Hexyltrimethylammonium ion enhances potential copper-chelating properties of ammonium thiomolybdate in an in vivo zebrafish model.

Ammonium and hexyltrimethylammonium thiomolybdates (ATM and ATM-C6) and thiotungstates (ATT and ATT-C6) were synthesized. Their toxicity was evaluated using both in vitro and in vivo approaches via the zebrafish embryo acute toxicity assay (ZFET), while the copper-thiometallate interaction was studied using cyclic voltammetry, as well as in an in vivo assay. Cyclic voltammetry suggests that all thiometallates form complexes with copper in a 2:1 Cu:thiometallate ratio. Both in vitro and in vivo assays demonstrated low toxicity in BALB/3T3 cells and in zebrafish embryos, with high IC50 and LC50 values. Furthermore, the hexyltrimethylammonium ion played a crucial role in enhancing viability and reducing toxicity during prolonged treatments for ATM and ATT. In particular, the ZEFT assay uncovered the accumulation of ATM in zebrafish yolk, averted by the incorporation of the hexyltrimethylammonium ion. Notably, the copper-thiometallate interaction assay highlighted the improved viability of embryos when cultured in CuCl2 and ATM-C6, even at high CuCl2 concentrations. The hatching assay further confirmed that copper-ATM-C6 interaction mitigates inhibitory effects induced by thiomolybdates and CuCl2 when administered individually. These results suggest that the incorporation of the hexyltrimethylammonium ion in ATM increase its ability to interact with copper and its potential application as a copper chelator.

Scorpion sting envenomation outbreak in Mexico. Strategies for prevention and control.

In Mexico occurs 25% of all worldwide cases of scorpion sting envenomation (SSE). An outbreak of SSE was identified in Villa Unión, Sinaloa, Mexico. The objective of this study is to describe the outbreak, and prevention and control strategies implemented. The design was a cross-sectional study. Eligibility criteria included confirmed cases (n = 425) identified from the date the outbreak was recognized (from November 08, 2023 to July 10, 2023). The cases from Villa Unión (n = 231) were included for the analysis of epidemiological and clinical findings. The research followed the recommendations of the Initiative Reporting of studies Conducted Using Observational Routinely collected Data (RECORD). Of the total cases (n = 425), 398 (93.6%) were from the municipality of Mazatlán, and 231 (58%) were from Villa Unión. The incidence rate was 13.64 per 1000 persons. The average cases per week was 51.5(SD ± 12). The male-to-female ratio was 3:4, the average age was 30.7(SD ± 19) years. Most of cases occurred in the 25-44 age group. The sting occurred mostly inside houses (n = 200, 86.5%). The predominant symptoms were local pain (95.2%), and local paresthesia (75.8%). The Case fatality rate was 0%. Implementation of prevention and control strategies based on field epidemiological research and scientific evidence are necessary to reduce the incidence and prevent fatal complications.

Akt Is Controlled by Bag5 through a Monoubiquitination to Polyubiquitination Switch.

The serine-threonine kinase Akt plays a fundamental role in cell survival, metabolism, proliferation, and migration. To keep these essential processes under control, Akt activity and stability must be tightly regulated; otherwise, life-threatening conditions might prevail. Although it is well understood that phosphorylation regulates Akt activity, much remains to be known about how its stability is maintained. Here, we characterize BAG5, a chaperone regulator, as a novel Akt-interactor and substrate that attenuates Akt stability together with Hsp70. BAG5 switches monoubiquitination to polyubiquitination of Akt and increases its degradation caused by Hsp90 inhibition and Hsp70 overexpression. Akt interacts with BAG5 at the linker region that joins the first and second BAG domains and phosphorylates the first BAG domain. The Akt-BAG5 complex is formed in serum-starved conditions and dissociates in response to HGF, coincident with BAG5 phosphorylation. BAG5 knockdown attenuated Akt degradation and facilitated its activation, whereas the opposite effect was caused by BAG5 overexpression. Altogether, our results indicate that Akt stability and signaling are dynamically regulated by BAG5, depending on growth factor availability.

Mathematical modeling for operative improvement of the decoloration of Acid Red 27 by a novel microbial consortium of Trametes versicolor and Pseudomonas putida: A multivariate sensitivity analysis.

In this work, it is presented a first approach of a mathematical and kinetic analysis for improving the decoloration and further degradation process of an azo dye named acid red 27 (AR27), by means of a novel microbial consortium formed by the fungus Trametes versicolor and the bacterium Pseudomonas putida. A multivariate analysis was carried out by simulating scenarios with different operating conditions and developing a specific mathematical model based on kinetic equations describing all stages of the biological process, from microbial growth and substrate consuming to decoloration and degradation of intermediate compounds. Additionally, a sensitivity analysis was performed by using a factorial design and the Response Surface Method (RSM), for determining individual and interactive effects of variables like, initial glucose concentration, initial dye concentration and the moment in time for bacterial inoculation, on response variables assessed in terms of the minimum time for: full decoloration of AR27 (R1 = 2.375 days); maximum production of aromatic metabolites (R2 = 1.575 days); and full depletion of aromatic metabolites (R3 = 12.9 days). Using RSM the following conditions improved the biological process, being: an initial glucose concentration of 20 g l-1, an initial AR27 concentration of 0.2 g l-1 and an inoculation moment in time of P. putida at day 1. The mathematical model is a feasible tool for describing AR27 decoloration and its further degradation by the microbial consortium of T. versicolor and P. putida, this model will also work as a mathematical basis for designing novel bio-reaction systems than can operate with the same principle of the described consortium.

Fermentation Patterns, Methane Production and Microbial Population under In Vitro Conditions from Two Unconventional Feed Resources Incorporated in Ruminant Diets.

In this study, four experimental treatments were evaluated: (T1) alfalfa hay + concentrate, (50:50%, DM); (T2) alfalfa hay + Leucaena leucocephala + concentrate, (30:20:50%, DM); (T3) alfalfa hay + prickly pear + concentrate, (30:20:50%, DM); and (T4) alfalfa hay + Leucaena leucocephala + prickly pear + concentrate, (30:10:10:50%, DM). NH3-N concentrations in T2 and T4 decreased when replaced with alfalfa hay in 20 and 10%, respectively. Treatments did not affect the concentration of total volatile fatty acids (TVFA) between T3 and T4 (p > 0.05), while the concentrations among T1 and T2 were different (p < 0.05). T2 showed a reduction of 25.5% in the methane production when compared to T1 (p < 0.05). The lowest concentrations of protozoa were observed in T2 and T4, which contained Leucaena leucocephala (T2) and Leucaena leucocephala + prickly pear (T4) (p < 0.05). The highest concentration of total methanogens was recorded in T1 and was different in T2, T3, and T4 (p < 0.05). Leucaena leucocephala, at an inclusion percentage of 20%, decreased the methane when compared to T1, whereas prickly pear increased methane production in relation to T1.

Modulating cyclic nucleotides pathways by bioactive compounds in combatting anxiety and depression disorders.

Anxiety and depression disorders are highly prevalent neurological disorders (NDs) that impact up to one in three individuals during their lifetime. Addressing these disorders requires reducing their frequency and impact, understanding molecular causes, implementing prevention strategies, and improving treatments. Cyclic nucleotide monophosphates (cNMPs) like cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cyclic uridine monophosphate (cUMP), and cyclic cytidine monophosphate (cCMP) regulate the transcription of genes involved in neurotransmitters and neurological functions. Evidence suggests that cNMP pathways, including cAMP/cGMP, cAMP response element binding protein (CREB), and Protein kinase A (PKA), play a role in the physiopathology of anxiety and depression disorders. Plant and mushroom-based compounds have been used in traditional and modern medicine due to their beneficial properties. Bioactive compound metabolism can activate key pathways and yield pharmacological outcomes. This review focuses on the molecular mechanisms of bioactive compounds from plants and mushrooms in modulating cNMP pathways. Understanding these processes will support current treatments and aid in the development of novel approaches to reduce the prevalence of anxiety and depression disorders, contributing to improved outcomes and the prevention of associated complications.

Ultrathin Partial Ceramic Veneers in the Esthetic Zone with Tooth Whitening: A 5-year Case Report.

OBJECTIVE: This case report describes a minimally invasive approach with tooth whitening and partial ceramic veneers in the esthetic zone with a 5-year follow-up. CLINICAL CONSIDERATIONS: The patient was initially concerned about the tooth color and previous direct resin composite restorations that chipped on the incisal edges of both maxillary central incisors. Tooth whitening and partial veneers for both central incisors were recommended after clinical evaluation. Two sessions of in-office tooth whitening, first with 35% hydrogen peroxide and later with 10% carbamide peroxide from first premolar to first premolar, were provided. Minimal tooth preparation that only removed the fractured composite restorations was performed followed by placement of feldspathic porcelain ultrathin partial ceramic veneers for both central incisors. We emphasize the benefits of minimal tooth preparation paired with partial ceramic veneers and the importance of masking discolored tooth structure with such thin veneers, including potential tooth whitening. CONCLUSIONS: Overall, we demonstrate a well-planned and executed restorative procedure combining tooth whitening and ultrathin partial ceramic veneers to achieve desired results in the esthetic zone that remained successful for five years.

SAFETY AND EFFICACY OF THYMIC PEPTIDES IN THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS IN HONDURAS.

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.

Consensus on the management of complications of cirrhosis of the liver in pediatrics.

The Asociación Mexicana de Hepatología A.C. carried out the Consensus on the Management of Complications of Cirrhosis of the Liver in Pediatrics to provide physicians with useful information for treating said complications. A group of pediatric gastroenterologists and experts in nutrition, nephrology, and infectious diseases participated and reviewed the medical literature. The Delphi method was applied to obtain the level of agreement on the statements that were formulated. The statements were sent to the participants to be analyzed and voted upon, after which they were discussed in virtual sessions, and the final versions were produced. The aim of the consensus results was to issue indications for the management of pediatric patients with liver cirrhosis, to prevent or control complications.

Band structure of a rotating helical phononic crystal.

We consider an elastic helical medium whose tensor stiffness twirls uniformly along the helix axis. We are interested in analyzing the band structure when the whole material is externally forced to rotate around the helix axis to a fixed constant frequency. Departing from a general dynamic description of the elastic phenomena, we establish a set of equations for the displacement vector and the stress tensor. These equations allow us to calculate the band structure parametrized by the externally imposed rotating frequency. We find that the band structure strongly depends on the rotation frequency, and we show that backward and forward modes propagate differently, particularly for the longitudinal and right-polarized modes.

Angiotensin II Inhibits Insulin Receptor Signaling in Adipose Cells.

Angiotensin II (Ang II) is a critical regulator of insulin signaling in the cardiovascular system and metabolic tissues. However, in adipose cells, the regulatory role of Ang II on insulin actions remains to be elucidated. The effect of Ang II on insulin-induced insulin receptor (IR) phosphorylation, Akt activation, and glucose uptake was examined in 3T3-L1 adipocytes. In these cells, Ang II specifically inhibited insulin-stimulated IR and insulin receptor substrate-1 (IRS-1) tyrosine-phosphorylation, Akt activation, and glucose uptake in a time-dependent manner. These inhibitory actions were associated with increased phosphorylation of the IR at serine residues. Interestingly, Ang II-induced serine-phosphorylation of IRS was not detected, suggesting that Ang II-induced desensitization begins from IR regulation itself. PKC inhibition by BIM I restored the inhibitory effect of Ang II on insulin actions. We also found that Ang II promoted activation of several PKC isoforms, including PKCα/ßI/ßII/δ, and its association with the IR, particularly PKCßII, showed the highest interaction. Finally, we also found a similar regulatory effect of Ang II in isolated adipocytes, where insulin-induced Akt phosphorylation was inhibited by Ang II, an effect that was prevented by PKC inhibitors. These results suggest that Ang II may lead to insulin resistance through PKC activation in adipocytes.

Behavioural and morphological traits influence sex-specific floral resource use by hummingbirds.

Research on resource partitioning in plant-pollinator mutualistic systems is mainly concentrated at the levels of species and communities, whereas differences between males and females are typically ignored. Nevertheless, pollinators often show large sexual differences in behaviour and morphology, which may lead to sex-specific patterns of resource use with the potential to differentially affect plant reproduction and diversification. We investigated variation in behavioural and morphological traits between sexes of hummingbird species as potential mechanisms underlying sex-specific flower resource use in ecological communities. To do so, we compiled a dataset of plant-hummingbird interactions based on pollen loads for 31 hummingbird species from 13 localities across the Americas, complemented by data on territorial behaviour (territorial or non-territorial) and morphological traits (bill length, bill curvature, wing length and body mass). We assessed the extent of intersexual differences in niche breadth and niche overlap in floral resource use across hummingbird species. Then, we tested whether floral niche breadth and overlap between sexes are associated with sexual dimorphism in behavioural or morphological traits of hummingbird species while accounting for evolutionary relatedness among the species. We found striking differences in patterns of floral resource use between sex. Females had a broader floral niche breadth and were more dissimilar in the plant species visited with respect to males of the same species, resulting in a high level of resource partitioning between sexes. We found that both territoriality and morphological traits were related to sex-specific resource use by hummingbird species. Notably, niche overlap between sexes was greater for territorial than non-territorial species, and moreover, niche overlap was negatively associated with sexual dimorphism in bill curvature across hummingbird species. These results reveal the importance of behavioural and morphological traits of hummingbird species in sex-specific resource use and that resource partitioning by sex is likely to be an important mechanism to reduce intersexual competition in hummingbirds. These findings highlight the need for better understanding the putative role of intersexual variation in shaping patterns of interactions and plant reproduction in ecological communities.

La investigación sobre la partición de recursos en los sistemas mutualistas planta-polinizador se concentra principalmente en los niveles de especies y comunidades, mientras que las diferencias entre machos y hembras suelen ser ignoradas. Sin embargo, los polinizadores suelen mostrar grandes diferencias sexuales en su comportamiento y morfología, lo que puede dar lugar a patrones específicos de uso de recursos para cada sexo con el potencial de afectar de forma diferencial la reproducción y la diversificación de las plantas. Se estudió la variación en los rasgos de comportamiento y morfológicos entre sexos de las especies de colibríes como posibles mecanismos que explican el uso de recursos florales específicos para cada sexo en las comunidades ecológicas. Para ello, se recopiló un conjunto de datos de interacciones planta-colibrí con base en las cargas de polen de 31 especies de colibríes de 13 localidades en las Américas, además de datos sobre su comportamiento territorial (territorial o no territorial) y rasgos morfológicos (longitud y curvatura del pico, longitud del ala y masa corporal). Se evaluaron las diferencias intersexuales en la amplitud y el solapamiento del nicho en el uso de los recursos florales para las distintas especies de colibríes. Posteriormente, se comprobó si la amplitud del nicho floral y el solapamiento entre sexos están asociados con el dimorfismo sexual en los rasgos de comportamiento o morfológicos de las especies de colibríes, teniendo en cuenta el parentesco evolutivo entre las especies. Se encontraron diferencias notables en los patrones de uso de los recursos florales entre sexos. Las hembras presentaron una mayor amplitud de nicho floral y fueron más disímiles en las especies de plantas visitadas con respecto a los machos de la misma especie, lo que resultó en un alto nivel de partición de recursos entre los sexos. Se encontró que tanto la territorialidad como los rasgos morfológicos están relacionados con el uso de recursos específicos por sexo en las especies de colibríes. En particular, el solapamiento de nicho entre sexos fue mayor para las especies territoriales que para las no territoriales y, además, el solapamiento de nicho se asoció negativamente con el dimorfismo sexual en la curvatura del pico en las especies de colibríes. Estos resultados revelan la importancia de los rasgos conductuales y morfológicos de las especies de colibríes en el uso de recursos según el sexo y que la partición de recursos entre sexos es probablemente un mecanismo importante para reducir la competencia intersexual en los colibríes. Estos resultados ponen de manifiesto la necesidad de comprender mejor el rol que tiene la variación intersexual en los patrones de interacción y en la reproducción de las plantas en las comunidades ecológicas.

Plantas medicinales utilizadas en la región de Teziutlán, Puebla, México / Medicinal plants used in the region of Teziutlán, Puebla, México

The objective of this work was to collect information on the curative use of plants in the municipality of Teziutlán, Puebla through semi-structured interviews. Thus, 78 plants used for medicinal purposes were identified, of which 40 are native to Mexico and 38 introduced; The value of use (UV) of each one and the Informant's Consensus Factor (FCI) of 10 categories of diseases were calculated. The five most frequently used plants are Ruta chalepensis L., Rosmarinus officinalis, Arnica montana, Loeselia mexicana (Lam.) Brandegee and Sambucus cerulea var., Neomexicana, which underwent a chemical and pharmacological review. On the other hand, the most frequent preparations are infusion and decoction, using mainly leaves (49.34%) and flowers (19.51%). It is concluded that the inhabitants of Teziutlán have a fairly homogeneous ethnomedical knowledge, setting the standard for research on its pharmacological properties.

El objetivo del presente trabajo fue recopilar información sobre el uso curativo de las plantas del municipio de Teziutlán, Puebla por medio de entrevistas semiestructuradas. Así, se identificaron 78 plantas utilizadas con fines medicinales, de las cuales 40 son propias de México y 38 introducidas; se calculó el valor de uso (UV) de cada una y el Factor de Consenso del Informante (FCI) de 10 categorías de padecimientos. Las cinco plantas utilizadas con mayor frecuencia son Ruta chalepensis L., Rosmarinus officinalis, Arnica montana, Loeselia mexicana (Lam.) Brandegee y Sambucus cerulea var., neomexicana, a las que se les hizo una revisión química y farmacológica. Por otro lado, las preparaciones más frecuentes son infusión y decocción, utilizando principalmente hojas (49.34 %) y flores (19.51 %). Se concluye que los habitantes de Teziutlán cuentan con un conocimiento etnomédico bastante homogéneo, dando la pauta para investigaciones sobre sus propiedades farmacológicas.

Cost-utility analysis of ceftazidime-avibactam versus colistin-meropenem in the treatment of infections due to Carbapenem-resistant Klebsiella pneumoniae in Colombia.

BACKGROUND: Ceftazidime-Avibactam (CAZ-AVI) is a new antimicrobial against carbapenem-resistant Klebsiella pneumoniae. The aim of the study is to examine the cost-effectiveness of CAZ-AVI compared to colistin-meropenem (COL+MEM) in Colombia. METHODS: A decision tree model was developed from health-care system perspective assuming a 30-day time horizon. The clinical course was simulated based on treatment response between 48 and 72 hours, and the duration of the treatment was 7-14 days. Cost inputs were extracted from a published Colombian manual tariffs and official databases, expressed in 2019 dollars (USD). RESULTS: In the base case analysis, CAZ-AVI was associated with reduced mortality, length of hospital stay and fewer add-on antibiotics, resulting in an increase of 1.76 QALYs per patient versus COL+MEM and incremental costs associated in CAZ-AVI were $2,521 higher per patient compared to COL+MEM ($755 versus $3,276). The incremental costs were partially increased due to the lower mortality rate observed with CAZ-AVI. The incremental cost-effectiveness ratio was estimated to be $3,317 per QALY. In the probabilistic sensitivity analysis, with a willingness to pay above $2,438, CAZ-AVI has higher probability of being cost-effective. CONCLUSION: CAZ-AVI demonstrates cost-effectiveness as a treatment for Carbapenem-resistant Klepsiella pneumoniae infections by reducing the number of deaths and increasing QALYs. EXPERT COMMENTARY: Previous studies and surveillance programs from Colombia have reported prevalence of pathogens and the antimicrobial susceptibility of infections caused by multidrug-resistant Gram-negative bacteria. The health authorities have to consider and plan adequate surveillance systems in order to predict the resistance type and in choose the optimal antibiotics when infections occur.

Incidence, clinical patterns, and risk factors of postpartum uterine diseases in dairy cows from high-altitude tropical herds.

The cow's uterus sustains bacterial contamination and active inflammation after calving as part of the normal physiological process of uterine involution. Although the definition, incidence, and risk factors for postpartum uterine diseases (PUD) have been documented in annual calving systems with high-producing cows on total mixed ration, the literature contains little information for other production systems. The objective of this study was to quantify the incidence risk and factors associated with metritis, clinical endometritis, and cytological endometritis in high-altitude tropical dairy herds in a pasture-based system. A total of 248 cows from 5 commercial dairy herds in northern Antioquia, Colombia, were enrolled in this prospective observational longitudinal cohort study. Data collection and PUD diagnosis were performed at d 0, 3, 10, 17, 24, 31, 38, 45, and 52 (±1) after parturition. Between 60 and 70 d, cows were systematically enrolled in a synchronization protocol, and herds were visited monthly for pregnancy diagnosis until 180 ±15 d. The multivariable logistic regression model of variables associated with PUD occurrence included (a) parity, season of calving, transition diet, and body condition score at calving; (b) blood calcium, phosphorus, and magnesium concentrations, and milk urea nitrogen, ß-hydroxybutyrate and fat-to-protein ratio; and (c) dystocia, retained placenta, and delayed uterine involution. The incidences of puerperal metritis, clinical metritis (MET), clinical endometritis (CE), and cytological endometritis (CYTO) were 2.8, 25, 29, and 26%, respectively. Retained placenta and dystocia were associated with MET, and MET was associated with CE. Low blood calcium concentration at calving was associated with CYTO. Overall, 51.2% of the cows suffered at least 1 category of PUD during the first 60 d postpartum (DPP). However, cows also suffered from different consecutive clinical events of PUD (MET, CE, and CYTO) during the follow-up period (0 to 180 ±15 DPP). These events could be grouped into 4 types (which were referred to as "clinical patterns") based on interactions between MET, CE, and CYTO.

The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation and Is Associated with Uncontrolled Glycemia in Patients with Type 2 Diabetes.

Experimental evidence in mice models has demonstrated that a high regulator of G-protein signaling 2 (RSG2) protein levels precede an insulin resistance state. In the same context, a diet rich in saturated fatty acids induces an increase in RGS2 protein expression, which has been associated with decreased basal metabolism in mice; however, the above has not yet been analyzed in humans. For this reason, in the present study, we examined the association between RGS2 expression and insulin resistance state. The incubation with palmitic acid (PA), which inhibits insulin-mediated Akt Ser473 phosphorylation, resulted in the increased RGS2 expression in human umbilical vein endothelial-CS (HUVEC-CS) cells. The RGS2 overexpression without PA was enough to inhibit insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells. Remarkably, the platelet RGS2 expression levels were higher in type 2 diabetes mellitus (T2DM) patients than in healthy donors. Moreover, an unbiased principal component analysis (PCA) revealed that RGS2 expression level positively correlated with glycated hemoglobin (HbA1c) and negatively with age and high-density lipoprotein cholesterol (HDL) in T2DM patients. Furthermore, PCA showed that healthy subjects segregated from T2DM patients by having lower levels of HbA1c and RGS2. These results demonstrate that RGS2 overexpression leads to decreased insulin signaling in a human endothelial cell line and is associated with poorly controlled diabetes.

Position statement: asthma in Latin America. IS short-acting beta-2 agonist helping or compromising asthma management?

In Latin-America, with 603 million inhabitants, the average prevalence of asthma is estimated at 17%, but with wide fluctuations, ranging from 5% in some cities (Mexico) to 30% in Costa Rica. The risk of severe exacerbations seems to be higher in Latin America compared with other regions. A majority of patients uses daily quick-relief medication, with the belief that it is the most important treatment because of its rapid onset of action; without treating the underlying inflammation. Overuse of short-acting beta2 agonists (SABAs) is associated with increased risk of asthma deaths in a dose-response manner. Beta2 agonists increase the severity of asthma through enhanced bronchial hyperresponsiveness and reduced lung function. Also, it has been shown that overreliance on SABA delays recognition of a potentially life-threatening asthma attack. We believe that overreliance on SABA in asthma is also an important public health issue. The fact that SABA use in GINA is not supported by a randomized trial but by an anonymous paper; makes us guess that we use SABA just because we are used to do so. In 2019 GINA strategy introduces one of the most important changes in the management of Asthma in the past 30 years, highlighting anti-inflammatory reliever therapy. A combination of low dose ICS/fast action bronchodilator will not only treat symptoms, but more importantly the underlying inflammation, protecting patients from preventable asthma attacks. After 50 years of a SABA centric approach in asthma management, it is time to leave behind a treatment based just on the bronchodilation and tackle the inflammation.

Caracterización clínico-epidemiológica de las enterocolitis necrosantes neonatales de siete hospitales públicos

Resumen Introducción: Enterocolitis necrosante (ECN) representa una elevada mortalidad y morbilidad post-quirúrgica, gastrointestinal y del neuro-desarrollo. Existe limitada información en Chile. Objetivo: Describir el comportamiento clínico/epidemiológico de recién nacidos que cursaron con ECN. Pacientes y Métodos: Estudio multicéntrico descriptivo de pacientes con ECN de siete hospitales de Santiago, Chile, durante el 2016. Se realizó estadística descriptiva y análisis univariable/multivariable (software SPSS v22). Resultados: Se recolectaron 75 casos. Mediana de edad al diagnóstico fue 11 días, el promedio de edad gestacional 29 semanas y peso de nacimiento 1.285 g. La incidencia fue 2,6 por 1.000/recién nacidos vivos y letalidad de 18,6%, mayor en ≤ 750 g, ≤ 25 semanas y ECN quirúrgica. Hubo aislamiento microbiológico en 45,3% y se utilizaron 19 distintos esquemas antimicrobianos empíricos para el tratamiento de ECN. El análisis multivariable mostró tendencia a que la ECN fuese quirúrgica en usuarios de catéter umbilical arterial, PCR > 10 mg/L y aislamiento microbiológico, y hubo tendencia a fallecer en usuarios de catéter umbilical arterial. Discusión: Es el primer estudio multicéntrico que recopila información de datos locales. La incidencia fue similar a la descrita en la literatura médica, en cambio la letalidad fue algo menor. No existen consensos del tratamiento antimicrobiano a utilizar. Con estos resultados esperamos avanzar en mejorar el diagnóstico y unificar tratamientos antimicrobianos, para reducir cifras de morbimortalidad.

Abstract Background: Necrotizing enterocolitis (NEC) presents high mortality and postoperative, gastrointestinal and neurodevelopmental morbidity. There is limited information about NEC in Chile. Aim: To describe the clinical/epidemiological behavior of newborns who underwent NEC. Methods: Multicenter descriptive study of patients with NEC from seven hospitals of Santiago, Chile, during 2016. Descriptive statistics and univariate/multivariate analysis were performed (SPSS v22 software). Results: 75 cases were collected. Median days of life at diagnosis was 11, gestational age was 29 weeks, birth weight 1,114 g. The incidence was 2.6 per 1,000 live newborns and mortality was 18.6%, higher in ≤ 750 g, ≤ 25 weeks and surgical NEC. There was 45.3% microbiological isolation and 19 different empirical antibiotic schemes were used for the treatment of NEC. The multivariate analysis showed a higher risk of surgery in umbilical arterial catheter users, CRP > 10 mg/L and positive microbiological isolation. The highest risk of death was in umbilical arterial catheter users. Discussion: This ie the first multicenter study that collects local data information. The incidence was similar to that found in medical reports but with a lower mortality. There is no consensus of antibiotic treatment to use. With these results we hope to advance in improving the diagnosis and unify antimicrobial treatments, to reduce morbidity and mortality figures.

Antimicrobianos en neonatología. Parte I: Recomendaciones de dosificaciones basadas, en la más reciente evidencia en recién nacidos Comité Consultivo de Infecciones Neonatales, Sociedad Chilena de Infectología / Antibiotics in neonatology. Part I: Dosage recommendations based on the most recent evidence in newborns Advisory Committee on Neonatal Infections, Chilean Society of Infectious Diseases

Resumen Los antimicrobianos son los medicamentos más utilizados en los neonatos durante su primer mes de vida cuando se encuentran en unidades neonatales, principalmente por el alto riesgo que presentan de adquirir infecciones graves como la sepsis. La mayoría de estos antimicrobianos se utilizan con dosis extrapoladas en base a las recomendaciones en población adulta y niños mayores, a pesar de que la fisiopatología en los recién nacidos es absolutamente diferente. Lo anterior lleva a un mayor riesgo a que ocurran más efectos adversos los que pueden conducir a una mayor toxicidad y a fallas terapéuticas, entre otros. En la última década se han realizado mayores estudios farmacocinéticos de antimicrobianos en neonatos; esta reciente evidencia ha permitido nuevas recomendaciones de dosificación considerando el peso y la edad gestacional del recién nacido, entre otras variables, de acuerdo al antimicrobiano estudiado. En base a una mayor evidencia sobre el comportamiento farmacocinético de los antimicrobianos en neonatos, se ha elaborado este documento para así facilitar y promover su correcto uso en las unidades neonatales.

Abstract Antibiotics are the most widely used medications in neonates during their first month of life in neonatal units, mainly due to the high risk they present of acquiring serious infections such as sepsis. Most of these antibiotics are used with extrapolated doses based on the suggestions in the adult population and older children, despite the fact that the pathophysiology in newborns is absolutely different. This leads to a higher risk of more adverse effects occurring, which can lead to greater toxicity and therapeutic failures, among others. In the last decade more and more pharmacokinetic studies of antibiotics have been carried out in neonates, this recent evidence has led to new dosage recommendations taking into account the weight and gestational age of the newborn, among other variables, in agreement to the antibiotic studied. Therefore, based on the need to order and summarize the most up-to-date and most evidence-based information on antibiotics in neonates, this document was prepared to facilitate and promote its correct use in neonatal units.