV occlusion during CB ablation in patients with atrial fibrillation (AF). Methods We enrolled 28 consecutive patients with paroxysmal or persistent AF. After transseptal access, a detailed image reconstruction of left atrium and PVs was achieved with an octapolar or decapolar mapping catheter (Achieve catheter, Medtronic Inc.) and KODEX-EPD system (EPD Solutions, a Philips company). The degree of PV occlusion with the inflated Arctic Front Advance Cryoballoon (Medtronic Inc.) was verified using the new "occlusion tool" software module (EPD Solutions, a Philips company) and compared to an angiogram obtained with contrast medium injection in each PV. Results A total of 105 PV CB occlusion were tested. The new occlusion tool software module showed a 91% sensitivity and 76% specificity in assessing a complete PV occlusion verified with contrast medium injection. The positive predictive value was 80%, and the negative predictive value was 88.6%. Mean procedure time was 81 ± 17 minutes. Mean fluoroscopy time was 6 ± 2 minutes. No 30-day complications were observed. Conclusion The new dielectric imaging system was able to assess the degree of PV occlusion during a CB ablation with good sensitivity and specificity.

Physical exercise affects the human gut microbiota, which in turn influences athletes’ performance. The current understanding of how the microbiota of professional athletes changes along with different phases of training is sparse. We aim to characterize the fecal microbiota in elite soccer players along with different phases of a competitive season using 16 S rRNA gene sequencing. Fecal samples were collected after the summer off-season period, the pre-season retreat, the first half of the competitive season, and the 8 weeks of COVID-19 lockdown that interrupted the season 2019–2020. According to our results, the gut microbiota of professional athletes changes along with the phases of the season, characterized by different training, diet, nutritional surveillance, and environment sharing. Pre-season retreat, during which nutritional surveillance and exercise intensity were at their peak, caused a decrease in bacterial groups related to unhealthy lifestyle and an increase in health-promoting symbionts. The competitive season and forced interruption affected other features of the athletes’ microbiota, i.e., bacterial groups that respond to dietary fiber load and stress levels. Our longitudinal study, focusing on one of the most followed sports worldwide, provides baseline data for future comparisons and microbiome-targeting interventions aimed at developing personalized training and nutrition plans for performance maximization.

Purpose Electrophysiological studies and ablation procedures expose both physicians and patients to a significant amount of radiation. Most 3-D mapping systems provide improved tracking of catheters and enable radiation exposure to be reduced or even eliminated. However, there are no data on the ability of the Rhythmia ™ mapping system (Boston Scientific) to minimize fluoroscopy time and dose. Methods Here, we report on the feasibility and safety of a novel non-fluoroscopic approach (NFA) that uses the Rhythmia ™ mapping system and a novel navigation-enabled ablation catheter in SVT and atrial flutter procedures, and describe in detail our modified procedural work-flow. A total of 20 consecutive patients who were referred to our center for RF ablation of SVT arrhythmias were included in this analysis to test our procedural work flow. Results In our preliminary experience of the NFA work-flow, fluoroscopy times and radiological exposure were significantly reduced in comparison with the conventional approach. Conclusion In our preliminary experience, arrhythmia ablation through a near-zero fluoroscopy approach involving the use of a novel ablation technology and the Rhythmia™ mapping system proved to be safe, feasible and effective in common atrial arrhythmias.

Precision medicine advances are opening new opportunities in the treatment of Her2 driven cancers. Her2 signaling activation was found in around 20% of breast cancers about 3 decades ago and define an aggressive subtype of the disease. Nowadays antiHer2 targeted approach is standard of care in both metastatic and early-stage Her2 -positive breast cancer and has changed the general course of the disease. However, the challenge of personalizing cancer treatments through de-escalation and escalation strategies is still open, especially in the early setting of the disease. New evidences are emerging on the role of Her2 dysregulation in the carcinogenesis of solid tumors other than breast cancer. Recently reported clinical trials of antiHer2 targeted therapies have shown promising results in a variety of tumors, especially gastrointestinal and lung cancers. In this review we report challenges and opportunities of tailored antiHer2 treatments in breast cancers and beyond based on the results of recent clinical trials.

The study examines statistical learning in the spelling of Italian children with dyslexia and typically developing readers by studying their sensitivity to probabilistic cues in phoneme-grapheme mappings. In the first experiment children spelled to dictation regular words and words with unpredictable spelling that contained either a high- or a low-frequency (i.e., typical or atypical) sound-spelling mappings. Children with dyslexia were found to rely on probabilistic cues in writing stimuli with unpredictable spelling to a greater extent than typically developing children. The difficulties of children with dyslexia on words with unpredictable spelling were limited to those containing atypical mappings. In the second experiment children spelled new stimuli, that is, pseudowords, containing phonological segments with unpredictable mappings. The interaction between lexical knowledge and reliance on probabilistic cues was examined through a lexical priming paradigm in which pseudowords were primed by words containing related typical or atypical sound-to-spelling mappings. In spelling pseudowords, children with dyslexia showed sensitivity to probabilistic cues in the phoneme-to-grapheme mapping but lexical priming effects were also found, although to a smaller extent than in typically developing readers. The results suggest that children with dyslexia have a limited orthographic lexicon but are able to extract regularities from the orthographic system and rely on probabilistic cues in spelling words and pseudowords.

Aims: \ud \ud To assess the correlation between cognitive functioning and 3 gait parameters (gait speed, cadence, and stride length) in persons with mild cognitive impairment (MCI) and cognitively healthy controls and investigate linear correlations between gait and gray matter volumes.\ud \ud Materials and Methods: \ud \ud Participants were recruited at IRCCS San Camillo Hospital, Venice, Italy (MCI=43; age-matched controls=43). Participants underwent comprehensive neuropsychological assessment. Gait speed, cadence, and stride length, were assessed with the BTS FREEMG 300 device. Three-dimensional (3D) T1-weighted MR images were acquired using a 1.5 T Philips Achieva MRI system with a Turbo Field Echo sequence.\ud \ud Results: \ud \ud In MCI there was a positive correlation between gait speed and memory tests (P

Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Mitotane, the standard treatment for ACC, impairs adrenocortical steroid biosynthesis and cholesterol metabolism. In the H295R cell line, a standard ACC in vitro model, mitotane was previously reported to enhance the production of some oxysterols. To verify the possible mechanistic involvement of oxysterols in the anti-ACC effect of mitotane, a gas chromatography mass spectrometry (GC-MS) profiling of oxysterols and the main cholesterol precursors was carried out in H295R cells. Among the oxysterols detected in mitotane-treated cells, 27OHC was markedly produced, as well as lanosterol and lathosterol cholesterol precursors. In this cell model, mitotane was confirmed to affect mitochondrial transmembrane potential and induce apoptosis. Such cytotoxic effects were perfectly matched by H295R cell treatment with a single identical micromolar amount of 27OHC. The mitotane-dependent strong increase in 27OHC was confirmed in vivo, in the plasma of ACC patients under treatment with the drug. Moreover, lanosterol, lathosterol, desmosterol and, to a minor extent, 24-hydroxycholesterol and 25-hydroxycholesterol plasma levels were significantly increased in those patients. The cytotoxic effect of mitotane on ACC cells may be partly related to the increased intracellular level of 27OHC induced by the drug itself.

The purpose of the present study was to investigate whether exercise training-induced adaptations in human skeletal muscle mitochondrial bioenergetics are magnified under thermal conditions resembling sustained intense contractile activity and whether training-induced changes in mitochondrial oxidative phosphorylation (OXPHOS) efficiency influence exercise efficiency. Twenty healthy men performed 6 wk of high-intensity exercise training [

The recent lockdown, resulting from the SARS-CoV-2 pandemic, has had a strong social and psychological impact on the most fragile individuals and family structures. In the present work we investigated the experience of families without specific elements of social or health vulnerability during the quarantine period that occurred in the spring of 2020.Between May and July 2020, 22 primary care pediatricians belonging to AUSL Romagna administered to a number of families a questionnaire to detect changes that occurred, during the lockdown, in family environment, school attendance and personal attitudes.A total of 721 questionnaires were collected, analyzing the associations between variables relating to home environment, daily rhythms, school and warning signs in relation to the age of children. As a result of the lockdown, family habits changed in 31% of cases, with a greater presence of the reference figure in 68% of these. Three out of four families reported they had sufficient domestic spaces, and nine out of ten had access to an outdoor, private or condominium space. Daily rhythms were preserved in 56.7% of cases; mood disorders appeared in 30% of adolescent children, followed by sleep, appetite and psychosomatic disorders. One in three children has made progress in terms of evolution and behavior, and one in 5 children has seen their relationships improve. The overall resilience of families during the lockdown period was considered good in 66.3%, sufficient in 31.3% and not satisfactory in only 2.4% of cases.Our data show that, in the interviewed families, the simultaneous presence of adults and children at home has generally intensified. Families refer, on the whole, a positive and resilient behavior in the lockdown period, even if initial emotional problems are reported in one out of three children-adolescents. The ability to maintain a family organized structure seems to be partially compromised. Forced cohabitation leads to competition for the same resources of time and space and affects the entire family unit. The school institution emerges as a protective factor for children, young people and also for the well-being of families themselves.

Background No data exist on the ability of the novel Rhythmia 3-D mapping system to minimize fluoroscopy exposure during transcatheter ablation of arrhythmias. We report data on the feasibility and safety of a minimal fluoroscopic approach using this system in supraventricular tachycardia (SVT) procedures. Methods Consecutive patients were enrolled in the CHARISMA registry at 12 centers. All right-sided procedures performed with the Rhythmia mapping system were analyzed. The acquired electroanatomic information was used to reconstruct 3-D cardiac geometry; fluoroscopic confirmation was used whenever deemed necessary. Results Three hundred twenty-five patients (mean age = 56 ± 17 years, 57% male) were included: 152 atrioventricular nodal reentrant tachycardia, 116 atrial flutter, 41 and 16 right-sided accessory pathway and atrial tachycardia, respectively. Overall, 27 481 s of fluoroscopy were used (84.6 ± 224 s per procedure, equivalent effective dose = 1.1 ± 3.7 mSv per patient). One hundred ninety-two procedures (59.1%) were completed without the use of fluoroscopy (zero fluoroscopy, ZF). In multivariate analysis, the presence of a fellow in training (OR = 0.15, 95% CI: 0.05-0.46; p = .0008), radiofrequency application (0.99, 0.99-1.00; p = .0002), and mapping times (0.99, 0.99-1.00; p = .042) were all inversely associated with ZF approach. Acute procedural success was achieved in 97.8% of the cases (98.4 vs. 97% in the ZF vs. non-ZF group; p = .4503). During a mean of 290.7 ± 169.6 days follow-up, no major adverse events were reported, and recurrence of the primary arrhythmia was 2.5% (2.1 vs. 3% in the ZF vs. non-ZF group; p = .7206). Conclusions The Rhythmia mapping system permits transcatheter ablation of right-sided SVT with minimal fluoroscopy exposure. Even more, in most cases, the system enables a ZF approach, without affecting safety and efficacy.

Background Bipolar electrogram (EGM) duration is indicative of local activation property and, if prolonged, is useful to discover areas of slow conduction favoring arrhythmias. Objective The present study aimed to create a map of EGM duration during the ventricular tachycardia (VT) (Ventricular Electrograms DUration as a Method map [VEDUM map]) to verify if the slowest activation area is crucial for reentry and could represent a suitable target for rapid VT interruption during ablation. Methods Prospectively 30 patients were enrolled for this study. Twenty-one patients were selected, and 24 VT maps with complete circuit delineation (>90% tachycardia cycle length) were analyzed. Activation and VEDUM maps during VT as well as voltage maps during sinus rhythm were created. Results Twenty-two of 24 VTs (88%) were interrupted during the first radiofrequency delivery (mean time 7.3 ± 5.4 seconds; range 3–25 seconds) at the area with the longest EGM duration (212 ± 47 ms; range 113–330 ms). The mean percentage of the cycle length of VT covered by the EGM with the longest duration was 58% ± 12%. In 9 patients (37%), the longest EGM was located at the isthmus entrance, at the exit in 7 maps (30%), and the mid-isthmuses in 8 maps (33%). In 6 patients (25%), the EGM covered the full diastolic phase. The mean isthmus width was 28 ± 11 mm (range 16–48 mm; median 25 mm). Conclusion A VEDUM map is highly accurate in defining a conductive vulnerable zone of the VT circuit. The longest EGM duration within the isthmus is highly predictive of rapid VT termination at the first radiofrequency delivery even in the case of large isthmuses.

BACKGROUND This study aimed to analyse the relationship of regional and whole body morphology to vertical jump performance and to compare the morphological features outlining high and low performers in professional soccer players. METHODS Twenty-one male soccer players were recruited. Whole and regional (upper and lower limbs) features were obtained in the form of body dimensional measurements. Then, all players were tested for vertical jump performance. A data-driven approach was used to group players according to their jump performance parameters (high vs low). RESULTS The regional morphological features presented higher correlations with vertical jump than whole body features. High and low performers were significantly different among upperand lower-limb morphology. No differences were observed among whole body features. CONCLUSIONS These findings indicate that, rather than the whole body, the use of morphological features linked to specific body regions may ensure a better interpretation of the soccer players' physical potential in jump performance.

Talent identification in sports is a heavily debated topic. Previous studies have separately explored either executive functions or gross motor skills to predict the success of top-level soccer players or, more generally, to characterize elite performance in soccer. However, at mid-childhood, the possibility to scope sport-specific requirements remains elusive. We aimed in this study to investigate a valid and simple method of testing for a unique combination of cognitive and speed abilities for identifying promising soccer players at mid-childhood. We measured cognitive functions by means of a Stroop smartphone application and agility with a T-Drill Ball-success test, in two groups of (a) elite- ( n = 31) and (b) low-division ( n = 37) Italian 7-year-old male soccer players. We administered the tests in a randomized order to both groups. We found better inhibitory control, cognitive flexibility and soccer-specific agility in high-division versus low-division players ( p

The BRCA1/2 germline and/or somatic pathogenic variants (PVs) are key players in the hereditary predisposition and therapeutic response for breast, ovarian and, more recently, pancreatic and prostate cancers. Aberrations in other genes involved in homologous recombination and DNA damage response (DDR) pathways are being investigated as promising targets in ongoing clinical trials. However, DDR genes are not routinely tested worldwide. Due to heterogeneity in cohort selection and dissimilar sequencing approaches across studies, neither the burden of PVs in DDR genes nor the prevalence of PVs in genes in common among pancreatic and prostate cancer can be easily quantified. We aim to contextualize these genes, altered in both pancreatic and prostate cancers, in the DDR process, to summarize their hereditary and somatic burden in different studies and harness their deficiency for cancer treatments in the context of currently ongoing clinical trials. We conclude that the inclusion of DDR genes, other than BRCA1/2, shared by both cancers considerably increases the detection rate of potentially actionable variants, which are triplicated in pancreatic and almost doubled in prostate cancer. Thus, DDR alterations are suitable targets for drug development and to improve the outcome in both pancreatic and prostate cancer patients. Importantly, this will increase the detection of germline pathogenic variants, thereby patient referral to genetic counseling.

Purpose The purpose of this article is to assess the diagnostic performance of computed tomography (CT) reformatted images for detection of superior semicircular canal (SSC) dehiscence. Material and methods Forty-two patients, with sound- and/or pressure-induced vestibular symptoms, and 42 control participants underwent helical CT examination with a highly collimated beam (0.5 mm). Reformatted images of the vestibular labyrinth were obtained in the standard axial and coronal planes (group A images), and in a plane parallel and perpendicular to the SSC (group B images). Diagnostic performance obtained by evaluating the group A images alone and the group B images alone was analyzed by using the area under the receiver operating characteristic curve (AUC). Results The diagnostic performance of group A images was AUC = 0.929 with an overall accuracy of 92.9%. The diagnostic performance of group B images was AUC = 0.988 with an overall accuracy of 98.8%. The evaluation of group B images alone showed an improved diagnostic performance over the group A images alone. Conclusion Thin-section 0.5-mm collimation CT with reformatted images oriented in the plane parallel and perpendicular to the SSC improves diagnostic accuracy in assessing for SSC dehiscence in comparison to CT images with reconstructions limited to traditional axial and coronal planes.

Background Literature shows that occurrence of comorbidities in people with severe acquired brain injury (sABI) is a common problem in rehabilitation stay. Consequently, patients could require an increase of interventions for diagnosis and treatment of clinical conditions, with a reduction of the rehabilitative take in charge for both clinical and organizational aspects. Aim The first aim was to evaluate the rate of clinical conditions of sABI patients at admission in rehabilitation and the types of rehabilitative interventions performed in the first week; second objective was to explore the impact of clinical conditions on real rehabilitative take in charge. Design Cross sectional study. Setting Inpatient rehabilitation centers. Population The study included data from 586 sABI patients. Methods Collected data regarded anamnestic information, functional status assessed by means of Glasgow Outcome Scale, Levels of cognitive functioning, Early Rehabilitation Barthel Index, comorbidities at admission and type of rehabilitative interventions carried out in first week of rehabilitation stay. Spearman correlation coefficients were applied to detect possible correlations between the number of treatments in first week and clinical variables; through a multiple regression analysis the effect of patient's characteristics on rehabilitative take in charge was explored. Results Data from the sABI patients: mean age 55.1±17.1 years; etiology of sABI was vascular in 315 patients (53.8%), anoxic in 83 (14.2%), neoplastic in 17 (2.9%), infectious in 15 (2.6%), traumatic in 150 (25.6%); 6 subjects (1%) presented a mixed etiology. Need of cardiorespiratory monitoring, pressure sores, infections or presence of multi drug resistant bacteria were the most frequent comorbidities. Passive mobilization, sitting positioning, arousal/awareness stimulation, evaluation and management of dysphagia were the interventions most frequently carried out in the first week. The regression analysis showed that severe neurological and clinical conditions, acute organ failure, cardio-respiratory instability and paroxysmal sympathetic hyperactivity significantly limit access to rehabilitative sessions. Conclusions In sABI patients clinical comorbidities requiring elevated care assistance are frequent at admission in rehabilitation from acute wards and may interfere with rehabilitative take in charge. Clinical rehabilitation impact The knowledge of clinical complexity of sABI patients may improve their care pathways, promoting early and appropriate transition from acute care to rehabilitation settings.

So far, the investigation in cancer cell lines of the modulation of cancer growth and progression by oxysterols, in particular 27-hydroxycholesterol (27HC), has yielded controversial results. The primary aim of this study was the quantitative evaluation of possible changes in 27HC levels during the different steps of colorectal cancer (CRC) progression in humans. A consistent increase in this oxysterol in CRC mass compared to the tumor-adjacent tissue was indeed observed, but only in advanced stages of progression (TNM stage III), a phase in which cancer has spread to nearby sites. To investigate possible pro-tumor properties of 27HC, its effects were studied in vitro in differentiated CaCo-2 cells. Relatively high concentrations of this oxysterol markedly increased the release of pro-inflammatory interleukins 6 and 8, monocyte chemoattractant protein-1, vascular endothelial growth factor, as well as matrix metalloproteinases 2 and 9. The up-regulation of all these molecules, which are potentially able to favor cancer progression, appeared to be dependent upon a net stimulation of Akt signaling exerted by supra-physiological amounts of 27HC.

Background Chronic supplementation with carnosine and β-alanine (Carn-βA) has been proposed to improve muscle contractility and reduce muscle fatigue mainly through an increase in intracellular pH buffering capacity. However, the acute ergogenic effects of Carn-βA supplementation are poorly investigated. This study aimed at evaluating the acute effects of a single Carn-βA supplementation on the cardiorespiratory and metabolic response during a ramp cycle-ergometric test. Methods This randomized, double-blind, placebo-controlled study, involved 10 healthy males (age 22.2±1.9 years, body mass 72.5±7.9 kg, stature 1.72±0.08 m, body mass index, 24.47±1.91 kg/m2, mean±standard deviation). All the participants performed two maximal incremental ramp tests on a cycle ergometer, with a prior randomized assumption of 2.5 g L-carnosine plus 2.5 g β-alanine (Carn-βA) or placebo (PLA). During exercise, gas exchange parameters were measured breath-by-breath, heart rate was monitored by electrocardiography and rate perceived exertion was determined on Borg scales. From the ramp test, peak cardiorespiratory and metabolic parameters and ventilatory thresholds (VT1 and VT2) were calculated off-line. Results No differences between the experimental conditions emerged at peak exercise. However, despite acute Carn-sA supplementation did not affect the single ventilatory thresholds, the compensated portion of the ramp test (i.e., the difference between VT2 and VT1) was significantly larger (P= 0.043) in Carn-sA. Conclusions These findings demonstrate a positive effect of acute Carn-sA supplementation on the compensated part of the exercise. This should be taken into account by nutritionists and athletes searching for nutritional supplements, when a quick effect based on an acute dose is required.

The present study aimed to determine the contribution of soccer players' anthropometric features to predict their physical performance. Sixteen players, from a professional youth soccer academy, were recruited. Several anthropometric features such as corrected arm muscle area (AMA

BackgroundTo explore the relationship between adult Attention Deficit/ Hyperactivity Disorder (ADHD), antistreptococcal titers, ABGA, and recurrent infections during early childhood.MethodChildhood history of recurrent infections and a blood sample were collected in a sample of DSM-IV adult outpatients with ADHD. The anti-streptolysin O (ASO), anti-deoxyribonuclease B (anti-DNase B), and anti-basal ganglia antibodies (ABGA) titers were determined in patient plasma by enzyme-linked immunosorbent assay (ELISA). Titers positivity was evaluated following manufacturer’s specifications. Absolute titers were also collected as continuous variables.ResultsFourteen out of 22 (63.6%) have had recurrent infections in childhood (i.e., seven, 31.8%, have had tonsillitis or adenoiditis and seven, 31.8%, have had any other infections). Eighteen patients (81.9%) were positive for anti-DNase B, five (22.7%) for ASO, and 4 (18.2%) were positive for both of them. Five participants (22.7%) were ABGA positive, whereas only two (9.1%) were positive for all three antibodies.Conclusionspatients with ADHD might be more prone to infections during childhood and subclinical streptococcal infections during adulthood. Moreover, they seem to have an increased risk for basal ganglia autoimmunity in adulthood. Both infections and the ensuing acquired autoimmunity could influence the neurodevelopmental process, by contributing, at least in part, to the ADHD pathogenesis.

In the last few years, the unprecedented results of immune checkpoint inhibitors have led to a paradigm shift in clinical practice for the treatment of several cancer types. However, the vast majority of patients with gastrointestinal cancer do not benefit from immunotherapy. To date, microsatellite instability high and DNA mismatch repair deficiency are the only robust predictive biomarkers of response to immune checkpoint inhibitors. Unfortunately, these patients comprise only 5%–10% of all gastrointestinal cancers. Several mechanisms of both innate and adaptive resistance to immunotherapy have been recognized that may be at least in part responsible for the failure of immune checkpoint inhibitors in this population of patients. In the first part of this review article, we provide an overview of the main clinical trials with immune checkpoint inhibitors in patients with gastrointestinal cancer and the role of predictive biomarkers. In the second part, we discuss the actual body of knowledge in terms of mechanisms of resistance to immunotherapy and the most promising approach that are currently under investigation in order to expand the population of patients with gastrointestinal cancer who could benefit from immune checkpoint inhibitors.

Objectives This study aimed to describe the preliminary results of a modified sympathicotomy for cardiac sympathetic denervation (CSD), which may reduce the predictive risk and intraoperative surgical time of the procedure. Background CSD, in patients with refractory ventricular tachycardia (VT), is comprehensively recognized as an important treatment option for patients with structural heart disease as well as congenital inherited arrhythmia syndrome. Methods We consecutively enrolled 5 patients with refractory VT. Baseline demographic, medical, and surgical data as well as arrhythmia outcomes and procedural complications were evaluated. Results A total of 5 patients (mean age: 67.4 years) were enrolled for the treatment of refractory VT with a modified CSD technique. In 3 of 5 patients, an overall reduction in VT burden (ranging from 75% to 100%) and VT number was observed after the CSD despite an in-hospital early recurrence. Conclusions A modified CSD (sympathicotomy T2–T5) with stellate ganglion sparing and the use of unipolar radiofrequency is feasible, effective, and safe in the setting of untreatable VT.

Purpose: No effective therapy is available for unresectable soft-tissue sarcomas (STS). This unmet clinical need prompted us to test whether chondroitin sulfate proteoglycan 4 (CSPG4)-specific chimeric antigen receptor (CAR)-redirected cytokine-induced killer lymphocytes (CAR.CIK) are effective in eliminating tumor cells derived from multiple STS histotypes in vitro and in immunodeficient mice. Experimental Design: The experimental platform included patient-derived CAR.CIK and cell lines established from multiple STS histotypes. CAR.CIK were transduced with a retroviral vector encoding second-generation CSPG4-specific CAR (CSPG4-CAR) with 4-1BB costimulation. The functional activity of CSPG4-CAR.CIK was explored in vitro, in two- and three-dimensional STS cultures, and in three in vivo STS xenograft models. Results: CSPG4-CAR.CIK were efficiently generated from patients with STS. CSPG4 was highly expressed in multiple STS histotypes by in silico analysis and on all 16 STS cell lines tested by flow cytometry. CSPG4-CAR.CIK displayed superior in vitro cytolytic activity against multiple STS histotypes as compared with paired unmodified control CIK. CSPG4-CAR.CIK also showed strong antitumor activity against STS spheroids; this effect was associated with tumor recruitment, infiltration, and matrix penetration. CSPG4-CAR.CIK significantly delayed or reversed tumor growth in vivo in three STS xenograft models (leiomyosarcoma, undifferentiated pleomorphic sarcoma, and fibrosarcoma). Tumor growth inhibition persisted for up to 2 weeks following the last administration of CSPG4-CAR.CIK. Conclusions: This study has shown that CSPG4-CAR.CIK effectively targets multiple STS histotypes in vitro and in immunodeficient mice. These results provide a strong rationale to translate the novel strategy we have developed into a clinical setting.

Trecroci, A, Porcelli, S, Perri, E, Pedrali, M, Rasica, L, Alberti, G, Longo, S, and Iaia, FM. Effects of different training interventions on the recovery of physical and neuromuscular performance after a soccer match. J Strength Cond Res 34(8): 2189-2196, 2020-In competitive soccer, players are frequently required to play in periods with congested fixtures in which they have limited time to recover between matches (3-4 days). Thus, finding the most appropriate intervention strategy to limit players' neuromuscular (muscle function of lower limbs) and physical (running performance) impairments in this short period becomes crucial. The aim of the study was to examine how muscle function of knee extensors and flexors and sprint performance recovered +72 hours after match in relation to different field-based training sessions. Using a crossover design, 9 subelite players (age 17.6 ± 0.5 years, height 1.77 ± 0.02 m, body mass 66.4 ± 5.8 kg) underwent a soccer-specific training (SST) session or an active recovery regime (AR) on the second day after a match. Immediately after (0 hour) and +72 hours after match, 30-m sprint and repeated sprint ability (RSA) were assessed. Maximum isometric voluntary force (MVF) of knee extensors and flexors was determined at 120° and 90° (with 180° being full extension), respectively. SST and AR promoted similar effects on the recovery kinetics of sprint, RSA, and MVF of knee extensors (p > 0.05). However, compared with SST, AR promoted a significantly better restoration of MVF of knee flexors (p < 0.05) after +72 hours from the match. Because muscle fatigue has been related with increased hamstring injury risk, a training based on AR can be a valid intervention to promote the recovery of muscle force production of knee flexors and reduce hamstring injury risk in the postmatch period.

The aim of the current study was to evaluate field-based physical performance of under 16 years (U16) elite and sub-elite soccer players. Forty elite (n = 20) and sub-elite (n = 20) soccer players were enrolled and tested for countermovement jump (CMJ), 10-m sprint and agility, in terms of sprint with 90° turns (S90), S90 with ball, Slalom, Slalom with ball, and reactive agility (RAT). Statistical and practical significant differences were observed in CMJ, S90 and RAT between elite and sub-elite. Elite players exhibited a likely better performance in Slalom, Slalom with ball and S90 with ball despite a non-significant difference by level of play. Concerning sprint ability, both groups showed similar performance in the 10-m sprint. Countermovement jump and agility tests are field-based physical assessments recommended to better distinguish between U16 elite and sub-elite soccer players.

The aim of this study was to evaluate the effects of 12-week balance and slackline training programs on physical performance and perceived enjoyment scale in young soccer players. Forty-one preadolescent soccer players were assigned to two experimental groups performing traditional balance (BLT) or slackline training (SLT), and a control group. Pre-post assessment encompassed Balance Error Scoring System (BESS), Star Excursion Balance test (SEBT), sprint with 90° turns (S90), and countermovement jump (CMJ). The rate of perceived enjoyment scale (PACES) was applied at the end of the experimental period. SLT and BLT improved similarly in BESS, SEBT and S90. No changes were detected in the CMJ. Regarding PACES score, SLT presented significantly higher values than BLT. Young athletes may benefit from a motivating training approach, thus, a designed program based on slackline drills should be preferable to improve physical performance in terms of balance and change of direction ability in preadolescent soccer players.

The emerging role of the diet in the incidence of intestinal inflammatory diseases has stimulated research on the influence of eating habits with pro-inflammatory properties in inducing epithelial barrier disturbance. Cholesterol oxidation products, namely oxysterols, have been shown to promote and sustain oxidative/inflammatory reactions in human digestive tract. This work investigated in an in vitro model the potential ability of a combination of dietary oxysterols representative of a hyper-cholesterol diet to induce the loss of intestinal epithelial layer integrity. The components of the experimental mixture were the main oxysterols stemming from heat-induced cholesterol auto-oxidation, namely 7-ketocholesterol, 5α,6α-and 5β,6β-epoxycholesterol, 7α- and 7β-hydroxycholesterol. These compounds added to monolayers of differentiated CaCo-2 cells in combination or singularly, caused a time-dependent induction of matrix metalloproteinases (MMP)-2 and -9, also known as gelatinases. The hyperactivation of MMP-2 and -9 was found to be associated with decreased levels of the tight junctions zonula occludens-1 (ZO-1), occludin and Junction Adhesion Molecule-A (JAM-A). Together with such a protein loss, particularly evident for ZO-1, a net perturbation of spatial localization of the three tight junctions was observed. Cell monolayer pre-treatment with the selective inhibitor of MMPs ARP100 or polyphenol (-)-epicathechin, previously shown to inhibit NADPH oxidase in the same model system, demonstrated that the decrease of the three tight junction proteins was mainly a consequence of MMPs induction, which was in turn dependent on the pro-oxidant property of the oxysterols investigated. Although further investigation on oxysterols intestinal layer damage mechanism is to be carried on, the consequent - but incomplete - prevention of oxysterols-dependent TJs alteration due to MMPs inhibition, avoided the loss of scaffold protein ZO-1, with possible significant recovery of intestinal monolayer integrity.

Objectives The purpose of our study was to evaluate whether peritumoural perfusion weighted and proton spectroscopic magnetic resonance imaging can be used in differentiating between primary gliomas and solitary metastases. Methods Ten low-grade gliomas, eight high-grade gliomas and 10 metastases were prospectively evaluated with magnetic resonance imaging, dynamic susceptibility contrast enhanced perfusion imaging and single-voxel proton magnetic resonance spectroscopy before surgical resection or stereotactic biopsy. Maximal relative cerebral blood volume values were calculated drawing three regions of interest of 2 cm2 in the non-enhancing peritumoural areas. Maximal relative cerebral blood volume values were normalised to that of contralateral normal-appearing white matter. Maximal choline/creatine ratios were calculated from three voxels of 10 cm3 placed in the peritumoural areas defined as non-enhancing peritumoural white matter surrounding the tumour. The tumour grade presumed with these values was compared to histopathological grading. Differences in the study parameters between groups were assessed using the Mann–Whitney test. A receiver operating characteristic analysis was performed to determine cut-off values. Results A clear relative cerebral blood volume cut-off value of 1.88 was detected for differentiating low-grade gliomas from high-grade gliomas. A clear relative cerebral blood volume cut-off value of 1.20 was detected for differentiation of metastases from gliomas. The differences in the choline/creatine ratios in the peritumoural regions of high-grade gliomas and of solitary metastasis were statistically significant ( P Conclusion Our preliminary data support the hypothesis that peritumoural perfusion-weighted imaging can assist in preoperative differentiation between a glioma and a solitary metastasis.

How numerical quantity is processed is a central issue for cognition. On the one hand the “number sense theory” claims that numerosity is perceived directly, and may represent an early precursor for acquisition of mathematical skills. On the other, the “theory of magnitude” notes that numerosity correlates with many continuous properties such as size and density, and may therefore not exist as an independent feature, but be part of a more general system of magnitude. In this study we examined interactions in sensitivity between numerosity and size perception. In a group of children, we measured psychophysically two sensory parameters: perceptual adaptation and discrimination thresholds for both size and numerosity. Neither discrimination thresholds nor adaptation strength for numerosity and size correlated across participants. This clear lack of correlation (confirmed by Bayesian analyses) suggests that numerosity and size interference effects are unlikely to reflect a shared sensory representation. We suggest these small interference effects may rather result from top-down phenomena occurring at late decisional levels rather than a primary “sense of magnitude”.

Introduction The artery of Percheron is a rare anatomic variant supplying bilateral medial thalamic nuclei and a variable portion of the rostral part of midbrain. Case report A 48-year-old female with massive subarachnoid hemorrhage due to a ruptured aneurysm of the paramedian artery of Percheron presented to the emergency room. Because of significant risk of recurrent intracranial hemorrhage, it was decided to proceed with endovascular embolization of the aneurysm. The patient was ultimately sent to a rehabilitation center and her presenting neurologic deficits showed significant improvements in the weeks following endovascular embolization treatment. Discussion The paramedian artery of Percheron is a rare anatomic variant and subarachnoid hemorrhage due to aneurysm of this artery is exceedingly rare. This case underlines the importance of a correct evaluation of cerebral arterial anatomy in order to choose the best endovascular therapeutic approach, reduce complications, and optimize patient outcome.

Objective: Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disease; a major health concern in the ageing population with an estimated prevalence of 46 million dementia cases worldwide. Early diagnosis is therefore crucial so mitigating treatments can be initiated at an early stage. Cerebral hypoperfusion has been linked with blood-brain barrier dysfunction in the early stages of AD, and screening for chronic cerebral hypoperfusion in individuals has been proposed for improving the early diagnosis of AD. However, ambulatory measurements of cerebral blood flow are not routinely carried out in the clinical setting. In this study, we combine physiological modeling with Holter blood pressure monitoring and carotid ultrasound imaging to predict 24-h cerebral blood flow (CBF) profiles in individuals. One hundred and three participants [53 with mild cognitive impairment (MCI) and 50 healthy controls] underwent model-assisted prediction of 24-h CBF. Model-predicted CBF and neuropsychological tests were features in lasso regression models for MCI diagnosis. Results: A CBF-enhanced classifier for diagnosing MCI performed better, area-under-the-curve (AUC) = 0.889 (95%-CI: 0.800 to 0.978), than a classifier based only on the neuropsychological test scores, AUC = 0.818 (95%-CI: 0.643 to 0.992). An additional cohort of 25 participants (11 MCI and 14 healthy) was recruited to perform model validation by arterial spin-labeling magnetic resonance imaging, and to establish a link between measured CBF that predicted by the model. Conclusion: Ultrasound imaging and ambulatory blood pressure measurements enhanced with physiological modeling can improve MCI diagnosis accuracy.

A 73 year old man with CRT-D system and pacemaker dependence was admitted to the emergency department due to a syncopal episode. The device interrogation was performed. An RV ventricular sensing test was executed in VVI mode at 50 b/m. During testing the patient developed transient loss of consciousness with full recovery after stopping the sensing test. Applying asynchronous pacing mode, a pacing spike occurred at a faster rate of 65 b/m without evoking any ventricular capture. Looking at the chest X-ray, we found an abandoned right sided, single chamber VVI pacemaker in a submuscular pocket. The CRT-D system was positioned on the left side. The abandoned pacemaker was in ERI and it switched to VVI 65 b/m resulting in inhibition CRTD device during sensing test. This troubleshooting highlights the possible interference between two devices.

Promoting four healthy behaviours among preschool children:⩾4 servings of fruit and vegetables/day, ⩾2 h/day of active play, ⩽1 h per day of TV-watching and 0 sugar sweetened beverages/day.We conducted a c-RCT on 425 3-year-old children at 16 childcare centres based in Cesena, Italy. We randomly allocated eight childcare centres (199 children) to the intervention group and eight childcare centres (226 children) to the control group. All the randomized childcare centres completed our study protocol. Parents recorded their children's target behaviours at home over 3 Saturdays, at baseline and at follow-up. Then trained nurses measured children's weight and height. We conducted a 6-month-long intervention trial in local health care centres where nurses and primary care pediatricians, respectively, conducted two subsequent motivational interviews with parents to encourage children's healthy behaviours at home. At the same time, teachers involved children in learning experiences about healthy behaviours. Our primary outcome is a children's combined health behaviour score (CHBS) at home. Our secondary outcomes measure the BMI z-score and the percentage of children that show a BMI trajectory crossing upward. After collecting the CHBS and BMI data at baseline as well as at 1- and 2-year follow-ups, we performed an Intent-to-Treat (ITT) analysis.After 2 years from baseline, 48.4% of intervention group children showed a low-risk CHBS in comparison with 28.0% of control group children. A multilevel analysis showed that they were by far more likely to achieve low-risk scores (adjusted OR: 3.41; 95% CI: 1.48-7.88; P=0.004). Our BMI outcomes showed no significant difference between groups.A multidimensional educational intervention, which consists of motivational interviews with parents and teacher-led learning experiences for children, improved preschool children's CHBS in the long term without influencing the outcomes of BMI z-score and BMI increase.

To examine the degree of neuromuscular fatigue development along with changes in muscle metabolism during two work-matched high-intensity intermittent exercise protocols in trained individuals.In a randomized, counter-balanced, crossover design, 11 endurance-trained men performed high-intensity intermittent cycle exercise protocols matched for total work and including either multiple short-duration (18 × 5 s; SS) or long-duration (6 × 20 s; LS) sprints. Neuromuscular fatigue was determined by preexercise to postexercise changes in maximal voluntary contraction force, voluntary activation level and contractile properties of the quadriceps muscle. Metabolites and pH were measured in vastus lateralis muscle biopsies taken before and after the first and last sprint of each exercise protocol.Peak power output (11% ± 2% vs 16% ± 8%, P0.01), maximal voluntary contraction (10% ± 5% vs 25% ± 6%, P0.05), and peak twitch force (34% ± 5% vs 67% ± 5%, P0.01) declined to a lesser extent in SS than LS, whereas voluntary activation level decreased similarly in SS and LS (10% ± 2% vs 11% ± 4%). Muscle [phosphocreatine] before the last sprint was 1.5-fold lower in SS than LS (P0.001). Preexercise to postexercise intramuscular accumulation of lactate and H was twofold and threefold lower, respectively, in SS than LS (P0.001), whereas muscle glycogen depletion was similar in SS and LS. Rate of muscle glycolysis was similar in SS and LS during the first sprint, but twofold higher in SS than LS during the last sprint (P0.05).These findings indicate that, in endurance-trained individuals, multiple long-sprints induce larger impairments in performance along with greater degrees of peripheral fatigue compared to work-matched multiple short-sprints, with these differences being possibly attributed to more extensive intramuscular accumulation of lactate/H and to lower rates of glycolysis during multiple long-sprint exercise.

Recent evidence has shown that the presence of abnormal substrate can be demonstrated also among patients with "lone" AF.Interatrial conduction slowing is likely to characterize patients with paroxysmal atrial fibrillation (AF) and it could be correlated to the left atrium area of prolonged local bipolar endocardial electrograms.P-wave duration (PWD), amplified PWD and endocavitary interatrial conduction time (IACT), were analyzed in 60 patients; 30 undergoing de novo ablation for paroxysmal AF with normal atrial volumes and without any other cardiac disease and 30 of similar age undergoing electrophysiological study for atrioventricular nodal reentrant tachycardia or atrioventricular re- entrant tachycardia. In patients with AF, voltage maps and local bipolar electrograms (LBE) duration map were evaluated.Although PWD was120 ms in 28 patients with AF and in 29 controls, patients with AF exhibited longer PWD, amplified-PWD and IACT. Although low-voltage areas (0.5 mV) were not found in the study population, 28 of them demonstrated areas with LBE longer than 60 ms. These LBE were found mainly in the roof of the left atrium and their extension was correlated to IACT (R = 0.51, p = 0.004). IACT135.5 ms identified the subjects who experienced AF with 90% sensitivity and 97% specificity.A subclinical interatrial conduction disturbance is demonstrable in subjects with paroxysmal AF and normal left atrial volume. IACT has a good correlation to the areas of abnormal LBE in the left atrium. IACT135 ms identified subjects who have experienced AF.

The occurrence of highly severe silica-related diseases among the resin- and silica-based artificial stone workers was claimed, associated to an extremely short latency. High levels of exposure and intrinsic properties of AS are thought to modulate the development of silicosis and auto-immune diseases. This study compares parent materials and processed dusts, to shed light on changes of AS occurring in the manufacturing process, through an XRF, EPR and XAS investigation. We point out the extremely wide variability of the materials, the occurrence of chemical signatures impressed by the processing techniques, and the unprecedented generation of stable radicals associated to the lysis of the Si-O chemical bond inside the resin coated respirable crystalline silica. These results suggest that the AS processing in industrial stone workshops can create respirable dusts with peculiar physical and chemical properties, to be correlated to the observed clinical evidences.

The aim of this retrospective case study is the longitudinal description of the physical and functional parameters of a top-level Paralympic swimmer class S9-SB8-SM9 during four swimming seasons of training, from the Paralympic games in London 2012 to the Paralympic games in Rio 2016. A 22-year-old male swimmer underwent a specific preventive dry-land training based on diaphragmatic breathing, postural alignment, and slow-velocity resistance training aimed to improve his muscle strength. He was tested by using the Functional Movement Screen™, photographic postural assessment and vertical jump. The swimmer improved his functional, postural and strength parameters indicating a better functional movement and muscular power. These results show that a four-year specific dry-land intervention could be capable of enhancing the functional and physical requirements of a top-level Paralympic swimmer. This approach might be a suitable novel alternative for coaches and athletic trainers to integrate their training protocols for athletes with similar impairments.

Purpose The objective of this study was to correlate the presence and distribution of cerebral microbleeds in Alzheimer’s disease patients with cerebrospinal fluid biomarkers (amyloid-beta and phosphorylated tau 181 protein levels) and cognitive decline by using susceptibility-weighted imaging magnetic resonance sequences at 1.5 T. Material and methods Fifty-four consecutive Alzheimer’s disease patients underwent brain magnetic resonance imaging at 1.5 T to assess the presence and distribution of cerebral microbleeds on susceptibility-weighted imaging images. The images were analyzed in consensus by two neuroradiologists, each with at least 10 years’ experience. Dementia severity was assessed with the Mini-Mental State Examination score. A multiple regression analysis was performed to assess the associations between the number and location of cerebral microbleed lesions with the age, sex, duration of the disease, cerebrospinal fluid amyloid-beta and phosphorylated tau 181 protein levels, and cognitive functions. Results A total of 296 microbleeds were observed in 54 patients; 38 patients (70.4%) had lobar distribution, 13 patients (24.1%) had non-lobar distribution, and the remaining three patients (5.6%) had mixed distribution, demonstrating that Alzheimer’s disease patients present mainly a lobar distribution of cerebral microbleeds. The age and the duration of the disease were correlated with the number of lobar cerebral microbleeds ( P Conclusion Lobar distribution of cerebral microbleeds is associated with Alzheimer’s disease and the number of lobar cerebral microbleeds directly correlates with cerebrospinal fluid amyloid-beta and phosphorylated tau 181 protein levels and with the cognitive decline of Alzheimer’s disease patients.

Karate is a martial art that partly depends on subjective scoring of complex movements. Principal component analysis (PCA)-based methods can identify the fundamental synergies (principal movements) of motor system, providing a quantitative global analysis of technique. In this study, we aimed at describing the fundamental multi-joint synergies of a karate performance, under the hypothesis that the latter are skilldependent; estimate karateka's experience level, expressed as years of practice. A motion capture system recorded traditional karate techniques of 10 professional and amateur karateka. At any time point, the 3D-coordinates of body markers produced posture vectors that were normalised, concatenated from all karateka and submitted to a first PCA. Five principal movements described both gross movement synergies and individual differences. A second PCA followed by linear regression estimated the years of practice using principal movements (eigenpostures and weighting curves) and centre of mass kinematics (error: 3.71 years; R2 = 0.91, P ≪ 0.001). Principal movements and eigenpostures varied among different karateka and as functions of experience. This approach provides a framework to develop visual tools for the analysis of motor synergies in karate, allowing to detect the multi-joint motor patterns that should be restored after an injury, or to be specifically trained to increase performance.

The alteration of the intestinal barrier function is currently believed to be involved in the pathogenesis of gut diseases mainly associated with the activation of inflammation processes. Diet plays an important role in the control of human gut integrity. Theobromine is a natural methylxanthine present in dark chocolate particularly abundant in cocoa bean shell. This is a polyphenol rich by-product generated in cocoa industrial processing, which is gaining value as a functional ingredient. This study aims to highlight for the first time the capability of theobromine in protecting the intestinal cell monolayer from a mixture of dietary oxysterols showing an inflammatory action in terms of IL-8 and MCP-1 overproduction. Differentiated CaCo-2 cells were treated with 60 μM oxysterol mixture and pre-incubated with 10 μM theobromine. Intestinal barrier damage was investigated in terms of tight junction claudin 1, occludin and JAM-A protein levels, matrix metalloproteinase (MMP) −2 and −9 activation and anti/pro-apoptotic protein changes. The observed cell monolayer permeability protection by theobromine may be due to its ability to inhibit the production of cytokines and MMPs that can be responsible for tight junction loss and apoptosis in intestinal cells. Our findings provide additional mechanistic hints on the healthy effect of theobromine cocoa component as an attractive natural molecule in the prevention of inflammatory gut diseases.

KEY POINTS: Low‐volume high‐intensity exercise training promotes muscle mitochondrial adaptations that resemble those associated with high‐volume moderate‐intensity exercise training. These training‐induced mitochondrial adaptations stem from the cumulative effects of transient transcriptional responses to each acute exercise bout. However, whether metabolic stress is a key mediator of the acute molecular responses to high‐intensity exercise is still incompletely understood. Here we show that, by comparing different work‐matched low‐volume high‐intensity exercise protocols, more marked metabolic perturbations were associated with enhanced mitochondrial biogenesis‐related muscle mRNA responses. Furthermore, when compared with high‐volume moderate‐intensity exercise, only the low‐volume high‐intensity exercise eliciting severe metabolic stress compensated for reduced exercise volume in the induction of mitochondrial biogenic mRNA responses. The present results, besides improving our understanding of the mechanisms mediating exercise‐induced mitochondrial biogenesis, may have implications for applied and clinical research that adopts exercise as a means to increase muscle mitochondrial content and function in healthy or diseased individuals. ABSTRACT: The aim of the present study was to examine the impact of exercise‐induced metabolic stress on regulation of the molecular responses promoting skeletal muscle mitochondrial biogenesis. Twelve endurance‐trained men performed three cycling exercise protocols characterized by different metabolic profiles in a randomized, counter‐balanced order. Specifically, two work‐matched low‐volume supramaximal‐intensity intermittent regimes, consisting of repeated‐sprint (RS) and speed endurance (SE) exercise, were employed and compared with a high‐volume continuous moderate‐intensity exercise (CM) protocol. Vastus lateralis muscle samples were obtained before, immediately after, and 3 h after exercise. SE produced the most marked metabolic perturbations as evidenced by the greatest changes in muscle lactate and pH, concomitantly with higher post‐exercise plasma adrenaline levels in comparison with RS and CM. Exercise‐induced phosphorylation of CaMKII and p38 MAPK was greater in SE than in RS and CM. The exercise‐induced PGC‐1α mRNA response was higher in SE and CM than in RS, with no difference between SE and CM. Muscle NRF‐2, TFAM, MFN2, DRP1 and SOD2 mRNA content was elevated to the same extent by SE and CM, while RS had no effect on these mRNAs. The exercise‐induced HSP72 mRNA response was larger in SE than in RS and CM. Thus, the present results suggest that, for a given exercise volume, the initial events associated with mitochondrial biogenesis are modulated by metabolic stress. In addition, high‐intensity exercise seems to compensate for reduced exercise volume in the induction of mitochondrial biogenic molecular responses only when the intense exercise elicits marked metabolic perturbations.

Purpose: The aim of the current study was to identify the external-training-load markers that are most influential on session rating of perceived exertion (RPE) of training load (RPE-TL) during elite soccer training. Methods: Twenty-two elite players competing in the English Premier League were monitored. Training-load data (RPE and 10-Hz GPS integrated with a 100-Hz accelerometer) were collected during 1892 individual training sessions over an entire in-season competitive period. Expert knowledge and a collinearity r < .5 were used initially to select the external training variables for the final analysis. A multivariateadjusted within-subjects model was employed to quantify the correlations of RPE and RPE-TL (RPE × duration) with various measures of external training intensity and training load. Results: Total high-speed-running (HSR; >14.4 km/h) distance and number of impacts and accelerations >3 m/s2 remained in the final multivariate model (P < .001). The adjusted correlations with RPE were r = .14, r = .09, and r = .25 for HSR, impacts, and accelerations, respectively. For RPE-TL, the correlations were r = .11, r = .45, and r = .37, respectively. Conclusions: The external-load measures that were found to be moderately predictive of RPE-TL in soccer training were HSR distance and the number of impacts and accelerations. These findings provide new evidence to support the use of RPE-TL as a global measure of training load in elite soccer. Furthermore, understanding the influence of characteristics affecting RPE-TL may help coaches and practitioners enhance training prescription and athlete monitoring.

In the current study, we attempted to determine normative inner ear volumetric measurements generated from three-dimensional computed tomography (CT) images. In addition, we investigated a correlation between the axial length and the volume of the labyrinth and discussed clinical outcomes of this correlation. Amira 5.2.2 software was used to create three-dimensional isosurface images of the human labyrinth using two-dimensional CT images from 35 anatomically normal patients. With the three-dimensional labyrinths, complete dimensional analysis was performed to gain insight into both the volume and the greatest axial length of the inner ear. Paired t test and Pearson correlation were used. Our volume of the inner ear inquiry reported a mean volume of 221.5 with SD of 24.3 μL (0.228 μL for males and 0.218 μL for females). The length showed a mean of 1.713 cm with SD of 0.064 cm (1.753 cm for males and 1.695 cm for females). The length was used to estimate the volume, and the estimates were within 10% of the measured volume 74.3% of the time. Normative volumetric measurements of the inner ear can be obtained by using three-dimensional CT Imaging by Amira 5.2.2 software. There was a statistically significant positive correlation between the axial length of the labyrinth and the volume of the labyrinth. The axial length of the labyrinth could be used to estimate the volume of the labyrinth, which may be clinically important to estimate the concentration of the drug distributed in the inner ear.