Genome organization around nuclear speckles drives mRNA splicing efficiency.

The nucleus is highly organized, such that factors involved in the transcription and processing of distinct classes of RNA are confined within specific nuclear bodies1,2. One example is the nuclear speckle, which is defined by high concentrations of protein and noncoding RNA regulators of pre-mRNA splicing3. What functional role, if any, speckles might play in the process of mRNA splicing is unclear4,5. Here we show that genes localized near nuclear speckles display higher spliceosome concentrations, increased spliceosome binding to their pre-mRNAs and higher co-transcriptional splicing levels than genes that are located farther from nuclear speckles. Gene organization around nuclear speckles is dynamic between cell types, and changes in speckle proximity lead to differences in splicing efficiency. Finally, directed recruitment of a pre-mRNA to nuclear speckles is sufficient to increase mRNA splicing levels. Together, our results integrate the long-standing observations of nuclear speckles with the biochemistry of mRNA splicing and demonstrate a crucial role for dynamic three-dimensional spatial organization of genomic DNA in driving spliceosome concentrations and controlling the efficiency of mRNA splicing.

Beeswax Alcohol Prevents Low-Density Lipoprotein Oxidation and Demonstrates Antioxidant Activities in Zebrafish Embryos and Human Subjects: A Clinical Study.

Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress severely affects low-density lipid & protein (LDL) oxidation, leading to several detrimental health effects. Therefore, in this study, the effect of beeswax alcohol (BWA) was evaluated in the prevention of LDL oxidation, enhancement of paraoxonase 1 (PON-1) activity of high-density lipid & protein (HDL), and zebrafish embryo survivability. Furthermore, the implication of BWA consumption on the oxidative plasma variables was assessed by a preliminary clinical study on middle-aged and older human subjects (n = 50). Results support BWA augmentation of PON-1 activity in a dose-dependent manner (10-30 µM), which was significantly better than the effect exerted by coenzyme Q10 (CoQ10). Moreover, BWA significantly curtails LDL/apo-B oxidation evoked by CuSO4 (final 0.5 µM) and a causes a marked reduction in lipid peroxidation in LDL. The transmission electron microscopy (TEM) analysis revealed a healing effect of BWA towards the restoration of LDL morphology and size impaired by the exposure of Cu2+ ions (final 0.5 µM). Additionally, BWA counters the toxicity induced by carboxymethyllysine (CML, 500 ng) and rescues zebrafish embryos from development deformities and apoptotic cell death. A completely randomized, double-blinded, placebo-controlled preliminary clinical study on middle- and older-aged human subjects (n = 50) showed that 12 weeks of BWA (100 mg/day) supplementation efficiently diminished serum malondialdehyde (MDA) and total hydroperoxides and enhanced total antioxidant status by 25%, 27%, and 22%, respectively, compared to the placebo-control and baseline values. Furthermore, the consumption of BWA did not exhibit any noteworthy changes in physical variables, lipid profile, glucose levels, and biomarkers pertinent to kidney and liver function, thus confirming the safety of BWA for consumption. Conclusively, in vitro, BWA prevents LDL oxidation, enhances PON-1 activity in HDL, and positively influences oxidative variables in human subjects.

Risk factors for bloodstream infections due to carbapenem-resistant Enterobacterales: a nested case-control-control study.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients). METHODS: A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied. RESULTS: From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65-32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01-1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51-34.24; acute care hospital: IRR 5.26; 95% CI 1.61-17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33-40.56), haemodialysis (IRR 8.59; 95% CI 1.82-40.53), invasive procedures (IRR 5.66; 95% CI 2.11-15.16), and ß-lactam/ß-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68-9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06-7.11) exposure within 3 months before enrolment. CONCLUSIONS: Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients.

Identification of novel biomarkers in the early diagnosis of malignant melanoma by untargeted liquid chromatography coupled to high-resolution mass spectrometry-based metabolomics: a pilot study.

BACKGROUND: Malignant melanoma (MM) is a highly aggressive form of skin cancer whose incidence continues to rise worldwide. If diagnosed at an early stage, it has an excellent prognosis, but mortality increases significantly at advanced stages after distant spread. Unfortunately, early detection of aggressive melanoma remains a challenge. OBJECTIVES: To identify novel blood-circulating biomarkers that may be useful in the diagnosis of MM to guide patient counselling and appropriate disease management. METHODS: In this study, 105 serum samples from 26 healthy patients and 79 with MM were analysed using an untargeted approach by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to compare the metabolomic profiles of both conditions. Resulting data were subjected to both univariate and multivariate statistical analysis to select robust biomarkers. The classification model obtained from this analysis was further validated with an independent cohort of 12 patients with stage I MM. RESULTS: We successfully identified several lipidic metabolites differentially expressed in patients with stage I MM vs. healthy controls. Three of these metabolites were used to develop a classification model, which exhibited exceptional precision (0.92) and accuracy (0.94) when validated on an independent sample. CONCLUSIONS: These results demonstrate that metabolomics using LC-HRMS is a powerful tool to identify and quantify metabolites in bodily fluids that could serve as potential early diagnostic markers for MM.

Melanoma is a type of skin cancer that can be deadly if it is not detected at an early stage. Unfortunately, the early detection of melanoma is challenging. Our team has developed a model that could be used to predict whether a person has stage I malignant melanoma based on blood serum analysis. The model was trained on data from a group of people with melanoma and it was found to be accurate in predicting melanoma at an early stage. This means that the model could be used to identify people who have skin cancer before it progresses and becomes more complicated to treat. Although the researchers recommend that further studies are conducted to validate the model in a larger population of people, this research could help with the early diagnosis of melanoma and work toward improving survival rates.

Cost-effectiveness of severe acute malnutrition treatment delivered by community health workers in the district of Mayahi, Niger.

BACKGROUND: A non-randomized controlled trial, conducted from June 2018 to March 2019 in two rural communes in the health district of Mayahi in Niger, showed that including community health workers (CHWs) in the treatment of severe acute malnutrition (SAM) resulted in a better recovery rate (77.2% vs. 72.1%) compared with the standard treatment provided solely at the health centers. The present study aims to assess the cost and cost-effectiveness of the CHWs led treatment of uncomplicated SAM in children 6-59 months compared to the standard national protocol. METHODS: To account for all relevant costs, the cost analysis included activity-based costing and bottom-up approaches from a societal perspective and on a within-trial time horizon. The cost-effectiveness analysis was conducted through a decision analysis network built with OpenMarkov and evaluated under two approaches: (1) with recovery rate and cost per child admitted for treatment as measures of effectiveness and cost, respectively; and (2) assessing the total number of children recovered and the total cost incurred. In addition, a multivariate probabilistic sensitivity analysis was carried out to evaluate the effect of uncertainty around the base case input data. RESULTS: For the base case data, the average cost per child recovered was 116.52 USD in the standard treatment and 107.22 USD in the CHWs-led treatment. Based on the first approach, the CHWs-led treatment was more cost-effective than the standard treatment with an average cost per child admitted for treatment of 82.81 USD vs. 84.01 USD. Based on the second approach, the incremental cost-effectiveness ratio of the transition from the standard to the CHWs-led treatment amounted to 98.01 USD per additional SAM case recovered. CONCLUSIONS: In the district of Mayahi in Niger, the CHWs-led SAM treatment was found to be cost-effective when compared to the standard protocol and provided additional advantages such as the reduction of costs for households. TRIAL REGISTRATION: ISRCTN with ID 31143316. https://doi.org/10.1186/ISRCTN31143316.

Assessment of Untargeted Metabolomics by Hydrophilic Interaction Liquid Chromatography-Mass Spectrometry to Define Breast Cancer Liquid Biopsy-Based Biomarkers in Plasma Samples.

An early diagnosis of cancer is fundamental not only in regard to reducing its mortality rate but also in terms of counteracting the progression of the tumor in the initial stages. Breast cancer (BC) is the most common tumor pathology in women and the second deathliest cancer worldwide, although its survival rate is increasing thanks to improvements in screening programs. However, the most common techniques to detect a breast tumor tend to be time-consuming, unspecific or invasive. Herein, the use of untargeted hydrophilic interaction liquid chromatography-mass spectrometry analysis appears as an analytical technique with potential use for the early detection of biomarkers in liquid biopsies from BC patients. In this research, plasma samples from 134 BC patients were compared with 136 from healthy controls (HC), and multivariate statistical analyses showed a clear separation between four BC phenotypes (LA, LB, HER2, and TN) and the HC group. As a result, we identified two candidate biomarkers that discriminated between the groups under study with a VIP > 1 and an AUC of 0.958. Thus, targeting the specific aberrant metabolic pathways in future studies may allow for better molecular stratification or early detection of the disease.

Investors' confidence in the crowdlending platform and the impact of Covid-19.

Crowdlending platforms have gained importance in recent years due to digitalization. The Covid-19 pandemic has severely impacted the entire economy, including repercussions on digital transactions. Investors considering transactions on these platforms require confidence in both the platform and the project in order to make the right decision. For this reason, this study analyzes the links between the parties involved in the process. A survey was sent to 135 investors on the Colectual platform in January 2022, and the research method adopted is Fuzzy Set Qualitative Comparative Analysis (fsQCA). The study examines the connections between the platform, the investors, and the project developers, to assess the influence exerted by the platform on the confidence of the parties seeking and providing investment. The main result is that Covid-19 has been a key factor in the confidence of investors in the platform, and it has had a significant influence on the investments made.

Implementing a multisector public-private partnership to improve urban hypertension management in low-and middle- income countries.

BACKGROUND: Cardiovascular disease presents an increasing health burden to low- and middle-income countries. Although ample therapeutic options and care improvement frameworks exist to address its prime risk factor, hypertension, blood pressure control rates remain poor. We describe the results of an effectiveness study of a multisector urban population health initiative that targets hypertension in a real-world implementation setting in cities across three continents. The initiative followed the "CARDIO4Cities" approach (quality of Care, early Access, policy Reform, Data and digital technology, Intersectoral collaboration, and local Ownership). METHOD: The approach was applied in Ulaanbaatar in Mongolia, Dakar in Senegal, and São Paulo in Brazil. In each city, a portfolio of evidence-based practices was implemented, tailored to local priorities and available data. Outcomes were measured by extracting hypertension diagnosis, treatment and control rates from primary health records. Data from 18,997 patients with hypertension in primary health facilities were analyzed. RESULTS: Over one to two years of implementation, blood pressure control rates among enrolled patients receiving medication tripled in São Paulo (from 12·3% to 31·2%) and Dakar (from 6·7% to 19·4%) and increased six-fold in Ulaanbaatar (from 3·1% to 19·7%). CONCLUSIONS: This study provides first evidence that a multisectoral population health approach to implement known best-practices, supported by data and digital technologies, and relying on local buy-in and ownership, can improve hypertension control in high-burden urban primary care settings in low-and middle-income countries.

Implant-supported overdenture with horizontal insertion for treating the edentulous atrophic maxilla: A case series.

STATEMENT OF PROBLEM: Rehabilitation of edentulous patients with severe maxillary atrophy is a clinical challenge. Although several treatment options are available, the implant-supported overdenture has been widely advocated. However vertical insertion implant-supported overdentures have drawbacks, including wear, aging, and the continuous maintenance of retention systems. Whether an implant-supported overdenture with a horizontal insertion pathway can overcome these problems is unclear. PURPOSE: The purpose of this observational study was to determine the clinical and biological behavior of a new type of implant-supported overdenture with a horizontal insertion pathway over a mean clinical follow-up period of 6 years. MATERIAL AND METHODS: Ten study participants with an atrophic maxilla underwent rehabilitation with horizontal overdentures supported by 6 implants. Follow-up visits were scheduled at 3 months, 6 months, and annually thereafter. The variables analyzed were implant and prosthetic survival, peri-implant tissue behavior, mechanical complications, and patient satisfaction. RESULTS: The follow-up period ranged from 5 to 8 years, mean ±standard deviation 6.3 ±1.2 years. A total of 60 implants and 10 horizontal overdentures were placed. The clinical survival of the implants was 98.3% (mean peri-implant bone loss, 1.3 ±0.4 mm) and was 80% of the prostheses. Overall, mean patient satisfaction as assessed with a visual analog scale was 7.4, with 8.5 for esthetics and 9.5 for function. CONCLUSIONS: The horizontal implant-supported overdenture provided a functional alternative to conventional prostheses.

Integrating augmented reality in language learning: pre-service teachers' digital competence and attitudes through the TPACK framework.

Although the use of Augmented Reality (AR) in language learning has increased over the last two decades, there is still little research on the preparation of pre-service teachers as AR content creators. This paper focuses on analyzing the digital competence and attitudes of teacher candidates to integrate AR in the foreign language classroom. For this purpose, eighty-five college students were assigned into different teams to create their own AR-based projects which aimed at teaching English and content to young learners. The teacher candidates employed several software development kits (SDKs) to construct collaborative AR projects in a five-week period, including discursive and illustrative representations of the learning content. In this research based on a mixed method, quantitative and qualitative data were gathered trough AR project presentations and surveys encompassing two validated scales, the Technological Pedagogical Content Knowledge (TPACK) framework and the Augmented Reality Applications Attitudes Scale (ARAAS). The statistical data and qualitative findings revealed that the participants lacked practical knowledge on AR content creation and implementation in Education. The major problems were related to the TPK (Technological Pedagogical Knowledge) intersection since participants had been previously trained in AR technology just as recipients and not as content creators and educators. Supplementary Information: The online version contains supplementary material available at 10.1007/s10639-022-11123-3.

Fostering cardiovascular health at work - case study from Senegal.

BACKGROUND: Of the 15 million annual premature deaths from non-communicable diseases (NCDs), 85% occur in low- and middle-income countries (LMICs). Affecting individuals in the prime of their lives, NCDs impose severe economic damage to economies and businesses, owing to the high mortality and morbidity within the workforce. The Novartis Foundation urban health initiative, Better Hearts Better Cities, was designed to improve cardiovascular health in Dakar, Senegal through a combination of interventions including a workplace health program. In this study, we describe the labor policy environment in Senegal and the outcomes of a Novartis Foundation-supported multisector workplace health coalition bringing together volunteering private companies. METHODS: A mixed method design was applied between April 2018 and February 2020 to evaluate the workplace health program as a case study. Qualitative methods included a desk review of documents relevant to the Senegalese employment context and work environment and in-depth interviews with eight key informants including human resource representatives and physicians working in the participating companies. Quantitative methods involved an analysis of workplace health program indicators, including data on diagnosis, treatment and control of hypertension in employees, provided by the coalition companies, and a cost estimate of NCD-related ill-health as compared to the investment needed for hypertension screening and awareness raising events. RESULTS: Senegal has a legal and regulatory system that ensures employee protection, supports social security benefits, and promotes health and hygiene in companies. The Dakar Workplace Health Coalition comprised 18 companies, with a range of staff between 300 and 4'220, covering 36'268 employees in total. Interviews suggested that the main enablers for workplace program success were strong leadership support within the company and a central coordination mechanism for the program. The main barrier to monitor progress and outcomes was the reluctance of companies to share data. Four companies provided aggregated anonymized cohort data, documenting a total of 21'392 hypertension screenings and an increasing trend in blood pressure control (from 34% in Q4 2018 to 39% in Q2 2019) in employees who received antihypertensive treatment. CONCLUSION: Evidence on workplace health and wellness programs in Africa is scarce. This study highlights how private sector companies can play a significant role in improving cardiovascular population health in LMICs.

Widening the applicability of AnMBR for urban wastewater treatment through PDMS membranes for dissolved methane capture: Effect of temperature and hydrodynamics.

AnMBR technology is a promising alternative to achieve future energy-efficiency and environmental-friendly urban wastewater (UWW) treatment. However, the large amount of dissolved methane lost in the effluent represents a potential high environmental impact that hinder the feasibility of this technology for full-scale applications. The use of degassing membranes (DM) to capture the dissolved methane from AnMBR effluents can be considered as an interesting alternative to solve this problem although further research is required to assess the suitability of this emerging technology. The aim of this study was to assess the effect of operating temperature and hydrodynamics on the capture of dissolved methane from AnMBR effluents by DMs. To this aim, a commercial polydimethylsiloxane (PDMS) DM was coupled to an industrial prototype AnMBR (demonstration scale) treating UWW at ambient temperature. Different operating temperatures have been evaluated: 11, 18, 24 and 30 °C. Moreover, the DM was operated at different ratios of liquid flow rate to membrane area (QL:A) ranging from 22 to 190 Lh-1m-2 in order to study the resistance of the system to methane permeation. Methane recovery was maximized when temperature raised and QL:A was reduced, giving methane recovery efficiencies (MRE) of about 85% at a temperature of 30 °C and a QL:A of 25 Lh-1m-2. The study showed that high QL:A ratios hinder methane recovery by the perturbation of the DM fibers, being this effect intensified at lower temperatures probably due the higher liquid viscosities. Also, the performed fouling evaluation showed that not significant membrane fouling may be expected in the DM unit at the short-term when treating AnMBR effluents. A resistance-in-series model was proposed to predict the overall mass transfer of the system according to operating temperature and QL:A, showing that methane capture was controlled by the liquid phase, which represented up to 80-90% of total mass transfer resistance. The energy and environmental evaluation performed in this study revealed that PDMS DMs would enhance energy recovery and environmental feasibility of AnMBR technology for UWW treatment, especially when operating at low temperatures. When MRE was maximized, the combination of AnMBR with DM achieved net energy productions and net greenhouse gas reductions of up to 0.87 kWh and 0.216 kg CO2-eq per m3 of treated water.

Liver manifestations in COVID-19 and the influence of pre-existing liver disease in the course of the infection.

INTRODUCTION: patients with advanced chronic liver disease (CLD) may be at an increased risk of a severe course due to cirrhosis-associated immune dysfunction. The aim of this study was to determine the prevalence of CLD in COVID-19 patients and to analyze the course of the infection, compared with patients with non-liver disease. MATERIALS AND METHODS: this was a retrospective single center study of all patients with a positive SARS-CoV-2 polymerase chain reaction (PCR) test from March 23rd to April 30th, 2020. Clinical and biochemical data of patients with and without CLD and COVID-19 were collected from the medical records. RESULT: four hundred and forty-seven patients with a SARS-CoV-2 positive PCR were included, 6.3 % had CLD; 69.7 % of patients with CLD were male, with a median age of 65.5 years and active alcohol consumption and smoking; 75 % had non-advanced liver fibrosis and most had non-alcoholic fatty liver disease (NAFLD). The hospital admission rate (92.9 % vs 47.7 %, p < 0.001), concomitant comorbidities (diabetes 38.5 vs 16.5 %, p = 0.011; obesity 30.8 vs 8.5 %, p = 0.033; cancer 23.1 vs 5 %, p = 0.027; and chronic obstructive pulmonary disease (COPD) 19.2 vs 9 %, p = 0.009) and concomitant antibiotics treatment (19.3 vs 5 %, p = 0.018) were higher in patients with CLD than in those without CLD. In-patient hospital mortality rates were similar in both groups (30.8 vs 19.6 %, p = 0.289). The presence of CLD was not associated with mortality (OR = 1.06; 95 % CI = 0.35-3.18; p = 0.924). However, patients with CLD and COVID-19 who were male, obese or under concomitant antibiotic treatment had the highest risk of mortality according to the univariate analysis. CONCLUSION: patients with CLD had a higher risk of hospital admission, with worse outcomes during the COVID-19 infection associated to other concomitant comorbidities and a suspicion of bacterial co-infection.

Personalized monitoring of electrical remodelling during atrial fibrillation progression via remote transmissions from implantable devices.

AIMS: Atrial electrical remodelling (AER) is a transitional period associated with the progression and long-term maintenance of atrial fibrillation (AF). We aimed to study the progression of AER in individual patients with implantable devices and AF episodes. METHODS AND RESULTS: Observational multicentre study (51 centres) including 4618 patients with implantable cardioverter-defibrillator +/-resynchronization therapy (ICD/CRT-D) and 352 patients (2 centres) with pacemakers (median follow-up: 3.4 years). Atrial activation rate (AAR) was quantified as the frequency of the dominant peak in the signal spectrum of AF episodes with atrial bipolar electrograms. Patients with complete progression of AER, from paroxysmal AF episodes to electrically remodelled persistent AF, were used to depict patient-specific AER slopes. A total of 34 712 AF tracings from 830 patients (87 with pacemakers) were suitable for the study. Complete progression of AER was documented in 216 patients (16 with pacemakers). Patients with persistent AF after completion of AER showed ∼30% faster AAR than patients with paroxysmal AF. The slope of AAR changes during AF progression revealed patient-specific patterns that correlated with the time-to-completion of AER (R2 = 0.85). Pacemaker patients were older than patients with ICD/CRT-Ds (78.3 vs. 67.2 year olds, respectively, P < 0.001) and had a shorter median time-to-completion of AER (24.9 vs. 93.5 days, respectively, P = 0.016). Remote transmissions in patients with ICD/CRT-D devices enabled the estimation of the time-to-completion of AER using the predicted slope of AAR changes from initiation to completion of electrical remodelling (R2 = 0.45). CONCLUSION: The AF progression shows patient-specific patterns of AER, which can be estimated using available remote-monitoring technology.

Health-related quality of life in nonvalvular atrial fibrillation patients with controlled or uncontrolled anticoagulation status.

BACKGROUND: There is a dearth of evidence regarding Health-Related Quality of Life (HRQoL) in nonvalvular atrial fibrillation (NVAF) patients undergoing oral anticoagulation therapy. Our objective was to describe HRQoL in NVAF patients on oral anticoagulation, focusing on uncontrolled patients on vitamin K antagonists (VKAs) versus controlled patients on VKAs or non-vitamin K antagonist oral anticoagulants (NOACs), in a real-world setting. Additionally, we assessed the clinical characteristics of patients with uncontrolled anticoagulation. METHODS: An observational, multicentre, and cross-sectional study, enrolling 38 Spanish Hospitals' Internal Medicine Departments. HRQoL was assessed using the validated Spanish version of the Sawicki questionnaire. High self-perceived HRQoL was indicated by high scores in the general treatment satisfaction and self-efficacy dimensions, and by low scores in the strained social network, daily hassles and distress dimensions. RESULTS: Five hundred and one patients were included for assessment. Mean scores ± SD were closer to a high perceived HRQoL in controlled than uncontrolled patients for the five dimensions of the questionnaire: 4.9 ± 1.0 versus 3.6 ± 1.3 for general treatment satisfaction; 4.3 ± 1.0 versus 3.6 ± 1.0 for self-efficacy, 3.1 ± 0.9 versus 3.9 ± 1.1 for strained social network, 2.1 ± 0.8 versus 3.0 ± 1.0 for daily hassles and 1.8 ± 0.9 versus 2.6 ± 1.2 for distress. CONCLUSIONS: HRQoL in patients with controlled anticoagulant status treated with NOACs or VKAs was better than in patients with uncontrolled anticoagulant status. This seems to indicate that anticoagulation control status influences perception of HRQoL, highlighting the importance of its evaluation when assessing HRQoL in NVAF patients.

Patient satisfaction with remote monitoring of cardiac implantable electronic devices: the VALIOSA questionnaire.

BACKGROUND: Remote monitoring of cardiac implantable electronic devices (CIEDs) has demonstrated substantial benefits. Treatment guidelines have therefore endorsed its use and is being increasingly adopted in the clinical setting, but the level of satisfaction they convey remains still unknown. We developed and validated a questionnaire to measure patient satisfaction with remote monitoring using Medtronic CareLink® Network and assessed its internal reliability and dimensional validity. METHODS: After a thorough literature review, cognitive debriefing of 18 patients, and an expert panel discussion, a 30-item instrument was proposed and grouped into 5 dimensions (items): 1- Information on cardiac condition (3), 2- Device convenience (3), 3- Transmission process (6), 4- Satisfaction with medical monitoring (8), and 5- General opinions (10). Correlation with the visual analog scale (VAS), overall health related quality of life (HRQoL) measured by the EuroQoL-5D accompanied by the VAS as well as with the Medical Outcomes Study (MOS) SF-36 were assessed. Psychometric properties, exploratory factor analysis and a second order confirmatory factor analysis (a hierarchical CFA with a general common factor explaining the relations between the first order common factors, See Figure 1) were estimated. Models were assessed based on item loading size, sign and statistical significance, and goodness-of-fit statistics. RESULTS: A total of 186 patients (77% male) with a mean age of 66.03 (SD = 13.94) years were assessed. 48% had implantable cardioverter-defibrillators, 24% had pacemakers, and 29% had cardiac resynchronization therapy devices. An overall Cronbach's α = 0.893 was achieved, with acceptable reliabilities for isolated dimensions. Correlations with corresponding VAS scales were meaningful and significant (p < 0.01). The second order factor solution yielded good goodness-of-fit indexes (χ2/df = 1.44, CFI = 0.96, TLI = 0.95, RMSEA = 0.05). Satisfaction with remote monitoring was not related to HRQoL (r < 0.05), except for the correlation between the SF-36 mental component and the information on cardiac condition dimension (r = 0.263, p < 0.001). CONCLUSIONS: The 30-item questionnaire showed good reliability and validity to assess satisfaction with remote monitoring in patients with CIEDs.

Safety and efficiency of a common and simplified protocol for pacemaker and defibrillator surveillance based on remote monitoring only: a long-term randomized trial (RM-ALONE).

AIMS: This trial aimed to evaluate the safety and efficiency of a common and simplified protocol for the surveillance of cardiac implantable electronic devices based on remote monitoring (RM) in patients with pacemakers (PMs) and implantable cardiac defibrillators (ICDs) for at least 24 months. METHODS AND RESULTS: The RM-ALONE is a multicentre prospective trial that randomly assigned 445 patients in two groups, both followed by RM: the home monitoring-only (HMo) based on RM + remote interrogations (RIs) every 6 months and the HM + IO that adds in-office evaluations every 6 months to RM. Four hundred and forty-five patients were enrolled in the study, 294 PMs and 151 ICDs recipients. In the HMo group, 20% of patients experienced ≥1 major adverse cardiac event (MACE) vs. 19.5% in HM + IO group (P = 0.006 for non-inferiority). The proportion of patients with a PM/ICD who experienced ≥1 MACE was 15.2/29.3% in HMo group and 16.1/26.3% in HM + IO group (hazard ratio 0.95/1.15, 95% confidence interval 0.53-1.70/0.62-2.10). There were 789 in-office evaluations (136 in the HMo and 653 in the HM + IO; P < 0.001). There was a 79.2% reduction of in-office evaluations with no significant differences in unscheduled visits between groups: 122 (54.5%) in HMo and 101 (45.3%) in HM + IO; P = 0.15. The time a physician/nurse spent per patient/follow-up was significantly reduced in the HMo group: 4/5 min (0-30)/(1-30) vs. 10/10 min (0-40)/(1-40) in HM + IO (P < 0.0001). CONCLUSION: The RM-ALONE protocol common for ICD and PM surveillance, consisting of RM + RI every 6 months has proven safe and efficient in reducing hospital visits and staff workload.

[Factors associated with early childhooddevelopment in mexican children]. / Características infantiles y contextuales asociadas con el desarrollo infantil temprano en la niñez mexicana.

OBJECTIVE: To estimate levels of early childhood develop-ment (ECD) and associated factors in Mexican population aged 19-59 months. MATERIALS AND METHODS: The Ensanut 2018-19 evaluated ECD using the Early Childhood Development Index (ECDI) and level of language develop-ment. We used multivariate models, with logistic or linear regression, depending on the outcome variable. RESULTS: Children of wealthier households and with children's books at home are more likely of having an adequate ECDI; in contrast, children who experienced violent discipline methods are less likely. Children living in rural areas, with more highly educated mothers, who were not undernourished, and with support for learning have higher language scores. CONCLUSIONS: Public policies aimed to enhance early childhood development should take into account the associated modifiable factors.

OBJETIVO: Estimar el nivel de desarrollo infantil temprano (DIT) y sus factores asociados en población mexicana de 19 a 59 meses. MATERIAL Y MÉTODOS: La Encuesta Nacional de Salud Pública y Nutrición 2018-19 evaluó el DIT mediante el Índice de Desarrollo Infantil Temprano (ECDI) y el nivel de desarrollo de lenguaje. Se estimaron modelos multivariados de acuerdo con la variable de resultado, usando modelos de regresión logística o lineal. RESULTADOS: Los niños/as de hogares con mayor nivel socioeconómico y que cuentan con libros infantiles en el hogar tienen mayores posibilidades de DIT adecuado, mientras que los/as niños/as educados con métodos de disciplina violenta tienen menores posibilidades. Además,los niños/as residentes de áreas rurales, hijos/as de madres con mayor escolaridad, sin desnutrición y con oportunidades de aprendizaje tienen un mayor puntaje de lenguaje. CONCLUSIONES: Las políticas públicas encaminadas a mejorar el desarrollo en la primera infancia deben tomar en cuenta los factores modificables asociados.

Harnessing inter-disciplinary collaboration to improve emergency care in low- and middle-income countries (LMICs): results of research prioritisation setting exercise.

BACKGROUND: More than half of deaths in low- and middle-income countries (LMICs) result from conditions that could be treated with emergency care - an integral component of universal health coverage (UHC) - through timely access to lifesaving interventions. METHODS: The World Health Organization (WHO) aims to extend UHC to a further 1 billion people by 2023, yet evidence supporting improved emergency care coverage is lacking. In this article, we explore four phases of a research prioritisation setting (RPS) exercise conducted by researchers and stakeholders from South Africa, Egypt, Nepal, Jamaica, Tanzania, Trinidad and Tobago, Tunisia, Colombia, Ethiopia, Iran, Jordan, Malaysia, South Korea and Phillipines, USA and UK as a key step in gathering evidence required by policy makers and practitioners for the strengthening of emergency care systems in limited-resource settings. RESULTS: The RPS proposed seven priority research questions addressing: identification of context-relevant emergency care indicators, barriers to effective emergency care; accuracy and impact of triage tools; potential quality improvement via registries; characteristics of people seeking emergency care; best practices for staff training and retention; and cost effectiveness of critical care - all within LMICs. CONCLUSIONS: Convened by WHO and facilitated by the University of Sheffield, the Global Emergency Care Research Network project (GEM-CARN) brought together a coalition of 16 countries to identify research priorities for strengthening emergency care in LMICs. Our article further assesses the quality of the RPS exercise and reviews the current evidence supporting the identified priorities.

A mathematical approach to predict the solids concentration in anaerobic membrane bioreactos (AnMBR): Evaluation of the volatile solids solubilization.

Anaerobic Membrane Bioreactors (AnMBR) are gaining attention as a suitable approach for sustainable low-strength wastewater treatment, as they bring together the advantages of both anaerobic treatments and membrane bioreactors. However, increasing the sludge retention time (SRT) necessary to favor hydrolysis increases the suspended solids concentration potentially leading to decreased permeate flux. Therefore, the availability of a mathematical approach to predict the solids concentration within an AnMBR can be very useful. In this work, a mathematical model describing the volatile solids concentration within the reactor as a function of the operating parameters and the influent characteristics is developed. The solubilization of organic particulates was clearly influenced by temperature and the SRT, whereas the hydraulic retention time influence was negligible. Furthermore, the activation energy value of about 20 kJ mol-1 confirms the idea that diffusion of hydrolytic enzymes from the bulk solution to the particle surface is the rate-limiting step of hydrolysis.