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This pilot study investigates distinctive features within the nail-enthesis complex among Psoriatic arthritis (PsA), Psoriasis (PSO), Rheumatoid Arthrit is (RA), and Healthy Control (HC) groups, utilizing a combined approach of ultrasound (US) and nailfold videocapillaroscopy (NVC). Clinical assessments and comprehensive US and NVC evaluations of the nail-enthesis complex were conducted on 72 subjects (18 PsA, 16 PSO, 19 RA, 19 HC). Unsupervised clustering models and factor analysis were employed to identify patterns and interrelationships between US and NVC parameters. Significant structural differences were detected, emphasizing the discriminatory power of semiquantitative US scores (GS BUNES, Wortsman type). Trends in vascularization aligned with literature, showcasing dysregulated angiogenesis in PsA and PSO. The clustering model effectively distinguished HC from PsA subjects, revealing a potential continuum between PSO and PsA. RA subjects exhibited subsets with features akin to both HC and PsA/PSO, underscoring the complexity of its manifestations. This study provides insights into nail-enthesis complex alterations, highlighting distinctions among PsA, PSO, RA, and HC subjects. The clustering model emphasizes potential overlap between PSO and PsA. Factor analysis elucidates collinearity in US-detected characteristics, while suggesting limited discriminative power of some quantitative parameters. These findings advocate for further exploration in prospective trials, potentially predicting the evolution of undifferentiated early arthritis and arthritis onset in PSO patients.

ObjectiveAssessment of circulating autoantibodies represents one of the earliest diagnostic procedures in patients with suspected connective tissue disease (CTD), providing important information for disease diagnosis, identification and prediction of potential clinical manifestations. The purpose of this study was to evaluate the ability of multiparametric assay to correctly classify patients with multiple CTDs and healthy controls (HC), independent of clinical features, and to evaluate whether serological status could identify clusters of patients with similar clinical features.MethodsPatients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren’s syndrome (SjS), undifferentiated connective tissue disease (UCTD), idiopathic inflammatory myopathies (IIM) and HC were enrolled. Serum was tested for 29 autoantibodies. An XGBoost model, exclusively based on autoantibody titres was built and classification accuracy was evaluated. A hierarchical clustering model was subsequently developed and clinical/laboratory features compared among clusters.Results908 subjects were enrolled. The classification model showed a mean accuracy of 60.84±4.05% and a mean area under the receiver operator characteristic curve of 88.99±2.50%, with significant discrepancies among groups. Cluster analysis identified four clusters (CL). CL1 included patients with typical features of SLE. CL2 included most patients with SjS, along with some SLE and UCTD patients with SjS-like features. CL4 included anti-Jo1 patients only. CL3 was the largest and most heterogeneous, including all the remaining subjects, overall characterised by low titre or lower-prevalence autoantibodies.ConclusionExtended multiparametric autoantibody assay allowed an accurate classification of CTD patients, independently of clinical features. Clustering according to autoantibody titres is able to identify clusters of CTD subjects with similar clinical features, independently of their final diagnosis.

In this paper the site categorization criteria and the corresponding site amplification factors proposed in the 2021 draft of Part 1 of Eurocode 8 (2021-draft, CEN/TC250/SC8 Working Draft N1017) are first introduced and compared with the current version of Eurocode 8, as well as with site amplification factors from recent empirical ground motion prediction equations. Afterwards, these values are checked by two approaches. First, a wide dataset of strong motion records is built, where recording stations are classified according to 2021-draft, and the spectral amplifications are empirically estimated computing the site-to-site residuals from regional and global ground motion models for reference rock conditions. Second, a comprehensive parametric numerical study of one-dimensional (1D) site amplification is carried out, based on randomly generated shear-wave velocity profiles, classified according to the new criteria. A reasonably good agreement is found by both approaches. The most relevant discrepancies occur for the shallow soft soil conditions (soil category E) that, owing to the complex interaction of shear wave velocity, soil deposit thickness and frequency range of the excitation, show the largest scatter both in terms of records and of 1D numerical simulations. Furthermore, 1D numerical simulations for soft soil conditions tend to provide lower site amplification factors than 2021-draft, as well as lower than the corresponding site-to-site residuals from records, because of higher impact of non-linear (NL) site effects in the simulations. A site-specific study on NL effects at three KiK-net stations with a significantly large amount of high-intensity recorded ground motions gives support to the 2021-draft NL reduction factors, although the very limited number of recording stations allowing such analysis prevents deriving more general implications. In the presence of such controversial arguments, it is reasonable that a standard should adopt a prudent solution, with a limited reduction of the site amplification factors to account for NL soil response, while leaving the possibility to carry out site-specific estimations of such factors when sufficient information is available to model the ground strain dependency of local soil properties.

Work organization, such as shifts and night work, can interfere with the perception of work-related stress and therefore on the development of pathological conditions. Night shift work, particularly, can have a negative impact on workers’ wellbeing by interfering with the biological sphere. The aim of this study is to evaluate the associations between work activities, shift work effects and stress-related responses in 106 dock workers enrolled in southeast Italy. Dock workers’ tasks consist of complex activities that seemed to affect more sleep quality than work-related stress. An analysis of salivary biomarkers such as cortisol, α-amylase, melatonin and lysozyme was performed along with validated psycho-diagnostic questionnaires. Alpha-amylase showed a significant negative correlation with the effort/reward imbalance score; thus, the measurement of salivary α-amylase is proposed as a sensitive and non-invasive biomarker of work-related stress. This study may provide new insights into developing strategies for the management of night shift work. Salivary biomarkers should be further investigated in the future in order to develop simple and effective tools for the early diagnosis of work-related stress or its outcomes.

BackgroundHamstring (HS) strength deficits and imbalances have been identified as risk factors for sustaining ACL injuries and muscular strains, with HS injuries being the most prevalent muscle injuries in soccer athletes.ObjectiveThe aim was to investigate HS eccentric strength before and after a football match in male and female athletes. The hypothesis is that HS fatigue could depend on sex.DesignCohort observational study.SettingSemi-professional football.ParticipantsSixty-four healthy men and women semi-professional football players aged from 14 to 25 years.InterventionsHS eccentric strength during the execution of the Nordic hamstring exercise (NHE test) and anterior-knee laxity (AKL) were measured before and after a 90-minute soccer match.Main Outcome MeasurementsThe pre- and post-match difference between genders in HS eccentric strength (mean and absolute peak torque and total work) and in AKL.ResultsMean and absolute eccentric HS peak torque decreased by 4.5 Nm (p<0.0005) and 21.9 Nm (p<0.0005) in females, whereas male peers improved by 19.9 Nm (p=0.01) and by 20.9 Nm (p=0.02), respectively. HS total work in females decreased by 831.1 J (p<0.0005) compared to the males’ reduction of 235.3 J. Both the pre- vs. postmatch intersex mean and absolute eccentric HS peak torque changes were significant (p<0.0005), as were the changes in HS total work (p=0.007). The pre- vs. postmatch AKL difference was not significantly different. Younger female athletes (14–19 years old) presented a greater decrease in mean and absolute peak HS eccentric strength compared to those in older female athletes and males.Abstract 419 Table 1Characteristics of the included participants. Sex, M/F (% M) Overall age mean (SD) Age M/F mean (SD) R dominant leg M/F Tegner M/F mean (SD) Time to begin post-match test (s) 27 M/37 F(42%) 19.2 y(3.0) 20.0 y (3.0) M18.7 y (2.9) F 23 on 27 (M)32 on 37 (F) 7.74 (0.98) M7.92 (1.01) F 394.44 s (228.43) M495.15 s (268.97) F Abbreviations: F = female; M = male; R = right; s = seconds; Tegner = Tegner Activity Scale; y = years old.Abstract 419 Table 2Prepost differences (delta) in mean and absolute eccentric peak torque and total work stratified by age and sex. Age/sex n° Mean SD CI inf. limit CI sup. limit Min. value Max value Delta prepost mean ECC HS peak 14–19 M 34 13,6 36,7 -0,8 26,4 -73 97 20–25 M 20 30,5 45,3 -9,3 51,7 -31 131 14–19 F 48 -37,9 50,6 -53,6 -23,2 -164 100 20–25 F 26 0,15 35,5 -14,2 14,5 -96 58 Total 128 -5,8 50,6 -14,6 3,1 -164 131 Delta prepost abs ECC HS peak 14–19 M 34 14,9 41,6 0,4 29,4 -89 107 20–25 M 20 31,05 52,3 6,6 55,5 -51 136 14–19 F 48 -36,46 51,1 -51,3 -21,6 -170 79 20–25 F 26 5,08 31,5 -7,7 17,8 -46 69 Total 128 -3,84 52,2 -13 5,3 -170 136 Delta prepost HS total work 14–19 M 34 -401,9 1488,7 -921,35 117,5 -3949 1778 20–25 M 20 47,95 1433,3 -622,9 718,8 -2233 2608 14–19 F 48 -914,1 1264,6 -1281,3 -546,9 -4720 1385 20–25 F 26 -677,65 902,5 -1042,2 -313,1 -2574 842 Total 128 -579,7 1322,9 -811,1 -348,3 -4720 2608 Abbreviations: CI = confidence interval; F = female; M = male; n° = number of individuals; SD = standard deviation.Abstract 419 Table 3Post hoc pairwise comparison (differences between the means of each subgroup with reported level of significance). The statistically significant differences are indicated in blue. Age/sex Age/sex ES Significance (p) Mean HS peak 14–19 M 20–25 M 0.42 0.675 14–19 F 1.13 <0.0005 20–25 F 0.37 0.803 20–25 M 14–19 F 1.39 <0.0005 20–25 F 0.76 0.117 14–19 F 20–25 F 0.83 0.003 Absolute HS peak 14–19 M 20–25 M 0.35 0.757 14–19 F 1.08 <0.0005 20–25 F 0.26 0.958 20–25 M 14–19 F 1.31 <0.0005 20–25 F 0.62 0.298 14–19 F 20–25 F 0.92 0.002 HS total work 14–19 M 20–25 M 0.31 0.774 14–19 F 0.38 0.393 20–25 F 0.21 0.960 20–25 M 14–19 F 0.73 0.036 20–25 F 0.62 0.318 14–19 F 20–25 F 0.21 0.974 Abbreviations: ES = effect size.Abstract 419 Figure 1ConclusionsHS eccentric strength and work differ based on the athlete’s sex, as measured by the NHE test. Mean peak, absolute peak, and total work showed greater reductions in females than those in their male peers. The subgroup of 14- to 19-year-old female athletes experienced the highest reduction in strength.

The aim of this study was to compare methadone and morphine for the management of postoperative. Open, controlled study. Postoperative recovering area, ward. Sixty-four patients, ASA I-III, undergoing gynecological surgery for cancer. Morphine or methadone 0.15 mg/kg given preoperatively. After operation an intravenous morphine or intravenous methadone infusion at doses of 12 mg/day was started. Pain intensity and opioid consumption. Methadone infusion provided a better analgesia in comparison with morphine infusion on the second day. Opioid consumption was significantly lower in the methadone group. No episodes of relevant desaturation or signs of respiratory depression were recorded. A preoperative bolus of methadone, followed by a continuous infusion of low doses post-operatively, provided a better analgesia, without adding risk of adverse effects, in comparison with morphine. •A preoperative bolus of methadone, followed post-operatively by a continuous infusion of low doses provided a potent and better analgesia than morphine in gynecological surgery.•The risks of adverse effects with methadone was similar to those produced by morphine.•Methadone could be a relevant resource for postoperative pain.

Fatty acid elongase ELOVL5 is part of a protein family of multipass transmembrane proteins that reside in the endoplasmic reticulum where they regulate long-chain fatty acid elongation. A missense variant (c.689G>T p.Gly230Val) in ELOVL5 causes Spinocerebellar Ataxia subtype 38 (SCA38), a neurodegenerative disorder characterized by autosomal dominant inheritance, cerebellar Purkinje cell demise and adult-onset ataxia. Having previously showed aberrant accumulation of p.G230V in the Golgi complex, here we further investigated the pathogenic mechanisms triggered by p.G230V, integrating functional studies with bioinformatic analyses of protein sequence and structure. Biochemical analysis showed that p.G230V enzymatic activity was normal. In contrast, SCA38-derived fibroblasts showed reduced expression of ELOVL5, Golgi complex enlargement and increased proteasomal degradation with respect to controls. By heterologous overexpression, p.G230V was significantly more active than wild-type ELOVL5 in triggering the unfolded protein response and in decreasing viability in mouse cortical neurons. By homology modelling, we generated native and p.G230V protein structures whose superposition revealed a shift in Loop 6 in p.G230V that altered a highly conserved intramolecular disulphide bond. The conformation of this bond, connecting Loop 2 and Loop 6, appears to be elongase-specific. Alteration of this intramolecular interaction was also observed when comparing wild-type ELOVL4 and the p.W246G variant which causes SCA34. We demonstrate by sequence and structure analyses that ELOVL5 p.G230V and ELOVL4 p.W246G are position-equivalent missense variants. We conclude that SCA38 is a conformational disease and propose combined loss of function by mislocalization and gain of toxic function by ER/Golgi stress as early events in SCA38 pathogenesis.

The new breakthrough cystic fibrosis (CF) drug combination of ivacaftor (IVA), tezacaftor (TEZ), and elexacaftor (ELX), namely “caftor” drugs, directly modulates the activity and trafficking of the defective CF transmembrane conductance regulator protein (CFTR) underlying the CF disease. The role of therapeutic drug monitoring (TDM) of caftor drugs in clinical settings has recently been established. The availability of reliable and robust analytical methods for the quantification of IVA, TEZ, and ELX is essential to support dose–concentration–effect studies. We have developed and validated a new liquid chromatography–tandem mass spectrometry (LC–MS/MS) for the rapid and simultaneous quantification of IVA, TEZ, and ELX from the plasma of CF patients. The method was based on a rapid extraction protocol from 50 μL human plasma and separation on a reversed-phase C-18 HPLC column after the addition of deuterated internal standards. Accurate analyte quantification using multiple reaction monitoring (MRM) detection was then obtained using a Thermofisher Quantiva triple-quadrupole MS coupled to an Ultimate 3000 UHPLC. The method has been validated following international (EMA) guidelines for bioanalytical method validation and has been tested on plasma samples from 62 CF patients treated with the three-drug combination IVA/TEZ/ELX, marketed as Kaftrio® or Trikafta®, in steady-state condition. The assay was linear over wide concentration ranges (0.008–12 mg/L) in plasma for IVA, TEZ, and ELX, suitable for a broad range of plasma concentrations, and accurate and reproducible in the absence of matrix effects. The stability of analytes for at least 30 days at room temperature could allow for cost-effective shipment and storage. On the same day of sample collection, a sweat test was evaluated for 26 associated patients’ samples, FEV1 (%) for 58, and BMI was calculated for 62. However, Spearman correlation showed no correlation between Cthrough plasma concentrations of analytes (IVA, TEZ, ELX) and sweat test, FEV1 (%), or BMI. Our method proved to be suitable for TDM and could be helpful in assessing dose–concentration–response correlations in larger studies.

IntroductionHamstring strength deficits have been identified as risk factors for ACL and muscular injuries, with hamstring strain being the most prevalent muscle injuries in soccer. The aim of this study was to investigate hamstring eccentric strength before and after a soccer match in soccer athletes.Material and MethodsHamstring eccentric strength was measured in 64 healthy male and female competitive football athletes (14-25 years) during the execution of the Nordic hamstring exercise (NHE test) before and after a soccer match. Anterior-knee laxity (AKL) was quantified as well.ResultsMean and absolute eccentric hamstring peak torque decreased by 24.5 Nm (p<0.005) and 21.9 Nm (p<0.0005) in females, whereas males improved by 19.9 Nm (p=0.01) and 20.9 Nm (p=0.02), respectively. Hamstring’s total work in females decreased by 831.1 J (p<0.0005) compared to the males’ reduction of 235.3 J. Both pre- vs. post-match intersex mean and absolute eccentric HS peak torque changes were significant (p<0.0005), as the changes in HS total work (p=0.007). Pre- vs. post-match AKL difference and dominant vs. nondominant limb comparison of strength parameters were not significantly different. Younger female athletes (14-19 years old) presented a greater decrease in mean and absolute peak HS eccentric strength than those in older female and overall male athletes.ConclusionsHS eccentric strength and work differ based on the athlete’s sex, as measured by the NHE test. Mean peak, absolute peak, and total work showed greater reductions in females than in males. The 14- to 19-year-old female athletes subgroup experienced the highest reduction.

Personal mobile phone has become an integral part of our lives. In the medical field, the growing popularity of medicine applications allows more rapid communication among healthcare professionals and quick access to helpful information, which facilitates and improves patient care practice. The use of smartphones during work activities by healthcare professionals can cause a lack of attention and errors while carrying out health procedures. The result might be an increased threat endangering the safety of patients. The purpose of the present study was to investigate the level of nomophobia (a psychological condition regarded as a fear of being detached from mobile phone connectivity) and its correlations with the use of smartphones in clinical practice, distraction due to personal use and policies regarding mobile phones use in a sample of resident doctors of a University of Southern Italy. A cross-sectional study was carried out on 204 hospital residents divided into three areas depending on their duties: clinical, surgical, and services. Two tools were used: nomophobia questionnaire (NMP-Q) and a composite questionnaire investigating smartphone use in the specific healthcare setting. Sixty percent of participants were affected by a moderate level of nomophobia and 10% by a severe degree, jeopardizing both the work and social relationships of young doctors. Smartphone use can certainly represent a helpful support tool for clinical practice; consequently, we believe it would be appropriate to find instruments to screen smartphone dependence or compulsive use to further prevent, early diagnose or treat this detrimental disorder for health professionals.