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Abstract Aims This study aims to assess the applicability of the mitral regurgitation (MR) proportionality concept in patients with atrial functional mitral regurgitation (aFMR) treated with transcatheter edge‐to‐edge repair (M‐TEER). We hypothesized that patients with disproportionate MR (higher MR relative to left ventricular size) would exhibit different outcomes compared to those with proportionate MR, despite undergoing M‐TEER. Methods and results We retrospectively analysed 98 patients with aFMR from the EuroSMR registry who underwent M‐TEER between 2008 and 2019. Patients met criteria for aFMR (normal indexed left ventricular end‐diastolic volume [LVEDV], preserved left ventricular ejection fraction [LVEF] ≥ 50% without regional wall motion abnormalities, and structurally normal mitral valves). We excluded patients with missing effective regurgitant orifice area (EROA) or LVEDV data. The primary endpoint was 2‐year mortality, with an EROA/LVEDV ratio employed to differentiate disproportionate from proportionate MR. Procedural success and baseline characteristics were analysed, and multivariate Cox proportional hazards models were used to identify mortality predictors. The mean patient age was 79 ± 7.3 years, with 68.8% female, and 79% had a history of atrial fibrillation. The mean EROA was 0.27 ± 0.14 cm2, and LVEDV was 95.6 ± 33.7 mL. Disproportionate MR was identified with an EROA/LVEDV ratio >0.339 cm2/100 mL. While procedural success was similar in both groups, disproportionate MR was associated with a numerically higher estimate of systolic pulmonary artery pressures (sPAP) and rates of NYHA ≥III and TR ≥ 3+. Disproportionate MR had a significant association with increased 2‐year mortality (P

Abstract Reducing disparities is vital for equitable access to precision treatments in cancer. Socioenvironmental factors are a major driver of disparities, but differences in genetic variation likely also contribute. The impact of genetic ancestry on prioritization of cancer targets in drug discovery pipelines has not been systematically explored due to the absence of pre-clinical data at the appropriate scale. Here, we analyze data from 611 genome-scale CRISPR/Cas9 viability experiments in human cell line models to identify ancestry-associated genetic dependencies essential for cell survival. Surprisingly, we find that most putative associations between ancestry and dependency arise from artifacts related to germline variants. Our analysis suggests that for 1.2-2.5% of guides, germline variants in sgRNA targeting sequences reduce cutting by the CRISPR/Cas9 nuclease, disproportionately affecting cell models derived from individuals of recent African descent. We propose three approaches to mitigate this experimental bias, enabling the scientific community to address these disparities.

IntroductionManaging burn injuries is a challenge in healthcare. Due to the alarming increase in antibiotic resistance, new prophylactic and therapeutic strategies are being sought. This study aimed to evaluate the potential of live Lactic Acid Bacteria for managing burn infections, using Galleria mellonella larvae as an alternative preclinical animal model and comparing the outcomes with a common antibiotic.MethodsThe antimicrobial activity of LAB isolated from human breast milk was assessed in vitro against Pseudomonas aeruginosa ATCC 27853. Additionally, the immunomodulatory effects of LAB were evaluated in vivo using the G. mellonella burn wound infection model.Results and discussionIn vitro results demonstrated the antimicrobial activity of Lactic Acid Bacteria against P. aeruginosa. In vivo results show that their prophylactic treatment improves, statistically significant, larval survival and modulates the expression of immunity-related genes, Gallerimycin and Relish/NF-κB, strain-dependently. These findings lay the foundation and suggest a promising alternative for burn wound prevention and management, reducing the risk of antibiotic resistance, enhancing immune modulation, and validating the potential G. mellonella as a skin burn wound model.

Exploring the ‘fragile crust of our planet’ is crucial for human survival holding an immense social and economic significance. Therefore, innovative approaches become of utmost importance for obtaining precise subsoil models in urban areas making the latter more resilient to natural disasters. Due to logistic issues and a high level of anthropogenic disturbance and related background noise, urban areas are usually intrinsically more problematic for applying geophysical prospecting methods. This work presents the results obtained by Deep Electrical Resistivity Tomography and P wave Seismic Reflection surveys performed along the Ferrara, north Italy, city walls documenting the adaptability of the geophysical surveys and how it is possible to obtain high-quality electrical resistivity and seismic data even in complex urban settings. The joint interpretation of geoelectrical and seismic data fully integrated with tectonic, geological and hydrogeological information allowed to reconstruct the stratigraphic evolution down to a depth of about 1.5 km. These results highlight the occurrence of a syndepositional Quaternary tectonic tilting associated with the growth of a fault-propagation fold.

Tuberculosis (TB) is a global threat, affecting one-quarter of the world's population. The World Health Organization (WHO) reports that 6 million people die annually due to chronic illnesses, a statistic that includes TB-related deaths. This high mortality is attributed to factors such as the emergence of drug-resistant strains and the exceptional survival mechanisms of Mycobacterium tuberculosis (MTB). Recently, microRNAs (miRNAs) have garnered attention for their crucial role in TB pathogenesis, surpassing typical small RNAs (sRNA) in their ability to alter the host's immune response. For instance, miR-155, miR-125b, and miR-29a have been identified as key players in the immune response to MTB, particularly in modulating macrophages, T cells, and cytokine production. While sRNAs are restricted to within cells, exo-miRNAs are secreted from MTB-infected macrophages. These exo-miRNAs modify the function of surrounding cells to favor the bacterium, perpetuating the infection cycle. Another significant aspect is that the expression of these miRNAs affects specific genes and pathways involved in immune functions, suggesting their potential use in diagnosing TB and as therapeutic targets. This review compiles existing information on the immunomodulatory function of exosomal miRNAs from MTB, particularly focusing on disease progression and the scientific potential of this approach compared to existing diagnostic techniques. Thus, the aim of the study is to understand the role of exosomal miRNAs in TB and to explore their potential for developing novel diagnostic and therapeutic methods.

The known intrinsic and polymorphic blaOXA-51-like genes of Acinetobacter baumannii were recently reported in other non-A. baumannii Gram-negative pathogens. Accurate detection of this potentially transferrable carbapenemase gene in the clinical setting is critical. This study developed a loop-mediated isothermal amplification (LAMP) assay targetting multiple alleles of blaOXA-51-like genes. Specifically, an alignment-based primer design, in silico primer screening, and in vitro assay confirmation were conducted. Both in silico and in vitro results revealed the tolerance of the LAMP assay to up to five primer-template mismatches outside the 3′-end primer regions. Within 90 min, the LAMP assay also detected the gene targets in other Gram-negative bacteria with known and novel blaOXA-51-like genes. Finally, it showed a superior limit of detection (as low as 101 CFU/mL) compared with polymerase chain reaction, and high specificity against non-targets. This study developed a highly adaptable LAMP assay to monitor blaOXA-51-like genes in the clinical setting and provided important insights into LAMP primer design and screening.

The aim of this retrospective cohort study is to understand if and how much the preventive self-isolation approach might have been a valid model to avoid care-related infection, not only from COVID-19 but also from other non-viral infectious diseases. From March to May 2020, the healthcare and management staff of the Villa Santa Maria long-term care facilities, located in the village of Montenero di Bisaccia (Campobasso, Molise, Italy), decided to carry out a preventive self-isolation plan to safeguard the residents from SARS-CoV-2. The impact on other infectious diseases was evaluated by analyzing the antibiotic therapies prescription trend among the inpatients. Our data showed that although self-isolation protected residents and caregivers from SARS-CoV-2, it can also be associated with mobility reduction, leading to an increase in bedridden pathologies, namely, pressure ulcers and pressure sores. The simultaneous isolation of residents and caregivers in the same location significantly reduced any outside influence as a cause of possible infections.

The global population is currently at unprecedented levels, with an estimated 7.8 billion people inhabiting the planet. We are witnessing a rise in cancer cases, attributed to improved control of cardiovascular diseases and a growing elderly population. While this has resulted in an increased workload for pathologists, it also presents an opportunity for advancement. The accurate classification of tumors and identification of prognostic and predictive factors demand specialized expertise and attention. Fortunately, the rapid progression of artificial intelligence (AI) offers new prospects in medicine, particularly in diagnostics such as image and surgical pathology. This article explores the transformative impact of AI in the field of uropathology, with a particular focus on its application in diagnosing, grading, and prognosticating various urological cancers. AI, especially deep learning algorithms, has shown significant potential in improving the accuracy and efficiency of pathology workflows. This comprehensive review is dedicated to providing an insightful overview of the primary data concerning the utilization of AI in diagnosing, predicting prognosis, and determining drug responses for tumors of the urinary tract. By embracing these advancements, we can look forward to improved outcomes and better patient care.

Background: Menopause, a natural phase in a woman’s life, often adversely affects physical, mental, sexual, and emotional well-being due to low estrogen levels. This study examines the impact of vaginal ovules with tocopherol acetate (Filme Gyno-V® ovules, manufactured by Panin Srl and distributed by Hulka Srl, Italy), 500 mg per ovule, on vaginal health in pre- and menopausal women. Methods: Fifty women aged 50–70 were divided into menopausal (28) and premenopausal (22) cohorts and treated with the ovules for two weeks, with assessments before and after treatment. Results: The findings showed that distressing symptoms of vaginal atrophy, such as dryness, itching, and pain during intercourse, were resolved post-treatment. A molecular analysis revealed a reduction in Escherichia coli in both cohorts and an increase in three species of Lactobacillus in premenopausal patients. Conclusions: This study concludes that Filme Gyno-V ovules may benefit vaginal health by alleviating atrophy symptoms and promoting healthy vaginal microbiota.

Background Minimally invasive mitral valve repair has a favorable risk–benefit profile in patients with significant de novo mitral regurgitation. Its role in patients with prior mitral valve repair is uncertain. We aimed to appraise the outcome of patients undergoing transcatheter edge‐to‐edge repair (TEER) with prior transcatheter or surgical mitral valve repair (SMVR). Methods and Results We queried the Italian multicenter registry on TEER with MitraClip, distinguishing naïve patients from those with prior TEER or (SMVR). Inhospital and long‐term clinical/echocardiographic outcomes were appraised. The primary outcome was the occurrence of death or rehospitalization for heart failure. A total of 2238 patients were included, with 2169 (96.9%) who were naïve to any mitral intervention, 29 (1.3%) with prior TEER, and 40 (1.8%) with prior SMVR. Several significant differences were found in baseline clinical and imaging features. Respectively, device success was obtained in 2120 (97.7%), 28 (96.6%), and 38 (95.0%, P=0.261) patients; procedural success in 2080 (95.9%), 25 (86.2%), and 38 (95.0%; P=0.047); and inhospital death in 61 (2.8%), 1 (3.5%), and no (P=0.558) patients. Clinical follow‐up after a mean of 14 months showed similar rates of death, cardiac death, rehospitalization, rehospitalization for heart failure, and their composite (all P>0.05). Propensity score–adjusted analysis confirmed unadjusted analysis, with lower procedural success for the prior TEER group (odds ratio, 0.28 [95% CI, 0.09–0.81]; P=0.019) but similar odds ratios and hazard ratios for all other outcomes in the naïve, TEER, and SMVR groups (all P>0.05). Conclusions In carefully selected patients, TEER can be performed using the MitraClip device even after prior TEER or SMVR.

Contribution: This work contributes to computer-supported collaborative learning (CSCL) offering support to the teaching presence among the enormous volume of interactions to provide a more active classroom posture in online environments. Background: Tracking interactions on collaborative learning environments (CLEs) with an increasing number of collaborative tools, offering real-time support for students, is one of the most intense and exhaustive challenges online teachers face. In this work context, social presence indicates a level of awareness of the other in the CLE, and it is necessary to improve and promote online social interactions. Research Questions: Aiming to answer the research question if the support of the teaching presence through Amadeus-SIMM helps to promote the learners' social presence in a distance learning course, an experiment was conducted through a Python Programming distance course with Computer Science and Electrical Engineering learners. Methodology: The research methods adopted were a survey and the reports generated by Amadeus-SIMM. The statistical models used were the difference between means calculated in two moments on the same sample and the chi-square test with two criteria. Findings: The conclusion is that the significant differences in six of the eight survey-independent questions related to the dependent question indicate an increase in learners' perception of social presence. The statistical analysis verified that the difference between the sample means in the two measurements of social behavior visibility, engagement, information intermediation, and prestige is statistically significant to confirm that Amadeus-SIMM supports teachers in promoting learners' social presence.

BACKGROUND: Coronary obstruction following transcatheter aortic valve replacement (TAVR) is a life-threatening complication. For patients at elevated risk, it is not known how valve choice is influenced by clinical and anatomic factors and how outcomes differ between valve platforms. For patients at high risk of coronary obstruction, we sought to describe the anatomical and clinical characteristics of patients treated with both balloon-expandable (BE) and self-expanding (SE) valves. METHODS: This was a multicenter international registry of patients undergoing TAVR who are considered to be at high risk of coronary obstruction and receiving pre-emptive coronary protection. RESULTS: A total of 236 patients were included. Patients receiving SE valves were more likely to undergo valve-in-valve procedures and also had smaller sinuses of Valsalva and valve-to-coronary distance. Three-year cardiac mortality was 21.6% with SE vs 3.7% with BE valves. This was primarily driven by increased rates of definite or probable coronary occlusion, which occurred in 12.1% of patients with SE valves vs 2.1% in patients with BE valves. CONCLUSIONS: In patients undergoing TAVR with coronary protection, those treated with SE valves had increased rates of clinical and anatomic features that increase the risk of coronary obstruction. These include an increased frequency of valve-in-valve procedures, smaller sinuses of Valsalva, and smaller valve-to-coronary distances. These patients were observed to have increased cardiac mortality compared with patients treated with BE valves, but this is likely due to their higher risk clinical and anatomic phenotypes rather than as a function of the valve type itself.

In the original publication [...]

Background: The COVID-19 pandemic has made antibiotic resistance (AMR) and healthcare-acquired infections (HAIs) increasingly serious problems. Point-prevalence Surveys (PPS) and other surveillance techniques are essential for antimicrobial management and prevention. Methods: In a hematology department of an Italian hospital, the prevalence of HAI, microbiology, and AMR were examined in this retrospective study in two different periods, namely 2019 and 2021 (pre-pandemic and during the pandemic, respectively). Comparisons were made between patient demographics, hospitalization duration, surveillance swabs, and HAIs. Findings: There was no discernible variation in the prevalence of HAI between 2019 and 2021. Higher rates of HAI were connected with longer hospital stays. Variations in antimicrobial susceptibility and species distribution were found by microbiological analysis. Discussion: The incidence of HAI stayed constant during the epidemic. Nevertheless, shifts in antibiotic susceptibility and microbiological profiles highlight the necessity of continuous monitoring and care. Conclusions: Despite the difficulties of COVID-19, ongoing surveillance and infection control initiatives are crucial for halting HAIs and battling antimicrobial resistance (AMR) in healthcare environments. To fully understand the pandemic’s long-term impact on the spread of infectious diseases and antibiotic resistance, more research is required.

Long-term inflammatory skin disease atopic dermatitis is characterized by dry skin, itching, and eczematous lesions. During inflammation skin barrier protein impairment promotes S. aureus colonisation in the inflamed skin, worsening AD patient’s clinical condition. Proteomic analysis revealed the presence of several immune evasion proteins and virulence factors in S. aureus extracellular vesicles (EVs), suggesting a possible role for these proteins in the pathophysiology of atopic dermatitis. The objective of this study is to assess the efficacy of a wall fragment obtained from a patented strain of C. acnes DSM28251 (c40) and its combination with a mucopolysaccharide carrier (HAc40) in counteract the pathogenic potential of EVs produced by S. aureus ATCC 14458. Results obtained from in vitro studies on HaCaT keratinocyte cells showed that HAc40 and c40 treatment significantly altered the size and pathogenicity of S. aureus EVs. Specifically, EVs grew larger, potentially reducing their ability to interact with the target cells and decreasing cytotoxicity. Additionally, the overexpression of the tight junctions mRNA zona occludens 1 (ZO1) and claudin 1 (CLDN1) following EVs exposure was decreased by HAc40 and c40 treatment, indicating a protective effect on the epidermal barrier’s function. These findings demonstrate how Hac40 and c40 may mitigate the harmful effects of S. aureus EVs. Further investigation is needed to elucidate the exact mechanisms underlying this interaction and explore the potential clinical utility of c40 and its mucopolysaccharide carrier conjugate HAc40 in managing atopic dermatitis.

Purpose Bio-fermentation has been routed as a viable alternative for the treatment of organic waste, which can provide renewable energy and can return nutrients to the soil with its byproducts. In this context, the objectives of the research were to analyze the benefits that a plastic plug-flow bio-digester can provide for treatment of bovine manure; and through biofermentation to control the E. coli number present in the bio-digester effluents. Methods The concentration of macronutrients and amount of the E. coli in the effluent was determined by the methods of analysis purposed by APHA standard methods and AOAC standard methods, respectively. In addition, the percentage composition of biogas was analyzed for determining the operative of the system. Results The production of biogas showed of 52.55% mol of methane concentration which it fed one blowtorch and one kitchenette. The bio-digester effluents showed appreciable amounts of nitrogen, potassium, phosphates, calcium, magnesium and sodium but with E. coli presence; the reason why the bio-digester effluent was treated later by a second fermentation inoculated with mountain effective microorganism, post-treatment which eliminated in 100% E. coli presence. Conclusion Both processes showed the viability as treatment of the bovine manure which brings renewable energy and effluents with nutritive loads to use it as a biofertilizer without risks to health and humanity. The project was located at the tropical zone into the Choco forest, at an average altitude of 1110 m above sea level and an average temperature annual of 21â22 °C.