Unmasking quantum effects in the surface thermodynamics of fluid nanodrops.

The focus of our study is an in-depth investigation of the quantum effects associated with the surface tension and other thermodynamic properties of nanoscopic liquid drops. The behavior of drops of quantum Lennard-Jones fluids is investigated with path-integral Monte Carlo simulations, and the test-area method is used to determine the surface tension of the spherical vapor-liquid interface. As the thermal de Broglie wavelength, λB, becomes more significant, the average density of the liquid drop decreases, with the drop becoming mechanically unstable at large wavelengths. As a consequence, the surface tension is found to decrease monotonically with λB, vanishing altogether for dominant quantum interactions. Quantum effects can be significant, leading to values that are notably lower than the classical thermodynamic limit, particularly for smaller drops. For planar interfaces (with infinite periodicity in the direction parallel to the interface), quantum effects are much less significant with the same values of λB but are, nevertheless, consequential for values representative of hydrogen or helium-4 at low temperatures corresponding to vapor-liquid coexistence. Large quantum effects are found for small drops of molecules with quantum interactions corresponding to water, ethane, methanol, and carbon dioxide, even at ambient conditions. The notable decrease in the density and tension has important consequences in reducing the Gibbs free-energy barrier of a nucleating cluster, enhancing the nucleation kinetics of liquid drops and of bubble formation. This implies that drops would form at a much greater rate than is predicted by classical nucleation theory.

Beta-Lactam Allergy De-labeling in a Pediatric Hospital.

OBJECTIVE: To assess the ability to de-label pediatric patients of their beta-lactam allergy by using a newly implemented institutional protocol and to identify potential barriers to the de-labeling process. METHODS: All patients with reported allergies to prespecified beta-lactam antibiotics were eligible for a -beta-lactam allergy interview. Following the interview, patients were grouped into 4 risk categories-no risk, low risk, moderate risk, and high risk-and assessed for intervention eligibility. Potential interventions included de-labeling based on the interview alone or proceeding to an oral amoxicillin challenge with or without penicillin allergy skin testing. RESULTS: Of the 62 patients eligible for beta-lactam allergy interviews, 40% (n = 25) were de-labeled. Among de-labeled patients, 60% (n = 15) were de-labeled on the basis of the interview alone. Additionally, no failures were documented in patients who underwent an oral amoxicillin challenge or penicillin skin testing. Barriers to performing oral amoxicillin challenges or penicillin skin testing included concomitant systemic steroid or antihistamine use, refusal of intervention, and insufficient resources to perform penicillin skin testing. CONCLUSIONS: There was a high frequency of patients de-labeled of their beta-lactam allergies in this study. Increased education to patients, parents, and providers on the de-labeling process, as well as increased personnel available to coordinate and perform de-labeling interventions, may result in more beta-lactam allergy de-labeling.

Effect of Industrial Pollution in Puchuncaví Valley on the Medicinal Properties of Senecio fistulosus Poepp. ex Les (Asteraceae): Content of Phytoconstituents and Their Antioxidant and Cytotoxic Activities.

Senecio fistulosus, an endemic plant in Chile, is highly regarded for its medicinal properties and is popular in alternative medicine. It thrives even in polluted areas, like Puchuncaví Valley, Chile. Therefore, the study aimed to assess the impact of industrial pollution in Puchuncaví Valley, Chile, on the phytoconstituent content, as well as the antioxidant and cytotoxic activities, of S. fistulosus. Phenols, flavonoids, and anthraquinones content were measured, alongside the assessment of antioxidant activities. Additionally, a GC-MS analysis was conducted to profile the phytoconstituents, while the cytotoxic potential was evaluated in HT-29 and MCF-7 and cell line non-tumorigenic MCF-10. The Wild sample exhibited a greater concentration of phytoconstituents (0 to 169.48 mg·L-1) compared to the Commercial control (0 to 95.38 mg·L-1), directly correlating with its antioxidant activity. While the Wild species showed cytotoxic activity, the Commercial control demonstrated cytotoxic effects on MCF-10 and MCF-7. Noteworthy compounds identified were hexadecanoic acid (12.76 to 19.57% relative area) and (Z,Z,Z)-9,12,15-octadecatrienoic acid (18.36% relative area), with anticancer properties. In conclusion, the abiotic stress experienced by S. fistulosus led to higher phytoconstituent content and improved antioxidant activity when contrasted with the Commercial control. The Commercial species showed increased cytotoxic activity against both tumorigenic and non-tumorigenic cell lines.

Effects of Duration of Calcium Propionate Supplementation in Lambs Finished with Supplemental Zilpaterol Hydrochloride: Productive Performance, Carcass Characteristics, and Meat Quality.

Forty-five male non-castrated crossbred Dorper lambs (40.17 ± 0.35 kg body weight, BW) were employed in a completely randomized design with five treatments to investigate the effects of the duration of calcium propionate (CaPr) supplementation (10 g CaPr/lamb/d for 0, 14, 28, or 42 d before slaughter) on lambs finished with zilpaterol hydrochloride (ZH, 7.2 mg/lamb/d for a fixed period of 28 d before slaughter) regarding their productive performance, carcass characteristics, and meat quality. Treatments consisted of the following: (1) No additives (CTL), (2) 0 days on CaPr plus 28 d on ZH, (3) 14 days on CaPr plus 28 d on ZH, (4) 28 days on CaPr plus 28 d on ZH, and (5) 42 days on CaPr plus 28 d on ZH. When compared with CTL, ZH lambs exhibited a similar average daily gain (ADG) but had lower dry matter intake (DMI), leading to increased feed efficiency. Supplementing with ZH alone did not affect carcass traits, visceral mass, whole cuts, or meat quality. Lambs that received both CaPr 28 d and ZH exhibited quadratic increases (p < 0.05) in final body weight (FBW), ADG, and dressing percentage (D%). These increases were optimal at estimated inclusion durations of 26 d for FBW, 30 for ADG, and 39 d for D%. The ADG:DMI ratio and the longissimus muscle area (LMA) both exhibited quadratic increases (p < 0.05). The optimal duration of CaPr supplementation for ADG:DMI ratio was found to be 28 d, while for LMA, it was 14 d. As the period of CaPr supplementation increased, there was a linear increase (p < 0.05) in hot carcass weight, leg circumference, and whole cuts of breast IMPS209 and shoulder IMPS207. Cook loss percent increased quadratically (p < 0.05), and was higher when CaPr was included for an estimated duration of 26 d. As the duration of CaPr supplementation increased, the purge loss percentage (PRL) also increased linearly (p < 0.05). In conclusion, including CaPr in the diet for a duration of 28 d in lambs improved the response to ZH supplementation on the productive performance, carcass weight, and some whole cuts. However, it can also have a negative effect on PRL%.

Human genetic adaptation related to cellular zinc homeostasis.

SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expression but also differ in the Met50Val substitution (rs1047626) in ZnT9, which we show is found in homozygosis in the Denisovan genome and displays accompanying signatures suggestive of archaic introgression. Although we found no significant differences in systemic zinc content between individuals with different rs1047626 genotypes, we demonstrate that the expression of the derived isoform (ZnT9 50Val) in HEK293 cells shows a gain of function when compared with the ancestral (ZnT9 50Met) variant. Notably, the ZnT9 50Val variant was found associated with differences in zinc handling by the mitochondria and endoplasmic reticulum, with an impact on mitochondrial metabolism. Given the essential role of the mitochondria in skeletal muscle and since the derived allele at rs1047626 is known to be associated with greater susceptibility to several neuropsychiatric traits, we propose that adaptation to cold may have driven this selection event, while also impacting predisposition to neuropsychiatric disorders in modern humans.

Twenty-five Years of Lung Transplantation in Medellín: Overcoming the Challenges of an Emerging Country.

The first successful lung transplant in Colombia was performed on October 28, 1997 in Medellín by Alberto Villegas Hernández at the "Clínica Cardiovascular Santa María" today called the Cardio VID Clinic. Here we present both survival outcomes and characteristics of the oldest and most experienced lung transplant program in Colombia. We conducted a retrospective study of all patients taken to lung transplantation at the Cardio VID Clinic in Medellín, Colombia from October 1997 to October 2022. Patient information from our institutional database and transplant archives were retrieved and reviewed. From October 1997 to October 2022, a total of 153 patients underwent orthotopic lung transplantation at our institution in Medellín, Colombia. Mean recipient age was 48±13 years, the youngest patient was 15 years old and the oldest patient was 73 years old at the time of transplant. 74 (48,4%) patients were men and 79 (51,6%) were women. Lung transplant survival in Medellin at 1-month, 1-year, 5-years and 10-years were 68%, 50%, 31% and 12% respectively. Although health care coverage in Colombia reaches nearly 100%, socioeconomic hurdles during post-transplant care, non-returning patients, infections and traumatic donor deaths lead to high mortality rates. Due to these factors, establishing successful and sustainable lung transplant programs in these settings is challenging.

Epidemiological and clinical characteristics of patients with human monkeypox infection in Mexico: a nationwide observational study.

Background: Human monkeypox, a zoonosis historically endemic to West and South Africa, has led to a worldwide outbreak driven by human-to-human transmission resulting in an international public health emergency. Endemic and outbreak monkeypox cases may differ in their affected populations, clinical features, and outcomes. Thus, profiling cases of the current monkeypox outbreak worldwide is crucial. Methods: We performed a nationwide observational surveillance-based study from May 24 to September 5, 2022. Patients that met the operational clinical definition of monkeypox or symptomatic close contacts of confirmed cases were tested by real-time polymerase chain reaction. Clinical data were collected with a standardized case-report form. We report epidemiologic, sociodemographic, and clinical characteristics of confirmed cases. Findings: Five-hundred and sixty-five human monkeypox confirmed cases were analysed; 97.2% were men, of whom 59.5% identified as men who have sex with men, and 54.5% had human immunodeficiency virus infection. The median age was 34 years. All patients but one had rash (99.8%), 78.9% had fever, and 47.8% reported myalgia. The anogenital area was the most commonly affected one by rash (49.6%), and proctitis occurred in 6.2% of patients. Six patients required hospitalization, of which one died due to causes unrelated to monkeypox. Interpretation: The 2022 monkeypox outbreak in Mexico is mainly driven by middle-aged men who have sex with men, of which a large proportion are persons who live with human immunodeficiency virus infection. Clinical features such as the high proportion of anogenital lesions suggest sexual contact is a pivotal transmission mechanism in this outbreak. Funding: This research was supported by grant A1-S-18342 from Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico (to S.I.V.-F.).

Population genetics and molecular identification of Crocodylus acutus and C. moreletii (Crocodilia: Crocodylidae) in captive and wildlife populations / Genética de poblaciones e identificación molecular de Crocodylus acutus y C. moreletii (Crocodilia: Crocodylidae) en poblaciones de cautiverio y de vida libre

Abstract Introduction: There is low evidence of genetic diversity and hybridization processes within Crocodylus acutus and C. moreletii populations. Objetive: To evaluate genetic diversity and some phylogenetic relationships in wild and captive populations of C. acutus and C. moreletii using the Barcode of Life Data System (COX1, cytochrome C oxidase subunit 1 gene). Methods: 28 individuals phenotypically like C. acutus located in the state of Guerrero, Oaxaca and Quintana Roo were sampled, as well as animals belonging to C. moreletii located in the states of Tabasco, Campeche, and Quintana Roo. 641 base pairs of nucleotide sequence from COX1 were used to obtain the haplotype and nucleotide diversity per population, and a phylogenetic and network analysis was performed. Results: Evidence of hybridization was found by observing C. moreletti haplotypes in animals phenotypically determined as C. acutus, as well as C. acutus haplotypes in animals classified as C. moreletti. Low haplotypic diversity was observed for C. acutus (0.455 ± 0.123) and for C. moreletii (0.505 ± 0.158). A phylogenetic tree was obtained in which the sequences of C. acutus and C. moreletii were grouped into two well-defined clades. Organisms identified phenotypically as C. acutus but with C. moreletii genes were separated into a different clade within the clade of C. moreletii. Conclusions: There are reproductive individuals with haplotypes different from those of the species. This study provides a small but significant advance in the genetic knowledge of both crocodile species and the use of mitochondrial markers, which in this case, the COX1 gene allowed the detection of hybrid organisms in wild and captive populations. Conservation efforts for both species of crocodiles should prevent the crossing of both threatened species and should require the genetic identification of pure populations, to design effective conservation strategies considering the possibility of natural hybridization in areas of sympatry.

Resumen Introducción: Existe poca evidencia de la diversidad genética y los procesos de hibridación dentro de las poblaciones de Crocodylus acutus y C. moreletii. Objetivo: Evaluar la diversidad genética y algunas relaciones filogenéticas en poblaciones silvestres y cautivas de C. acutus y C. moreletii utilizando el Sistema de Código de Barras de la vida (COX1, subunidad I del gen del citocromo C oxidasa). Métodos: Se muestrearon 28 individuos fenotípicamente similares a C. acutus ubicados en los estados de Guerrero, Oaxaca y Quintana Roo, así como animales pertenecientes a C. moreletii ubicados en los estados de Tabasco, Campeche y Quintana Roo. Se utilizaron 641 pares de bases de la secuencia de nucleótidos de la subunidad I del gen del citocromo C oxidasa para obtener el haplotipo y la diversidad de nucleótidos por población, y se realizó un análisis filogenético y de redes. Resultados: Se encontró evidencia de hibridación al observar haplotipos de C. moreletti en animales determinados fenotípicamente como C. acutus, así como haplotipos de C. acutus en animales clasificados como C. moreletti. Se observó una baja diversidad haplotípica para C. acutus (0.455 ± 0.123) y para C. moreletii (0.505 ± 0.158). Se obtuvo un árbol filogenético en el que las secuencias propias de C. acutus y C. moreletii se agruparon en dos grandes y bien definidos clados. Los organismos identificados fenotípicamente como C. acutus pero con genes de C. moreletii se separaron en un clado diferente dentro del clado de C. moreletii. Conclusiones: Existen individuos reproductores con haplotipos diferentes a los de la especie. Este estudio aporta un pequeño pero significativo avance en el conocimiento genético tanto de las especies de cocodrilos como del uso de marcadores mitocondriales, que, en este caso, el gen COX1 permitió la detección de organismos híbridos en poblaciones silvestres y cautivas. Los esfuerzos de conservación para ambas especies de cocodrilos deben evitar el cruce de ambas especies amenazadas y deben requerir la identificación genética de poblaciones puras, para diseñar estrategias de conservación efectivas considerando la posibilidad de hibridación natural en áreas de simpatría.

Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial.

BACKGROUND: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. METHODS: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. RESULTS: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). CONCLUSION: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.

Central nervous system effects of 5-HT7 receptors: a potential target for neurodegenerative diseases.

5-HT7 receptors (5-HT7R) are the most recently identified among the family of serotonin receptors. Their role in health and disease, particularly as mediators of, and druggable targets for, neurodegenerative diseases, is incompletely understood. Unlike other serotonin receptors, for which abundant preclinical and clinical data evaluating their effect on neurodegenerative conditions exist, the available information on the role of the 5-HT7R receptor is limited. In this review, we describe the signaling pathways and cellular mechanisms implicated in the activation of the 5-HT7R; also, we analyze different mechanisms of neurodegeneration and the potential therapeutic implications of pharmacological interventions for 5-HT7R signaling.

Implementation of an Automatic 48-Hour Vancomycin Hard-Stop in a Pediatric Community Hospital.

OBJECTIVE: Previous studies evaluating antimicrobial time-outs and required stop dates on antimicrobial orders indicate that these strategies are effective in decreasing antimicrobial duration and cost without a negative impact on patient outcomes. Few have evaluated use of a hard-stop strategy. The purpose of this study was to determine the feasibility and impact of a vancomycin hard-stop at 48 hours of therapy on vancomycin use. METHODS: This retrospective review compared 2 groups, a hard-stop pre-implementation group from April 2018 through March 2019 and a hard-stop post-implementation group from May 2019 through April 2020. The primary outcome was change in days of therapy (DOT) per ordered course of vancomycin therapy. Secondary outcomes included DOT per 1000 patient days (PD), number of courses continued beyond 48 hours, number of vancomycin concentrations drawn and drug acquisition cost. RESULTS: A total of 554 courses of vancomycin were prescribed (228 in the pre-implementation group and 326 in the post-implementation group). The median DOT per ordered course of vancomycin was 1.58 days (IQR, 1.00-2.59) in the pre-implementation group compared with 1.55 days (IQR, 1.00-1.99) in the post-implementation group (p = 0.51). Fewer vancomycin courses continued beyond 48 hours after hard-stop implementation (23% versus 33%) and fewer vancomycin concentrations were obtained in the post-implementation period than in the pre-implementation period despite more ordered courses of vancomycin therapy, 114 concentrations versus 153 concentrations, respectively. Overall, the total yearly drug acquisition cost savings to the pharmacy equated to $3000. CONCLUSIONS: Implementation of a vancomycin hard-stop at 48 hours of therapy is a feasible antimicrobial stewardship tool that may have significant clinical and operational impacts.

Long-time relaxation dynamics in nematic and smectic liquid crystals of soft repulsive colloidal rods.

Understanding the relaxation dynamics of colloidal suspensions is crucial to identifying the elements that influence the mobility of their constituents, assessing their macroscopic response across the relevant time and length scales, and thus disclosing the fundamentals underpinning their exploitation in formulation engineering. In this work, we specifically assess the impact of long-ranged ordering on the relaxation dynamics of suspensions of soft repulsive rodlike particles, which are able to self-organize into nematic and smectic liquid-crystalline phases. Rods are modeled as soft repulsive spherocylinders with a length-to-diameter ratio L^{★}=5, interacting via the truncated and shifted Kihara potential. By performing dynamic Monte Carlo simulations, we analyze the effect of translational and orientational order on the diffusion of the rods along the relevant directions imposed by the morphology of the background phases. To provide a clear picture of the resulting dynamics, we assess its dependence on temperature, which can dramatically determine the response time of the system relaxation and the self-diffusion coefficients of the rods. The computation of the van Hove correlation functions allows us to identify the existence of rods that diffuse significantly faster than the average and whose concentration can be accurately adjusted by a suitable choice of temperature.

Confined Quantum Hard Spheres.

We present computer simulation and theoretical results for a system of N Quantum Hard Spheres (QHS) particles of diameter σ and mass m at temperature T, confined between parallel hard walls separated by a distance Hσ, within the range 1≤H≤∞. Semiclassical Monte Carlo computer simulations were performed adapted to a confined space, considering effects in terms of the density of particles ρ*=N/V, where V is the accessible volume, the inverse length H-1 and the de Broglie's thermal wavelength λB=h/2πmkT, where k and h are the Boltzmann's and Planck's constants, respectively. For the case of extreme and maximum confinement, 0.5

Consenso Colombiano para la prevención, diagnóstico y manejo de condiciones trombóticas en pacientes adultos con COVID-19: aplicando el Marco de la Evidencia a la Decisión (EtD) GRADE / Colombian consensus for the prevention, diagnosis and treatment of thrombotic conditions in adult patients with COVID-19: applying GRADE Evidence to Decision (EtD) Frameworks

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Abstract Recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. In this context, the aim was to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: A rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection; b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: Recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.

Severe Acute Respiratory Syndrome Coronavirus-2 Pneumonia in a Newborn Treated With Remdesivir and Coronavirus Disease 2019 Convalescent Plasma.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel pandemic virus. Mounting evidence supports the possibility of vertical transmission, which at the present time appears to be rare. We report a newborn with vertically acquired SARS-CoV-2 who developed acute respiratory failure and received remdesivir and coronavirus disease 2019 convalescent plasma.

High-level ceftaroline resistance in a paediatric patient with invasive methicillin-resistant Staphylococcus aureus infection without previous ceftaroline exposure.

WHAT IS KNOWN AN OBJECTIVE: Our objective is to report a paediatric case of high-level ceftaroline resistance without previous ceftaroline exposure. CASE DESCRIPTION: A 20-month-old, 12 kg, female with invasive MRSA infection presented with high-level ceftaroline resistance with no previous ceftaroline exposure. WHAT IS NEW AND CONCLUSION: To our knowledge, our case is the first report of high-level ceftaroline resistance evident in a paediatric patient with invasive infection due to MRSA, without history of prior ceftaroline exposure. This case illustrates the importance of weighing the risk of resistance with the benefits of use when starting therapy empirically prior to susceptibility results, even in patients without previous drug exposure.

Assessment of the Wolf method using the Stillinger-Lovett sum rules: From strong electrolytes to weakly charged colloidal dispersions.

The Ewald method has been the cornerstone in molecular simulations for modeling electrostatic interactions of charge-stabilized many-body systems. In the late 1990s, Wolf and collaborators developed an alternative route to describe the long-range nature of electrostatic interactions; from a computational perspective, this method provides a more efficient and straightforward way to implement long-range electrostatic interactions than the Ewald method. Despite these advantages, the validity of the Wolf potential to account for the electrostatic contribution in charged fluids remains controversial. To alleviate this situation, in this contribution, we implement the Wolf summation method to both electrolyte solutions and charged colloids with moderate size and charge asymmetries in order to assess the accuracy and validity of the method. To this end, we verify that the proper selection of parameters within the Wolf method leads to results that are in good agreement with those obtained through the standard Ewald method and the theory of integral equations of simple liquids within the so-called hypernetted chain approximation. Furthermore, we show that the results obtained with the original Wolf method do satisfy the moment conditions described by the Stillinger-Lovett sum rules, which are directly related to the local electroneutrality condition and the electrostatic screening in the Debye-Hückel regime. Hence, the fact that the solution provided by the Wolf method satisfies the first and second moments of Stillinger-Lovett proves, for the first time, the reliability of the method to correctly incorporate the electrostatic contribution in charge-stabilized fluids. This makes the Wolf method a powerful alternative compared to more demanding computational approaches.

A Memory-Efficient Encoding Method for Processing Mixed-Type Data on Machine Learning.

The most common machine-learning methods solve supervised and unsupervised problems based on datasets where the problem's features belong to a numerical space. However, many problems often include data where numerical and categorical data coexist, which represents a challenge to manage them. To transform categorical data into a numeric form, preprocessing tasks are compulsory. Methods such as one-hot and feature-hashing have been the most widely used encoding approaches at the expense of a significant increase in the dimensionality of the dataset. This effect introduces unexpected challenges to deal with the overabundance of variables and/or noisy data. In this regard, in this paper we propose a novel encoding approach that maps mixed-type data into an information space using Shannon's Theory to model the amount of information contained in the original data. We evaluated our proposal with ten mixed-type datasets from the UCI repository and two datasets representing real-world problems obtaining promising results. For demonstrating the performance of our proposal, this was applied for preparing these datasets for classification, regression, and clustering tasks. We demonstrate that our encoding proposal is remarkably superior to one-hot and feature-hashing encoding in terms of memory efficiency. Our proposal can preserve the information conveyed by the original data.

A parallel-group, multicenter randomized, double-blinded, placebo-controlled, phase 2/3, clinical trial to test the efficacy of pyridostigmine bromide at low doses to reduce mortality or invasive mechanical ventilation in adults with severe SARS-CoV-2 infection: the Pyridostigmine In Severe COvid-19 (PISCO) trial protocol.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic inflammatory response, pulmonary damage, and even acute respiratory distress syndrome (ARDS). This in turn may result in respiratory failure and in death. Experimentally, acetylcholine (ACh) modulates the acute inflammatory response, a neuro-immune mechanism known as the inflammatory reflex. Recent clinical evidence suggest that electrical and chemical stimulation of the inflammatory reflex may reduce the burden of inflammation in chronic inflammatory diseases. Pyridostigmine (PDG), an ACh-esterase inhibitor (i-ACh-e), increases the half-life of endogenous ACh, therefore mimicking the inflammatory reflex. This clinical trial is aimed at evaluating if add-on of PDG leads to a decrease of invasive mechanical ventilation and death among patients with severe COVID-19. METHODS: A parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19. DISCUSSION: This study will provide preliminary evidence of whether or not -by decreasing systemic inflammation- add-on PDG can improve clinical outcomes in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04343963 (registered on April 14, 2020).

Consenso colombiano para la prevención, el diagnóstico y el tratamiento de condiciones trombóticas en adultos con COVID-19: aplicando el Marco de la Evidencia a la Decisión (EtD) GRADE / Colombian consensus for the prevention, diagnosis and treatment of thrombotic conditions in adults with COVID-19: applying GRADE Evidence to Decision (EtD) Frameworks

Introducción estudios recientes han reportado fenómenos trombóticos o coagulopatía en pacientes con COVID-19. Hay posiciones divergentes en cuanto a la prevención, el diagnóstico y el tratamiento de estos fenómenos, y la práctica clínica actual está basada únicamente en deducciones por extensión a partir de estudios retrospectivos, series de casos, estudios observacionales y guías internacionales desarrolladas previas a la pandemia. Objetivo establecer una serie de recomendaciones sobre prevención, diagnóstico y manejo de las complicaciones trombóticas asociadas a COVID-19. Métodos se desarrolló una guía rápida en la que se aplicó el marco de la evidencia a la decisión (EtD) de GRADE y un sistema de participación iterativo, con análisis estadísticos y cualitativos de sus resultados. Resultados se generaron 31 recomendaciones clínicas enfocadas a: a) Pruebas de coagulación en adultos sintomáticos con sospecha de infección o infección confirmada por SARS-CoV-2; b) Tromboprofilaxis en personas adultas con diagnóstico de COVID-19 (escalas de riesgo, tromboprofilaxis de manejo ambulatorio, intrahospitalario y duración de tromboprofilaxis después del egreso de hospitalización), c) Diagnóstico y tratamiento de las complicaciones trombóticas y d) Manejo de personas con indicación previa a usar agentes anticoagulantes. Conclusiones las recomendaciones clínicas de este consenso orientan la toma de decisiones clínicas respecto a prevención, diagnóstico y tratamiento de fenómenos trombóticos en pacientes con COVID-19, y representan un acuerdo que ayudará a disminuir la dispersión en las prácticas clínicas acorde con el desafío que impone la pandemia.

Abstract Introduction: recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. Objective: to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: a rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection; b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.