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Abstract To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia. Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.

Abstract Aim of the present study is to evaluate the relationship between genetic and phenotypic data in a series of patients affected by grade I and II of foveal hypoplasia with stable fixation and good visual acuity using multimodal imaging techniques. All patients underwent complete clinical and instrumental assessment including structural Optical Coherence Tomography (OCT), OCT Angiography and Adaptive Optics (AO) imaging. Central macular thickness (CMT), inner nuclear layer (INL), vessel density in superficial capillary plexus were the main variables evaluated with OCT technology. Cone density, cone spacing, cone regularity, cone dispersion and angular density were the parameters evaluated with AO. Genetic evaluation and trio exome sequencing were performed in all affected individuals. Eight patients (3 males and 5 females) with a mean age of 12.62 years (range 8–18) were enrolled. The mean best corrected visual acuity (BCVA) was 0.18 ± 0.13 logMAR, mean CMT was 291.9 ± 16.6 µm and INL was 26.2 ± 4.6 µm. The absence of a foveal avascular zone (FAZ) was documented by examination of OCT-A in seven patients in the superficial capillary plexus. However, there was a partial FAZ in the deep plexus in patients P5 and P8. Of note, all the patients presented with major retinal vessels clearly crossing the foveal center. All individuals exhibited a grade I or II of foveal hypoplasia. In 5 patients molecular analyses showed an extremely mild form of albinism caused by compound heterozygosity of a TYR pathogenic variant and the hypomorphic p.[Ser192Tyr;Arg402Gln] haplotype. One patient had Waardenburg syndrome type 2A caused by a de novo variant in MITF. Two patients had inconclusive molecular analyses. All the patients displayed abnormalities on OCT-A. Photoreceptor count did not differ from normal subjects according to the current literature, but qualitative analysis of AO imaging showed distinctive features likely related to an abnormal pigment distribution in this subset of individuals. In patients with foveal hypoplasia, genetic and multimodal imaging data, including AO findings, can help understand the physiopathology of the foveal hypoplasia phenotype. This study confirms that cone density and visual function can both be preserved despite the absence of a pit.

Objective: We aimed to identify the factors associated with using digital platforms for physical activity during the COVID-19 pandemic among adults living in Southern Brazil. We also compared the trajectory of physical activity between users and non-users and by type of digital platform used. Methods: We analyzed data from the PAMPA (Prospective Study About Mental and Physical Health in Adults) cohort. The study started in June 2020, and tracked participants through three waves (December 2020, June 2021, and June 2022). The exposure variable was usingf digital platforms for physical activity. The outcome measure was minutes per week of physical activity. We employed a generalized linear model with robust variance to explore the interaction between time and the use of digital platforms, adjusting for sociodemographic covariates and the presence of chronic diseases. Results: The proportion of participants using digital platforms for physical activity declined from 36.8% in 2020 to 25.6% in 2021 and further to 13.5% in 2022. Using digital platforms for physical activity was associated with a higher mean daily physical activity during the COVID-19 pandemic. Participants who used digital platforms were more likely to be physically active when compared to their inactive contemparts throughout the entire study period. Notably, social media emerged with greater influence in the physical activity practice among digital platforms. Conclusion: Using these platforms had a positive impact on increasing the level of physical activity among the participants.

As well known success in orthodontics is related to a correct diagnosis and to a carefull treatment planning. Our study aims to provide clinician with a reproducible and precise method, for orthodontic indirect bonding, thanks to CBCT images and due to a CAD-CAM process. Methods: A case of an orthodontic treatment plan, of a female patient, 37 years old, was selected. Plaster models were digitally acquired using the Extra-Oral scanner Maestro 3D and processed within the Studio Maestro 3D software. CBCT images in DICOM format were imported into the MIMICS software, in order to perform the segmentation of the dental elements, and to obtain a three-dimensional coronal-root dental arches model. The DICOM file thus processed was exported in an STL file, reworked with Meshmixer software to improve image quality, and imported into the 3D Maestro software to be superimposed on the digital model. In this way a three-dimensional real model of the dental arches was developed. After an accurate orthodontic virtual set-up, we proceeded to brackets positioning on the 3D model of the dental arches. Subsequently, a virtual transfer template was created, in order to carry out the digital printing of a thermo-printed mask necessary to perform an indirect bonding of the orthodontic appliance. Results: The original digital workflow proposed in this study allows the development of a real and non-ideal three-dimensional coronal-root model of the dental arches; this model can be used for indirect orthodontic bonding eliminating any errors in the expression of 1st, 2nd and 3rd order information of the pre-informed orthodontic appliance. Conclusions: Technological advancements in oral scanning and 3D printing will allow the achievement of an easy and reproducible ideal positioning of the orthodontic brackets.

Abstract BackgroundThe Society of Thoracic Surgeons and European System for Cardiac Operative Risk Evaluation (EuroSCORE) II risk scores are the most commonly used risk prediction models for in-hospital mortality after adult cardiac surgery. However, they are prone to miscalibration over time and poor generalization across data sets; thus, their use remains controversial. Despite increased interest, a gap in understanding the effect of data set drift on the performance of machine learning (ML) over time remains a barrier to its wider use in clinical practice. Data set drift occurs when an ML system underperforms because of a mismatch between the data it was developed from and the data on which it is deployed. ObjectiveIn this study, we analyzed the extent of performance drift using models built on a large UK cardiac surgery database. The objectives were to (1) rank and assess the extent of performance drift in cardiac surgery risk ML models over time and (2) investigate any potential influence of data set drift and variable importance drift on performance drift. MethodsWe conducted a retrospective analysis of prospectively, routinely gathered data on adult patients undergoing cardiac surgery in the United Kingdom between 2012 and 2019. We temporally split the data 70:30 into a training and validation set and a holdout set. Five novel ML mortality prediction models were developed and assessed, along with EuroSCORE II, for relationships between and within variable importance drift, performance drift, and actual data set drift. Performance was assessed using a consensus metric. ResultsA total of 227,087 adults underwent cardiac surgery during the study period, with a mortality rate of 2.76% (n=6258). There was strong evidence of a decrease in overall performance across all models (P ConclusionsAll models show a decrease in at least 3 of the 5 individual metrics. CEM and variable importance drift detection demonstrate the limitation of logistic regression methods used for cardiac surgery risk prediction and the effects of data set drift. Future work will be required to determine the interplay between ML models and whether ensemble models could improve on their respective performance advantages.

The epidemic of chronic cardiovascular diseases must be managed and prevented. We examine if a sample of 65-75-yearolds knows and practices the right lifestyles to prevent chronic cardiovascular diseases, their habits and risk levels, and whether the paradigm of cardiovascular prevention needs to change. We recruited 153 men (50.2%) and 152 women (49.8%), aged 65- 70 for 55% and 71-75 for 45%. Most were overweight (38.2%), obese (28.2%), and normal (33.6%). 67.1% trusted to eat right, and only 20.6% always ate low-salt. 54.4% of our population considers their exercise sufficient, but 83% do not practice it, and 72.3% know the importance of daily exercise. 54.3% consider themselves healthy, but 51% have chronic diseases, including arterial hypertension (37.2%), diabetes (23.1%), heart failure (20.5%), and chronic obstructive bronchopathy (21.8%). Understanding the disease, its effects, and complications, and taking care of one’s health can help people live longer and prevent cardiovascular events.

Abstract Obesity and metabolic disorders have been associated with poor outcomes in non-Mediterranean breast cancer (BC) patients. The purpose of this study was to investigate the prognostic potential of anthropometric variables in patients with early BC living in Southern Mediterranean region of Italy. We enrolled 955 consecutive early BC patients treated in hospitals in Naples between 2009 and 2013 (median follow-up 11.8-year ending 15/09/2022). Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and metabolic syndrome (MetS) were collected. All-cause and BC-specific mortality were calculated. At the last day of contact 208 (22%) patients had died, 131 (14%) from BC. High WC (≥ 88 cm) or WHR (> 0.85) and the MetS were significantly associated with moderately increased risk of all-cause mortality (HR=1.39, 1.62, 1.61, respectively). A significant increased risk of BC-specific mortality was found in obese patients, in those with high WC, high WHR and those with MetS (HR=1.72, 1.71, 1.80, 1.81, respectively). Central obesity significantly increased total and BC-specific mortality particularly in pre-menopausal women and in luminal subtypes, while in post-menopause MetS was a stronger risk factor. Obesity and MetS may impair the effectiveness of BC therapies hence active lifestyle interventions are encouraged.

Abstract Miniaturization and electrochemical performance enhancement of electrodes and microelectrode arrays in emerging long-term implantable neural stimulation devices improves specificity, functionality, and performance of these devices. However, surgical site and post-implantation infections are amongst the most devastating complications after surgical procedures and implantations. Additionally, with the increased use of antibiotics, the threat of antibiotic resistance is significant and is increasingly being recognized as a global problem. Therefore, the need for alternative strategies to eliminate post-implantation infections and reduce antibiotic use has led to the development of medical devices with antibacterial properties. In this work, we report on the development of electrochemically active antibacterial platinum-iridium electrodes targeted for use in neural stimulation and sensing applications. A two-step development process was used. Electrodes were first restructured using femtosecond laser hierarchical surface restructuring. In the second step of the process, atomic layer deposition was utilized to deposit conformal antibacterial copper oxide thin films on the hierarchical surface structure of the electrodes to impart antibacterial properties to the electrodes with minimal impact on electrochemical performance of the electrodes. Morphological, compositional, and structural properties of the electrodes were studied using multiple modalities of microscopy and spectroscopy. Antibacterial properties of the electrodes were also studied, particularly, the killing effect of the hierarchically restructured antibacterial electrodes on Escherichia coli and Staphylococcus aureus—two common types of bacteria responsible for implant infections.

Background/Objectives: Carbon dioxide digital-subtraction angiography (CO2-DSA) is an increasingly adopted technique in endovascular aortic repair (EVAR) and fenestrated/branched EVAR (F/B-EVAR); it is used to reduce the amount of iodinate contrast medium (ICM) and prevent postoperative renal function worsening (PO-RFW). Our aim is to report results from the literature on EVAR and F/B-EVAR procedures using CO2-DSA, together with wider applications in aortic endovascular treatment. Methods: We performed a literature review by searching electronic databases for published data on CO2-DSA during EVAR and F/B-EVAR procedures. The endpoints were postoperative renal function worsening (PO-RFW) and efficacy of intraoperative arterial visualization. Further, applications of CO2 for thoracic endovascular aortic repair (TEVAR) were described. Results: Seventeen studies reporting results on CO2-DSA in EVAR (644 patients) were retrieved. Overall, 372 (58%) procedures were performed with CO2 alone, and 272 (42%) were performed with CO2+ICM. Eight studies analyzed the effect of CO2-DSA angiography on PO-RFW; four studies showed a significantly lower rate of PO-RFW compared to ICM. Five studies (153 patients) analyzed intraoperative arterial visualization with CO2-DSA; renal and hypogastric arteries were effectively visualized in 69% and 99% of cases, respectively. The use of CO2-DSA in F/B-EVAR has not been widely investigated. The largest series reported that PO-RFW was lower in the CO2 vs. ICM group. Conclusions: Carbon dioxide is widely applied in modern aortic endovascular treatment. CO2-DSA for EVAR and F/B-EVAR is an efficient technique for reducing PO-RFW while allowing acceptable arterial intraoperative visualization.

Background/Objectives: Grafting of LIMA to LAD has long been considered the gold-standard conduit choice for patients undergoing CABG. Despite this, the LSV remains the most used conduit by volume and some patients may not receive even a single arterial conduit. However, the outcomes in this group are not frequently explored. This study, therefore, compares in-hospital outcomes of patients who underwent CABG without any arterial conduits to those who received at least one arterial conduit. Methods: Retrospective propensity-matched database analysis of consecutive patients undergoing CABG in the UK between 1996 and 2019 using data from the National Adult Cardiac Surgery Audit. Results: 335,144 patients underwent CABG, with 6% receiving venous conduits only; matched outcomes are reported for 39,812 patients. In both unmatched and matched groups, we found a significant increase in mortality with the use of veins only (matched mortality 5.3% vs. 3.8%, p < 0.001) with estimated treatment effect for mortality OR 1.43, p < 0.001 (95% CI: 1.31–1.57). We also identified greater rates of post-operative dialysis, IABP insertion, and length of hospital stay in this group. Conclusions: We identified a significant increase in in-hospital mortality with the use of veins only compared to using at least one arterial graft to the LAD. While a single arterial graft should be prioritised wherever possible, venous revascularisation retains a critical role for specific patients. We must, therefore, continue to conduct research addressing the mechanisms underlying and propagating vein graft disease in order better to optimise outcomes for this niche patient group after CABG.

Introduction: Statistical shape modelling (SSM) is used to analyse morphology, discover qualitatively and quantitatively unique shape features within a population, and generate mean shapes and shape modes that show morphological variability. Hierarchical agglomerative clustering is a machine learning analysis used to identify subgroups within a given population in relation to shape features. We tested the application of both methods in the clinically relevant scenario of patients undergoing aortic valve repair (AVR). Every year, around 5000 patients undergo surgical AVR in the UK. Aims: Evaluate aortic morphology and identify subgroups amongst patients who had undergone AVR, including Ozaki, Ross, and valve-sparing procedures using SSM and unsupervised hierarchical clustering analysis. This methodological framework can evaluate both pre- and post-surgical variability across subgroups undergoing different surgeries. Methods: Pre- (n = 47) and post- (n = 35) operative three-dimensional (3D) aortic models were reconstructed from computed tomography (CT) and cardiac magnetic resonance (CMR) images. Computational analyses for SSM and hierarchical clustering were run separately for the two subgroups, assessing (a) ascending aorta only and (b) the whole aorta. This allows for exploring possible variations in morphological classification related to the input shape. Results: Most patients in the Ross procedure subgroup exhibited differences in aortic morphology from other subgroups, including an elongated ascending and wide aortic arch pre-operatively, and an elongated ascending aorta with a slightly enlarged sinus post-operatively. In hierarchical clustering, the Ross aortas also appeared to cluster together compared to the other surgical procedures, both pre-operatively and post-operatively. There were significant differences between clusters in terms of clustering distance in the pre-operative analyses (p = 0.003 for ascending aortas, p = 0.016 for whole aortas). There were no significant differences between the clusters in post-operative analyses (p = 0.47 for ascending, p = 0.19 for whole aorta). Conclusions: We demonstrated the feasibility of evaluating aortic morphology before and after different aortic valve surgeries using SSM and hierarchical clustering. This framework could be used to further explore shape features associated with surgical decision-making pre-operatively and, importantly, to identify subgroups whose morphology is associated with poorer clinical outcomes post-operatively. Statistical shape modelling (SSM) and unsupervised hierarchical clustering are two statistical methods that can be used to assess morphology, show morphological variations, with the latter being able to identify subgroups within a population. These methods have been applied to the population of aortic valve replacement (AVR) patients since there are different surgical procedures (traditional AVR, Ozaki, Ross, and valve-sparing). The aim is to evaluate aortic morphology and identify subgroups within this population before and after surgery. Computed tomography and cardiac magnetic resonance images were reconstructed into 3D models of the ascending aorta and whole aorta, which were then input into SSM and hierarchical clustering. The results show that the Ross aortic morphology is quite different from the other aortas. The clustering did not classify the aortas based on the surgical procedures; however, most of the Ross group did cluster together, indicating low variability within this surgical group.

PurposeThe coronavirus pandemic (COVID-19) significantly impacted the global economy and health. Italy was one of the first and most affected countries. The objective of our study was to assess the impact of the pandemic and the vaccination campaign on the radiological examinations performed in a radiology department of a tertiary center in Southern Italy.Materials and methodsWe analyzed weekly and retrospectively electronic medical records of case volumes performed at the Radiology Department of “Mater Domini” University Hospital of Catanzaro from March 2020 to March 2022, comparing them with the volumes in the same period of the year 2019. We considered the origin of patients (outpatient, inpatient) and the type of examinations carried out (x-ray, mammography, CT, MRI, and ultrasound). A non-parametric test (Wilcoxon Signed Rank test) was applied to evaluate the average volumes.ResultsTotal flows in the pandemic period from COVID-19 were lower than in the same pre-pandemic period with values of 552 (120) vs. 427 (149) median (IQR) (p

BackgroundSARS-CoV-2 vaccines are safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. This study was performed to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population.Methods and findingsA retrospective clinical cohort study was performed utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. The primary outcome was the incidence and time to the first positive SARS-CoV-2 molecular test in the Omicron predominant era. Multivariable Cox modeling analyses to determine the hazard of SARS-CoV-2 infection were stratified by calendar time (Period 1: January 1 -June 30, 2022; Period 2: July 1 -December 31, 2022) due to violations in the proportional hazards assumption. In total, 133,191 patients were analyzed. During Period 1, having 3+ comorbidities was associated with increased hazard for breakthrough (HR = 1.16 CI 1.08-1.26). During Period 2 of the study, having 2 comorbidities (HR = 1.45 95% CI 1.26-1.67) and having 3+ comorbidities (HR 1.73, 95% CI 1.51-1.97) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in Period 1 of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period.ConclusionsOmicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age plays an important role in breakthrough infection with the highest incidence among young adults, which may be due to age-related behavioral factors. These findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

High School students, recognized as a high-risk group for sexually transmitted infections (STIs), were the focal point of an educational campaign in Southern Italy to share information and good practices about STIs and HIV/AIDS. A baseline survey comprising 76 items was conducted via the REDCap platform to assess students' initial knowledge, attitudes, and practices (KAP) related to STIs and HIV/AIDS. Sociodemographic variables were also investigated. The association between variables and KAP score was assessed by Kruskal-Wallis' or Spearman's test, as appropriate. An ordinal regression model was built to estimate the effect size, reported as odds ratio (OR) with a 95% confidence interval (CI), for achieving higher KAP scores among students features. On a scale of 0 to 29, 1702 participants achieved a median KAP score of 14 points. Higher scores were predominantly reported by students from classical High Schools (OR 3.19, 95% C.I. 1.60-6.33, p

Abstract The continuous growth of annual production and consumption of polyethylene terephthalate (PET) is coined with increasing waste that leaks into the environment, landfills and oceans as microplastics and nano plastics fragments. Upcycling the recycled PET to make a feedstock for the fast-growing material-extrusion additive manufacturing (MEX-AM) technology can contribute to the solution and supports the concept of sustainable materials. In this work, extrudable filaments comprising recycled polyethylene terephthalate (rPET) with low-cost additives, such as pyromellitic dianhydride (PMDA) as a chain extender, styrene-ethylene-butylene-styrene terpolymer functionalized with maleic anhydride (SEBS-g-MA), a thermal modifier and toughening agent, ethylene-ethyl acrylate-glycidyl methacrylate terpolymer (E-EA-GMA), a functional reactive elastomeric impact modifier and ethylene-ethyl-acrylate (EEA), a non-reactive elastomeric impact modifier, have been fabricated using the twin-screw extruder. The optimum extrusion process parameters for producing uniform filaments of different rPET compounded formulations have been identified, this includes the extrusion die temperature of 280 °C and the screw speed of 150 ± 3 rpm. The compounded filaments are then printed into standard ASTM test specimens for thermal characterization and mechanical characterization, including glass transition and melting temperatures, crystallinity and crystallization temperature, tensile strength, tensile modulus, ductility, flexural strength, and Izod impact energy. Furthermore, the melt flow index for the filaments was measured. More significantly, the experimental data showed that compounding rPET with such additives in the reactive twin-screw extrusion process results in uniform filaments that display advantageous thermal and mechanical properties and can be used as a feedstock in the MEX-AM technology. This study suggests that compounding the recycled PET pellets with low-cost additives while extruding them into filaments for MEX-AM offers excellent potential to make high-value-added customized products from a sustainable polymer feedstock, such as prototyping, tooling, testing components or end-use internal components for small machines and cars.

Abstract Background Non-syndromic inherited retinal dystrophies (IRDs) such as retinitis pigmentosa or Leber congenital amaurosis generally manifest between early childhood and late adolescence, imposing profound long-term impacts as a result of vision impairment or blindness. IRDs are highly heterogeneous, with often overlapping symptoms among different IRDs, and achieving a definite diagnosis is challenging. This narrative review provides a clinical overview of the non-syndromic generalized photoreceptor dystrophies, particularly retinitis pigmentosa and Leber congenital amaurosis. The clinical investigations and genetic testing needed to establish a diagnosis are outlined, and current management approaches are discussed, focusing on the importance of the involvement of an interdisciplinary team from diagnosis and initial care to long-term follow-up and support. Results The effective management of IRDs requires a multidisciplinary, and ideally interdisciplinary, team of experts knowledgeable about IRDs, with experienced professionals from fields as diverse as ophthalmology, neuropsychiatry, psychology, neurology, genetics, orthoptics, developmental therapy, typhlology, occupational therapy, otolaryngology, and orientation and mobility specialties. Accurate clinical diagnosis encompasses a range of objective and subjective assessments as a prerequisite for the genetic testing essential in establishing an accurate diagnosis necessary for the effective management of IRDs, particularly in the era of gene therapies. Improvements in genome sequencing techniques, such as next-generation sequencing, have greatly facilitated the complex process of determining IRD-causing gene variants and establishing a molecular diagnosis. Genetic counseling is essential to help the individual and their family understand the condition, the potential risk for offspring, and the implications of a diagnosis on visual prognosis and treatment options. Psychological support for patients and caregivers is important at all stages of diagnosis, care, and rehabilitation and is an essential part of the multidisciplinary approach to managing IRDs. Effective communication throughout is essential, and the patient and caregivers’ needs and expectations must be acknowledged and discussed. Conclusion As IRDs can present at an early age, clinicians need to be aware of the clinical signs suggesting visual impairment and follow up with multidisciplinary support for timely diagnoses to facilitate appropriate therapeutic or rehabilitation intervention to minimize vision loss.

Background: Tuberculosis (TB) continues to be a major public health issue, with high mortality rates reported worldwide. It is worth noting that most of the hospitalizations for tuberculosis in the Sicilian region involve Italian-born individuals, underscoring the need to address this problem. Recent research on the geographic area and seasonality of infectious diseases, including tuberculosis, may aid in developing effective preventive measures. Objectives: This study aimed to evaluate the impact of the season and geographical area on tuberculosis disease prevalence in the Sicilian region. Methods: A retrospective study from January 2018 to May 2023 was conducted on patients with tuberculosis in the Sicilian region by analyzing computerized records on the Infectious Diseases Information System, currently named the Italian National Notification System (NSIS), of the Epidemiology Unit at Policlinico Paolo Giaccone University Hospital of Palermo and the Regional Reference Laboratory for Tuberculosis Surveillance and Control. Results: Eastern and Western Sicily were the geographical Sicilian areas with the highest frequency of patients with tuberculosis (52.2% and 42.6%, respectively). In comparison, Central Sicily had a significantly lower frequency of patients with tuberculosis (5.2%). Regarding the season, autumn was the season with the highest number of notification cases (28.9%), while spring was the season with the lowest frequency of patients with tuberculosis (19.7%). In autumn, we found significantly fewer patients with tuberculosis from Eastern Sicily (39.3%) and Central Sicily (1.5%), while Western Sicily had more patients with tuberculosis (59.3%). In spring, we found significantly more patients with tuberculosis from Eastern Sicily (64.1%), while Western and Central Sicily had significantly fewer patients with tuberculosis (23.9% and 12%, respectively). The presence of patients with tuberculosis did not significantly differ between geographical regions in summer and winter. Conclusions: Geographical area and seasonality significantly impact the distribution of tuberculosis cases in Sicily. These factors may be linked to different climatic conditions across the various geographical areas considered. Our findings suggest that climate can play a critical role in the spread of airborne infectious diseases, such as tuberculosis.

Fine-needle aspiration cytology (FNAC) is commonly used to obtain a pre-surgical pathological diagnosis in many organs, but its cost-effectiveness in lymphadenopathy has not been studied yet. We calculated the cost and diagnostic accuracy of a diagnostic algorithm that uses FNAC as a first-line procedure and compared it to a purely surgical approach in 545 consecutive lymphadenopathies. In 74% of the cases, FNAC alone can obtain a sufficiently detailed diagnosis, avoiding the surgical biopsy. In doing so, the average cost of diagnosis is cut to less than one-third, the patient avoids an invasive procedure and the diagnosis is reached earlier. In conclusion, the systematic use of lymph node-FNAC in the initial assessment of lymphadenopathy is clinically and economically advantageous as it avoids surgical biopsies in cases where cytology can suffice.

Baricitinib, a reversible Janus-associated kinase-inhibitor, is approved for treating COVID-19, combined with Dexamethasone and, eventually, with Remdesivir (RDV). This retrospective cohort study assesses the real-life advantages and limits of Baricitinib in the current pandemic scenario. Data of all patients consecutively hospitalized with moderate/severe COVID-19 between 1 October 2021 and 31 March 2022 were retrospectively collected and described according to the treatment received (Baricitinib, Baricitinib + RDV, none). We performed survival analyses to estimate the 21-day probability of Intensive Care Unit (ICU) admission, death, and composite. We built multivariate Cox regression models to identify ICU admission/death predictors among patients’ features. Of 111 subjects, 28 received Baricitinib, 21 received Baricitinib + RDV, and 62 could not be treated due to pre-existing conditions. Treated patients had a comparable risk of death (HR 0.50, 95% C.I. 0.20–1.26, p = 0.14) but remarkably lower risk of 21-day ICU admission (H.R., 0.10, 95% C.I., 0.01–0.86, p = 0.03), regardless of the type of treatment received. At multivariable analysis, older age was the only predictor of ICU admission/death (HR 1.14, 95% C.I. 1.03–1.26, p ≤ 0.01).Although effective, the high prevalence of elderly, co-morbid patients limits Baricitinib use in the current pandemic setting.

Despite the availability of vaccines and antivirals and the biological evolution of SARS-CoV-2, the rate of hospitalizations and deaths from COVID-19 remains high in Italy. It is crucial to understand whether and how the clinical characteristics of patients hospitalized for COVID-19 have changed over 2021–2022 and which risk factors are currently associated with adverse outcomes to develop targeted interventions. In this study, we present and compare the characteristics and outcomes of 310 patients with COVID-19 who were hospitalized between 1 August and 9 December 2021, when the Delta SARS-CoV-2 variant was prevalent (Group A), and between 3 January and 30 June 2022, when the Omicron variant was predominant (Group B). Using Survival Analysis, we estimated the cumulative 28-day hazard ratio (H.R.) of Intensive Care Unit (ICU) admission/death of patients in Group B vs. A. We built uni- and multivariate Cox regression models for the overall population and each group to identify risk factors for ICU admission/death among patient features. We found that Group B had a comparable risk of ICU admission/death (HR 1.60, 95% Confidence Interval, C.I. 1.00–2.58, p = 0.05) but a higher prevalence of elderly and co-morbid subjects than Group A. Non-invasive ventilation requirement was associated with adverse outcomes in both Group A (HR 21.03, 95% C.I. 5.34–82.80, p < 0.001) and Group B (HR 4.53, 95% C.I. 2.39–8.59, p < 0.001), as well as in the overall population (HR 3.88, 95% C.I. 2.49–6.06, p < 0.001). During the Omicron wave, elderly and co-morbid subjects had the highest risk of hospitalization and poor outcomes.

Abstract Determining the drivers of prey selection in marine predators is critical when investigating ecosystem structure and function. The newly recognized Rice’s whale (Balaenoptera ricei) is one of the most critically endangered large whales in the world and endemic to the industrialized Gulf of Mexico. Here, we investigated the drivers of resource selection by Rice’s whales in relation to prey availability and energy density. Bayesian stable isotope (δ13C, δ15N) mixing models suggest that Rice’s whales feed primarily on a schooling fish, Ariomma bondi (66.8% relative contribution). Prey selection using the Chesson’s index revealed that active prey selection was found to be positive for three out of the four potential prey identified in the mixing model. A low degree of overlap between prey availability and diet inferred from the mixing model (Pianka Index: 0.333) suggests that prey abundance is not the primary driver of prey selection. Energy density data suggest that prey selection may be primarily driven by the energy content. Results from this study indicate that Rice’s whales are selective predators consuming schooling prey with the highest energy content. Environmental changes in the region have the potential to influence prey species that would make them less available to Rice’s whales.

ABSTRACT BACKGROUND: The High Activity Arthroplasty Score (HAAS) is a self-administered questionnaire, developed in British English, that reliably and validly measures the levels of sports activities in patients following hip and knee arthroplasty surgery. OBJECTIVE: To cross-culturally adapt the HAAS to Brazilian Portuguese language. DESIGN AND SETTING: A cross-sectional study was conducted at a public university hospital in Brazil. METHODS: The Brazilian version of the HAAS was created through a six-step process: translation, synthesis, committee review, pretesting, back-translation, and submission to developers. The translation step was conducted by two independent bilingual translators, both native speakers of Brazilian Portuguese. The back-translation was performed by an independent translator, a native speaker of British English. To ensure the questionnaire's comprehensibility, 46 volunteers (51% men; average age 34-63) participated in the pre-testing step. RESULTS: The cross-cultural adaptation process necessitated modifications to certain terms and expressions to achieve cultural equivalence with the original HAAS. CONCLUSION: The HAAS has been translated from English into Brazilian Portuguese and culturally adapted for Brazil. The validation process for HAAS-Brazil is currently underway.

Abstract: Most COVID-19 survivors have reported experiencing persistent symptoms after the infection - these types of cases are known as long COVID. Since Brazil was an epicenter of the COVID-19 pandemic, a high burden of long COVID is expected. This study aimed to identify the prevalence and factors associated with long COVID in adults in Southern Brazil, analyzing data from the PAMPA cohort. Participants filled out a self-reported online questionnaire in June 2022. This study only included subjects who tested positive for COVID-19. Long COVID was defined by any symptoms that persisted for at least three months after the SARS-CoV-2 infection. Poisson’s regression models with robust variance were used to identify factors associated with long COVID; and results were reported as prevalence ratios (PR) and respective 95% confidence intervals (95%CI). A total of 1,001 participants (77.4% women, mean age [SD] = 38.3 [11.9] years) were analyzed. The prevalence of long COVID among these patients was 77.4% (95%CI: 74.7; 79.9). The likelihood of long COVID was higher in unvaccinated participants (PR = 1.23, 95%CI: 1.06; 1.42), in those with chronic conditions (PR = 1.13, 95%CI: 1.04; 1.24), and in those who were hospitalized due to the COVID-19 infection (PR = 1.24, 95%CI: 1.16; 1.32). This prevalence was also higher in women (PR = 1.21, 95%CI: 1.09; 1.33) than in men. Physical activity was associated with a reduced likelihood of fatigue, neurological complications, coughing, and headaches as persistent symptoms after a COVID-19 infection. It was found that three out of four adults in Southern Brazil experienced long COVID. Public policies aiming to reduce the burden of long COVID must be prioritized, especially in groups that are at higher risk of developing this harmful condition.

Abstract Background Congenital heart diseases (CHDs) remain a significant cause of infant morbidity and mortality. Epidemiological studies have explored maternal risk factors for offspring CHDs, but few have used genetic epidemiology methods to improve causal inference. Methods Three birth cohorts, including 65,510 mother/offspring pairs (N = 562 CHD cases) were included. We used Mendelian randomisation (MR) analyses to explore the effects of genetically predicted maternal body mass index (BMI), smoking and alcohol on offspring CHDs. We generated genetic risk scores (GRS) using summary data from large-scale genome-wide association studies (GWAS) and validated the strength and relevance of the genetic instrument for exposure levels during pregnancy. Logistic regression was used to estimate the odds ratio (OR) of CHD per 1 standard deviation (SD) higher GRS. Results for the three cohorts were combined using random-effects meta-analyses. We performed several sensitivity analyses including multivariable MR to check the robustness of our findings. Results The GRSs associated with the exposures during pregnancy in all three cohorts. The associations of the GRS for maternal BMI with offspring CHD (pooled OR (95% confidence interval) per 1SD higher GRS: 0.95 (0.88, 1.03)), lifetime smoking (pooled OR: 1.01 (0.93, 1.09)) and alcoholic drinks per week (pooled OR: 1.06 (0.98, 1.15)) were close to the null. Sensitivity analyses yielded similar results. Conclusions Our results do not provide robust evidence of an effect of maternal BMI, smoking or alcohol on offspring CHDs. However, results were imprecise. Our findings need to be replicated, and highlight the need for more and larger studies with maternal and offspring genotype and offspring CHD data.

Abstract Background Morning report is a core educational activity in internal medicine resident education. Attending physicians regularly participate in morning report and influence the learning environment, though no previous study has described the contribution of attending physicians to this conference. This study aims to describe attending comments at internal medicine morning reports. Methods We conducted a prospective, observational study of morning reports conducted at 13 internal medicine residency programs between September 1, 2020, and March 30, 2021. Each attending comment was described including its duration, whether the comment was teaching or non-teaching, teaching topic, and field of practice of the commenter. We also recorded morning report-related variables including number of learners, report format, program director participation, and whether report was scripted (facilitator has advance knowledge of the case). A regression model was developed to describe variables associated with the number of attending comments per report. Results There were 2,344 attending comments during 250 conferences. The median number of attendings present was 3 (IQR, 2–5). The number of comments per report ranged across different sites from 3.9 to 16.8 with a mean of 9.4 comments/report (SD, 7.4). 66% of comments were shorter than one minute in duration and 73% were categorized as teaching by observers. The most common subjects of teaching comments were differential diagnosis, management, and testing. Report duration, number of general internists, unscripted reports, and in-person format were associated with significantly increased number of attending comments. Conclusions Attending comments in morning report were generally brief, focused on clinical teaching, and covered a wide range of topics. There were substantial differences between programs in terms of the number of comments and their duration which likely affects the local learning environment. Morning report stakeholders that are interested in increasing attending involvement in morning report should consider employing in-person and unscripted reports. Additional studies are needed to explore best practice models of attending participation in morning report.

Abstract Throughout the SARS-CoV-2 pandemic, the use of botanical dietary supplements in the United States has increased, yet their safety and efficacy against COVID-19 remains underexplored. The Quave Natural Product Library is a phylogenetically diverse collection of botanical and fungal natural product extracts including popular supplement ingredients. Evaluation of 1867 extracts and 18 compounds for virus spike protein binding to host cell ACE2 receptors in a SARS-CoV-2 pseudotyped virus system identified 310 extracts derived from 188 species across 76 families (3 fungi, 73 plants) that exhibited ≥ 50% viral entry inhibition activity at 20 µg/mL. Extracts exhibiting mammalian cytotoxicity > 15% and those containing cardiotoxic cardiac glycosides were eliminated. Three extracts were selected for further testing against four pseudotyped variants and infectious SARS-CoV-2 and were then further chemically characterized, revealing the potent (EC50

With improved survival, adults living with HIV (ALHIV) are increasingly likely to experience age-related and HIV-related comorbidities, including renal insufficiency. Other risk factors for renal insufficiency (high blood pressure (BP), obesity, diabetes, and dyslipidemia) are also growing more common among ALHIV. To determine the prevalence of renal insufficiency (defined as an eGFR < 60 mL/min/1.73 m2) and factors associated with reduced eGFR, we conducted a cross-sectional study at six HIV clinics in Dar-es-Salaam, Tanzania. We applied multivariable (MV) ordinal logistic regression models to identify factors associated with reduced eGFR and examined the interaction of age with BP levels. Among the 450 ALHIV on ART analyzed [26% males; median age 43 (IQR: 18–72) years; 89% on tenofovir-containing ART; 88% HIV viral load ≤50 copies/mL], 34 (7.5%) had renal insufficiency. Prevalence was higher among males (12%) vs. females (6%), p = 0.03; ALHIV ≥50 (21%) vs. p < 0.001; those with high [≥130/80 mmHg (15%)] vs. normal [p < 0.01 and those with dyslipidemia (10%) vs. those without (4.5%), p < 0.03. After adjusting for covariates, age (in years) was the only covariate with a statistically significant association with reduced eGFR (OR = 1.09 (1.07–1.12), p < 0.001). No significant interaction between age and BP was found. Interventions to increase routine screening for renal insufficiency, especially among older ALHIV, and improve BP control are critical to reducing kidney disease-related morbidity and mortality.

Objectives This study aims to characterise the physical and psychological well-being of maternal and newborn healthcare workers (MNHCWs) during the COVID-19 pandemic.Design Observational repeated cross-sectional study.Setting An online questionnaire was distributed to MNHCWs around the globe in three separate rounds from March 2020 to March 2021.Participants Total samples of N=1357 (round 1) and N=420 (round 3) primarily consisted of doctors, midwives and nurses in maternal and newborn specialties. Samples represented all WHO regions, with 33% (round 1) and 42% (round 3) from low- or middle-income countries (LMICs).Primary and secondary outcome measures Responses from rounds 1 (March–June 2020) and 3 (December 2020–March 2021) were analysed to measure self-reported levels of relative stress and workplace protection from COVID-19, while associated factors were determined through multivariable ordinal logistic regression.Results In round 1, 90% of MNHCWs reported increased stress levels and 45% reported insufficient personal protective equipment (PPE) access. Nurses and physicians were less likely to report increased stress than midwives at the pandemic onset. Factors associated with increased stress included being female, being from an LMIC and insufficient PPE. In round 3, 75% reported similar or increased stress while 10% reported insufficient PPE. In both rounds, over 50% of MNHCWs felt relatively or completely unprotected from COVID-19 in the workplace. Those from LMICs were more likely to report feeling unprotected, while receiving organisational information that valued safety was associated with better feelings of protection in the workplace.Conclusions Among our international sample of MNHCWs, we observed high rates of self-reported stress increase at the start of the pandemic with persistence or increase up to a year later. High rates of feeling unprotected persisted even as PPE became more available. These results may inform interventions needed to support and protect MNHCWs during this and future pandemics.

Introduction Congenital heart disease (CHD) represents the most common birth defect, affecting from 0.4% to 1.2% of children born in developed countries. The survival of these patients has increased significantly, but CHD remains one of the major causes of neonatal and childhood death. The aetiology of CHD is complex, with some evidence of both genetic and environmental causes. However, there is still lack of knowledge regarding modifiable risk factors and molecular and genetic mechanisms underlying the development of CHD. This study aims to develop a prospective cohort of patients undergoing cardiac procedures that will bring together routinely collected clinical data and biological samples from patients and their biological mothers, in order to investigate risk factors and predictors of postoperative-outcomes, as well as better understanding the effect of the surgical intervention on the early and long-term outcomes.Methods and analysis Children OMACp (OMACp, outcome monitoring after cardiac procedure in congenital heart disease) is a multicentre, prospective cohort study recruiting children with CHD undergoing a cardiac procedure. The study aims to recruit 3000 participants over 5 years (2019–2024) across multiple UK sites. Routine clinical data will be collected, as well as participant questionnaires collecting sociodemographic, NHS resource use and quality of life data. Biological samples (blood, urine and surgical waste tissue from patients, and blood and urine samples from biological mothers) will be collected where consent has been obtained. Follow-up outcome and questionnaire data will be collected for 5 years.Ethics and dissemination The study was approved by the London–Brent Research Ethics Committee on 30 July 2019 (19/SW/0113). Participants (or their parent/guardian if under 16 years of age) must provide informed consent prior to being recruited into the study. Mothers who wish to take part must also provide informed consent prior to being recruited. The study is sponsored by University Hospitals Bristol and Weston Foundation Trust and is managed by the University of Bristol. Children OMACp is adopted onto the National Institute for Health Research Clinical Research Network portfolio. Findings will be disseminated through peer-reviewed publications, presentation at conference, meetings and through patient organisations and newsletters.Trial registration number ISRCTN17650644.

Abstract Functional implications of left ventricular (LV) morphological characterization in congenital heart disease are not widely explored. This study qualitatively and quantitatively assessed LV shape associations with a) LV function and b) thoracic aortic morphology in patients with aortic coarctation (CoA) with/without bicuspid aortic valve (BAV), and healthy controls. A statistical shape modelling framework was employed to analyse three-dimensional (3D) LV shapes from cardiac magnetic resonance (CMR) data in isolated CoA (n = 25), CoA + BAV (n = 30), isolated BAV (n = 30), and healthy controls (n = 25). Average 3D templates and deformations were computed. Correlations between shape data and CMR-derived morphometric parameters (i.e., sphericity, conicity) or global and apical strain values were assessed to elucidate possible functional implications. The relationship between LV shape features and arch architecture was also explored. The LV template was shorter and more spherical in CoA patients. Sphericity was overall associated with global and apical radial (p = 0.001, R2 = 0.09; p

Abstract Due to the SARS-CoV-2 outbreak, wearing a disposable face mask has become a worldwide daily routine, not only for medical operators or specialized personnel, but also for common people. Notwithstanding the undeniable positive effect in reducing the risk of virus transmission, it is important to understand if a prolonged usage of the same face mask can have effectiveness on filtering capability and potential health consequences. To this aim, we present three investigations. A survey, carried out in central Italy, offers an overview of the distorted public awareness of face mask usage. A functional study shows how prolonged wearing leads to substantial drops in humid air filtration efficiency. Finally, a morphological analysis reports the proliferation of fungal or bacteria colonies inside an improperly used mask. Our study highlights therefore that wearing a face mask is really beneficial only if it is used correctly.

Abstract Dielectric singularities (DSs) constitute one of the most exotic features occurring in the effective permittivity of artificial multilayers called hyperbolic metamaterials (HMMs). Associated to DSs, a rich phenomenology arises that justifies the ever-increasing interest profuse by the photonic community in achieving an active control of their properties. As an example, the possibility to “canalize” light down to the nanoscale as well as the capability of HMMs to interact with quantum emitters, placed in their proximity, enhancing their emission rate (Purcell effect), are worth mentioning. HMMs, however, suffer of an intrinsic lack of tunability of its DSs. Several architectures have been proposed to overcome this limit and, among them, the use of graphene outstands. Graphene-based HMMs recently shown outstanding canalization capabilities achieving λ/1660 light collimation. Despite the exceptional performances promised by these structures, stacking graphene/oxide multilayers is still an experimental challenge, especially envisioning electrical gating of all the graphene layers. In this paper, we propose a valid alternative in which indium-tin-oxide (ITO) is used as an electrically tunable metal. Here we have numerically designed and analyzed an ITO/SiO2 based HMM with a tunable canalization wavelength within the range between 1.57 and 2.74 μm. The structure feature light confinement of λ/8.8 (resolution of about 178 nm), self-focusing of the light down to 0.26 μm and Purcell factor of approximately 700. The proposed HMM nanoarchitecture could be potentially used in many applications, such as ultra-fast signal processing, high harmonic generation, lab-on-a-chip nanodevices, bulk plasmonic waveguides in integrated photonic circuits and laser diode collimators.

Introducción: el progreso en los tratamientos para el lupus eritematoso sistémico (LES) resultó en una disminución de la mortalidad; sin embargo, la enfermedad cardiovascular y las complicaciones infecciosas aún son las principales causas de muerte. La evidencia apoya la participación del sistema inmunológico en la generación de la placa aterosclerótica, así como su conexión con las enfermedades autoinmunes. Objetivos: describir la frecuencia de eventos cardiovasculares (ECV) en el RELESSAR transversal (Registro de Lupus Eritematoso Sistémico de la Sociedad Argentina de Reumatología), así como sus principales factores de riesgo asociados. Materiales y métodos: estudio descriptivo y transversal para el cual se tomaron los pacientes ingresados en el registro RELESSAR transversal. Se describieron las variables sociodemográficas y clínicas, las comorbilidades, score de actividad y daño. ECV se definió como la presencia de al menos una de las siguientes patologías: enfermedad arterial periférica, cardiopatía isquémica o accidente cerebrovascular. El evento clasificado para el análisis fue aquel posterior al diagnóstico del LES. Se conformaron dos grupos macheados por edad y sexo 1:2. Resultados: 1515 pacientes mayores de 18 años participaron del registro. Se describieron 80 pacientes con ECV (5,3%). En este análisis se incluyeron 240 pacientes conformando dos grupos. La edad media fue de 47,8 (14,4) y 47,6 (14,2) en el grupo con y sin ECV respectivamente. Los pacientes con ECV tuvieron mayor duración del LES en meses, mayor índice de Charlson, mayor SLICC (Systemic Lupus International Collaborating Clinics/American College of Rheumatology), mayor frecuencia de manifestaciones neurológicas, síndrome antifosfolípido, hospitalizaciones y uso de ciclofosfamida. Las únicas variables asociadas en el análisis multivariado fueron el índice de Charlson (p=0,004) y el SLICC (p

Objectives To assess the effectiveness of injectable tissue pulmonary valve compared with standard pulmonary valve in patients requiring pulmonary valve replacement surgery.Design A multicentre, single-blind, parallel two-group randomised controlled trial. Participants were blind to their allocation. Follow-up continued for 6 months. Randomised allocations were generated by a computer using block randomisation, stratified by centre.Setting Two National Health Service secondary care centres in the UK.Participants People aged 12–80 years requiring pulmonary valve replacement.Interventions Participants were randomly allocated (1:1 ratio) to injectable pulmonary valve replacement (IPVR) without cardiopulmonary bypass (CPB) or standard pulmonary valve replacement (SPVR) with CPB.Primary and secondary outcome measures The primary outcome was chest drainage volume over the first 24 hours after surgery. Secondary outcomes included in-hospital clinical outcomes; valve and heart function 6 months postsurgery and health-related quality of life 6 weeks and 6 months postsurgery.Results Nineteen participants agreed to take part. Eleven were allocated to IPVR and eight to SPVR. The trial was stopped before the target sample size of 60 participants was reached due to challenges in recruitment. The primary analysis includes all randomised participants; there were no withdrawals. Chest drain volume 24 hours after surgery was on average 277.6 mL lower with IPVR (IPVR mean 340.0 mL; SPVR mean 633.8 mL; mean difference, −277.6; 95% CI, −484.0 to −71.2; p=0.005). There were no statistically significant differences in time to readiness for extubation (p=0.476), time to fitness for discharge (p=0.577) and time to first discharge from the intensive care unit (p=0.209). Six participants with IPVR required CPB. Safety profiles and quality of life scores were similar.Conclusions IPVR reduced chest drain volume despite >50% of participants requiring CPB. There was no evidence of any other benefit of IPVR.Trial registration number ISRCTN23538073.

Objective To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.Design Registry based observational study.Setting 74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021Participants All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients).Main outcome measures Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.Results Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).Conclusions In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.

Parenteral prostanoids are being recommended in pulmonary arterial hypertension (PAH) treatment, but the prognostic relevance of delayed treatment initiation is still debated. This study assessed the impact of the timing of prostacyclin treatment initiation on reducing PVR and achieving a low-risk profile in PAH patients. The study enrolled 151 patients who started on parenteral prostanoids with different treatment strategies. All patients underwent right heart catheterization, clinical evaluation, and risk assessments at baseline and after 1-year follow-up. Patients with an upfront strategy including parenteral prostanoid plus one oral drug had −5.3 ± 6.2 WU (−50 ± 19%) reduction in PVR, patients with an upfront strategy including parenteral prostanoid plus double oral drug had −12.8 ± 5.9 WU (−68 ± 17%) reduction in PVR, while patients with an add-on strategy including parenteral prostanoid after oral drugs had −3.9 ± 3.5 WU (−23 ± 19%) reduction in PVR. An upfront strategy including parenteral prostanoids was independently associated with an increased likelihood of achieving the greater reduction of PVR compared with an add-on strategy. Additionally, the greater the severity of PH at the time of diagnosis, in terms of PVR and RV reverse remodeling, the higher the probability of treatment failure. An upfront strategy including a parenteral prostanoid is associated with the highest likelihood of achieving a low-risk profile and a greater reduction of PVR compared with parenteral prostanoid as an add-on to oral treatment.

In the last two decades, the study of the renin–angiotensin–aldosterone system (RAAS) has revealed a counterregulatory protective axis. This protective arm is characterized by ACE2/Ang 1-7/MasR and Ang 1-9 that largely counteracts the classic arm of the RAAS mediated by ACE/Ang II/AT1R/aldosterone and plays an important role in the prevention of inflammation, oxidative stress, hypertension, and cardiovascular remodeling. A growing body of evidence suggests that enhancement of this counterregulatory arm of RAAS represents an important therapeutic approach to facing cardiovascular comorbidities. In this review, we provide an overview of the beneficial effects of ACE2, Ang 1-7/MasR, and Ang 1-9 in the context of oxidative stress, vascular dysfunction, and organ damage.

Abstract Background Triple negative breast cancer (TNBC) is an aggressive disease characterized by high risk of relapse and development of resistance to different chemotherapy agents. Several targeted therapies have been investigated in TNBC with modest results in clinical trials. Among these, PI3K/AKT inhibitors have been evaluated in addition to standard therapies, yielding conflicting results and making attempts on elucidating inherent mechanisms of resistance of great interest. Increasing evidences suggest that PI3K/AKT inhibitors can induce autophagy in different cancers. Autophagy represents a supposed mechanism of drug-resistance in aggressive tumors, like TNBC. We, therefore, investigated if two PI3K/AKT inhibitors, ipatasertib and taselisib, could induce autophagy in breast cancer models, and whether chloroquine (CQ), a well known autophagy inhibitor, could potentiate ipatasertib and taselisib anti-cancer effect in combination with conventional chemotherapy. Methods The induction of autophagy after ipatasertib and taselisib treatment was evaluated in MDAMB231, MDAM468, MCF7, SKBR3 and MDAB361 breast cancer cell lines by assaying LC3-I conversion to LC3-II through immunoblotting and immunofluorescence. Other autophagy-markers as p62/SQSTM1 and ATG5 were evaluated by immunoblotting. Synergistic antiproliferative effect of double and triple combinations of ipatasertib/taselisib plus CQ and/or paclitaxel were evaluated by SRB assay and clonogenic assay. Anti-apoptotic effect of double combination of ipatasertib/taselisib plus CQ was evaluated by increased cleaved-PARP by immunoblot and by Annexin V- flow cytometric analysis. In vivo experiments were performed on xenograft model of MDAMB231 in NOD/SCID mice. Results Our results suggested that ipatasertib and taselisib induce increased autophagy signaling in different breast cancer models. This effect was particularly evident in PI3K/AKT resistant TNBC cells, where the inhibition of autophagy by CQ potentiates the therapeutic effect of PI3K/AKT inhibitors in vitro and in vivo TNBC models, synergizing with taxane-based chemotherapy. Conclusion These data suggest that inhibition of authophagy with CQ could overcome mechanism of drug resistance to PI3K/AKT inhibitors plus paclitaxel in TNBC making the evaluation of such combinations in clinical trials warranted.

Objectives The aim of this study is to investigate the effect of artificial intelligence (AI) and/or algorithms on drug management in primary care settings comparing AI and/or algorithms with standard clinical practice. Second, we evaluated what is the most frequently reported type of medication error and the most used AI machine type.Methods A systematic review of literature was conducted querying PubMed, Cochrane and ISI Web of Science until November 2021. The search strategy and the study selection were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Population, Intervention, Comparator, Outcome framework. Specifically, the Population chosen was general population of all ages (ie, including paediatric patients) in primary care settings (ie, home setting, ambulatory and nursery homes); the Intervention considered was the analysis AI and/or algorithms (ie, intelligent programs or software) application in primary care for reducing medications errors, the Comparator was the general practice and, lastly, the Outcome was the reduction of preventable medication errors (eg, overprescribing, inappropriate medication, drug interaction, risk of injury, dosing errors or in an increase in adherence to therapy). The methodological quality of included studies was appraised adopting the Quality Assessment of Controlled Intervention Studies of the National Institute of Health for randomised controlled trials.Results Studies reported in different ways the effective reduction of medication error. Ten out of 14 included studies, corresponding to 71% of articles, reported a reduction of medication errors, supporting the hypothesis that AI is an important tool for patient safety.Conclusion This study highlights how a proper application of AI in primary care is possible, since it provides an important tool to support the physician with drug management in non-hospital environments.

IntroductionLow Molecular Weight Heparins (LMWHs) and Fondaparinux have been widely used as anticoagulants. Mass prescription may lead to prescriptive inappropriateness, which causes Heparin-induced thrombocytopenia and other side effects.ObjectivesThe study investigates the appropriate prescription of LMWHs and Fondaparinux in Tuscany. We aim to validate the crude measure of prescription appropriateness of the Key Performance Indicator (KPI) "Patients treated with LMWHs and Fondaparinux every hundred residents in Tuscany" as a proxy for monitoring prescription appropriateness.MethodsTo compare a crude KPI based only on drug consumption with a refined KPI based on exclusions listed in the clinical guidelines, a retrospective observational cohort study was carried out, using the RECORD guidelines for the year 2019. The refined indicator is computed via record linkage of different datasets regarding (a) pharmaceutical services; (b) hospital discharge records; (c) outpatient services; and (d) birth certificates. We apply exclusion criteria to identify the cohort of patients. Values of the KPI are compared, by ranking, with those obtained from its refined version. A Spearman test was performed to validate the use of the crude KPI as a proxy.Results208,717 LMWH and Fondaparinux users are identified, of which 103,299 fall within the study's inclusion criteria. 16,817 (16%) of LMWHs and Fondaparinux users are classified as high consumption. The refined version of the KPI produces the same ranking results in terms of local health districts (rho = 0.98 pConclusionsAlthough the crude KPI is less refined and detailed than the adjusted indicator computed by our study, it has proven capable to provide an accurate snapshot of the use of these drugs across the region. This analysis is useful to enable regional and local managers to run rapid and simple indicators to monitor the appropriateness of LMWHs and Fondaparinux. This analysis should be reviewed periodically to confirm its accuracy.

Background/aimsTomographic analysis of macular and peripapillary retinal nerve fibers layer (RNFL) thickness in patients with history of congenital (CC) and developmental cataract (DC).MethodsAnalysis of macular and RNFL thickness using a spectral-domain optical coherence tomography was performed. Retinal layers thickness was measured using the internal segmentation software. Measurements of affected (unilateral and bilateral), contralateral eyes and control eyes were compared.ResultsPatients with history of CC or DC (n = 13 and 11 respectively) and 35 healthy control subjects were enrolled. Thicker inner and outer nuclear layers (INL, ONL) and thicker ONL were found when CC and DC group when compared to controls respectively. Bilateral CC showed the most relevant differences. Slight thickening of CC inner retinal layers were found when compared to DC. Increased superonasal RNFL thickness was found in CC group when compared to DC and controls. Thickening of RNFL of contralateral unaffected eyes of unilateral CC were found when compared to controls.ConclusionSignificant macular and RNFL thickness changes between CC, DC patients and controls that partially involve also contralateral unaffected eyes of unilateral congenital cataract were found. CC and DC groups show significant differences only in inner retinal layers thickness. Our data suggest that early visual deprivation may influence retinal arrangements occurring during development involving predominantly the outer nuclear layer and para/perifoveal inner retinal layers, and confirm that early treatment of CC allow to achieve better long-term visual outcome. Moreover functional and structural data support the hypothesis that unilateral amblyopia is not exclusively an unilateral issue.

Abstract Oregano (Origanum vulgare L.) is mainly cultivated, both as fresh and dried herb, for several purposes, such as ailments, drugs, and spices. To evaluate the influence of some drying methods on the chemical composition of the essential oil of oregano, its aerial parts were dehydrated by convective drying techniques (shade, static oven), microwave-assisted heating (three different treatments) and osmotic treatment. The oils were analyzed by GC-FID and GC–MS. The highest essential oil yield was achieved from microwave and shade drying methods. In total, 39 components were found, with carvacrol (ranging from 56.2 to 81.4%) being the main constituent; other compounds present in lower amounts were p-cymene (1.6–17.7%), γ-terpinene (0.8–14.2%), α-pinene (0.1–2.1%), thymol methyl ether (0.4–1.8%) and thimoquinone (0.5–3.5%). The essential oil yields varied among the different treatments as well as the relative compositions. The percentages of p-cymene, γ-terpinene and α-pinene decreased significantly in the dried sample compared with the fresh sample; on the other hand, carvacrol, isoborneol and linalool increased significantly in the dried materials. The choice of the drying method for obtaining the essential oil therefore appears crucial not only in relation to the higher yield but also and above all in reference to the percentage presence of components that can direct the essential oil toward an appropriate use.

Abstract In this work, the design of a monolithic softener obtained by geopolymer gel conversion is proposed. The softener used consists in a geopolymeric macroporous matrix functionalized by the co-crystallization of zeolite A and X in mixture. The dual nature of the proposed material promotes a softening process based on the synergistic effect of cation exchange and alkaline precipitation. A softening capacity of 90% and 54% for Ca2+ and Mg2+ respectively was attained in 24 h. In fact, the softener reported a Cation Exchange Capacity (CEC) value of 4.43 meq g−1. Technical features such as density, porosity and mechanical resistance were also measured. The use of this monolithic softener can improve performance and sustainability of hardness removal from tap water, reducing the production of sludge and adding the possibility to partially regenerate or reuse it.

Abstract DNA methylation is a reversible process catalyzed by the ten–eleven translocation (TET) family of enzymes (TET1, TET2, TET3) that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Altered patterns of 5hmC and 5mC are widely reported in human cancers and loss of 5hmC correlates with poor prognosis. Understanding the mechanisms leading to 5hmC loss and its role in oncogenesis will advance the development of epigenetic-based therapeutics. We show that TET2 loss associates with glioblastoma (GBM) stem cells and correlates with poor survival of GBM patients. We further identify a SOX2:miR-10b-5p:TET2 axis that represses TET2 expression, represses 5hmC, increases 5mC levels, and induces GBM cell stemness and tumor-propagating potential. In vivo delivery of a miR-10b-5p inhibitor that normalizes TET2 expression and 5hmC levels inhibits tumor growth and prolongs survival of animals bearing pre-established orthotopic GBM xenografts. These findings highlight the importance of TET2 and 5hmC loss in Sox2-driven oncogenesis and their potential for therapeutic targeting.

Uveal melanoma (UM) is the most common intra-ocular tumor in Caucasian adults and may derive from melanocytes. Historically, the first therapeutic approach to treat UM has been surgical removal of the eye, with obvious consequences in terms of function, cosmesis, and psychological impact on patients. Collaborative Ocular Melanoma Study (COMS) introduced the first uniform approach to perform interventional radiotherapy (IRT – brachytherapy) procedure in a standardized way that allowed to demonstrate equivalence of IRT with enucleation in terms of overall survival. Since this milestone, several international guidelines have been issued with regard to several technical aspects of this procedure, which has become the mainstream therapy worldwide. However, nowadays, there is still a lack of consensus about the criteria to definitively assess UM response after IRT. We present a collection of paradigmatic cases treated in our institution, and then discuss in detail the latest available evidence on the topic.

Background: Recent studies have evaluated the upper esophageal sphincter (UES) with high-resolution manometry (HRM) in some esophageal diseases, but not eosinophilic esophagitis (EoE). The aim of our study was to evaluate the function of the UES across EoE, gastroesophageal reflux disease (GERD), functional dysphagia (FD), and the relationship with esophageal symptoms, esophageal body contraction, and esophagogastric junction (EGJ) metrics. Methods: HRM was performed on 30 EoE, 18 GERD, and 29 FD patients according to the Chicago Classification 3.0. The study data were exported to the online analysis platform Swallow Gateway. The UES was assessed in terms of UES Resting Pressure (UES-RP), UES Basal Pressure (UES-BP), UES Integrated Relaxation Pressure (UES-IRP), UES Relaxation Time (UES-RT), Basal UES Contractile Integral (Basal UES-CI), Post-Deglutitive UES Contractile Integral (Post-Deglutitive UES-CI), and Proximal Contractile Integral (PCI). Results: ANOVA analysis showed significantly higher values of Post-Deglutitive UES-CI in EoE patients compared with FD patients (p = 0.001). Basal UES-CI and UES-RP showed significantly higher values in EoE (p = 0.002, p = 0.038) and GERD (p < 0.001, p = 0.001) patients compared with FD patients. Correlations between LES-CI and Post-Deglutitive UES-CI, Basal UES-CI, and UES-RP (p ≤ 0.001, p = 0.027, p = 0.017, respectively), and between LES-BP and Post-Deglutitive UES-CI (p = 0.019), independent of diagnosis, were shown. No correlations have been demonstrated between the UES, EGJ metrics, and esophageal symptoms. Conclusions: Some differences in UES metrics in the three different diseases were found. Further studies are needed to confirm the results of our pilot study and possible applications in clinical practice.

Introduction: Data on peri-operative management of direct-acting oral anticoagulants (DOACs) during transcatheter pacing leadless system (TPS) implantations remain limited. This study aimed to evaluate a standardized DOAC management regime consisting of interruption of a single dose prior to implantation and reinitiation within 6–24 h; also, patient clinical characteristics associated with this approach were identified. Method: Consecutive patients undergoing standard TPS implantation procedures from two Swiss tertiary centers were included. DOAC peri-operative management included the standardized approach (Group 1A) or other approaches (Group 1B). Results: Three hundred and ninety-two pts (mean age 81.4 ± 7.3 years, 66.3% male, left ventricular ejection fraction 55.5 ± 9.6%) underwent TPS implantation. Two hundred and eighty-two pts (71.9%) were under anticoagulation therapy; 192 pts were treated with DOAC; 90 pts were under vitamin-K antagonist. Patients treated with DOAC less often had structural heart disease, diabetes mellitus, and advanced renal failure. The rate of major peri-procedural complications did not differ between groups 1A (n = 115) and 1B (n = 77) (2.6% and 3.8%, p = 0.685). Compared to 1B, 1A patients were implanted with TPS for slow ventricular rate atrial fibrillation (AF) (p = 0.002), in a better overall clinical status, and implanted electively (