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BackgroundOnline resources are a valuable source of information for patients and have been reported to improve engagement and adherence to medical care. However, readability of online patient educational materials (OPEMs) is crucial for them to serve their intended purpose. The American Medical Association (AMA) recommends that OPEM be written at or below the sixth grade reading level. To avoid disparities in access to comprehensible health information on peripheral artery disease (PAD), it is imperative that the readability of PAD OPEM is appropriate for both English-speaking and Spanish-speaking patients. The aim of this study is to evaluate the readability of PAD OPEM in Spanish and compare to English-language OPEM.MethodsWe conducted a Google search in English and Spanish using "peripheral arterial disease" and "enfermedad arterial periferica", respectively, and the top 25 patient-accessible articles were collected for each. Articles were categorized by source type: hospital, professional society, or other. Readability of English-language OPEM was measured using the Flesch Reading Ease Readability Formula, Automated Readability Index, Coleman-Liau Index, Flesch-Kincaid Grade Level, Gunning Fog, Linsear Write Formula, and the Simple Measure of Gobbledygook Index. Readability of Spanish OPEM was measured using the Fernández-Huerta Index and Índice Flesch-Szigriszt Scale. Readability of the articles was compared to the AMA recommendation, between English- and Spanish-language, and across sources using statistical tests appropriate to the data.ResultsOPEM from professional societies represented the fewest number of English- (n = 7, 28%) and Spanish-language (n = 6, 24%) articles. Most English-speaking (n = 18, 72%) and Spanish-language (n = 20, 80%) OPEM were considered difficult as measured by the Flesch Reading Ease Readability Formula and Fernández-Huerta Index, respectively, but did not significantly differ between languages (P = 0.59). There were no significant differences in the average readability of all readability measurements across sources (hospital, professional society, or other). All the average readability grade levels for English-speaking and Spanish-language OPEM was significantly higher than the sixth grade reading level (P

Abstract Background CRISPR-Cas9 dropout screens are formidable tools for investigating biology with unprecedented precision and scale. However, biases in data lead to potential confounding effects on interpretation and compromise overall quality. The activity of Cas9 is influenced by structural features of the target site, including copy number amplifications (CN bias). More worryingly, proximal targeted loci tend to generate similar gene-independent responses to CRISPR-Cas9 targeting (proximity bias), possibly due to Cas9-induced whole chromosome-arm truncations or other genomic structural features and different chromatin accessibility levels. Results We benchmarked eight computational methods, rigorously evaluating their ability to reduce both CN and proximity bias in the two largest publicly available cell-line-based CRISPR-Cas9 screens to date. We also evaluated the capability of each method to preserve data quality and heterogeneity by assessing the extent to which the processed data allows accurate detection of true positive essential genes, established oncogenetic addictions, and known/novel biomarkers of cancer dependency. Our analysis sheds light on the ability of each method to correct biases under different scenarios. AC-Chronos outperforms other methods in correcting both CN and proximity biases when jointly processing multiple screens of models with available CN information, whereas CRISPRcleanR is the top performing method for individual screens or when CN information is not available. In addition, Chronos and AC-Chronos yield a final dataset better able to recapitulate known sets of essential and non-essential genes. Conclusions Overall, our investigation provides guidance for the selection of the most appropriate bias-correction method, based on its strengths, weaknesses and experimental settings.

Abstract Background Pre-exposure prophylaxis (PrEP) with oral emtricitabine/tenofovir disoproxil (FTC/TDF) proved highly efficient in preventing HIV. Since 09/2019, FTC/TDF-PrEP is covered by health insurances in Germany, if prescribed by licensed specialists. However, methods to longitudinally monitor progress in PrEP implementation in Germany are lacking. Methods Utilizing anonymous FTC/TDF prescription data from 2017-2021, we developed a mathematical model to disentangle HIV-treatment from PrEP prescriptions, as well as to translate PrEP prescriptions into number of PrEP users. We used the model to estimate past- and future PrEP uptake dynamics, to predict coverage of PrEP needs and to quantify the impact of COVID-19 on PrEP uptake on a national and regional level. Results We identified significant (p

Si pubblica il testo dell’audizione orale svolta il giorno 28 marzo 2024 presso la Camera dei Deputati, Commissioni permanenti riunite I (Affari costituzionali) e II (Giustizia), sul disegno di legge in materia di «Disposizioni in materia di rafforzamento della cybersicurezza nazionale e di reati informatici» (AC 1717). Sono qui avanzate considerazioni sull’impianto generale della proposta e su alcune disposizioni del disegno di legge.

Abstract X-ray absorption (XA) spectroscopy is an essential experimental tool to investigate the local structure of liquid water. Interpretation of the experiment poses a significant challenge and requires a quantitative theoretical description. High-quality theoretical XA spectra require reliable molecular dynamics simulations and accurate electronic structure calculations. Here, we present the first successful application of coupled cluster theory to model the XA spectrum of liquid water. We overcome the computational limitations on system size by employing a multilevel coupled cluster framework for large molecular systems. Excellent agreement with the experimental spectrum is achieved by including triple excitations in the wave function and using molecular structures from state-of-the-art path-integral molecular dynamics. We demonstrate that an accurate description of the electronic structure within the first solvation shell is sufficient to successfully model the XA spectrum of liquid water within the multilevel framework. Furthermore, we present a rigorous charge transfer analysis of the XA spectrum, which is reliable due to the accuracy and robustness of the electronic structure methodology. This analysis aligns with previous studies regarding the character of the prominent features of the XA spectrum of liquid water.

OBJECTIVE: Designing practical decision support tools and other health care technology in health services research relies on a clear understanding of the cognitive processes that underlie the use of these tools. Unfortunately, methods to explore cognitive processes are rarely used in health services research. Thus, the objective of this manuscript is to introduce cognitive task analysis (CTA), a family of methods to study cognitive processes involved in completing a task, to a health services research audience. This methods article describes CTA procedures, proposes a framework for their use in health services research studies, and provides an example of its application in a pilot study. DATA SOURCES AND STUDY SETTING: Observations and interviews of health care providers involved in discharge planning at six hospitals in the Veterans Health Administration. STUDY DESIGN: Qualitative study of discharge planning using CTA. DATA COLLECTION/EXTRACTION METHODS: Data were collected from structured observations and semi-structured interviews using the Critical Decision Method and analyzed using thematic analysis. PRINCIPAL FINDINGS: We developed an adaptation of CTA that could be used in a clinical environment to describe clinical decision-making and other cognitive processes. The adapted CTA framework guides the user through four steps: (1) Planning, (2) Environmental Analysis, (3) Knowledge Elicitation, and (4) Analyses and Results. This adapted CTA framework provides an iterative and systematic approach to identifying and describing the knowledge, expertise, thought processes, procedures, actors, goals, and mental strategies that underlie completing a clinical task. CONCLUSIONS: A better understanding of the cognitive processes that underly clinical tasks is key to developing health care technology and decision-support tools that will have a meaningful impact on processes of care and patient outcomes. Our adapted framework offers a more rigorous and detailed method for identifying task-related cognitive processes in implementation studies and quality improvement. Our adaptation of this underutilized qualitative research method may be helpful to other researchers and inform future research in health services research.

Awake intubation is considered the standard of care for the management of the anticipated difficult airway. For its pharmacological properties, remifentanil is ideal for managing difficult endotracheal insertions. This process is augmented by the use of transtracheal injection of lidocaine as it disperses evenly around the area and facilitates the action of remifentanil further. A 48-year-old male patient, weight 200 kg, 184cm tall (BMI>40) came into the emergency room for severe hypercapnic hypoxic respiratory failure. Awake fiberoptic intubation was the option to secure the airway. Successful airway management is critical to the practice of emergency medicine. All anesthesiologists should be familiar with the airway management of obese patients.

IntroductionDiffuse pleural mesothelioma (DPM) of the pleura is a highly aggressive and treatment-resistant cancer linked to asbestos exposure. Despite multimodal treatment, the prognosis for DPM patients remains very poor, with an average survival of 2 years from diagnosis. Cisplatin, a platinum-based chemotherapy drug, is commonly used in the treatment of DPM. However, the development of resistance to cisplatin significantly limits its effectiveness, highlighting the urgent need for alternative therapeutic strategies. New selective inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have shown promise in various malignancies by inhibiting cell cycle progression and suppressing tumor growth. Recent studies have indicated the potential of abemaciclib for DPM therapy, and a phase II clinical trial has shown preliminary encouraging results.MethodsHere, we tested abemaciclib, palbociclib, and ribociclib on a panel of DPM cell lines and non-tumor mesothelial(MET-5A) cells.ResultsSpecifically, we focused on abemaciclib, which was the mosteffective cytotoxic agent on all the DPM cell lines tested. Abemaciclib reduced DPM cell viability, clonogenic potential, and ability to grow as three-dimensional (3D) spheroids. In addition, abemaciclib induced prolonged effects, thereby impairing second-generation sphere formation and inducing G0/G1 arrest and apoptosis/ necrosis. Interestingly, single silencing of RB family members did not impair cell response to abemaciclib, suggesting that they likely complement each other in triggering abemaciclib’s cytostatic effect. Interestingly, abemaciclib reduced the phosphorylation of AKT, which is hyperactive in DPM and synergized with the pharmacological AKT inhibitor (AKTi VIII). Abemaciclib also synergized with cisplatin and reduced the viability of DPM cells with acquired resistance to cisplatin.DiscussionOverall, our results suggest that CDK4/6 inhibitors alone or in combination with standard of care should be further explored for DPM therapy.

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). Conclusions: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

Abstract Robertsonian translocations, specifically rob(1;29) translocation, have reportedly been the most prevalent chromosomal abnormalities in cattle, affecting various breeds and leading to a decrease in fertility and reproductive value. Currently, the identification of rob(1;29) carriers relies on cytogenetic analysis that has limitations in terms of accessibility, cost, and sample requirements. To address these limitations, a novel genomic biomarker was developed in this study for the rapid and precise identification of rob(1;29) carriers. Using q-PCR, a specific copy number variation associated with translocation was targeted, which effectively distinguished between wild-type, homozygous and heterozygous carriers. Crucially, the biomarker can be applied to DNA extracted from various biological matrices, such as semen, embryos, oocytes, milk, saliva, coat, and muscle, and it is compatible with fresh, refrigerated, or frozen samples. Furthermore, this approach offers significant reductions in cost compared to those associated with traditional cytogenetic analysis and provides results within a short turnaround time. The successful development of this genomic biomarker has considerable potential for widespread adoption in screening programs. It facilitates timely identification and management of rob(1;29) carriers while mitigating economic losses and preserving genetic integrity in bovine populations.

Abstract COVID-19 typically presents with flu-like symptoms due to the viral infection itself. The most severe cases are characterised by lung damage, an important factor in fatal outcome due to alveolar damage. In some cases, patients develop a long COVID with persistent symptoms of chest pain and fatigue. Causes, including organ damage or inflammation, are being investigated. Clinical outcomes are variable and permanent lung damage is not fully understood, while vaccination is effective against severe infection but its effect on respiratory function in mild cases remains uncertain. This retrospective study aims to analyse changes in lung function in HCWs who had COVID-19 between 2020 and 2022, comparing their spirometric test results before and after the pandemic and taking into account their vaccination status. 321 HCWs were included in the study. The study examined spirometric parameters both before and after the pandemic, and all measured outcomes except the FEV1/FVC ratio showed a significant decrease during the study period. We then assessed the association between SARS-CoV-2 infection and changes in lung function parameters, analysing infections in 2020, 2021 and 2022 separately. We found a statistically significant difference in Forced vital capacity (FVC) between infected and non-infected subjects in 2020 and 2021, but not in 2022. To evaluate the protective effect of SARS-CoV-2 vaccination on respiratory function, a linear regression analysis was performed using changes in FVC, Forced expiratory volume in 1 s (FEV1), FVC/FEV1 ratio and Peak expiratory flow (PEF) as dependent variables. The analysis showed that the decline in FVC was significantly lower in subjects who had been vaccinated prior to infection. The study concludes that subclinical SARS-CoV-2 infections in 2020 and 2021 worsened respiratory parameters (FVC and FEV1), but vaccination protected against these effects. Even healthy individuals with previous infections showed respiratory changes, with vaccination providing protection, especially for FVC decline. This highlights the importance of vaccinating healthcare workers against COVID-19.

ObjectiveVenous thromboembolism (VTE) is an important cause of postoperative morbidity and mortality. However, the reported incidence after major vascular surgery has ranged from as low as 1% to >10%. Furthermore, little is known about optimal chemoprophylaxis regimens or rates of postdischarge VTE in this population. In the present study, we aimed to better characterize the rates of in-hospital and postdischarge VTE after major vascular surgery, the role of chemoprophylaxis timing, and the association of VTE with mortality.MethodsA single-center retrospective study of 1449 major vascular operations (2013-2020) was performed and included 189 endovascular abdominal aortic aneurysm repairs (13%), 169 thoracic endovascular aortic aneurysm repairs (12%), 318 open aortic operations (22%), 640 lower extremity bypasses (44%), and 133 femoral endarterectomies (9%). The baseline characteristics, anticoagulant and antiplatelet medications, and outcomes were abstracted from an electronic database with medical record auditing. Postoperative VTE (pulmonary embolism and deep vein thrombosis) within 90 days of surgery was classified by the location, symptoms, and treatment. A cut point analysis using Youden's index identified the most VTE discriminating timing of chemoprophylaxis (including therapeutic vs prophylactic anticoagulant and antiplatelet medications) and Caprini score. Multivariable logistic regression was used to test the association of VTE with chemoprophylaxis timing, Caprini score, and additional risk factors. Cox proportional hazard modeling was used to measure the association between VTE and mortality.ResultsThe overall VTE incidence was 3.4% (65% deep vein thrombosis; 25% pulmonary embolism; 10% both), and 37% had occurred after discharge. The rate of symptomatic VTE was 2.4%, which was lowest for endovascular abdominal aortic aneurysm repair (0.0%) and highest for open aortic surgery (4.1%; P = .02). Those who had developed VTE had had a longer length of stay, higher rates of end-stage renal disease and prior VTE, and higher Caprini scores (8 vs 5 points; P < .01 for all). Those who had developed VTE were also more likely to have received ≥2 U of blood postoperatively, required an unplanned return to the operating room, had delayed chemoprophylaxis, anticoagulation, and/or antiplatelet initiation of >4 days postoperatively, and had increased 90-day mortality (P < .01 for all). A Caprini score of ≥7 (29% of patients) was associated with postdischarge VTE (2.6% vs 0.7%; P = .01), and chemoprophylaxis, anticoagulation, and antiplatelet timing of >4 days was associated with an increased adjusted odds of VTE (odds ratio, 2.4; 95% confidence interval, 1.1-4.9). Although no fatal VTEs were identified, VTE was an independent predictor of 90-day mortality (adjusted hazard ratio, 2.7; 95% confidence interval, 1.3-5.9).ConclusionsThese data have shown that patients undergoing major vascular surgery are particularly prone to the development of VTE, with frequent hypercoagulable comorbidities. The earlier initiation of chemoprophylaxis was associated with a reduced risk of VTE development. Furthermore, the postdischarge VTE rates might reach thresholds warranting postdischarge chemoprophylaxis, especially for patients with a Caprini score of ≥7.

Teenage siblings of children with autism spectrum disorder (ASD) are at risk of worse mental health outcomes than their peers, yet there have been few interventions focused on improving their psychosocial wellbeing. This study explored the acceptability of an 8-session virtual group mind-body resiliency intervention for teen siblings of children with ASD. We used mixed methods to assess quantitative and qualitative survey results. Participants reported that the intervention had the right amount of sessions (88%), structure (74%), and duration (89%). Most participants felt comfortable during sessions (74%), found it helpful to learn mind-body exercises (74%), and that the intervention helped in coping with stress (71%). Though participants were satisfied with the opportunity to meet peers, they desired more social connection.