Innova4Health: an integrated approach for prevention of recurrence and personalized treatment of Major Depressive Disorder.

Background: Major Depressive Disorder (MDD) is a prevalent mental health condition characterized by persistent low mood, cognitive and physical symptoms, anhedonia (loss of interest in activities), and suicidal ideation. The World Health Organization (WHO) predicts depression will become the leading cause of disability by 2030. While biological markers remain essential for understanding MDD's pathophysiology, recent advancements in social signal processing and environmental monitoring hold promise. Wearable technologies, including smartwatches and air purifiers with environmental sensors, can generate valuable digital biomarkers for depression assessment in real-world settings. Integrating these with existing physical, psychopathological, and other indices (autoimmune, inflammatory, neuroradiological) has the potential to improve MDD recurrence prevention strategies. Methods: This prospective, randomized, interventional, and non-pharmacological integrated study aims to evaluate digital and environmental biomarkers in adolescents and young adults diagnosed with MDD who are currently taking medication. The study implements a sensor-integrated platform built around an open-source "Pothos" air purifier system. This platform is designed for scalability and integration with third-party devices. It accomplishes this through software interfaces, a dedicated app, sensor signal pre-processing, and an embedded deep learning AI system. The study will enroll two experimental groups (10 adolescents and 30 young adults each). Within each group, participants will be randomly allocated to Group A or Group B. Only Group B will receive the technological equipment (Pothos system and smartwatch) for collecting digital biomarkers. Blood and saliva samples will be collected at baseline (T0) and endpoint (T1) to assess inflammatory markers and cortisol levels. Results: Following initial age-based stratification, the sample will undergo detailed classification at the 6-month follow-up based on remission status. Digital and environmental biomarker data will be analyzed to explore intricate relationships between these markers, depression symptoms, disease progression, and early signs of illness. Conclusion: This study seeks to validate an AI tool for enhancing early MDD clinical management, implement an AI solution for continuous data processing, and establish an AI infrastructure for managing healthcare Big Data. Integrating innovative psychophysical assessment tools into clinical practice holds significant promise for improving diagnostic accuracy and developing more specific digital devices for comprehensive mental health evaluation.

Donor-derived carbapenem-resistant gram-negative bacterial infections in solid organ transplant recipients: Active surveillance enhances recipient safety.

Donor-derived infections (DDIs) caused by carbapenem-resistant gram-negative bacteria (CR-GNB) in solid organ transplant recipients are potentially life-threatening. In this prospective study, we evaluated the incidence, factors associated with transmission, and the outcome of recipients with unexpected CR-GNB DDIs after the implementation of our local active surveillance system (LASS). LASS provides for early detection of unexpected donor CR-GNB infections, prophylaxis of recipients at high risk, and early diagnosis and treatment of DDIs. Whole genome sequencing confirmed DDI. Among 791 recipients, 38 (4.8%) were at high risk of unexpected CR-GNB DDI: 25 for carbapenem-resistant Enterobacterales (CRE) and 13 for carbapenem-resistant Acinetobacter baumannii (CRAB). Transmission did not occur in 27 (71%) cases, whereas DDIs occurred in 9 of 25 of CRE and 2 of 13 of CRAB cases. Incidence of CR-GNB DDI was 1.4%. Recipients of organs with CR-GNB-positive preservation fluid and liver recipients from a donor with CRE infection were at the highest risk of DDI. There was no difference in length of hospital stay or survival in patients with and without CR-GNB DDI. Our LASS contains transmission and mitigates the negative impacts of CR-GNB DDI. Under well-defined conditions, organs from donors with CR-GNB may be considered after a thorough evaluation of the risk/benefit profile.

Outcomes in people with eating disorders: a transdiagnostic and disorder-specific systematic review, meta-analysis and multivariable meta-regression analysis.

Eating disorders (EDs) are known to be associated with high mortality and often chronic and severe course, but a recent comprehensive systematic review of their outcomes is currently missing. In the present systematic review and meta-analysis, we examined cohort studies and clinical trials published between 1980 and 2021 that reported, for DSM/ICD-defined EDs, overall ED outcomes (i.e., recovery, improvement and relapse, all-cause and ED-related hospitalization, and chronicity); the same outcomes related to purging, binge eating and body weight status; as well as mortality. We included 415 studies (N=88,372, mean age: 25.7±6.9 years, females: 72.4%, mean follow-up: 38.3±76.5 months), conducted in persons with anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), other specified feeding and eating disorders (OSFED), and/or mixed EDs, from all continents except Africa. In all EDs pooled together, overall recovery occurred in 46% of patients (95% CI: 44-49, n=283, mean follow-up: 44.9±62.8 months, no significant ED-group difference). The recovery rate was 42% at <2 years, 43% at 2 to <4 years, 54% at 4 to <6 years, 59% at 6 to <8 years, 64% at 8 to <10 years, and 67% at ≥10 years. Overall chronicity occurred in 25% of patients (95% CI: 23-29, n=170, mean follow-up: 59.3±71.2 months, no significant ED-group difference). The chronicity rate was 33% at <2 years, 40% at 2 to <4 years, 23% at 4 to <6 years, 25% at 6 to <8 years, 12% at 8 to <10 years, and 18% at ≥10 years. Mortality occurred in 0.4% of patients (95% CI: 0.2-0.7, n=214, mean follow-up: 72.2±117.7 months, no significant ED-group difference). Considering observational studies, the mortality rate was 5.2 deaths/1,000 person-years (95% CI: 4.4-6.1, n=167, mean follow-up: 88.7±120.5 months; significant difference among EDs: p<0.01, range: from 8.2 for mixed ED to 3.4 for BN). Hospitalization occurred in 26% of patients (95% CI: 18-36, n=18, mean follow-up: 43.2±41.6 months; significant difference among EDs: p<0.001, range: from 32% for AN to 4% for BN). Regarding diagnostic migration, 8% of patients with AN migrated to BN and 16% to OSFED; 2% of patients with BN migrated to AN, 5% to BED, and 19% to OSFED; 9% of patients with BED migrated to BN and 19% to OSFED; 7% of patients with OSFED migrated to AN and 10% to BN. Children/adolescents had more favorable outcomes across and within EDs than adults. Self-injurious behaviors were associated with lower recovery rates in pooled EDs. A higher socio-demographic index moderated lower recovery and higher chronicity in AN across countries. Specific treatments associated with higher recovery rates were family-based therapy, cognitive-behavioral therapy (CBT), psychodynamic therapy, and nutritional interventions for AN; self-help, CBT, dialectical behavioral therapy (DBT), psychodynamic therapy, nutritional and pharmacological treatments for BN; CBT, nutritional and pharmacological interventions, and DBT for BED; and CBT and psychodynamic therapy for OSFED. In AN, pharmacological treatment was associated with lower recovery, and waiting list with higher mortality. These results should inform future research, clinical practice and health service organization for persons with EDs.

A narrative review of digital biomarkers in the management of major depressive disorder and treatment-resistant forms.

Introduction: Depression is the leading cause of worldwide disability, until now only 3% of patients with major depressive disorder (MDD) experiences full recovery or remission. Different studies have tried to better understand MDD pathophysiology and its resistant forms (TRD), focusing on the identification of candidate biomarkers that would be able to reflect the patients' state and the effects of therapy. Development of digital technologies can generate useful digital biomarkers in a real-world setting. This review aims to focus on the use of digital technologies measuring symptom severity and predicting treatment outcomes for individuals with mood disorders. Methods: Two databases (PubMed and APA PsycINFO) were searched to retrieve papers published from January 1, 2013, to July 30, 2023, on the use of digital devices in persons with MDD. All papers had to meet specific inclusion criteria, which resulted in the inclusion of 12 articles. Results: Research on digital biomarkers confronts four core aspects: (I) predicting diagnostic status, (II) assessing symptom severity and progression, (III) identifying treatment response and (IV) monitoring real-word and ecological validity. Different wearable technologies have been applied to collect physiological, activity/sleep, or subjective data to explore their relationships with depression. Discussion: Depression's stable rates and high relapse risk necessitate innovative approaches. Wearable devices hold promise for continuous monitoring and data collection in real world setting. Conclusion: More studies are needed to translate these digital biomarkers into actionable interventions to improve depression diagnosis, monitoring and management. Future challenges will be the applications of wearable devices routinely in personalized medicine.

TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase.

Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7+ mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target.

Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies.

OBJECTIVE: To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs). DESIGN: Umbrella review. DATA SOURCES: PubMed, PsychInfo, Embase, up to 9 February 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted. RESULTS: 101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive). CONCLUSIONS: Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events. STUDY REGISTRATION: PROSPERO CRD42018093045. FUNDING: None.

Incidence, prevalence, and global burden of schizophrenia - data, with critical appraisal, from the Global Burden of Disease (GBD) 2019.

Schizophrenia substantially contributes to the burden of mental disorders. Schizophrenia's burden and epidemiological estimates in some countries have been published, but updated estimates of prevalence, incidence, and schizophrenia-related disability at the global level are lacking. Here, we present the data from and critically discuss the Global Burden of Diseases, Injuries, and Risk Factors Study data, focusing on temporal changes in schizophrenia's prevalence, incidence, and disability-adjusted life years (DALYs) globally. From 1990 to 2019, schizophrenia raw prevalence (14.2 to 23.6 million), incidence (941,000 to 1.3 million), and DALYs (9.1 to 15.1 million) increased by over 65%, 37%, and 65% respectively, while age-standardized estimates remained stable globally. In countries with high socio-demographic index (SDI), both prevalence and DALYs increased, while in those with low SDI, the age-standardized incidence decreased and DALYs remained stable. The male/female ratio of burden of schizophrenia has remained stable in the overall population over the past 30 years (i.e., M/F = 1.1), yet decreasing from younger to older age groups (raw prevalence in females higher than males after age 65, with males having earlier age of onset, and females longer life expectancy). Results of this work suggest that schizophrenia's raw prevalence, incidence, and burden have been increasing since 1990. Age-adjusted estimates did not reduce. Schizophrenia detection in low SDI countries is suboptimal, and its prevention/treatment in high SDI countries should be improved, considering its increasing prevalence. Schizophrenia sex ratio inverts throughout the lifespan, suggesting different age of onset and survival by sex. However, prevalence and burden estimates for schizophrenia are probably underestimated. GBD does not account for mortality from schizophrenia (and other mental disorders, apart from anorexia nervosa).

Association between childhood maltreatment and cortical folding in women with eating disorders.

Childhood maltreatment (CM) is associated with distinct clinical and biological characteristics in people with eating disorders (EDs). The measurement of local gyrification index (lGI) may help to better characterize the impact of CM on cortical structure. Thus, the present study investigated the association of CM with lGI in women with EDs. Twenty-six women with anorexia nervosa (AN) and 24 with bulimia nervosa (BN) underwent a 3T MRI scan. All participants filled in the Childhood Trauma Questionnaire. All neuroimaging data were processed by FreeSurfer. LGI maps underwent a general linear model to evaluate differences between groups with or without CM. People with AN and BN were merged together. Based on the Childhood Trauma Questionnaire cutoff scores, 24 participants were identified as maltreated and 26 as non-maltreated. Maltreated people with EDs showed a significantly lower lGI in the left middle temporal gyrus compared with non-maltreated people, whereas no differences emerged in the right hemisphere between groups. The present study showed that in people with EDs, CM is associated with reduced cortical folding in the left middle temporal gyrus, an area that could be involved in ED psychopathology. This finding corroborates the hypothesis of a 'maltreated ecophenotype', which argues that CM may allow to biologically, other than clinically, distinguish individuals with the same psychiatric disorder.

Inhibition of Fatty Acid Amide Hydrolase (FAAH) Regulates NF-kb Pathways Reducing Bleomycin-Induced Chronic Lung Inflammation and Pulmonary Fibrosis.

The deadly interstitial lung condition known as idiopathic pulmonary fibrosis (IPF) worsens over time and for no apparent reason. The traditional therapy approaches for IPF, which include corticosteroids and immunomodulatory drugs, are often ineffective and can have noticeable side effects. The endocannabinoids are hydrolyzed by a membrane protein called fatty acid amide hydrolase (FAAH). Increasing endogenous levels of endocannabinoid by pharmacologically inhibiting FAAH results in numerous analgesic advantages in a variety of experimental models for pre-clinical pain and inflammation. In our study, we mimicked IPF by administering intratracheal bleomycin, and we administered oral URB878 at a dose of 5 mg/kg. The histological changes, cell infiltration, pro-inflammatory cytokine production, inflammation, and nitrosative stress caused by bleomycin were all reduced by URB878. Our data clearly demonstrate for the first time that the inhibition of FAAH activity was able to counteract not only the histological alteration bleomycin-induced but also the cascade of related inflammatory events.

Toxic and Potentially Toxic Mineral Elements of Edible Gastropods Land Snails (Mediterranean Escargot).

The meat of snails can be considered a high-quality food for the human diet and demand is already increasing across Europe. Due to the bioaccumulation of trace elements in their tissues, land snails can be a significant tool also for environmental pollution evaluation. In this study, 28 mineral elements (Ag, Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, K, Li, Na, Mg, Mn, Mo, Ni, Pb, Sb, Se, Sr, Ti, Tl, V, Zn) in both the edible part and the shell of edible land snails commercially available in Southern Italy belonging to Cernuella virgata, Helix aperta, Theba pisana species were investigated by ICP-MS and direct mercury analyser. The concentration of trace elements was variable among the samples. The variability demonstrates the close connection among the type of snail, the geographical origin, and the habitat in which the species grows. The edible part of the snails analysed in this study was found to be a good source of macro-nutrients. Toxic elements were detected in some samples, especially in shells; nevertheless, the values fell within the safety limits. Further investigations and monitoring of mineral contents in edible land snails are suggested both for human health and environmental pollution evaluation.

Cellular and molecular features of COVID-19 associated ARDS: therapeutic relevance.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can be asymptomatic or cause a disease (COVID-19) characterized by different levels of severity. The main cause of severe COVID-19 and death is represented by acute (or acute on chronic) respiratory failure and acute respiratory distress syndrome (ARDS), often requiring hospital admission and ventilator support.The molecular pathogenesis of COVID-19-related ARDS (by now termed c-ARDS) is still poorly understood. In this review we will discuss the genetic susceptibility to COVID-19, the pathogenesis and the local and systemic biomarkers correlated with c-ARDS and the therapeutic options that target the cell signalling pathways of c-ARDS.

RNA-Binding Proteins as a Molecular Link between COPD and Lung Cancer.

Chronic obstructive pulmonary disease (COPD) represents an independent risk factor for lung cancer development. Accelerated cell senescence, induced by oxidative stress and inflammation, is a common pathogenic determinant of both COPD and lung cancer. The post transcriptional regulation of genes involved in these processes is finely regulated by RNA-binding proteins (RBPs), which regulate mRNA turnover, subcellular localization, splicing and translation. Multiple pro-inflammatory mediators (including cytokines, chemokines, proteins, growth factors and others), responsible of lung microenvironment alteration, are regulated by RBPs. Several mouse models have shown the implication of RBPs in multiple mechanisms that sustain chronic inflammation and neoplastic transformation. However, further studies are required to clarify the role of RBPs in the pathogenic mechanisms shared by lung cancer and COPD, in order to identify novel biomarkers and therapeutic targets. This review will therefore focus on the studies collectively indicating the role of RBPs in oxidative stress and chronic inflammation as common pathogenic mechanisms shared by lung cancer and COPD.

Childhood maltreatment is associated with cortical thinning in people with eating disorders.

Childhood maltreatment (CM) is a non-specific risk factor for eating disorders (ED) and is associated with a greater severity in their clinical presentation and poorer treatment outcome. These data suggest that maltreated people with ED may be biologically other than clinically different from non-maltreated people. The aim of the present study was to investigate cortical thickness (CT), a possible biomarker of neurodevelopment, in people with ED with or without history of CM and in healthy women. Twenty-four healthy women, 26 with anorexia nervosa and 24 with bulimia nervosa underwent a 3T MRI scan. All participants filled in the childhood trauma questionnaire. All neuroimaging data were processed by FreeSurfer. Twenty-four participants with ED were identified as maltreated and 26 participants with ED as non-maltreated. All healthy women were non-maltreated. Compared to healthy women, maltreated people with ED showed lower CT in the left rostral anterior cingulate gyrus, while compared to people with ED without history of CM showed lower CT values in the left superior frontal and in right caudal middle frontal and superior parietal gyri. No significant differences emerged in CT measures between healthy women and people with ED without history of CM. The present findings show for the first time that in adult people with ED childhood maltreatment is associated with cortical thinning in areas implicated in the modulation of brain processes that are acknowledged to play a role in the psychopathology of ED.

Molecular Analysis With 16S rRNA PCR/Sanger Sequencing and Molecular Antibiogram Performed on DNA Extracted From Valve Improve Diagnosis and Targeted Therapy of Infective Endocarditis: A Prospective Study.

BACKGROUND: Molecular analysis (MA) on heart valve (HV) improves the microbiologic diagnosis of infectious endocarditis (IE). The main drawback of MA is the lack of antimicrobial susceptibility information. METHODS: We conducted a prospective cohort observational study of consecutive adult patients from April 2012 to May 2021 who underwent valve surgery at our hospital. The performance of MA, blood cultures (BC) and valve cultures (VC), and the diagnostic and therapeutic impact of MA were evaluated. Molecular antibiogram results were compared to culture-based antimicrobial susceptibility testing (AST). RESULTS: A total of 137 patients with definite IE and 52 patients with no IE were enrolled in the study. Among IE cases BC, VC, and MA were positive in 75 (55%), 30 (22%), and 120 (88%) of IE cases, respectively. Among 62 cases of BC-negative IE (BCNE), 57 achieved diagnosis with MA. MA led to a change of antimicrobial therapy in 92% of BCNE. MA was negative in 100% of patients with no IE. Molecular antibiogram performed on 17 valve specimens that resulted positive for pathogens potential carrier of genes encoding for multidrug resistant mechanisms showed 100% concordance with AST. CONCLUSIONS: MA showed a high specificity and sensitivity in etiological diagnosis of IE. Molecular antibiogram could overcome the major limitation of MA that is the lack of susceptibility testing. We advocate for the inclusion of MA among diagnostic criteria for IE and for a more extensive use of molecular antibiogram when the culture result is negative, and MA is the only positive test.

Postoperative Quality of Life After Full-sternotomy and Ministernotomy Aortic Valve Replacement.

BACKGROUND: Few longitudinal data exist comparing quality of life (QoL) after full sternotomy (fs) aortic valve replacement (AVR) (fsAVR) with ministernotomy AVR (msAVR). METHODS: A total of 1844 consecutive patients undergoing AVR who were prospectively enrolled in a European multicenter registry were dichotomized according to surgical access. Nonparsimonious propensity score matching selected 187 pairs of patients who underwent fsAVR or msAVR with comparable baseline characteristics. Hospital outcome was compared in the 2 groups. QoL was assessed with the Short Form-36, further detailed in its Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score. QoL was investigated at hospital admission, at discharge, and at 1 month, 6 months, and 1 year thereafter. RESULTS: There were 1654 patients undergoing fsAVR and 190 undergoing msAVR in the entire population. The fsAVR group showed a worse preoperative risk profile, a longer intensive care unit length of stay (59.7 hours vs 38.8 hours; p = .002), and a higher rate of life-threatening or disabling bleeding (4.1% vs 0%; P = .011); the msAVR group had a higher rate of early reintervention for failed index intervention (2.1% vs 0.5%; P = .001). QoL investigations showed better PCS and MCS at 1 month after fsAVR, but no temporal trend differences (PCS group-time P = .202; MCS group-time P = .141). Propensity-matched pairs showed comparable baseline characteristics and hospital outcomes (P = not significant for all end points) and comparable improvements of PCS and MCS over time, but no between-group differences over time (PCS group time P = .834; MCS group time P = .737). CONCLUSIONS: Patients with similar baseline profiles report comparable hospital outcomes and comparable improvements of physical and mental health, up to 1 year after surgery, with both fsAVR and msAVR. As for QoL, ministernotomy does not seem to offer any advantage compared with the traditional approach.

Growth Performance and Recovery of Nosocomial Aspergillus spp. in Blood Culture Bottles.

Theoretically, Aspergillus spp. grow in culture media, but frequently, blood cultures of patients with invasive Aspergillosis are negative, even if until now, the reasons are not clear. This aspect underlines the lack of a good strategy for the cultivation and isolation of Aspergillus spp. In order to develop a complete analytical method to detect Aspergillus in clinical and pharmaceutical samples, we investigated the growth performance of two blood culture systems versus the pharmacopeia standard method. At <72 h, all test systems showed comparable sensitivity, about 1−2 conidia. However, the subculture analysis showed a suboptimal recovery for the methods, despite the positive growth and the visualization of the "Aspergillus balls" in the culture media. To investigate this issue, we studied three different subculture approaches: (i) the use of a sterile subculture unit, (ii) the use of a sterile subculture unit and the collection of a larger aliquot (100 µL), following vigorous agitation of the vials, and (iii) to decapsulate the bottle, withdrawing and centrifuging the sample, and aliquot the pellet onto SDA plates. Our results showed that only the third procedure recovered Aspergillus from all positive culture bottles. This work confirmed that our strategy is a valid and faster method to culture and isolate Aspergillus spp. from blood culture bottles.

Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology.

Klebsiella pneumoniae is a Gram-negative pathogen of clinical relevance, which can provoke serious urinary and blood infections and pneumonia. This bacterium is a major public health threat due to its resistance to several antibiotic classes. Using a reverse vaccinology approach, 7 potential antigens were identified, of which 4 were present in most of the sequences of Italian carbapenem-resistant K. pneumoniae clinical isolates. Bioinformatics tools demonstrated the antigenic potential of these bacterial proteins and allowed for the identification of T and B cell epitopes. This led to a rational design and in silico characterization of a multiepitope vaccine against carbapenem-resistant K. pneumoniae strains. As adjuvant, the mycobacterial heparin-binding hemagglutinin adhesin (HBHA), which is a Toll-like receptor 4 (TLR-4) agonist, was included, to increase the immunogenicity of the construct. The multiepitope vaccine candidate was analyzed by bioinformatics tools to assess its antigenicity, solubility, allergenicity, toxicity, physical and chemical parameters, and secondary and tertiary structures. Molecular docking binding energies to TLR-2 and TLR-4, two important innate immunity receptors involved in the immune response against K. pneumoniae infections, and molecular dynamics simulations of such complexes supported active interactions. A codon optimized multiepitope sequence cloning strategy is proposed, for production of recombinant vaccine in classical bacterial vectors. Finally, a 3 dose-immunization simulation with the multiepitope construct induced both cellular and humoral immune responses. These results suggest that this multiepitope construct has potential as a vaccination strategy against carbapenem-resistant K. pneumoniae and deserves further validation.

Effect of Dietary Enrichment with Flaxseed, Vitamin E and Selenium, and of Market Class on the Broiler Breast Meat-Part 2: Technological and Sensorial Traits.

The influence of diet enrichment with flaxseed, selenium and vitamin E, and market class on breast meat was investigated in terms of technological and sensorial quality of breast meat. A randomized complete block design with an experimental unit of n = 6000 broilers receiving a standard or enriched diet, and slaughtered at 37 (light class), 47 (medium class), or 57 (heavy class) days of life, was developed. Then, enriched and standard breast muscles from every market class were studied for their technological and sensorial traits­both at 24 h post-mortem and after one month of frozen storage­by a statistical multiple linear model. Redness and yellowness of muscles significantly (p < 0.05) increased and decreased with increasing market age. Moreover, the yellowness significantly (p < 0.05) raised after frozen storage. However, obtained data were always indicative of a normal meat color. The water holding capacity improved following fed enrichment and significantly (p < 0.05) worsened after frozen storage. For the sensory analysis, juiciness and chewing rest of meat resulted significantly (p < 0.05) improved with increasing slaughtering age and diet enrichment, as well as their mutual interaction, while they deteriorated after frozen storage. Overall, fresh and enriched muscles from heavy broilers had the best technological and sensorial traits, thus, confirming that market size and diet should be highly considered to obtain breast meat with greater consumer acceptance.

Treatment of eating disorders: A systematic meta-review of meta-analyses and network meta-analyses.

MONTELEONE, A.M., F. Pellegrino, G. Croatto, M. Carfagno, A. Hilbert, J. Treasure, T. Wade, C. Bulik, S. Zipfel, P. Hay, U. Schmidt, G. Castellini, A. Favaro, F. Fernandez-Aranda, J. Il Shin, U. Voderholzer, V. Ricca, D. Moretti, D. Busatta, G. Abbate-Daga, F. Ciullini, G. Cascino, F. Monaco, C.U. Correll and M. Solmi. Treatment of Eating Disorders: a systematic meta-review of meta-analyses and network meta-analyses. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2022.- Treatment efficacy for eating disorders (EDs) is modest and guidelines differ. We summarized findings/quality of (network) meta-analyses (N)MA of randomized controlled trials (RCTs) in EDs. Systematic meta-review ((N)MA of RCTs, ED, active/inactive control), using (anorexia or bulimia or eating disorder) AND (meta-analy*) in PubMed/PsycINFO/Cochrane database up to December 15th, 2020. Standardized mean difference, odds/risk ratio vs control were summarized at end of treatment and follow-up. Interventions involving family (family-based therapy, FBT) outperformed active control in adults/adolescents with anorexia nervosa (AN), and in adolescents with bulimia nervosa (BN). In adults with BN, individual cognitive behavioural therapy (CBT)-ED had the broadest efficacy versus active control; also, antidepressants outperformed active. In mixed age groups with binge-eating disorder (BED), psychotherapy, and lisdexamfetamine outperformed active control. Antidepressants, stimulants outperformed placebo, despite lower acceptability, as did CBT-ED versus waitlist/no treatment. Family-based therapy is effective in AN and BN (adolescents). CBT-ED has the largest efficacy in BN (adults), followed by antidepressants, as well as psychotherapy in BED (mixed). Medications have short-term efficacy in BED (adults).