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Pre-clinical and clinical evidence proposes that creatine monohydrate, an affordable nutraceutical, could be a useful adjunct to conventional antidepressant treatments. In this pilot feasibility and exploratory study, we investigate the 8-week effects of creatine in addition to cognitive-behavioural therapy (CBT) versus placebo plus CBT in depression. For the primary efficacy outcome of change in Patient Health Questionnaire-9 depression score at study endpoint, we used mixed-model repeated measures analysis of covariance. Logistic regressions were employed to assess acceptability (any-cause dropouts), tolerability (dropouts for adverse events), and safety (patients experiencing one or more adverse events). We calculated effect sizes adjusted for age, sex, and baseline depression score. One-hundred participants (50 females, mean age= 30.4 ± 7.4 years) with depression (mean PHQ-9 = 17.6 ± 6.3) were randomised to either creatine+CBT (N = 50) or placebo+CBT (N = 50). At 8 weeks, PHQ-9 scores were lower in both study arms, but significantly more so in participants taking creatine (mean difference= -5.12). Treatment discontinuations due to any cause and to adverse events, and proportion of participants with at least one adverse event were comparable between study arms. This hypothesis-generating trial suggests that creatine could be a useful and safe supplement to CBT for depression. Longer and larger clinical trials are warranted., Competing Interests: Declaration of competing interest The authors declare none., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Neurobrucellosis presents diverse clinical challenges and risks of long-term complications., Objective: We aimed to assess the relationship between the duration of antibiotic therapy, clinical factors, and the outcome of neurobrucellosis with a case report combined with a systematic review of the literature., Methods: We present a case of a 31 years-old man successfully treated at our Institution. We then searched Ovid MEDLINE, Embase and Scopus for articles that encompassed neurobrucellosis cases, duration of treatment, and outcome. The primary outcome was to assess an association between the duration of treatment and the risk of sequelae or relapses. Univariate, multivariate and sensitivity analysis were carried out to define which variables affect​ed​ the clinical outcome. Quality assessment was performed using a dedicated tool., Results: A total of 123 studies were included, totaling 221 patients. Median duration of treatment was 4 months (IQR 3 - 6), 69% patients recovered without sequelae, 27% had sequelae. Additionally, five patients had a relapse, and 4 patients died. Multivariate analysis found that the duration of treatment, age, and the use of ceftriaxone were not associated with a higher risk of sequelae or relapses. A significant association was found for corticosteroids use (OR 0.39, 95% IC 0.16 - 0.96, p = 0.038), motor impairment (OR 0.29, 95% IC 0.14 - 0.62, p = 0.002), and hearing loss (OR 0.037, 95% IC 0.01 - 0.11, p < 0.001)., Conclusions: This study highlights the variability in clinical presentations and treatment approaches for neurobrucellosis. Patients with factors indicating higher sequelae risk require meticulous follow-up., (© 2024. The Author(s).)

Objective: To assess the overall survival (OS) of internal cerebrospinal fluid shunt (ICSFS) in the adult population., Methods: Medline database was searched from 2000 to 2023 to identify studies reporting on ICSFS OS. Only articles reporting on adult ICSFS OS by a Kaplan-Meier (KM) OS curve were included. Numerical data were extracted from KM curves and, were then reconstructed to estimate 3, 6, 9, 12, 18, 24, 36, 48 and 60 months restricted mean survival times (RMST). RMST of ICSFS and its standard error (SE) at each time of interest were used as summary measure and primary outcome across studies. To account for the effect of between-study heterogeneity, RMST were pooled using a random effects model., Results: Out of 421 screened studies, solely 6 were included in the meta-analysis. Calculated ICSFS OS at 3, 6, 12, 18, 24, 36, 48 and 60 months were 92.4%, 95% CI[89.6-95.2]; 89.5%, 95% CI[86.3-92.8]; 87.5%, 95% CI[83.9-91.1]; 85.2%, 95% CI[80.4-90.0]; 83.4%, 95% CI[79.0-87.9]; 81.6%, 95% CI[76.7-86.5]; 78.8%, 95% CI[72.9-84.6]; 76.7%, 95% CI[70.3-83.1]; 74.5%, 95% CI[67.8-81.1] respectively. There was a significant heterogeneity as indicated by a high I 2 of 82.5%, 95% CI[63.1-91.7]. Heterogeneity test of Q=28.63 was also significant (p-value<0.001)., Conclusions: On contrary to what one might think, there are few available studies assessing adult ICSFS OS. We used a novel technique to meta-analyse adult ICSFS OS. ICSFS failure rate is maximal within the 3 to 6 post-operative months. Afterwards, the risk slowly decrease over time. At 5 years, less than three quarters of the patients still have a naïve functional ICSFS never revised., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Timely detection of congenital anomalies using ultrasound improves neonatal care. As specialist sonographers are often geographically dispersed, they are sometimes requested to provide a second opinion via tele-expertise. The present study aimed to evaluate the economic impact of asynchronous tele-expertise in obstetric ultrasound care in private medical practice through a comparison with face-to-face consultations. We conducted a cost minimization analysis using decision tree modeling in order to determine whether asynchronous tele-expertise or face-to-face consultation had the lowest cost, under the assumption of equivalent effectiveness in terms of prenatal diagnosis. Costs were measured from the societal perspective. The data for the base case of our modeling came from a retrospective analysis of the clinical practice of an expert who had been conducting asynchronous tele-expertise for 4 years in France. The study included 260 patients for whom 322 requests for expert opinions were made by physicians/midwives from January 2016 to January 2020. The expected average total cost for tele-expertise for a patient was €74.45 (95% CI: €66.36-€82.54) compared to €195.02 (95% CI: €183.90-€206.14) for the conventional face-to-face strategy. Accordingly, using tele-expertise led to a statistically significant reduction of €120.57 in the average total cost per patient. A sensitivity analysis confirmed the robustness of the model produced. The results of the present study underline the efficiency of tele-expertise and highlight related economic benefits. Accordingly, they could inform public health policy on the dissemination of tele-expertise in the field of obstetric ultrasound care., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Edwin Quarello is a member of the medical committee of Rofim, a telemedicine startup based in France. There are no patents, products in development or marketed products associated with this research to declare.

The contribution of non-indigenous species to the transfer of contaminants in invaded food webs represents an active research area. Here we measured trace metals and CN stable isotopes in five populations of the invasive Atlantic blue crab Callinectes sapidus and in baseline bivalve species from Spain, Italy and Greece. They were used to estimate trophic transfer effects and the trophic position and isotopic niche of C. sapidus. Maximum trophic transfer effects occurred where the crab showed the largest isotopic niches and highest trophic positions; furthermore, the consistency of trace metal profiles between bivalves and crabs co-varied with the trophic position of the latters. Omnivory may influence the success of an invasive species, but also limit its effectiveness for biomonitoring. However, our results indicated that stable isotopes analysis provides a clarifying background where to cast patterns of contamination of the blue crab as well as of other omnivorous biomonitor species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The UK National Institute for Health and Care Excellence (NICE) guidance for the treatment of depression is widely followed and has international influence. According to these guidelines, antidepressant medications are recommended for moderate to severe depression. Nonetheless, antidepressants are increasingly prescribed, including for cases of subthreshold and mild depression. This may indicate that a proportion of depressed patients uses pharmacological interventions with unclear evidence-base, though other factors such as physical and mental health comorbidities need to be accounted for. This study aims to investigate the prevalence and trends of antidepressant prescriptions among community-dwelling adults diagnosed with depression according to NICE recommendations. We conducted a systematic review of PsycInfo, PubMed/MEDLINE, and Scopus databases. Observational studies reporting on the prevalence of antidepressant treatments in UK adults diagnosed with depression were sought. Fifteen studies were included. The prevalence of antidepressants for depression treatment ranged from 30.8 to 95% and mainly concerned selective serotonin reuptake inhibitors (SSRIs) among classes of antidepressant drugs. Little information about depression severity as well as comorbid conditions was reported. High prevalence rates of antidepressant drug use highlight the widespread adoption of pharmacological interventions, while also raising concerns about compliance with NICE guidelines. Careful assessment of depressive illness severity and comorbidities is needed to ensure the delivery of adequate care to people with depression. Systematic Review Registration Number (PROSPERO) CRD42023448152., Competing Interests: Declarations Ethics Approval and Consent to Participate This systematic review does not require ethical approval. Consent for Publication Not applicable. Competing Interests The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Handling missing data in clinical prognostic studies is an essential yet challenging task. This study aimed to provide a comprehensive assessment of the effectiveness and reliability of different machine learning (ML) imputation methods across various analytical perspectives. Specifically, it focused on three distinct classes of performance metrics used to evaluate ML imputation methods: post-imputation bias of regression estimates, post-imputation predictive accuracy, and substantive model-free metrics. As an illustration, we applied data from a real-world breast cancer survival study. This comprehensive approach aimed to provide a thorough assessment of the effectiveness and reliability of ML imputation methods across various analytical perspectives. A simulated dataset with 30% Missing At Random (MAR) values was used. A number of single imputation (SI) methods - specifically KNN, missMDA, CART, missForest, missRanger, missCforest - and multiple imputation (MI) methods - specifically miceCART and miceRF - were evaluated. The performance metrics used were Gower's distance, estimation bias, empirical standard error, coverage rate, length of confidence interval, predictive accuracy, proportion of falsely classified (PFC), normalized root mean squared error (NRMSE), AUC, and C-index scores. The analysis revealed that in terms of Gower's distance, CART and missForest were the most accurate, while missMDA and CART excelled for binary covariates; missForest and miceCART were superior for continuous covariates. When assessing bias and accuracy in regression estimates, miceCART and miceRF exhibited the least bias. Overall, the various imputation methods demonstrated greater efficiency than complete-case analysis (CCA), with MICE methods providing optimal confidence interval coverage. In terms of predictive accuracy for Cox models, missMDA and missForest had superior AUC and C-index scores. Despite offering better predictive accuracy, the study found that SI methods introduced more bias into the regression coefficients compared to MI methods. This study underlines the importance of selecting appropriate imputation methods based on study goals and data types in time-to-event research. The varying effectiveness of methods across the different performance metrics studied highlights the value of using advanced machine learning algorithms within a multiple imputation framework to enhance research integrity and the robustness of findings., (© 2024. The Author(s).)

Background: Art therapy has a long history of applications in cognitive and motor rehabilitation. More recently, a growing body of scientific literature has highlighted the potential of virtual reality in neurorehabilitation, though it has focused more on the technology itself than on the principles adopted in digital scenarios., Methods: This study is a single-blind randomized controlled trial conducted on 40 patients with stroke, comparing conventional therapy (physical therapy for the upper and lower limbs, for posture and balance, cognitive therapy, occupational therapy, speech therapy, and specific therapy for swallowing, bowel, and bladder dysfunctions) to a protocol in which the upper limb physical therapy was substituted with art therapy administered by means of virtual reality exploiting the so-called Michelangelo effect., Results: After 12 sessions, patients in the virtual art therapy group showed a significantly greater improvement in independence in activities of daily living, as assessed by the Barthel Index (interaction of time and group: p = 0.001). Significant differences were also found in terms of upper limb muscle strength (Manual Muscle Test, p < 0.01) and reduction in spasticity (Ashworth scale, p = 0.007) in favor of the experimental group. In the virtual art therapy group, the effectiveness of the intervention was significantly correlated with patient participation (Pittsburgh Rehabilitation Participation Scale: R = 0.41), patient satisfaction (R = 0.60), and the perceived utility of the intervention by the therapist (R = 0.43)., Conclusions: These findings support the efficacy of virtual art therapy leveraging the Michelangelo effect. Further studies should also focus on cognitive domains that could benefit from this type of approach.

Cystic echinococcosis, a zoonosis caused by cestodes belonging to the Echinococcus granulosus sensu lato (s.l.) genetic complex, affects humans and diverse livestock species. Although a veterinary vaccine exhibiting high levels of antibody-mediated protection has successfully reached the market, the large genetic diversity among parasite isolates and their particular host preferences, makes still necessary the search for novel vaccine candidates. Glutathione transferases (GSTs) constitute attractive targets for immunoprophylaxis due to their outstanding relevance in helminth detoxification processes, against both exogenous and endogenous stressors. Among the six GSTs known to be expressed in E. granulosus s.l., EgGST1 (Mu-class), EgGST2 (Sigma-class), and EgGST3 (a still non-classifiable isoenzyme), show the highest proteomic expression. Therefore, their recombinant forms -rEgGST1, rEgGST2 and rEgGST3- were herein analyzed regarding their potential to induce long-term antiparasite protection in mice. Only immunization with rEgGST1 induced long-lasting protection; and accordingly, rEgGST1-specific antibodies enhanced the parasite killing through both the classical activation of the host complement system and the antibody-dependent cellular cytotoxicity by macrophages. These results support further testing of rEgGST1 as a vaccine candidate in diverse hosts due to the broad expression of EgGST1 in different parasite stages and tissues., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: Despite the availability of effective antidepressant strategies, numerous people with depressive disorders remain untreated. The Covid-19 pandemic has affected healthcare services, especially the mental health sector. This study aims to explore the coverage of depression treatments in the general Spanish population and the impact of the Covid-19 pandemic., Methods: We used longitudinal data (2018 and 2022) from the general Spanish population: pre-pandemic n = 1512; mean age = 65.43 years ± 14.90; 56 % females; post-pandemic n = 909; mean age = 68.00 years ± 14.24; 54 % women. The International Classification of Disease 10th edition was used to diagnose lifetime depressive episodes and severity. We explored psychological and pharmacological treatment coverage via multiple logistic regressions adjusted for 4 covariates (sex assigned at birth, education level, age, Covid-19 pandemic) for participants with a diagnosis of depression., Results: Treatment coverage for depression in the pre-pandemic and post-pandemic samples was, respectively, 53.3 % and 51.9 %. We observed an association between severe depression and treatment coverage (OR = 2.77, 95%CI 1.05 to 7.75). We found no association between the COVID-19 pandemic and treatment coverage., Conclusions: The pharmacological treatment coverage was associated with severe types of depression. The prevalence rates of treatment coverage were similar in the pre- and post-COVID-19 pandemic attesting to the resilience of the mental health system in Spain., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Purpose: To establish typical clinical and radiological profiles of primary low-grade parotid cancers in order to tailor therapeutic strategy., Materials and Methods: Retrospective study of 57 patients operated on for primary parotid cancer between 2010 and 2021, with review of preoperative MRI and histopathology according to a standardized scoring grid., Objective: To study prognostic factors and determine the preoperative clinical and radiological profile of low-grade cancers., Results: Good prognostic factors for specific survival were: staging ≤ cT3 (p = 0.014), absence of adenopathy on cN0 MRI (p < 0.001), superficial lobe location (p = 0.033), pN0 (p < 0.001), absence of capsular rupture (p = 0.004), as well as the absence of peri-tumoral nodules (p = 0.033), intra-parotid adenopathies (p < 0.001), vascular emboli (p < 0.001), peri-neural sheathing (p = 0.016), nuclear atypia (p = 0.031), and necrosis (p = 0.002). It was not possible to define a reliable clinical and radiological profile for low-grade cancers (sensitivity 38%, specificity 79%)., Conclusion: Our study demonstrated multiple factors of good prognosis, but it was not possible to define a clinical and radiological profile of patients likely to benefit from more limited surgery, nor to diagnose, a priori, low-grade cancers., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: New National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially in people with severe mental illness. However, the evidence base for their safety and risk/benefit balance in depression is not established., Objectives: This study aims to assess the real-world mortality and adverse events of statins in depressive disorders., Methods: Population-based, nationwide (England), between-subject, cohort study. We used electronic health records (QResearch database) of people aged 18-100 years with first-episode depression, registered with English primary care practices over January 1998-August 2020 for 12(+) months, divided into statin users versus non-users.Primary safety outcomes included all-cause mortality and any adverse event measured at 2, 6 and 12 months. Multivariable logistic regression was employed to control for several potential confounders and calculate adjusted ORs (aORs) with 99% CIs., Findings: From over 1 050 105 patients with depression (42.64% males, mean age 43.23±18.32 years), 21 384 (2.04%) died, while 707 111 (67.34%) experienced at least one adverse event during the 12-month follow-up. Statin use was associated with lower mortality over 12 months (range aOR 2-12months 0.66-0.67, range 99% CI 0.60 to 0.73) and with lower adverse events over 6 months (range aOR 2-6months 0.90-0.96, range 99% CI 0.91 to 0.99), but not at 1 year (aOR 12months 0.99, 99% CI 0.96 to 1.03). No association with any other individual outcome measure (ie, any other neuropsychiatric symptoms) was identified., Conclusions: We found no evidence that statin use among people with depression increases mortality or other adverse events., Clinical Implications: Our findings support the safety of updated NICE guidelines for prescribing statins in people with depressive disorders., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare the following: RDG is supported by the Wellcome Trust (award 102176/Z/13/Z, grant 216452/Z/19/Z, title 'The effects of anti-inflammatory drugs on emotional and reward processing'). FDC is supported by the National Institute for Health Research (NIHR) Research Professorship to AC (grant RP-2017-08-ST2-006) and by the NIHR Oxford Health Biomedical Research Centre (grant BRC-1215-20005). EGO is supported by the NIHR Research Professorship to AC (grant RP-2017-08-ST2-006). PC is supported by the Medical Research Council (MRC) (grant MR/S003037/1, title 'Clinical Psychopharmacology of Depression'). CJH is supported by the NIHR Oxford Health Biomedical Research Centre. SF is supported by the NIHR Oxford Health Biomedical Research Centre. AC is supported by the NIHR Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration, by the NIHR Oxford Health Biomedical Research Centre (grant BRC-1215-20005) and by Wellcome Trust (GALENOS Project). CJH has received consultancy fees from P1vital, Lundbeck, Servier, UCB, Zogenix, J&J and Syndesi outside of the current work. AC has received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), CARIPLO, Lundbeck and Angelini Pharma outside of the current work. The other authors declare that they have no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Infective endocarditis (IE) is a serious condition which is difficult to diagnose and to treat, both medically and surgically., Objectives: The objective of this study was to evaluate the impact of the SARS-CoV-2 pandemic on the management of patients with IE., Methods: We conducted a single-centre retrospective study including patients hospitalized for IE during the pandemic (Group 2) compared with the same period the year before (Group 1). We compared clinical, laboratory, imagery, therapeutic, and patient outcomes between the two groups., Results: A total of 283 patients were managed for possible or definite IE (164 in Group 1 and 119 in Group 2). There were more intravenous drug-related IE patients in Group 2 ( p = 0.009). There was no significant difference in surgery including intra-cardiac device extraction ( p = 0.412) or time to surgery ( p = 0.894). The one-year mortality was similar in both groups (16% versus 17.7%, p = 0.704). The recurrence rate was not significantly different between the two groups (5.9% in Group 2 versus 9.1% in Group 1, p = 0.311)., Conclusions: The SARS-CoV-2 pandemic did not appear to have had a negative impact on the management of patients with IE. Maintenance of the activities of the endocarditis team within the referral centre probably contributed to this result. Nevertheless, the high proportion of intravenous drug-addicted patients in the pandemic cohort suggests that the SARS-CoV-2 pandemic had a major psychosocial impact.

Accidents caused by Bothrops jararaca (Bj) snakes result in several local and systemic manifestations, with pain being a fundamental characteristic. The inflammatory process responsible for hyperalgesia induced by Bj venom (Bjv) has been studied; however, the specific roles played by the peripheral and central nervous systems in this phenomenon remain unclear. To clarify this, we induced hyperalgesia in rats using Bjv and collected tissues from dorsal root ganglia (DRGs) and spinal cord (SC) at 2 and 4 h post-induction. Samples were labeled for Iba-1 (macrophage and microglia), GFAP (satellite cells and astrocytes), EGR1 (neurons), and NK1 receptors. Additionally, we investigated the impact of minocycline, an inhibitor of microglia, and GR82334 antagonist on Bjv-induced hyperalgesia. Our findings reveal an increase in Iba1 in DRG at 2 h and EGR1 at 4 h. In the SC, markers for microglia, astrocytes, neurons, and NK1 receptors exhibited increased expression after 2 h, with EGR1 continuing to rise at 4 h. Minocycline and GR82334 inhibited venom-induced hyperalgesia, highlighting the crucial roles of microglia and NK1 receptors in this phenomenon. Our results suggest that the hyperalgesic effects of Bjv involve the participation of microglial and astrocytic cells, in addition to the activation of NK1 receptors.

Here, we describe the use of proactive therapeutic drug monitoring (TDM) to individualize the optimal timing of drug injections in 16 adult patients with chronic osteoarticular infections receiving a median of 7 injections of dalbavancin (up to 12 injections in 15 months). Dalbavancin injections were repeated at medians of 39-47 days, with infusion intervals ranging from 26 to 69 days. TDM can facilitates a precise, targeted use of dalbavancin for infections requiring prolonged treatments., Competing Interests: The authors declare no conflict of interest.

Introduction: The life expectancy of β-thalassemia patients has increased over the last 20 years. In this study, we evaluated the current health status and quality of life of these patients managed in a reference center in Marseille., Methods: This is a single-center, descriptive study conducted between June and August 2019 in patients over 18 years of age with β-thalassemia major or intermedia. Clinical and paraclinical data were collected retrospectively and the SF-36 health survey questionnaire was proposed to each patient., Results: 43 of 64 selected patients were included and divided into 2 groups: 35 patients with transfusion-dependent β-thalassemia and 8 patients with non-transfusion-dependent β-thalassemia. Liver iron overload is the most frequent complication, present in 80% of transfusion-dependent and 62.5% of non-transfusion-dependent patients. Cardiac iron overload is present only in the transfusion dependent β-thalassemia group (20%). Hypogonadotropic hypogonadism remains the most common endocrine disorder (41.9%) followed by osteoporosis (37.2%). Among the 31 patients who completed the SF-36 questionnaire, physical and mental quality of life scores were lowered in transfusion dependent (respectively 42.7 and 46.8) as in non-transfusion-dependent patients (respectively 43.8 and 28.9)., Conclusion: Despite an improvement in medical care, our patients with β-thalassemia show an alteration in their quality of life that will need to be characterized in the entire French cohort., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Background: MicroRNAs (miRNAs) are small non-coding RNAs capable of regulating gene expression post-transcriptionally. MiRNAs are recognized as key regulators of diverse biological and developmental processes. During the pregnancy-puerperal cycle, numerous changes occur in the female body for the formation, growth, and development of the baby. After birth, there is a critical period in child development, as rapid gains in the physical, cognitive, and socio-emotional domains constitute the "building blocks" of children's later growth., Objective: The aim of this study was to investigate the association between maternal expression of hsa-miR-423-5p during the first and second trimesters of pregnancy and neurocognitive development at 90 days of life in infants. Methods: This is a longitudinal study included in a population-based cohort study, carried out in a city in southern Brazil. The Bayley III was used to assess the babies' cognitive development. Blood samples from mothers were obtained for RNA extraction from serum and analysis of miRNA expression by qRT-PCR., Results: In total, 87 dyads (mother-baby) were included. The average gestational age was 15.86 weeks (SD ± 5.55). An association of maternal miRNA with infant cognitive development was found; as maternal miR-423-5p increases, infants' cognitive development increases by 2.40 (95% CI 0.37; 4.43, p  = 0.021) points at 3 months of age., Conclusion: In this context, it is suggested to use this miRNA as a biomarker of child neurocognitive development detectable in the prenatal period, thus allowing the planning of early interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 do Amaral, Nedel, Ferrúa, Garcia, Corrêa, Giorgi, Longoni dos Santos, de Assis, de Avila Quevedo, Ghisleni, de Matos, Pinheiro, Trettim and Pinheiro.)

Dalbavancin is a long-acting lipoglycopeptide that is registered for the treatment of acute bacterial skin and skin structure infections, and it is also increasingly used for infections that require prolonged antibiotic treatment. Here, we present the results from the first 2 years of a service set up in December 2021 for the therapeutic drug monitoring (TDM) of dalbavancin in clinical settings. In particular, we compared the trough concentration (Cmin) to maximum concentration (Cmax) in patients with osteoarticular infections receiving prolonged treatment with dalbavancin. Log-linear regression models were used to estimate the timing of dalbavancin administration with the goal of maintaining Cmin concentrations of >8 mg/L in the two TDM-based strategies. From December 2021 to November 2023, 366 TDMs of dalbavancin from 81 patients were performed. The Cmin and Cmax concentrations of dalbavancin ranged from 4.1 to 70.5 mg/L and from 74.9 to 995.6 mg/L, respectively. With log-linear regression models, we estimated that each injection should be administered every 42-48 days to maintain the Cmin concentrations. Out of the 81 patients, 37 received at least three doses of dalbavancin for the treatment of osteoarticular infections. Despite there being no significant differences in the days of dalbavancin treatment (130 ± 97 versus 106 ± 102 days), the patients in the Cmax-based TDM group received a significantly lower number of dalbavancin injections (5.2 ± 1.8 versus 7.3 ± 2.6 injections, p = 0.005), and they were administered over a longer period of time (40 ± 10 versus 29 ± 14 days, p = 0.013) than in the Cmin-based TDM group. In conclusion, Cmax-based TDM was associated with a significant reduction in the inter-individual variability of dalbavancin concentrations and lower drug dosing frequency than those of Cmin-based TDM. This approach could, therefore, favor a more rational and targeted use of dalbavancin in patients requiring prolonged treatment.

Background: Antidepressants are licensed for use in depressive disorders, but non-response and poor adherence to treatment affect a considerable number of patients. Pre-clinical and clinical evidence suggest that statins can augment the effects of antidepressants. However, the acceptability and tolerability of combining statins with antidepressants are unclear, and their add-on efficacy has only been shown in small, short-term clinical trials. Observational data can provide complementary information about treatment effects on larger samples over longer follow-ups. In this study, we therefore assessed the real-world acceptability, tolerability, and efficacy of concomitant antidepressant and statin treatment in depression., Methods: We conducted a population-based cohort study investigating QResearch primary care research database, which comprises the anonymised electronic healthcare records of 35 + million patients over 1574 English general practices. Patients aged 18-100 years, registered between January 1998 and August 2020, diagnosed with a new episode of depression, and commencing an antidepressant were included. Using a between-subject design, we identified two study groups: antidepressant + statin versus antidepressant-only prescriptions. Outcomes of interest included the following: antidepressant treatment discontinuations due to any cause (acceptability) and due to any adverse event (tolerability) and effects on depressive symptoms (efficacy) measured as response, remission, and change in depression score on the Patient Health Questionnaire-9. All outcomes were assessed at 2, 6, and 12 months using multivariable regression analyses, adjusted for relevant confounders, to calculate adjusted odds ratios (aORs) or mean differences (aMDs) with 99% confidence intervals (99% CIs)., Results: Compared to antidepressant-only (N 626,335), antidepressant + statin (N 46,482) was associated with higher antidepressant treatment acceptability (aOR 2months 0.88, 99% CI 0.85 to 0.91; aOR 6months 0.81, 99% CI 0.79 to 0.84; aOR 12months 0.78, 99% CI 0.75 to 0.81) and tolerability (aOR 2months 0.92, 99% CI 0.87 to 0.98; aOR 6months 0.94, 99% CI 0.89 to 0.99, though not long term aOR 12 months 1.02, 99% CI 0.97 to 1.06). Efficacy did not differ between groups (range aOR 2-12 months 1.00 and 1.02 for response and remission, range aOR 2-12 months  - 0.01 and - 0.02 for change in depression score)., Conclusions: On real-world data, there is a positive correlation between antidepressant treatment adherence and statin use, partly explained by fewer dropouts due to adverse events. The main limitation of our study is its observational design, which restricts the potential to make causal inferences., (© 2023. The Author(s).)

Purpose: Sleeve gastrectomy (SG) has become the most common bariatric procedure, but it is often characterized by the onset of postoperative gastroesophageal reflux disease (GERD). High-resolution manometry (HRM) is a useful tool to detect risk factors for GERD. The aim of this study was to evaluate preoperative manometric parameters as possible predictors of postoperative GERD., Materials and Methods: This was a monocentric retrospective study. We analyzed 164 patients, with preoperative esophagitis/GERD symptoms who underwent preoperative HRM and were submitted to SG (July 2020-February 2022)., Results: Postoperative GERD was observed in 60 patients (36.6%): 41 of them (68%) already had preoperative GERD symptoms, whereas the remaining 19 patients (32%) developed postoperative symptoms. Female patients developed postoperative GERD in a significantly higher fraction of cases as compared to male patients (82% versus 18%; p < 0.001). DCI (distal contractile integral) was identified as the only HRM parameter correlating with the presence of GERD. Patients with DCI ≤ 1623 mmHg*cm*s developed postoperative GERD in 46% of cases (n = 43/94), as compared to 24% of cases (n = 17/70) among patients with DCI > 1623 mmHg*cm*s (p = 0.005). At multivariable analysis, female sex (OR 3.402, p = 0.002), preoperative GERD symptoms (OR 2.489, p = 0.013), and DCI ≤ 1623 mmHg*s*cm (OR 0.335, p = 0.003) were identified as independent determinants of postoperative GERD., Conclusion: All the patients with preoperative risk factors for reflux, such as GERD symptoms or esophagitis on EGDS (esophagogastroduodenoscopy), should be considered for an HRM. Moreover, when a DCI ≤ 1623 mmHg*s*cm is found, a bariatric procedure different from SG might be considered., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study evaluates the feasibility, efficacy, the complications rate, and the long-term results of laparoscopic treatment of gastroesophageal reflux disease (GERD) at a dedicated center. Materials and Methods: From 01/11/1993 to 01/12/2019, we performed 620 fundoplication surgeries by laparoscopic approach according to Rossetti technique and 160 according to Toupet technique, totally 780 procedures for gastroesophageal reflux disease. The average duration of surgery was 40 minutes (range 19 - 160) for Rossetti fundoplication, 50 (range 30 - 180), and for Toupet 60 (range 45 - 190). All patients were investigated by upper digestive tract radiography, esophagogastroscopy, 24h computerized pH-metry, manometry and scintigraphy to assess esophageal clearance and gastric emptying times. In the 180 (23 %) patients with associated hiatal hernia, direct hiatoplasty was performed in 108 cases, and hiatoalloplasty in the remaining 72. Results: There were no cases of perioperative mortality; the morbidity rate was 6.28 %. We had 16.7 % long-term failures, requiring reintervention in 46 cases (6.5 %). Thirty patients (3.84 %) had to resume occasional 40 mg PPI therapy and 48 patients (6.15 %) had to resume 40 mg PPI therapy continuously. Manometry in these patients revealed lower esophageal sphincter tone between 10- and 16-mm hg with complete and coordinated relaxations. Of the 44 patients who underwent redo surgery 26 were reoperated to repackage a tighter plastic. Six patients required reoperation for dysphagia. Twelve paraesophageal hernias were recorded in the group of patients in whom only hiatoplasty without prosthesis was performed. In all cases, a hiatoplasty with prosthesis was repackaged laparoscopically. Conclusions: We emphasize the importance of accurate morphologic and functional evaluation of the esophagus preoperatively for selection of the most appropriate intervention and postoperatively for evaluation of the causes of failures. In the presence of hiatal hernia, it is always advisable to perform hiatoplasty with the placement of a prosthesis., (Celsius.)

Statins are commonly prescribed medications widely investigated for their potential actions on the brain and mental health. Pre-clinical and clinical evidence suggests that statins may play a role in the treatment of depressive disorders, but only the latter has been systematically assessed. Thus, the physiopathological mechanisms underlying statins' putative antidepressant or depressogenic effects have not been established. This review aims to gather available evidence from mechanistic studies to strengthen the pharmacological basis for repurposing statins in depression. We used a broad, well-validated search strategy over three major databases (Pubmed/MEDLINE, Embase, PsychINFO) to retrieve any mechanistic study investigating statins' effects on depression. The systematic search yielded 8068 records, which were narrowed down to 77 relevant papers. The selected studies (some dealing with more than one bodily system) described several neuropsychopharmacological (44 studies), endocrine-metabolic (17 studies), cardiovascular (6 studies) and immunological (15 studies) mechanisms potentially contributing to the effects of statins on mood. Numerous articles highlighted the beneficial effect of statins on depression, particularly through positive actions on serotonergic neurotransmission, neurogenesis and neuroplasticity, hypothalamic-pituitary axis regulation and modulation of inflammation. The role of other mechanisms, especially the association between statins, lipid metabolism and worsening of depressive symptoms, appears more controversial. Overall, most mechanistic evidence supports an antidepressant activity for statins, likely mediated by a variety of intertwined processes involving several bodily systems. Further research in this area can benefit from measuring relevant biomarkers to inform the selection of patients most likely to respond to statins' antidepressant effects while also improving our understanding of the physiopathological basis of depression., (© 2023. The Author(s).)

Background: Evidence suggests inflammation may be a key mechanism by which psychosocial stress, including loneliness, predisposes to depression. Observational and clinical studies have suggested simvastatin, with its anti-inflammatory properties, may have a potential use in the treatment of depression. Previous experimental medicine trials investigating 7-day use of statins showed conflicting results, with simvastatin displaying a more positive effect on emotional processing compared with atorvastatin. It is possible that statins require longer administration in predisposed individuals before showing the expected positive effects on emotional processing., Aims: Here, we aim to test the neuropsychological effects of 28-day simvastatin administration versus placebo, in healthy volunteers at risk for depression owing to loneliness., Method: This is a remote experimental medicine study. One hundred participants across the UK will be recruited and randomised to either 28-day 20 mg simvastatin or placebo in a double-blind fashion. Before and after administration, participants will complete an online testing session involving tasks of emotional processing and reward learning, processes related to vulnerability to depression. Working memory will also be assessed and waking salivary cortisol samples will be collected. The primary outcome will be accuracy in identifying emotions in a facial expression recognition task, comparing the two groups across time.

Introduction: Laparoscopic sleeve gastrectomy (SG) has rapidly become one of the most commonly performed procedures in bariatric surgery. Weight regain and insufficient weight loss are the most common causes for surgical failure. Re-sleeve gastrectomy (ReSG) can represent an option when there is evidence of a dilated gastric tube., Objectives: The aim of the study is to evaluate safety, efficacy and rate of gastro-esophageal reflux disease (GERD) after ReSG in one of the largest series present in literature with long-term follow up., Methods and Study Design: Retrospective study design. From February 2010 to August 2018, 102 patients underwent ReSG at our Centre. We divided patients into two groups, according to the main reason for surgical failure: insufficient weight loss or progressive weight regain., Results: One hundred-two patients (78 women, 24 men) with BMI 38 ± 6 kg/m 2 underwent ReSG (mean age 44 years). Rate of postoperative complications was 3.9% (4/102). After a mean follow-up of 55 months, mean BMI decreased to 30,4 kg/m 2 and the mean percentage of excess weight loss (%EWL) was 51 ± 38.6. Symptoms of GERD were present in 35/102 patients (34.3%) and the need for a new operation occurred in six patients. Forty-five patients were submitted to ReSG for progressive weight regain (group A) and 57 for insufficient weight loss (group B). No differences were found in terms of postoperative BMI and %EWL., Conclusion: ReSG is a feasible procedure after primary SG failure in selected patients, but its efficacy in reducing the BMI under 30 kg/m 2 is still unclear. In addition, over 30% of patients suffer from long-term gastro-esophageal reflux., (© 2023. Italian Society of Surgery (SIC).)

Background: The excess mortality observed in Acute Myeloblastic Leukaemia (AML) patients, partly attributed to unequal access to curative treatments, could be linked to care pathways., Methods: We included 1039 AML incident cases diagnosed between 2012-2016 from the 3 French blood cancer registries (3,625,400 inhabitants). We describe patients according to age, the medical entry unit and access to the specialised haematology unit (SHU) during follow-up. Multivariate logistic regression model was done to determine the association between covariables and access to SHU. A total of 713 patients (69%) had access to SHU during care., Results: The most common care pathway concerned referral from the general practitioner to SHU, n = 459(44%). The univariate analysis observed a downward trend for the most deprived patients. Patients who consulted in SHU were younger (66 years vs. 83, p < 0.001), and 92% had access to cytogenetic analysis (vs. 54%, p < 0.001). They also had less poor prognosis AML-subtypes (AML-MRC, t-AML/MDS and AML-NOS) (38% vs. 69%); 77% with de novo AML (vs. 67%, p < 0.003)], more favourable cytogenetic prognostic status (23% vs. 6%, p < 0.001), less comorbidities (no comorbidity = 55% vs. 34%, p < 0.001) and treatments proposed were curative 68% (vs. 5.3%, p < 0.001). Factors limiting access to SHU were age over 80 years (OR, 0.14; 95% CI, 0.04-0.38), severe comorbidities (OR, 0.39; 95% CI, 0.21-0.69), emergency unit referral (OR, 0.28; 95% CI, 0.18-0.44) and non-SHU referral (OR, 0.12; 95% CI, 0.07-0.18). Consultation in an academic hospital increased access to SHU by 8.87 times (95% CI, 5.64-14.2)., Conclusion: The high proportion of access to cytogenetic testing and curative treatment among patients admitted to SHU, and the importance of early treatment in AML underlines the importance of access to SHU for both diagnosis and treatment., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

In the presence of competing causes of event occurrence (e.g., death), the interest might not only be in the overall survival but also in the so-called net survival, that is, the hypothetical survival that would be observed if the disease under study were the only possible cause of death. Net survival estimation is commonly based on the excess hazard approach in which the hazard rate of individuals is assumed to be the sum of a disease-specific and expected hazard rate, supposed to be correctly approximated by the mortality rates obtained from general population life tables. However, this assumption might not be realistic if the study participants are not comparable with the general population. Also, the hierarchical structure of the data can induces a correlation between the outcomes of individuals coming from the same clusters (e.g., hospital, registry). We proposed an excess hazard model that corrects simultaneously for these two sources of bias, instead of dealing with them independently as before. We assessed the performance of this new model and compared it with three similar models, using extensive simulation study, as well as an application to breast cancer data from a multicenter clinical trial. The new model performed better than the others in terms of bias, root mean square error, and empirical coverage rate. The proposed approach might be useful to account simultaneously for the hierarchical structure of the data and the non-comparability bias in studies such as long-term multicenter clinical trials, when there is interest in the estimation of net survival., (© 2023 The Authors. Biometrical Journal published by Wiley-VCH GmbH.)

In neurorehabilitation, some studies reported the effective use of art therapy for reducing psychological disorders and for enhancing physical functions and cognitive abilities. Neuroaesthetical studies showed that seeing an art masterpiece can spontaneously elicit a widespread brain arousal, also involving motor networks. To combine contemplative and performative benefits of art therapy protocols, we have developed an immersive virtual reality system, giving subjects the illusion that they are able to paint a copy of famous artistic paintings. We previously observed that during this virtual task, subjects perceived less fatigue and performed more accurate movements than when they were asked to color the virtual canvas. We named this upshot the Michelangelo effect. The aim of this study was to test the rehabilitative efficacy of our system. Ten patients with stroke in the subacute phase were enrolled and trained for one month with virtual art therapy (VAT) and physiotherapy. Their data were compared with those of ten patients matched for pathology, age and clinical parameters, trained only with conventional therapy for the same amount of time. The VAT group showed a significantly higher improvements in the Barthel Index score, a measure of independency in activities of daily living (66 ± 33% vs. 31 ± 28%, p = 0.021), and in pinching strength (66 ± 39% vs. 18 ± 33%, p = 0.008), with respect to the group treated with conventional rehabilitation.

Hypothesis: Materials and colloids science can provide significant contributions to the conservation of Cultural Heritage. Hybrid systems made of a castor oil-derived polymeric network and a disperse phase of zinc oxide particles (ZnO/COPs) can be more effective absorbers of acetic acid (AcOH, a major pollutant harmful to artifacts in museums and art collections) than state-of-the-art materials, provided the acid uptake mechanism by the hybrids is elucidated and optimized. The starting hypothesis was that the polymer matrix might act as transporter, while acid adsorption would take place at the ZnO particles surface. The effect of particles size was expected to play a significant role., Experiments: The adsorption kinetics of the hybrids were studied in the 23-45˚C range, in comparison with activated charcoal, the benchmark employed by conservators. Morphological and fractal dimension of ZnO micro- and nano-particles in the hybrid networks were investigated and correlated to the adsorption kinetics., Findings: The presence of a two-steps mechanism for AcOH uptake by the hybrids was demonstrated for the first time: a combination of Fickian diffusion and Case-II transport occurs in the COP matrix, and adsorption dominates acid uptake (followed by neutralization) at the particles surface. This mechanism is likely key to explain the enhanced performances of the hybrids vs activated charcoal and state-of-the-art tools to remove AcOH. The hybrids have high uptake capacity, and lower activation energies for the removal process than materials where the uptake of acid relies solely on adsorption. The size of the ZnO particles contributes to the process, i.e. nanoparticles form smaller and ramified fractal clusters that are able to adsorb AcOH more effectively than microparticles. These insights demonstrated the efficacy of the novel hybrids in art conservation, where the control of minimal concentrations of VOCs is crucial for the preventive conservation of masterpieces, and can be useful to other fields where efficient capture of acetic acid is critical (food industry, textile dyeing/printing, etc.)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Heart failure- (HF) and arrhythmia-related complications are the main causes of morbidity and mortality in patients with nonischemic dilated cardiomyopathy (NIDCM). Cardiovascular magnetic resonance (CMR) imaging is a noninvasive tool for risk stratification based on fibrosis assessment. Diffuse interstitial fibrosis in NIDCM may be a limitation for fibrosis assessment through late gadolinium enhancement (LGE), which might be overcome through quantitative T1 and extracellular volume (ECV) assessment. T1 and ECV prognostic value for arrhythmia-related events remain poorly investigated. We asked whether T1 and ECV have a prognostic value in NIDCM patients., Methods: This prospective multicenter study analyzed 225 patients with NIDCM confirmed by CMR who were followed up for 2 years. CMR evaluation included LGE, native T1 mapping and ECV values. The primary endpoint was the occurrence of a major adverse cardiovascular event (MACE) which was divided in two groups: HF-related events and arrhythmia-related events. Optimal cutoffs for prediction of MACE occurrence were calculated for all CMR quantitative values., Results: Fifty-eight patients (26%) developed a MACE during follow-up, 42 patients (19%) with HF-related events and 16 patients (7%) arrhythmia-related events. T1 Z-score (p = 0.008) and global ECV (p = 0.001) were associated with HF-related events occurrence, in addition to left ventricular ejection fraction (p < 0.001). ECV > 32.1% (optimal cutoff) remained the only CMR independent predictor of HF-related events occurrence (HR 2.15 [1.14-4.07], p = 0.018). In the arrhythmia-related events group, patients had increased native T1 Z-score and ECV values, with both T1 Z-score > 4.2 and ECV > 30.5% (optimal cutoffs) being independent predictors of arrhythmia-related events occurrence (respectively, HR 2.86 [1.06-7.68], p = 0.037 and HR 2.72 [1.01-7.36], p = 0.049)., Conclusions: ECV was the sole independent predictive factor for both HF- and arrhythmia-related events in NIDCM patients. Native T1 was also an independent predictor in arrhythmia-related events occurrence. The addition of ECV and more importantly native T1 in the decision-making algorithm may improve arrhythmia risk stratification in NIDCM patients. Trial registration NCT02352129. Registered 2nd February 2015-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02352129., (© 2023. The Author(s).)

Background: Animal studies have demonstrated that fetal exposure to high maternal cholesterol levels during pregnancy predisposes to aortic atheroma in the offspring. In humans, little is known about the consequences of this exposure on the development of atherosclerotic cardiovascular disease later in life. We wanted to assess whether maternal/paternal inheritance of familial hypercholesterolemia (FH) gene mutation could be associated with subclinical coronary atherosclerosis., Methods: We retrospectively included 1350 patients, followed in the French registry of FH, with a documented genetic diagnosis. We selected 556 age- and sex-matched pair of patients based on the sex of the parents who transmitted the FH gene mutation, free of coronary cardiovascular event, and with a subclinical coronary atherosclerosis evaluation assessed using coronary artery calcium (CAC) score. We performed univariate and multivariate analysis to assess the individual effect of parental inheritance of the FH gene mutation on the CAC score., Results: In the whole population, patients with maternal inheritance of FH gene mutation (n=639) less frequently had a family history of premature cardiovascular events (27.7% versus 45%, P <0.0001) and were 2 years older (46.9±16.8 versus 44.7±15.9 years old, P =0.02) than those with paternal inheritance (n=711). There was no difference in the prevalence of cardiovascular events between the two groups. In the matched subgroup, maternal inheritance was significantly associated with an increase in CAC score value by 86% (95% CI, 23%-170%; P =0.003), a 1.81-fold risk of having a CAC score ≥100 Agatston units (95% CI, 1.06-3.11; P =0.03), and a 2.72-fold risk of having a CAC score ≥400 Agatston units (95% CI, 1.39-5.51; P =0.004) when compared with paternal inheritance in multivariate analysis., Conclusions: Maternal inheritance of FH gene mutation was associated with more severe subclinical coronary atherosclerosis assessed by CAC score and may be considered as a potential cardiovascular risk factor.

Background: Laparoscopic sleeve gastrectomy (LSG) is associated with the long-term development of gastroesophageal reflux disease (GERD). Recent studies on LSG with fundoplication showed a lower rate of postoperative GERD than LSG alone; however, there is a lack of objective instrumental data in the literature. This study aimed to evaluate whether and how fundoplication associated with Sleeve Gastrectomy affects the esophagogastric physiology. Materials and Methods: This prospective observational study included 20 patients with morbid obesity, GERD, and lower esophageal sphincter (LES) hypotonia. All the patients underwent LSG with Rossetti fundoplication. High-resolution manometry was performed pre- and postoperatively. All the patients completed the 6 months follow-up. Results: The fundoplication increased LES tone in all patients. The increase in the LES tone was statistically significant (330% increase). The integrated relaxation pressure and the distal contractile integral both increased accordingly, indicating an increased esophageal effort to pass through the modified esophagogastric junction. Conclusion: Rossetti fundoplication associated with LSG increased LES tone and decreased the chance of developing long-term GERD after LSG.

Processing large-scale graphs is challenging due to the nature of the computation that causes irregular memory access patterns. Managing such irregular accesses may cause significant performance degradation on both CPUs and GPUs. Thus, recent research trends propose graph processing acceleration with Field-Programmable Gate Arrays (FPGA). FPGAs are programmable hardware devices that can be fully customised to perform specific tasks in a highly parallel and efficient manner. However, FPGAs have a limited amount of on-chip memory that cannot fit the entire graph. Due to the limited device memory size, data needs to be repeatedly transferred to and from the FPGA on-chip memory, which makes data transfer time dominate over the computation time. A possible way to overcome the FPGA accelerators' resource limitation is to engage a multi-FPGA distributed architecture and use an efficient partitioning scheme. Such a scheme aims to increase data locality and minimise communication between different partitions. This work proposes an FPGA processing engine that overlaps, hides and customises all data transfers so that the FPGA accelerator is fully utilised. This engine is integrated into a framework for using FPGA clusters and is able to use an offline partitioning method to facilitate the distribution of large-scale graphs. The proposed framework uses Hadoop at a higher level to map a graph to the underlying hardware platform. The higher layer of computation is responsible for gathering the blocks of data that have been pre-processed and stored on the host's file system and distribute to a lower layer of computation made of FPGAs. We show how graph partitioning combined with an FPGA architecture will lead to high performance, even when the graph has Millions of vertices and Billions of edges. In the case of the PageRank algorithm, widely used for ranking the importance of nodes in a graph, compared to state-of-the-art CPU and GPU solutions, our implementation is the fastest, achieving a speedup of 13 compared to 8 and 3 respectively. Moreover, in the case of the large-scale graphs, the GPU solution fails due to memory limitations while the CPU solution achieves a speedup of 12 compared to the 26x achieved by our FPGA solution. Other state-of-the-art FPGA solutions are 28 times slower than our proposed solution. When the size of a graph limits the performance of a single FPGA device, our performance model shows that using multi-FPGAs in a distributed system can further improve the performance by about 12x. This highlights our implementation efficiency for large datasets not fitting in the on-chip memory of a hardware device., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2023.)

Kombucha is a mildly sweet, slightly acidic fermented beverage, commercially available worldwide, that has attracted increasing consumers' interest due to its potential health benefits. Kombucha is commonly prepared using sugared black or green tea, but also other plant substrates are frequently utilised. Kombucha is obtained by fermentation using a symbiotic culture of bacteria and yeasts, whose composition varies depending on inoculum origin, plant substrates and environmental conditions. After fermentation, kombucha drinks are usually refrigerated at 4 °C, in order to maintain their biological and functional properties. There are no reports on the fate of microbial communities of kombucha in relation to long-term storage time and temperature. Here, for the first time, we monitored the diversity and dynamics of the microbial communities of a kombucha beverage fermented with different herbs during storage at 4 °C and at room temperature, for a period of 90 days, utilising culture-dependent and independent approaches. Moreover, cultivable yeasts and acetic acid bacteria (AAB) were isolated from the beverage, inoculated in pure culture, identified by molecular methods, and yeasts assessed for their functional properties. Total yeast counts were not affected by storage temperature and time, although their community composition changed, as Saccharomyces species significantly decreased after 45 days of storage at room temperature, completely disappearing after 90 days. On the other hand, Dekkera anomala (Brettanomyces anomalus), representing 52 % of the yeast isolates, remained viable up to 90 days at both storage temperatures, and was able to produce high levels of organic acids and exopolysaccharides. Data from DGGE (Denaturing Gradient Gel Electrophoresis) band sequencing confirmed that it was the dominant yeast species in all samples across storage. Other yeast isolates were represented by Saccharomyces and Zygosaccharomyces species. Among AAB, Gluconobacter oxydans, Novacetimonas hansenii and Komagataeibacter saccharivorans represented 46, 36 and 18 % of the isolates, whose occurrence remained unchanged across storage at 4 °C and did not vary up to 20 days of storage at room temperature. This work showed that the combination of culture-dependent and independent approaches is important for obtaining a complete picture of the distinctive core microbial community in kombucha beverages during storage, elucidating its diversity and composition, and preliminary characterizing yeast strains with putative functional activities., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier B.V.)

Depression has a large burden, but the development of new drugs for its treatment has proved difficult. Progresses in neuroscience have highlighted several physiopathological pathways, notably inflammatory and metabolic ones, likely involved in the genesis of depressive symptoms. A novel strategy proposes to repurpose established medical treatments of known safety and to investigate their potential antidepressant activity. Among numerous candidates, growing evidence suggests that statins may have a positive role in the treatment of depressive disorders, although some have raised concerns about possible depressogenic effects of these widely prescribed medications. This narrative review summarises relevant findings from translational studies implicating many interconnected neurobiological and neuropsychological, cardiovascular, endocrine-metabolic, and immunological mechanisms by which statins could influence mood. Also, the most recent clinical investigations on the effects of statins in depression are presented. Overall, the use of statins for the treatment of depressive symptoms cannot be recommended based on the available literature, though this might change as several larger, methodologically robust studies are being conducted. Nevertheless, statins can already be acknowledged as a driver of innovation in mental health, as they provide a novel perspective to the physical health of people with depression and for the development of more precise antidepressant treatments.

Background: Gastroesophageal reflux disease (GERD), including erosive esophagitis, is highly prevalent in the obese population. Barrett's esophagus is the consequence of untreated GERD. Laparoscopic sleeve gastrectomy is one of the most frequently performed bariatric procedures. This study presents results after 5 years of follow-up of combined LSG and Rossetti fundoplication for the treatment of GERD, esophagitis, and Barrett's esophagus in patients with morbid obesity., Objective: To evaluate long-term results after sleeve gastrectomy with Rossetti fundoplication., Setting: Public university hospital in Italy., Methods: Since January 2015, more than 450 patients with obesity underwent sleeve gastrectomy with a Rossetti fundoplication procedure as part of prospective studies underway at our center performed by 4 different expert bariatric surgeons. Currently, 127 patients have a follow-up of 5 years or more., Results: Mean patient age was 42.9 ± 10.3 years, and mean body mass index was 42.4 ± 6.1 kg/m 2 . In total, 74.8% of patients were experiencing GERD before surgery. In 29 of 127 patients (22.8%), preoperative gastroscopy showed signs of esophagitis and/or Barrett's esophagus. In particular, 23 of 127 patients (18.1%) had grade A esophagitis, 2 of 127 (1.6%) had grade B, 2 of 127 (1.6%) had grade C, and 2 of 127 (1.6%) had Barrett's esophagus. Mean operative time was 51 ± 21 minutes. No intraoperative complications or conversions were reported. A regular postoperative course was seen in 91.3% of patients. Sixty months after surgery, more than 95% of patients did not experience any reflux symptoms. Percent total weight loss at follow-up was comparable with that with sleeve gastrectomy. Endoscopic follow-up demonstrated improvement of esophagitis lesions (including Barrett's esophagus) present in the preoperative setting., Conclusion: Laparoscopic sleeve gastrectomy with Rossetti fundoplication is well tolerated, feasible, and safe in patients with obesity, providing adequate weight loss results and complete resolution of clinical signs of GERD. We have recorded an improvement in esophagitis lesions present at preoperative gastroscopy and complete resolution of Barrett's esophagus within 5 years of follow-up., (Copyright © 2022 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Rheumatoid arthritis (RA) composite disease activity indices have become handy tools in daily clinical practice and crucial in defining remission or low disease activity, the main target of the RA treatment. However, there is no definition of the best index to assess disease activity in clinical practice., Objectives: To compare the residual activity among the indices with the ACR/EULAR remission criteria (Boolean method) to identify the most feasible for assessing remission in daily practice, also considering correlation and concordance, sensibility, and specificity., Patients and Methods: We selected 1116 patients with established RA from the real-life rheumatoid arthritis study database-REAL. The composite disease activity indices-DAS28-ESR, DAS28-CRP, SDAI, and CDAI-and their components were compared to the Boolean method to identify residual activity using binomial regression. The indices were analyzed for correlation and agreement using the Spearman index and weighted kappa. The chi-square test evaluated sensibility and specificity for remission based on the Boolean method., Results: DAS28-CRP overestimated remission and confirmed higher residual activity than SDAI and CDAI. The indices showed good correlation and agreement, with a better relationship between SDAI and CDAI (k:0,88). CDAI and SDAI showed higher sensitivity and specificity for remission based on the Boolean method. CDAI was performed in 99% of patients, while DAS28 and SDAI were completed in approximately 85%., Conclusions: Although all composite indices of activity can be used in clinical practice and showed good agreement, CDAI and SDAI have better performance in evaluating remission based on the Boolean method, showing less residual activity and higher sensibility and specificity. In addition, CDAI seems to be more feasible for disease activity evaluation in daily clinical practice, especially in developing countries., Competing Interests: The authors have declared that no competing interests exist.

Aims: To determine the prognosis of patients treated for infective endocarditis (IE) according to their healthcare pathway. To assess how the ESC guidelines are implemented concerning the performance of transoesophageal echocardiography, the use of antibiotic therapy, and the performance of valve surgery; and to compare the epidemiological profile of IE according to the type of centres in which the patients are hospitalized., Methods and Results: In a prospective multicentric study including 22 hospitals in the South-East of France, 342 patients were classified into three groups according to their healthcare pathway: 119 patients diagnosed and taken care entirely in a reference centre or hospital with cardiac surgery [Referral Center (RC) group], 111 patients diagnosed and initially taken care in a non-RC (NRC), then referred in a centre including cardiac surgery [transferred to the Referral Center (TRC) group] and 112 patients totally taken care in the NRC (NRC group). One-year mortality was 26% (88 deaths) and was not significantly different between Groups 1 and 2 (20 vs. 21%, P = 0.83). Patients in the NRC group had a higher mortality (37%) compared with patients in the RC and TRC groups (P < 0.001). ESC guidelines were not implemented similarly depending on the healthcare pathway (P = 0.04). Patients in the NRC group were significantly older (P < 0.001) and had more comorbidities (P < 0.001) than patients treated in referral centres., Conclusion: Prognosis of patients with IE is influenced by their healthcare pathway. Patients treated exclusively in NRC have a worse prognosis than patients treated in referral or surgical centres., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Statins have been proposed as a strategy for treating depression, but their benefit in the absence of concurrent antidepressant treatment is unclear. This meta-analysis investigated the antidepressant effects of statin monotherapy in the general population., Methods: We conducted a literature search of randomised controlled trials using any statin monotherapy versus any control condition for depressive symptoms. Our primary efficacy outcome was the mean value on any standardised scale for depression at study endpoint. We also measured efficacy at three further timepoints (<6 months, 6-12 months, >12 months), as well as acceptability, tolerability, and safety. Respectively, continuous and dichotomous outcomes were computed using standardised mean difference (SMD) or relative risk (RR) with 95% confidence intervals (CI) using a random-effect model., Results: Pooled analyses did not show that statin monotherapy improves depressive symptoms at endpoint (N = 2712 SMD = -0.18; 95% CI = -0.41 to 0.04), nor at any other specific timepoint. No difference between statins and control was identified for any of the other outcome measures., Discussion: These results differ from those of previous meta-analyses and, compounded by more recently available evidence, suggest that statins may not have intrinsic antidepressant properties, but may be useful for the management of depression in add-on to antidepressants., Limitations: Data from heterogeneous populations and using different statins were pooled, though several sensitivity and subgroup analyses were performed to account for that. PROSPERO registration: CRD42022306653. https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=306653., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Rationale: Clinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant translational value about simvastatin's influence on mood and cognition., Objectives: We aimed to investigate the effects of simvastatin on a battery of psychological tests and inflammatory markers in healthy volunteers., Methods: Fifty-three healthy subjects were randomly assigned to 7 days of either simvastatin (N = 27) or sucrose-based placebo (N = 26) given in a double-blind fashion. Then, participants were administered questionnaires measuring subjective rates of mood and anxiety, and a battery of tasks assessing emotional processing, reward learning, and verbal memory. Blood samples for C-reactive protein were also collected., Results: Compared to placebo, participants on simvastatin showed a higher number of positively valenced intrusions in the emotional recall task (F 1,51  = 4.99, p = 0.03), but also an increase in anxiety scores (F 1,51  = 5.37, p = 0.02). An exploratory analysis of the females' subgroup (N = 27) showed lower number of misclassifications as sad facial expression in the simvastatin arm (F 1,25  = 6.60, p = 0.02). No further statistically significant changes could be observed on any of the other outcomes measured., Conclusions: We found limited evidence that 7-day simvastatin use in healthy volunteer induces a positive emotional bias while also being associated with an increase in anxiety, potentially reflecting the early effects of antidepressants in clinical practice. Such effect might be more evident in female subjects. Different drug dosages, treatment lengths, and sample selection need consideration in further experimental medicine and clinical studies., Trial Registration: Clinicaltrials.gov: NCT04652089., (© 2022. The Author(s).)

Purpose: Aim of this study was to analyse feasibility, safety and effectiveness of laparoscopic transperitoneal hernia repair (TAPP) approach to inguinal hernias in the emergency setting, with a longer follow-up than the studies present in literature., Methods: We retrospectively analysed all patients who underwent emergency TAPP hernia repair in San Marco Hospital (Zingonia, Italy), from September 2010 to June 2020. A prospectively collected database of 685 consecutive TAPP hernia repair was reviewed. Feasibility and safety were evaluated through operative time, conversion rate, perioperative mortality, morbidity and prosthesis infection rate. Effectiveness was assessed by recurrence and complication rate, acute (during admission) and chronic (during follow-up) pain by Visual Analogic Scale (VAS), and recovery to normal activity in a long-term follow-up (mean period 1718 days)., Results: The final study group included 47 patients. The mean age was 59.6 years (range 22-89), 29 patients were male and 18 were female. The mean operation time was 64 min. Two cases were converted to open approach (4%). In four cases bowel resection became necessary (8.5%). Appendicectomy and omentectomy occurred once and twice, respectively (2% and 4%), and orchiectomy was required in two patients (4%). Seroma was the only postoperative complication that we registered in four patients. During a mean follow-up period of 1718 days, there was no recurrence of the hernia or other complications. Five patients referred mild occasional groin pain (VAS < 3), with quick relief without taking any pain killers., Conclusion: TAPP approach is a safe, feasible and effective therapeutic option for groin hernias in emergency setting. No recurrence or severe complications were reported in over 4 years of follow-up., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: To analyze worldwide practices regarding the initiation of oral feeding after total laryngectomy (TL)., Methods: Online survey., Results: Among the 332 responses received, 278 from 59 countries were analyzed. Our results showed that 45.6% of respondents started water and 45.1% started liquid diet between postoperative days 7 and 10. Semi-solid feeds were initiated between days 10 and 14 for 44.9% of respondents and a free diet was allowed after day 15 for 60.8% of respondents. This timing was significantly delayed in cases of laryngo-pharyngectomy and after prior radiotherapy (p < 0.001). A greater proportion of respondents in Africa and Oceania allowed early oral feeding before day 6 as compared with the rest of the world (p < 0.001)., Conclusion: Despite increasing number of publications, there is still a lack of evidence to support early oral feeding. The majority of respondents preferred to delay its initiation until at least 7 days after surgery., (© 2022 Wiley Periodicals LLC.)

Objective: The objective of this study was to assess the potential of the use of asynchronous tele-expertise (ASTE) to provide prenatal diagnosis from a medical and economic point of view., Population: Patients screened by a midwife at a primary center., Methods: A technical and clinical evaluation was conducted retrospectively, and a cost minimization study compared asynchronous tele-expertise to face-to-face consultations that would have been performed without ASTE., Main Outcome Measures: In our study we assessed the feasibility of ASTE, what were the origins of the requests for expertise, whether patients need to be moved and the reasons for doing so, and the costs of tele-expertise and conventional consultation., Results: In this retrospective analysis 322 advices from 260 patients were interpreted remotely via a platform. The results revealed a 90.68% feasibility of transmitting in a satisfactory and interpretable way ultrasound images and videos via the tele-expertise platform (292/322 files). In our series, asynchronous analysis allowed the required physician to make an accurate diagnosis and identify 74 (28.5%, 95% CI [23% -33.9%]) pregnancies associated with malformations and rule out abnormalities in 186 (71.5%, 95% CI [66.1% -77%]) of the cases. The ASTE was not associated with face-to-face consultations for 72.7% (189/260) of the patients, who without moving, were able to have access to a precise diagnosis by ruling out the presence of anomalies in 163/189 of these patients and confirming them in 26/189 patients. The practice of ASTE would result from a societal point of view, an average saving of 61.8% (€ 120.57) per patient compared to a face-to-face consultation., Conclusion: The use of asynchronous tele-expertise (ASTE) using fetal ultrasound, is feasible and may contribute to increased diagnostic accuracy while generating a significant reduction in costs for society., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Edwin Quarello is a member of the medical committee of Rofim, a telemedicine startup based in France. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Hypothesis: Acetic acid, a common pollutant present in museums and art galleries, can irreversibly damage works of art. Herein, a sustainable and scalable synthesis of zinc oxide-castor oil polyurethane hybrids (ZnO/COPs), to be used as acetic acid removers in the preventive conservation of Cultural Heritage, is reported., Experiments: The adsorption capacities of ZnO/COPs were studied in saturated acetic acid atmosphere, at low acetic acid gas concentration, and inside a wooden crate (naturally emitting acetic acid) representative of those used in the storage deposits of museums and art collections., Findings: Upon exposure, acetic acid interacts with the castor oil polyurethane and diffuses to the surface of ZnO particles where is stably fixed as zinc acetate crystals. Zinc acetate domains form homogeneously on the surface and are distributed evenly within the ZnO/COPs, thanks to weak interactions between the polyurethane matrix and acetic acid that favour the transport of the acid up to reach the zinc oxide surfaces, resulting in a synergistic effect. The ZnO/COPs composites showed significantly enhanced adsorption capacities of acetic acid surpassing those of the activated carbon benchmark, with the advantage of being easily handled and movable, without the health issues and risks associated to the use of non-confined micro/nano-powders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Whether left ventricular non-compaction (LVNC) bears a different prognosis than dilated cardiomyopathy (DCM) is still a matter of debate., Methods: From a multicenter French prospective registry, we compared the outcomes of 98 patients with LVNC and 65 with DCM. The primary endpoint combined cardiovascular death, heart transplantation, and hospitalization for cardiovascular events. The two groups presented similar outcomes but different left ventricular ejection fractions (LVEF) (43.3% in LVNC vs. 35.95% in DCM, p = 0.001). For this reason, a subgroup analysis was performed comparing only patients with LVEF ≤ 45%, including 56 with LVNC and 49 with DCM., Results: Among patients with LVEF ≤ 45%, at 5-year follow-up, the primary endpoint occurred in 33 (58.9%) among 56 patients with LVNC and 18 (36.7%) among 49 patients with DCM ( p = 0.02). Hospitalization for heart failure (18 [32.14%] vs. 5 [10.20%], p = 0.035) and heart transplantation were more frequent in the LVNC than in the DCM group. The incidences of rhythmic complications (24 [42.85%] vs. 12 [24.48%], p = 0.17), embolic events, and cardiovascular death were similar between LVNC and DCM cases. Among the 42 patients with LVNC and LVEF > 45%, the primary endpoints occurred in only 4 (9.52%) patients, including 2 hospitalizations for heart failure and 3 rhythmic complications, but no embolic events., Conclusion: In this prospective cohort, patients with LVNC who have left ventricular dysfunction present a poorer prognosis than DCM patients. Heart failure events were especially more frequent, but embolic events were not. Patients with LVNC and preserved ejection fraction present very few events in 5 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gerard, Iline, Martel, Nguyen, Richard, Donal, Eicher, Huttin, Selton-Suty, Raud-Raynier, Jondeau, Mansencal, Sawka, Ader, Pruny, Casalta, Michel, Donghi, Faivre, Giorgi, Charron and Habib.)

Aim: Describe the use of the emergency department of a tertiary-level children's hospital in Italy by adolescents., Methods: This retrospective study was based on the medical records of patients aged 13 to 17 years, who accessed the emergency department of the Institute for Maternal and Child Health of Trieste, from 1 January to 31 December 2018. The primary outcome was to describe the leading causes of access, diagnoses, rate of hospitalization, and ward of destination among adolescent patients., Results: During the study period, 24,599 patients accessed the department. Among them, 3,062 were adolescents, for a total of 3,895 unscheduled visits. The principal causes of access were trauma (45.3%) and organic diseases (38.8%). Two hundred and forty nine adolescents (6.4%) had mental health problems. One hundred and forty two adolescents (3.6%) Were Admitted to the Hospital, 54 of Whom (38%) to the Neuropsychiatric Ward, for Mental Health Problems., Conclusions: Among adolescents seen in this Italian tertiary-level children's hospital, mental health problems represented a small proportion of emergency department visits but were the leading cause of urgent hospitalization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cozzi, Passaglia, Agrusti, Giangreco, Giorgi and Barbi.)