Revisiting Classical Controller Design and Tuning with Genetic Programming.

This paper introduces the application of a genetic programming (GP)-based method for the automated design and tuning of process controllers, representing a noteworthy advancement in artificial intelligence (AI) within the realm of control engineering. In contrast to already existing work, our GP-based approach operates exclusively in the time domain, incorporating differential operations such as derivatives and integrals without necessitating intermediate inverse Laplace transformations. This unique feature not only simplifies the design process but also ensures the practical implementability of the generated controllers within physical systems. Notably, the GP's functional set extends beyond basic arithmetic operators to include a rich repertoire of mathematical operations, encompassing trigonometric, exponential, and logarithmic functions. This broad set of operations enhances the flexibility and adaptability of the GP-based approach in controller design. To rigorously assess the efficacy of our GP-based approach, we conducted an extensive series of tests to determine its limits and capabilities. In summary, our research establishes the GP-based approach as a promising solution for automating the controller design process, offering a transformative tool to address a spectrum of control problems across various engineering applications.

[Consensus on the use of iSGLT2 in the treatment of patients with type 2 diabetes mellitus]. / Documento de consenso sobre el uso de los iSGLT2 en el tratamiento de pacientes con diabetes mellitus tipo 2.

Although in recent years in Mexico the quality of diabetes mellitus (DM) care has improved and access to health services and medications has increased, there is a lack of adherence to the recommendations of the clinical guidelines, which could explain the poor glycemic control in many of the patients with DM. Sodium-glucose cotransporter type 2 (iSGLT2) inhibitors have been the last class of antidiabetic agents to receive approval from the Food and Drug Administration (FDA) and COFEPRIS (Mexico). In order to improve the use of SGLT2i in clinical practice in Mexico, this paper presents the recommendations issued by a panel of eleven Mexican experts based on the new published evidence for the treatment of patients with DM2.

Aunque en los últimos años en México ha mejorado la calidad de la atención de la diabetes mellitus (DM) y ha aumentado el acceso a servicios de salud y medicamentos, existe una falta de apego a las recomendaciones de las guías de práctica clínica, que podría explicar la falta de un control glucémico adecuado en muchos de los pacientes con DM. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) han sido la última clase de agentes antidiabéticos en recibir la aprobación de la Food and Drug Administration (FDA) y de la Comisión Federal para la Protección contra Riesgos Sanitarios de México (COFEPRIS). Con el fin de mejorar el uso de los iSGLT2 en la práctica clínica en México, en este documento se presentan las recomendaciones emitidas por un panel de 11 expertos mexicanos con base en las nuevas evidencias publicadas para el tratamiento de los pacientes con DM2.

COVID-19 transmission during swimming-related activities: a rapid systematic review.

BACKGROUND: There are uncertainties about mitigating strategies for swimming-related activities in the context of the COVID-19 pandemic. There is an opportunity to learn from the experience of previous re-openings to better plan the future one. Our objectives are to systematically review the evidence on (1) the association between engaging in swimming-related activities and COVID-19 transmission; and (2) the effects of strategies for preventing COVID-19 transmission during swimming-related activities. METHODS: We conducted a rapid systematic review. We searched in the L·OVE (Living OVerview of Evidence) platform for COVID-19. The searches covered the period from the inception date of each database until April 19, 2021. We included non-randomized studies for the review on association of COVID-19 transmission and swimming-related activities. We included guidance documents reporting on the strategies for prevention of COVID-19 transmission during swimming-related activities. We also included studies on the efficacy and safety of the strategies. Teams of two reviewers independently assessed article eligibility. For the guidance documents, a single reviewer assessed the eligibility and a second reviewer verified the judgement. Teams of two reviewers extracted data independently. We summarized the findings of included studies narratively. We synthesized information from guidance documents according to the identified topics and subtopics, and presented them in tabular and narrative formats. RESULTS: We identified three studies providing very low certainty evidence for the association between engaging in swimming-related activities and COVID-19 transmission. The analysis of 50 eligible guidance documents identified 11 topics: ensuring social distancing, ensuring personal hygiene, using personal protective equipment, eating and drinking, maintaining the pool, managing frequently touched surfaces, ventilation of indoor spaces, screening and management of sickness, delivering first aid, raising awareness, and vaccination. One study assessing the efficacy of strategies to prevent COVID-19 transmission did not find an association between compliance with precautionary restrictions and COVID-19 transmission. CONCLUSIONS: There are major gaps in the research evidence of relevance to swimming-related activities in the context of the COVID-19 pandemic. However, the synthesis of the identified strategies from guidance documents can inform public health management strategies for swimming-related activities, particularly in future re-opening plans.

Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence.

BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. DATA SOURCES: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization. (PROSPERO: CRD42020178187).

Real world outcomes with Bortezomib Thalidomide dexamethasone and Cyclophosphamide Bortezomib dexamethasone induction treatment for transplant eligible multiple myeloma patients in a Latin American country. A Retrospective Cohort Study from Grupo Argentino de Mieloma Múltiple.

Data about treatment outcomes and toxicity in Latin America are scarce. There are differences with central countries based on access to healthcare system and socioeconomic status. Argentinean Society of Hematology recommends bortezomib-based triplets for induction treatment of transplant eligible newly diagnosed multiple myeloma patients. Most common options are CyBorD (cyclophosphamide, bortezomib and dexamethasone) and VTD (bortezomib, thalidomide and dexamethasone). Main goal of our retrospective, multicentric study was to compare very good partial response rate (VGPR) or better after induction treatment in a real-world setting in Argentina. Secondary objectives included comparison of complete response (CR) post-induction and after bone marrow transplantation, grade 3-4 adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Three hundred twenty-two patients were included (median age at diagnosis: 57 years; 52% male; 28% had ISS3; 14% with high-risk cytogenetics; median follow up: 34 months). CyBorD was indicated in 74% and 26% received VTD. In VTD arm, 72.62% of patients achieved at least VGPR vs 53.36% receiving CyBorD (odds ratio, OR: 1.96 [95% confidence interval, CI: 1.08-3.57; P = .026] after adjusting by age, ISS [International Staging System], lactate dehydrogenase levels (LDH) and cytogenetic risk. Difference in VGPR was 19.26% (95% CI: 15-24). CR rate were 35.92% (VTD) vs 22.55% (CyBorD) (adjusted OR: 2.13 [95% CI: 1.12-4.05]). Difference in CR was 13.37% (95% CI: 9.6-17.53). Adverse events (AEs) were more common with VTD (69.05% vs 55.46% for CyBorD; P = .030), especially grade 3-4 neuropathy (P = .005) and thrombosis (P = .001). Thromboprophylaxis was inadequate in 20.24% of patients. Hematological AEs were more common with CyBorD, especially thrombocytopenia (P = .017). PFS and OS at 24 months were not different between treatments. In this real-world setting, VTD was associated with better CR and VGPR than CyBorD. Nevertheless, CyBorD continues to be the preferred induction regimen in Argentina, based on safety profile. Frontline autologous stem cell transplantation improves quality of responses, especially in countries with limited access to new drugs.

Early Mobilization in Critically Ill Children: A Systematic Review.

OBJECTIVE: To characterize how early mobilization is defined in the published literature and describe the evidence on safety and efficacy on early mobilization in critically ill children. STUDY DESIGN: Systematic search of randomized and nonrandomized studies assessing early mobilization-based physical therapy in critically ill children under 18 years of age in MEDLINE, Embase, CINAHL, CENTRAL, the National Institutes of Health, Evidence in Pediatric Intensive Care Collaborative, Physiotherapy Evidence Database, and the Mobilization-Network. We extracted data to identify the types of mobility-based interventions and definitions for early, as well as barriers, feasibility, adverse events, and efficacy outcomes (mortality, morbidities, and length of stay). RESULTS: Of 1199 titles found, we included 11 studies (2 pilot trials and 9 observational studies) and 1 clinical practice guideline in the analyses. Neurodevelopmentally appropriate increasing mobility levels have been described for critically ill children, and "early" mobilization was defined as either a range (within 48-72 hours) from admission to the pediatric intensive care unit or when clinical safety criteria are met. Current evidence suggests that early mobilization is safe and feasible and institutional practice guidelines significantly increase the frequency of rehabilitation consults, improve the proportion of patients who receive early mobilization, and reduce the time to mobilization. However, there were inconsistencies in populations and interventions across studies, and imprecision and risk of bias in included studies that precluded us from pooling data to evaluate the efficacy outcomes of early mobilization. CONCLUSIONS: The definition of early mobilization varies, but seems to be feasible and safe in critically ill children. The efficacy for early mobilization in this population is yet undetermined because of the low certainty of the evidence available.

Smectite for acute infectious diarrhoea in children.

BACKGROUND: As mortality secondary to acute infectious diarrhoea has decreased worldwide, the focus shifts to adjuvant therapies to lessen the burden of disease. Smectite, a medicinal clay, could offer a complementary intervention to reduce the duration of diarrhoea. OBJECTIVES: To assess the effects of smectite for treating acute infectious diarrhoea in children. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Pubmed), Embase (Ovid), LILACS, reference lists from studies and previous reviews, and conference abstracts, up to 27 June 2017. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing smectite to a control group in children aged one month to 18 years old with acute infectious diarrhoea. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and the full texts for inclusion, extracted data, and assessed risk of bias. Our primary outcomes were duration of diarrhoea and clinical resolution at day 3. We summarized continuous outcomes using mean differences (MD) and dichotomous outcomes using risk ratios (RR), with 95% confidence intervals (CI). Where appropriate, we pooled data in meta-analyses and assessed heterogeneity. We explored publication bias using a funnel plot. MAIN RESULTS: Eighteen trials with 2616 children met our inclusion criteria. Studies were conducted in both ambulatory and in-hospital settings, and in both high-income and low- or middle-income countries. Most studies included children with rotavirus infections, and half included breastfed children.Smectite may reduce the duration of diarrhoea by approximately a day (MD -24.38 hours, 95% CI -30.91 to -17.85; 14 studies; 2209 children; low-certainty evidence); may increase clinical resolution at day 3 (risk ratio (RR) 2.10, 95% CI 1.30 to 3.39; 5 trials; 312 children; low-certainty evidence); and may reduce stool output (MD -11.37, 95% CI -21.94 to -0.79; 3 studies; 634 children; low-certainty evidence).We are uncertain whether smectite reduces stool frequency, measured as depositions per day (MD -1.33, 95% CI -2.28 to -0.38; 3 studies; 954 children; very low-certainty evidence). There was no evidence of an effect on need for hospitalization (RR 0.93, 95% CI 0.75 to 1.15; 2 studies; 885 children; low-certainty evidence) and need for intravenous rehydration (RR 0.77, 95% CI 0.54 to 1.11; 1 study; 81 children; moderate-certainty evidence). The most frequently reported side effect was constipation, which did not differ between groups (RR 4.71, 95% CI 0.56 to 39.19; 2 studies; 128 children; low-certainty evidence). No deaths or serious adverse effects were reported. AUTHORS' CONCLUSIONS: Based on low-certainty evidence, smectite used as an adjuvant to rehydration therapy may reduce the duration of diarrhoea in children with acute infectious diarrhoea by a day; may increase cure rate by day 3; and may reduce stool output, but has no effect on hospitalization rates or need for intravenous therapy.

Sliding scale insulin for non-critically ill hospitalised adults with diabetes mellitus.

BACKGROUND: Diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, function, or both. Hyperglycaemia in non-critically ill hospitalised people is associated with poor clinical outcomes (infections, prolonged hospital stay, poor wound healing, higher morbidity and mortality). In the hospital setting people diagnosed with diabetes receive insulin therapy as part of their treatment in order to achieve metabolic control. However, insulin therapy can be provided by different strategies (sliding scale insulin (SSI), basal-bolus insulin, and other modalities). Sliding scale insulin is currently the most commonly used method, however there is uncertainty about which strategy provides the best patient outcomes. OBJECTIVES: To assess the effects of SSI for non-critically ill hospitalised adults with diabetes mellitus. SEARCH METHODS: We identified eligible trials by searching MEDLINE, Embase, LILACS, and the Cochrane Library. We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov trial registers. The date of the last search for all databases was December 2017. We also examined reference lists of identified randomised controlled trials (RCTs) and systematic reviews, and contacted trial authors. SELECTION CRITERIA: We included RCTs comparing SSI with other strategies for glycaemic control in non-critically ill hospitalised adult participants of any sex with diabetes mellitus. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, assessed trials for risk of bias, and evaluated the overall certainty of evidence utilising the GRADE instrument. We synthesised data using a random-effects model meta-analysis with 95% prediction intervals, if possible, or descriptive analysis, as appropriate. MAIN RESULTS: Of 720 records screened, we included eight trials that randomised 1048 participants with type 2 diabetes (387 SSI participants and 615 participants in comparator groups were available for final analysis). We included non-critically ill medical and surgical adults with the diagnosis of diabetes mellitus. The mean follow-up time was measured by the mean length of hospital stay and ranged between five and 24 days. The mean age of participants was 44.5 years to 71 years.Overall, we judged the risk of bias on the trial level as unclear for selection bias, high for outcome-related performance and detection bias with regard to hypoglycaemic episodes, other adverse events, and mean glucose levels, and low for all-cause mortality and length of hospital stay. Attrition bias was low for all outcome measures.Six trials compared SSI with a basal-bolus insulin scheme, three of which investigating 64% of all participants in this category also applying an SSI approach in the bolus comparator part. One trial had a basal insulin-only comparator arm, and the remaining trial used continuous insulin infusion as the comparator. For our main comparison of SSI versus basal-bolus insulin, the results were as follows. Four trials reported mortality data. One out of 268 participants in the SSI group (0.3%) compared with two out of 334 participants in the basal-bolus group (0.6%) died (low-certainty evidence). Severe hypoglycaemic episodes, defined as blood glucose levels below 40 mg/dL (2.2 mmol/L), showed a risk ratio (RR) of 0.22, 95% confidence interval (CI) 0.05 to 1.00; P = 0.05; 5 trials; 667 participants; very low-certainty evidence. The 95% prediction interval ranged between 0.02 and 2.57. All nine severe hypoglycaemic episodes were observed among the 369 participants on basal-bolus insulin (2.4%). The mean length of hospital stay was 0.5 days longer for the SSI group, 95% CI -0.5 to 1.4; P = 0.32; 6 trials; 717 participants; very low-certainty evidence. The 95% prediction interval ranged between -1.7 days and 2.7 days. Adverse events other than hypoglycaemic episodes, such as postoperative infections, showed a RR of 1.16, 95% CI 0.25 to 5.37; P = 0.85; 3 trials; 481 participants; very low-certainty evidence. The mean blood glucose levels ranged across basal-bolus groups from 156 mg/dL (8.7 mmol/L) to 221 mg/dL (12.3 mmol/L). The mean blood glucose level in the SSI groups was 14.8 mg/dL (0.8 mmol/L) higher (95% CI 7.8 (0.4) to 21.8 (1.2); P < 0.001; 6 trials; 717 participants; low-certainty evidence). The 95% prediction interval ranged between -3.6 mg/dL (-0.2 mmol/L) and 33.2 mg/dL (1.8 mmol/L). No trial reported on diabetes-related mortality or socioeconomic effects. AUTHORS' CONCLUSIONS: We are uncertain which insulin strategy (SSI or basal-bolus insulin) is best for non-critically hospitalised adults with diabetes mellitus. A basal-bolus insulin strategy in these patients might result in better short-term glycaemic control but could increase the risk for severe hypoglycaemic episodes. The certainty of the body of evidence comparing SSI with basal-bolus insulin was low to very low and needs to be improved by adequately performed, well-powered RCTs in different hospital environments with well-educated medical staff using identical short-acting insulins in both intervention and comparator arms to compare the rigid SSI approach with flexible insulin application strategies.

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision.

BACKGROUND: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. OBJECTIVE: We sought to provide a targeted update of the ARIA guidelines. METHODS: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. RESULTS: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. CONCLUSIONS: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.

Energetic and environmental assessment of thermochemical and biochemical ways for producing energy from agricultural solid residues: Coffee Cut-Stems case.

Forest residues are an important source of biomass. Among these, Coffee Cut-Stems (CCS) are an abundant wood waste in Colombia obtained from coffee crops renovation. However, only low quantities of these residues are used directly in combustion processes for heating and cooking in coffee farms where their energy efficiency is very low. In the present work, an energy and environmental assessment of two bioenergy production processes (ethanol fermentation and gasification) using CCS as raw material was performed. Biomass gasification seems to be the most promising thermochemical method for bioenergy production whereas, ethanol fermentation is a widely studied biochemical method to produce biofuels. Experimental runs of the CCS gasification were carried out and the synthesis gas composition was monitored. Prior to the fermentation process, a treatment of the CCS is required from which sugar content was determined and then, in the fermentation process, the ethanol yield was calculated. Both processes were simulated in order to obtain the mass and energy balance that are used to assess the energy efficiency and the potential environmental impact (PEI). Moderate high energy efficiency and low environmental impacts were obtained from the CCS gasification. In contrast, high environmental impacts in different categories and low energy efficiencies were calculated from the ethanolic fermentation. Biomass gasification seems to be the most promising technology for the use of Coffee Cut-Stems with high energy yields and low environmental issues.

Bartonella quintana and Typhus Group Rickettsiae Exposure among Homeless Persons, Bogotá, Colombia.

In 2015, we investigated Bartonella quintana and typhus group rickettsiae in body lice from homeless persons in Bogotá, Colombia. We found B. quintana-infected body lice and seroprevalence of this microorganism in 19% of homeless persons and typhus group rickettsiae in 56%. Public health professionals should start preemptive measures and active vector control.

18F-FDG-PET SUV AS A PROGNOSTIC MARKER OF INCREASING SIZE IN THYROID CANCER TUMORS.

OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) scans with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (18F-FDG) are used in high-risk thyroid cancer patients to identify metastasis. The prognostic significance of increases in standardized uptake values (SUVs) has not been clearly defined. This pilot study investigated the correlation between SUV increases and subsequent changes in individual lesion size. METHODS: A retrospective chart review of patients with histologically confirmed thyroid cancer who were monitored with serial 18F-FDG-PET/CT scans from 2008 to 2013 was performed. Forty-seven patients were selected for analysis. A mixed-effects statistical model was used after data normalization. RESULTS: For a 10% increase in SUV, a 6% increase in tumor area was observed (P<.0001). Analysis on cube root-transformed data from serial scans was significant in 4 of 5 groups: scans 1 to 2 (P = .0001), scans 2 to 3 (P = .0005), scans 3 to 4 (P = .008), scans 4 to 5 (P = .66), and overall (P<.0001). After exclusion of outliers, for a 10% increase in SUV, the expected percentage increases in area on subsequent scans were found to be 3.4% (P = .0006), 2.6% (P = .005), 4% (P = .074), and 4.1% (P = .27) for the second, third, fourth, and fifth scans, respectively. The association was similarly significant in cases with a ≥25% increase in SUV. Secondary analysis showed a significant association of SUV with thyroglobulin (Tg) level (P = .035) but not with thyroid-stimulating hormone (TSH) level (P = .85). CONCLUSIONS: A significant positive correlation was noted between the increase in lesional SUV and subsequent increase in lesion area. An increase in lesional SUV in subsequent scans may portend tumor growth and could prompt consideration for earlier or more aggressive intervention. ABBREVIATIONS: DTC = differentiated thyroid cancer EORTC = European Organization for Research and Treatment of Cancer 18F-FDG = 2-[fluorine-18] fluoro-2-deoxy-D-glucose FNA = fine-needle aspiration MTC = medullary thyroid cancer PET/CT = positron emission tomography/computed tomography PVE = partial volume effect RAI = radioactive iodine SUV = standardized uptake value Tg = thyroglobulin TSH = thyroid-stimulating hormone.

Stand-alone and biorefinery pathways to produce hydrogen through gasification and dark fermentation using Pinus Patula.

New efforts in the search of alternative clean and renewable energy to replace the current energy precursors have been assessed in order to reduce emissions to the environment. Lignocellulosic Biomass (LB) can be used to produce bioenergy due to its high energy potential and availability. Different ways are proposed for the transformation of these residues into high added-value products. Thermochemical and biochemical technologies are the most interest concepts focusing on the use of biomass as source for energy production at positive net balances. This study presents the techno-economic, energy and environmental assessment of five scenarios for the hydrogen production through gasification and dark fermentation based on the biorefinery and stand-alone concepts. The results demonstrated that the production of hydrogen based on the concept of a biorefinery can improve the profitability, energy efficiency and reduce the emissions of the processes compared to that based on the stand-alone way. The selection of ethanol and electricity as valuable co-products of the biorefinery in the hydrogen production process confirmed that the process scale and products diversity makes possible a flexible and suitable process to produce hydrogen and other energy carriers from Pinus Patula.

An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline.

BACKGROUND: This document updates the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guideline on idiopathic pulmonary fibrosis treatment. METHODS: Systematic reviews and, when appropriate, meta-analyses were performed to summarize all available evidence pertinent to our questions. The evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and then discussed by a multidisciplinary panel. Predetermined conflict-of-interest management strategies were applied, and recommendations were formulated, written, and graded exclusively by the nonconflicted panelists. RESULTS: After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications to health equity, recommendations were made for or against specific treatment interventions. CONCLUSIONS: The panel formulated and provided the rationale for recommendations in favor of or against treatment interventions for idiopathic pulmonary fibrosis.

Probiotics for the prevention of allergy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Allergic diseases are considered a health burden because of their high and constantly increasing prevalence, high direct and indirect costs, and undesirable effects on quality of life. Probiotics have been suggested as an intervention to prevent allergic diseases. OBJECTIVE: We sought to synthesize the evidence supporting use of probiotics for the prevention of allergies and inform World Allergy Organization guidelines on probiotic use. METHODS: We performed a systematic review of randomized trials assessing the effects of any probiotic administered to pregnant women, breast-feeding mothers, and/or infants. RESULTS: Of 2403 articles published until December 2014 identified in Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, 29 studies fulfilled a priori specified inclusion criteria for the analyses. Probiotics reduced the risk of eczema when used by women during the last trimester of pregnancy (relative risk [RR], 0.71; 95% CI, 0.60-0.84), when used by breast-feeding mothers (RR, 0.57; 95% CI, 0.47-0.69), or when given to infants (RR, 0.80; 95% CI, 0.68-0.94). Evidence did not support an effect on other allergies, nutrition status, or incidence of adverse effects. The certainty in the evidence according to the Grading of Recommendation Assessment Development and Evaluation approach is low or very low because of the risk of bias, inconsistency and imprecision of results, and indirectness of available research. CONCLUSION: Probiotics used by pregnant women or breast-feeding mothers and/or given to infants reduced the risk of eczema in infants; however, the certainty in the evidence is low. No effect was observed for the prevention of other allergic conditions.

User-experience testing of an evidence-to-decision framework for selecting essential medicines.

Essential medicine lists (EMLs) are important medicine prioritization tools used by the World Health Organization (WHO) EML and over 130 countries. The criteria used by WHO's Expert Committee on the Selection and Use of Essential Medicines has parallels to the GRADE Evidence-to-Decision (EtD) frameworks. In this study, we explored the EtD frameworks and a visual abstract as adjunctive tools to strengthen the integrate evidence and improve the transparency of decisions of EML applications. We conducted user-experience testing interviews of key EML stakeholders using Morville's honeycomb model. Interviews explored multifaceted dimensions (e.g., usability) on two EML applications for the 2021 WHO EML-long-acting insulin analogues for diabetes and immune checkpoint inhibitors for lung cancer. Using a pre-determined coding framework and thematic analysis we iteratively improved both the EtD framework and the visual abstract. We coded the transcripts of 17 interviews with 13 respondents in 103 locations of the interview texts across all dimensions of the user-experience honeycomb. Respondents felt the EtD framework and visual abstract presented complementary useful and findable adjuncts to the traditional EML application. They felt this would increase transparency and efficiency in evidence assessed by EML committees. As EtD frameworks are also used in health practice guidelines, including those by the WHO, respondents articulated that the adoption of the EtD by EML applications represents a tangible mechanism to align EMLs and guidelines, decrease duplication of work and improve coordination. Improvements were made to clarify instructions for the EtD and visual abstract, and to refine the design and content included. 'Availability' was added as an additional criterion for EML applications to highlight this criterion in alignment with WHO EML criteria. EtD frameworks and visual abstracts present additional important tools to communicate evidence and support decision-criteria in EML applications, which have global health impact. Access to essential medicines is important for achieving universal health coverage, and the development of essential medicine lists should be as evidence-based and trustworthy as possible.

Response predictors to cardiac resynchronization therapy in chronic heart failure: a 10-year-cardiovascular center experience.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been established as an effective therapy for heart failure with reduced ejection fraction. Randomized clinical trials have shown its impact on mortality and HF hospitalizations, as well as improvement of symptoms and quality of life. OBJECTIVES: Finding clinical, electrocardiographic, and echocardiographic variables that may predict the response to cardiac resynchronization therapy (CRT). METHODS: We performed a single-center, observational, analytic, and retrospective study that included 102 patients with heart failure (HF) diagnosis who underwent CRT according to guideline-directed therapy from January 2010 to April 2020 in a third-level center. CRT response was defined as an improvement of New York Heart Association functional class in at least 1 category associated with a recovery of ≥ 5% in the left ventricular ejection fraction (LVEF). RESULTS: Our study population was 102 patients of which 61 (59.8%) were men. The mean age at HF diagnosis was 54 ± 18.7 years. Ischemic heart disease was the etiology in 37 (36.3%) cases. Fifty-one (50%) patients were classified as responders. Responders had wider QRS, and lower LVEF and right ventricular fractional area change at baseline. After CRT, responders had a greater reduction of QRS duration, and improvement in LVEF, global longitudinal strain, and echocardiographic dyssynchrony parameters. Multivariate regression analysis showed that left bundle branch block (LBBB), left ventricular end-diastolic volume (LVEDV), tricuspid annular plane systolic excursion (TAPSE), and baseline difference of pre-ejection periods were predictors of a positive response to CRT in this population. CONCLUSIONS: LBBB, TAPSE, LVEDV, and pre-ejection time difference are independent variables that can predict adequate response to CRT.

ANTECEDENTES: La terapia de resincronización cardíaca (TRC) se ha establecido como una terapia efectiva para la insuficiencia cardíaca con fracción de eyección reducida. Ensayos clínicos aleatorizados han demostrado su impacto en la mortalidad y hospitalizaciones por insuficiencia cardíaca, así como la mejora de los síntomas y la calidad de vida. OBJETIVOS: Determinar las variables clínicas, electrocardiográficas y ecocardiográficas que puedan predecir la respuesta a la terapia de resincronización cardíaca (TRC). MÉTODO: Estudio unicéntrico, observacional, analítico, retrospectivo, que incluyó 102 pacientes con diagnóstico de IC sometidos a TRC y terapia dirigida por guías, de enero de 2010 a abril de 2020, en un centro de tercer nivel. La respuesta a TRC fue definida como mejoría de la clase funcional de la New York Heart Association en al menos 1 categoría, asociado con una recuperación ≥ 5% en la fracción de expulsión del ventrículo izquierdo (FEVI). RESULTADOS: Incluimos a 102 pacientes, 61 (59.8%) fueron hombres. El promedio de edad al diagnóstico de IC fue 54 ± 18.7 años. La cardiopatía isquémica fue la etiología en 37 (36.3%) pacientes. 51 (50%) pacientes, fueron clasificados como respondedores. Los respondedores presentaron QRS amplio, menor FEVI y menor fracción de acortamiento del ventrículo derecho al inicio del estudio. Después de la TRC, los respondedores tuvieron una mayor reducción en la duración del QRS, mejoría en la FEVI, strain longitudinal global y parámetros de disincronía ecocardiográfica. El análisis de regresión multivariado mostró que el bloqueo de rama izquierdo (BRI), el volumen telediastólico del ventrículo izquierdo (VTDVI) la excursión sistólica del plano anular tricuspídeo (TAPSE) y la diferencia basal del período expulsivo fueron predictores de respuesta positiva a TRC. CONCLUSIONES: BRI, TAPSE, VTDVI y la diferencia basal de períodos preexpulsivos son variables independientes que predicen respuesta adecuada a TRC.

The role of glycogen synthase kinase 3 in regulating IFN-ß-mediated IL-10 production.

The ability of IFN-ß to induce IL-10 production from innate immune cells is important for its anti-inflammatory properties and is believed to contribute to its therapeutic value in treating multiple sclerosis patients. In this study, we identified that IFN-ß stimulates IL-10 production by activating the JAK1- and PI3K-signaling pathways. JAK1 activity was required for IFN-ß to activate PI3K and Akt1 that resulted in repression of glycogen synthase kinase 3 (GSK3)-ß activity. IFN-ß-mediated suppression of GSK3-ß promoted IL-10, because IL-10 production by IFN-ß-stimulated dendritic cells (DC) expressing an active GSK3-ß knockin was severely reduced, whereas pharmacological or genetic inhibition of GSK3-ß augmented IL-10 production. IFN-ß increased the phosphorylated levels of CREB and STAT3 but only CREB levels were affected by PI3K. Also, a knockdown in CREB, but not STAT3, affected the capacity of IFN-ß to induce IL-10 from DC. IL-10 production by IFN-ß-stimulated DC was shown to suppress IFN-γ and IL-17 production by myelin oligodendrocyte glycoprotein-specific CD4(+) T cells, and this IL-10-dependent anti-inflammatory effect was enhanced by directly targeting GSK3 in DC. These findings highlight how IFN-ß induces IL-10 production and the importance that IL-10 plays in its anti-inflammatory properties, as well as identify a therapeutic target that could be used to increase the IL-10-dependent anti-inflammatory properties of IFN-ß.

Convergence of the mammalian target of rapamycin complex 1- and glycogen synthase kinase 3-ß-signaling pathways regulates the innate inflammatory response.

The PI3K pathway and its regulation of mammalian target of rapamycin complex 1 (mTORC1) and glycogen synthase kinase 3 (GSK3) play pivotal roles in controlling inflammation. In this article, we show that mTORC1 and GSK3-ß converge and that the capacity of mTORC1 to affect the inflammatory response is due to the inactivation of GSK3-ß. Inhibition of mTORC1 attenuated GSK3 phosphorylation and increased its kinase activity. Immunoprecipitation and in vitro kinase assays demonstrated that GSK3-ß associated with a downstream target of mTORC1, p85S6K, and phosphorylated GSK3-ß. Inhibition of S6K1 abrogated the phosphorylation of GSK3-ß while increasing and decreasing the levels of IL-12 and IL-10, respectively, in LPS-stimulated monocytes. In contrast, the direct inhibition of GSK3 attenuated the capacity of S6K1 inhibition to influence the levels of IL-10 and IL-12 produced by LPS-stimulated cells. At the transcriptional level, mTORC1 inhibition reduced the DNA binding of CREB and this effect was reversed by GSK3 inhibition. As a result, mTORC1 inhibition increased the levels of NF-κB p65 associated with CREB-binding protein. Inhibition of NF-κB p65 attenuated rapamycin's ability to influence the levels of pro- or anti-inflammatory cytokine production in monocytes stimulated with LPS. These studies identify the molecular mechanism by which mTORC1 affects GSK3 and show that mTORC1 inhibition regulates pro- and anti-inflammatory cytokine production via its capacity to inactivate GSK3.

Treating BCG-induced disease in children.

BACKGROUND: Bacillus Calmette-Guerín (BCG) is a live attenuated vaccine to prevent tuberculosis, routinely administered at birth as part of the World Health Organization global expanded immunisation programme. Given intradermally, it can cause adverse reactions, including local, regional, distant and disseminated manifestations that may cause parental distress. Rarely, it can cause serious illness and even death. Among those patients with immunocompromised conditions, such as the human immunodeficiency virus (HIV) infection, the complication rate is even higher. OBJECTIVES: To assess the effects of different interventions for treating BCG-induced disease in children. SEARCH METHODS: The following databases were searched: the Cochrane Infectious Diseases Group Specialized Register and Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (The Cochrane Library 2012, Issue 4); MEDLINE (1966 to November 2012); EMBASE (1947 to November 2012); and LILACS (1980 to November 2012). The metaRegister of Controlled Trials (mRCT) and the WHO trials search portal. Conference proceedings for relevant abstracts and experts were also contacted to identify studies. No language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing any medical or surgical treatment modality for BCG-induced disease in children. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated titles, applied inclusion criteria, and assessed the risk of bias of studies. The primary outcomes were the failure rate of therapies for all types of BCG vaccine-induced complications and the time to resolution of illness measured in months. The secondary outcomes were death from BCG vaccine-induced disease and the all-cause mortality. Risk ratios (RRs) were used as measure of effect for dichotomous outcomes and mean differences for continuous outcomes. MAIN RESULTS: Five RCTs analysing 341 children addressed the primary outcomes and were included. Four arms compared oral antibiotics to no intervention or placebo, one arm evaluated needle aspiration compared to no intervention, and another evaluated the use of locally instilled isoniazid versus oral erythromycin.Two small studies evaluated oral isoniazid; we are uncertain of whether this intervention has an effect on clinical failure (RR 1.48; 95% Confidence Interval (CI) 0.79 to 2.78; 54 participants, two studies, very low quality evidence). Similarly, for oral erythromycin, we are uncertain if there is an effect (clinical failure RR 1.03; 95% CI 0.70 to 1.53; 148 participants, three studies, very low quality evidence), and for oral isoniazid plus rifampicin (clinical failure, RR 1.20; 95% CI 0.51 to 2.83; 35 participants, one study, very low quality evidence).In patients with lymphadenitis abscess, needle aspiration may reduce clinically persistent BCG-induced disease at 6 to 9 months of follow-up (RR 0.13; 95% CI 0.03 to 0.55; 77 participants, one study, low quality evidence). In another study of patients with the same condition, aspiration plus local instillation of isoniazid reduces time to clinical cure compared to aspiration plus oral erythromycin (mean difference 1.49 months less; 95% CI 0.82 to 2.15 less; 27 participants, one study).No RCTs of HIV-infected infants with a BCG-induced disease evaluated the use of antibiotics or other therapies for reducing the rate of clinical failure or the time to clinical resolution. No data on mortality secondary to the interventions for treating BCG-induced disease were reported. AUTHORS' CONCLUSIONS: It is unclear if oral antibiotics (isoniazid, erythromycin, or a combination of isoniazid plus rifampicin) are effective for the resolution of BCG-induced disease. Most non-suppurated lymphadenitis will resolve without treatment in 4 to 6 months. Patients with lymphadenitis abscess might benefit from needle aspiration and possibly local instillation of isoniazid could shorten recovery time. Included studies were generally small and could be better conducted. Further research should evaluate the use of needle aspiration and local instillation of isoniazid in fluctuant nodes. Therapeutic and preventive measures in HIV-infected infants could be important given the higher risk of negative outcomes in this group.