Fetal hemoglobin regulating genetic variants identified in homozygous (HbSS) and heterozygous (HbSA) subjects from South Mexico.

Hemoglobin S is caused by a nucleotide change in HBB gene (HBB:c.20A>T, p.Glu6Val), is presented in diverse forms: simple carriers (HbSA), homozygotes (HbSS) also known as sickle cell anemia, and compound heterozygotes with other ß-hemoglobinopathies. It is worldwide distributed, in Mexico, is frequently observed in the southern states Guerrero, Oaxaca and Chiapas. Elevated fetal hemoglobin (HbF) is associated with mild phenotype; single-nucleotide variants (SNVs) in modifier genes, such as BCL11A, HBG2, HBBP1 pseudogene and HBS1L-MYB intergenic region, upregulate HbF synthesis. The aim of this study was to identify HbF regulating genetic variants in HbSS and HbSA Mexican subjects. We studied 39 individuals (HbSS = 24, 61%, HbSA = 15, 39%) from Chiapas (67%) and Guerrero (33%), peripheral blood was collected in ethylenediamine tetraacetic acid (EDTA) for molecular and hematological studies, DNA was isolated by salting-out technic and genotyping was performed through allelic discrimination by real time polymerase chain reaction (RT-PCR) using Taqman® probes for 15 SNV (in BCL11A: rs6706648, rs7557939, rs4671393, rs11886868, rs766432, rs7599488, rs1427407; HBS1L-MYB: rs28384513, rs7776054, rs9399137, rs4895441, rs9402686, rs1320963; HBG2: rs7482144; and HBBP1: rs10128556). The obtained data were analyzed using IMB SPSS v.22.0 software. All minor alleles were observed in frequencies over 0.05, the most frequent was rs9402686 (0.82), while the less frequent was rs101028556 (0.08). In HbSS group, the mean fetal hemoglobin was 11.9 ± 5.9% and was significantly elevated in BCL11A rs11886868 wildtype homozygotes and in carriers of HBS1L-MYB intergenic region rs7776054 (p = 0.04 and p = 0.03, respectively). In conclusion, in HbSS Mexican patients, two SNVs were observed related to increased HbF; BCL11A rs11886868 and HBS1L-MYB rs7776054.

Sickle cell anemia (SCA) is one of the most common types of hemoglobinopathies in people of African ancestry, it is caused by homozygosity of HbS mutation (HBB:c.20A>T). It is known that fetal hemoglobin plays a key role in decreasing HbS polymerization which damages the erythrocyte structure and is responsible for the characteristic hemolytic crises endured by these patients. Single-nucleotide variant (SNV) in genes that regulate fetal hemoglobin (HbF) after birth have been associated with its increment, thus ameliorating the hematologic phenotype of this pathology and other ß-hemoglobinopathies. Therefore, in this study, we identified, for the first time in Mexican patients with SCA (HbSS) and HbS carriers (HbSA), the presence of 15 SNVs on BCL11A, HBS1L-MYB and HBG2; all HbSS patients had anemia and elevated HbF; 2 variants were related to increased HbF rs11688888C of BCL11A and rs7776054G of HBSIL-MYB; and finally, all minor alleles were found at a frequency higher than 0.05.

Pharyngocutaneous fistula in irradiated patients: systematic review and our experience.

OBJECTIVE: Radiotherapy is considered a risk factor for pharyngocutaneous fistula after a total laryngectomy. This study aimed to analyse the impact of exclusive radiotherapy versus chemoradiotherapy and the time interval between radiotherapy and surgery on the risk of pharyngocutaneous fistula. METHOD: This study was a retrospective revision of 171 patients treated with a total laryngectomy after radiotherapy or chemoradiotherapy. RESULTS: Pharyngocutaneous fistula occurred in 33 patients (19.3 per cent). Patients previously treated with chemoradiotherapy showed a non-significant higher pharyngocutaneous fistula rate compared with patients treated with radiotherapy (25.0 per cent vs 18.0 per cent; p = 0.455). Patients with a pharyngocutaneous fistula after chemoradiotherapy treatment required a surgical repair more frequently than patients treated with radiotherapy (p = 0.005). There were no significant differences in the pharyngocutaneous fistula rate depending on the time interval between radiotherapy and surgery (p = 0.580). CONCLUSION: There were no differences in the pharyngocutaneous fistula rate after total laryngectomy depending on the previous treatment with radiotherapy or chemoradiotherapy, or depending on the interval between radiotherapy treatment and surgery.

Influence of the ripening chamber's geographical location on dry-cured Iberian ham's key odorants.

Olfactometric and sensory analyses have been applied to study the possible influence of the ripening chamber's geographical location on the aroma sensory profiles and key odorants of Iberian ham. Dry-cured Iberian ham was obtained from 3 acorn-fed pigs and, for the first time, both of the participating production facilities, located in two different Andalusian municipalities with different altitudes above mean sea level, processed one of the two hind legs from each pig. The descriptive sensory profile of orthonasal and retronasal odours was determined by trained panellists, while odour-active compounds were determined by gas chromatography/mass spectrometry-olfactometry (GC/MS-O). The results obtained showed that, separately, both techniques enable Iberian ham samples to be differentiated by their ripening chamber's geographical location. For sensory analysis, retronasal sensory analysis appeared to be the most suitable for this goal, highlighting the "meat broth odour" and "roasted nuts odour" descriptors which presented significant differences between geographical locations for samples from all pigs. Moreover, ripening chamber's geographical location characteristics and the initial composition of the raw material seemed to influence the content of some odour-active compounds. The odour-active compound identified as octane/acetone and isobutanol were conditioned by the ripening chamber's geographical location, while decanal/2-ethyl-1-hexanol, 1-undecanol, 2-furanmethanol and cis-2-nonenal were also influenced by the individual pig itself. This study showed that slight climatological differences due to the location of the ripening chamber seem to have somewhat of an influence on the aromatic profile.

Vaccination coverage among migrants: A systematic review and meta-analysis

Background: Migrants, a population vulnerable to communicable diseases, face multiple barriers in access to immunization programs. Individual studies suggest that they suffer immunization inequity compared to non-migrants, but the gap in vaccination has not been quantified. This systematic review assessed quantitatively the level of vaccination coverage among migrants, in comparison with non-migrants, collating the published literature. Methods: Review protocol was prospectively registered (PROSPERO CRD42021228061). A literature search without language restrictions was conducted in PubMed, Scopus and Web of Science, from database inception to February 2021. This review included observational studies that provided the vaccination rates among migrant and non-migrant groups. Study quality was assessed using Newcastle-Ottawa scale. Data were synthesized pooling data from individual studies to generate summary odds ratio (OR) with 95% confidence interval (CI) using random effects model, assessing heterogeneity with I2 statistic and publication bias with funnel asymmetry analysis. Findings: There were 44 relevant studies (7,937,996 participants). Overall risk of bias was low in 13 (30%), moderate in 22 (50%) and high in 9 (20%) studies. Point estimates of individual ORs showed lower vaccination coverage among migrants in 36 of 39 meta-analyzable studies. Overall, the odds of vaccination coverage among migrants were lower compared to non-migrants (7,375,184 participants; summary OR 0.50; 95% CI 0.37–0.66; I2 99.9%). There was no funnel asymmetry. Interpretation: Migrants are half as often vaccinated compared to non-migrants. Public health prevention programs need to prioritize vaccination equity, not just to protect migrants but also to protect the host communities (AU)

Antecedentes: Los migrantes, una población vulnerable a enfermedades transmisibles, se enfrentan a múltiples barreras en el acceso a los programas de inmunización. Estudios individuales sugieren que este colectivo poblacional sufre desigualdad en la cobertura de inmunización, en comparación con población no migrante; sin embargo, hasta el momento no se ha cuantificado la brecha en la cobertura de vacunación. Esta revisión sistemática evaluó cuantitativamente el nivel de cobertura de vacunación entre los migrantes, en comparación con los no migrantes, recopilando la literatura publicada. Métodos: El protocolo de revisión fue registrado prospectivamente (PROSPERO CRD42021228061). Se realizó una búsqueda de literatura sin restricciones de idioma en PubMed, Scopus y Web of Science, desde el inicio de las bases de datos hasta febrero de 2021. Esta revisión incluyó estudios observacionales que proporcionaran coberturas de vacunación entre grupos de migrantes y no migrantes. La calidad de los estudios se evaluó mediante la escala Newcastle-Ottawa. Los datos se sintetizaron y se extrajeron los valores de odds ratio (OR) e intervalo de confianza (IC) del 95%, utilizando un modelo de efectos aleatorios para cada uno de los estudios incluidos. Finalmente, se evaluó la heterogeneidad de los mismos con la prueba estadística de I2 y, el sesgo de publicación con el análisis de asimetría de embudo. Resultados: Hubo 44 estudios relevantes (7.937.996 participantes). El riesgo de sesgo fue bajo en 13 (30%), moderado en 22 (50%) y alto en nueve (20%) estudios. Las estimaciones puntuales de las OR individuales mostraron una menor cobertura de vacunación entre los migrantes en 36 de 39 estudios metaanalizables. En general, las probabilidades de cobertura de vacunación entre los migrantes fueron menores, en comparación con los no migrantes (7.375.184 participantes; OR resumen 0,50; IC 95%: 0,37-0,66; I2 99,9%)s (AU)

Vaccination coverage among migrants: A systematic review and meta-analysis.

BACKGROUND: Migrants, a population vulnerable to communicable diseases, face multiple barriers in access to immunization programs. Individual studies suggest that they suffer immunization inequity compared to non-migrants, but the gap in vaccination has not been quantified. This systematic review assessed quantitatively the level of vaccination coverage among migrants, in comparison with non-migrants, collating the published literature. METHODS: Review protocol was prospectively registered (PROSPERO CRD42021228061). A literature search without language restrictions was conducted in PubMed, Scopus and Web of Science, from database inception to February 2021. This review included observational studies that provided the vaccination rates among migrant and non-migrant groups. Study quality was assessed using Newcastle-Ottawa scale. Data were synthesized pooling data from individual studies to generate summary odds ratio (OR) with 95% confidence interval (CI) using random effects model, assessing heterogeneity with I2 statistic and publication bias with funnel asymmetry analysis. FINDINGS: There were 44 relevant studies (7,937,996 participants). Overall risk of bias was low in 13 (30%), moderate in 22 (50%) and high in 9 (20%) studies. Point estimates of individual ORs showed lower vaccination coverage among migrants in 36 of 39 meta-analyzable studies. Overall, the odds of vaccination coverage among migrants were lower compared to non-migrants (7,375,184 participants; summary OR 0.50; 95% CI 0.37-0.66; I2 99.9%). There was no funnel asymmetry. INTERPRETATION: Migrants are half as often vaccinated compared to non-migrants. Public health prevention programs need to prioritize vaccination equity, not just to protect migrants but also to protect the host communities.

First Direct Detection Constraints on Planck-Scale Mass Dark Matter with Multiple-Scatter Signatures Using the DEAP-3600 Detector.

Dark matter with Planck-scale mass (≃10^{19} GeV/c^{2}) arises in well-motivated theories and could be produced by several cosmological mechanisms. A search for multiscatter signals from supermassive dark matter was performed with a blind analysis of data collected over a 813 d live time with DEAP-3600, a 3.3 t single-phase liquid argon-based detector at SNOLAB. No candidate signals were observed, leading to the first direct detection constraints on Planck-scale mass dark matter. Leading limits constrain dark matter masses between 8.3×10^{6} and 1.2×10^{19} GeV/c^{2}, and ^{40}Ar-scattering cross sections between 1.0×10^{-23} and 2.4×10^{-18} cm^{2}. These results are interpreted as constraints on composite dark matter models with two different nucleon-to-nuclear cross section scalings.

Diabetic neuropathy: Molecular approach a treatment opportunity.

Diabetic neuropathy (DN) encompasses a group of clinical or subclinical manifestations involving a dysfunction in the peripheral nervous system. The cause of the dysfunction is the development of microvascular complications related to diabetes, a disease that affects about 381 million people worldwide. Approximately 50% of patients currently diagnosed with diabetes are expected to manifest DN in the next 10 years. The diagnosis can be made clinically by establishing a good patient history and delving into the symptoms to rule out other etiologies. Treatment of DN focuses on glycemic control and the use of medications to reduce pain, including NSAIDs, antidepressants and antiepileptic drugs. The pathogenesis is of multifactorial origin, associated with various metabolic, vascular, inflammatory and neurodegenerative disorders. The three fundamental cellular alterations participating in the development of DN are chronic inflammation, endothelial dysfunction and oxidative stress. Since the combination of all three is capable of giving rise to nerve ischemia and direct axonal injury, these factors play a key role in the development of polyneuropathy. However, neuronal and microvascular changes do not occur in the same way in all patients with DN, some of whom have no detectable blood abnormalities.

Predictive value of transcriptional expression of Krüppel-like factor-6 (KLF6) in head and neck carcinoma patients treated with radiotherapy

Purpose To analyse the relationship between the transcriptional expression of Krüppel-like factor-6 (KLF6) and local response to treatment with radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC). Methods We determined the transcriptional expression of KLF6 in tumour biopsies obtained before treatment with radiotherapy in 83 HNSCC patients. The KLF6 expression was categorized according to the local control of the disease with a recursive partitioning analysis. Results During the follow-up period, 27 patients (32.5%) had a local recurrence of the tumour. Patients with local recurrence had significantly higher levels of KLF6 expression than patients in which radiotherapy achieved local control of the disease (P = 0.029). Five-year local recurrence-free survival for patients with a high transcriptional expression of KLF6 (n = 46) was 51.1% (95% CI 36.4–66.2%), and for patients with low expression it was 85.6% (95% CI 73.9–97.3%) (P = 0.0001). The results of a multivariate analysis showed that patients with a high KLF6 expression had a 3.8 times higher risk of local recurrence after treatment with radiotherapy (95% CI 1.4–10.5, P = 0.008). Conclusion Transcriptional expression of KLF6 was significantly related to local control in HNSCC patients treated with radiotherapy. Patients with high levels of KLF6 expression had a significantly higher risk of local recurrence after treatment (AU)

Pulse-shape discrimination against low-energy Ar-39 beta decays in liquid argon with 4.5 tonne-years of DEAP-3600 data.

The DEAP-3600 detector searches for the scintillation signal from dark matter particles scattering on a 3.3 tonne liquid argon target. The largest background comes from 39 Ar beta decays and is suppressed using pulse-shape discrimination (PSD). We use two types of PSD estimator: the prompt-fraction, which considers the fraction of the scintillation signal in a narrow and a wide time window around the event peak, and the log-likelihood-ratio, which compares the observed photon arrival times to a signal and a background model. We furthermore use two algorithms to determine the number of photons detected at a given time: (1) simply dividing the charge of each PMT pulse by the mean single-photoelectron charge, and (2) a likelihood analysis that considers the probability to detect a certain number of photons at a given time, based on a model for the scintillation pulse shape and for afterpulsing in the light detectors. The prompt-fraction performs approximately as well as the log-likelihood-ratio PSD algorithm if the photon detection times are not biased by detector effects. We explain this result using a model for the information carried by scintillation photons as a function of the time when they are detected.

Predictive value of transcriptional expression of Krüppel-like factor-6 (KLF6) in head and neck carcinoma patients treated with radiotherapy.

PURPOSE: To analyse the relationship between the transcriptional expression of Krüppel-like factor-6 (KLF6) and local response to treatment with radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: We determined the transcriptional expression of KLF6 in tumour biopsies obtained before treatment with radiotherapy in 83 HNSCC patients. The KLF6 expression was categorized according to the local control of the disease with a recursive partitioning analysis. RESULTS: During the follow-up period, 27 patients (32.5%) had a local recurrence of the tumour. Patients with local recurrence had significantly higher levels of KLF6 expression than patients in which radiotherapy achieved local control of the disease (P = 0.029). Five-year local recurrence-free survival for patients with a high transcriptional expression of KLF6 (n = 46) was 51.1% (95% CI 36.4-66.2%), and for patients with low expression it was 85.6% (95% CI 73.9-97.3%) (P = 0.0001). The results of a multivariate analysis showed that patients with a high KLF6 expression had a 3.8 times higher risk of local recurrence after treatment with radiotherapy (95% CI 1.4-10.5, P = 0.008). CONCLUSION: Transcriptional expression of KLF6 was significantly related to local control in HNSCC patients treated with radiotherapy. Patients with high levels of KLF6 expression had a significantly higher risk of local recurrence after treatment.

Remission and low disease activity state prevent hospitalizations in systemic lupus erythematosus patients.

OBJECTIVE: The aim of this study was to determine whether remission and low disease activity state protect systemic lupus erythematosus patients from being hospitalized. MATERIALS AND METHODS: Patients from the Almenara Lupus Cohort were included. Visits were performed every 6 months. Variables were measured at each visit. Hospitalizations were evaluated in the interval between two visits. Remission was defined as: a SLEDAI-2 K of 0, prednisone ≤5 mg/day and immunosuppressants on maintenance dose; low disease activity state as: a SLEDAI-2 K of ≤4, prednisone ≤7.5 mg/day and immunosuppressants on maintenance dose. Univariable and multivariable interval-censored survival regression models were used. In multivariable analysis, possible confounders were gender, age at diagnosis, socioeconomic status, educational level, disease duration, antimalarial use, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI) and Charlson comorbidity index. Confounders were determined in the same visit as disease activity state. RESULTS: Of the 308 patients, 92.5% of them (n = 285) were women, had a mean age at diagnosis of 34.8 (13.4) years and a disease duration of 7.7 (6.5) years. At baseline the mean SDI was 1.13 (1.34). A total of 163 of the patients were hospitalized. In the multivariable analysis remission (hazard ratio 0.445 (0.274-0.725), P = 0.001) and low disease activity state (relative risk 0.504 (0.336-0.757), P = 0.001) at baseline were found to decrease the risk of hospitalization in systemic lupus erythematosus patients. A total of 158 hospitalizations presented a discernible cause. Disease activity was the most common cause of hospitalization, with 84 admissions (53.16%), the majority, 38, was due to active kidney disease (45.23%). CONCLUSION: Remission and low disease activity state decreased the risk of hospitalizations in these systemic lupus erythematosus patients. Disease activity, particularly renal, was the most frequent cause of hospitalization.

Evaluation of risk factors in the development of type 2 diabetes in a Mexican population.

Type 2 diabetes (T2D), which causes many adverse effects such as endothelial dysfunction and cardiovascular disease, affects approximately 425 million people worldwide. However, about half have not yet been diagnosed. For what is recommended the use of screening tools to identify individuals at risk for T2D or in the early stages of the disease in order to impement preventive strategies or early treatment. According to a widely used survey, the FINDRISC scale, a hereditary family history of T2D (FH-T2D) is as important a risk factor as having had high glucose levels. The aim of the present study was to carry out non-probabilistic sampling in a Mexican population to evaluate key factors in the development of diabetes. The participants were divided into three groups: with and without FH-T2D and diagnosed with T2D. A comparison of the groups with and without FH-T2D revealed higher values in the former for body mass index (BMI: 24.5 vs 21.9 kg/m2), glycosylated hemoglobin [Hb1Ac: 5.775% (39 mmol/mol) vs 4.825% (29 mmol/mol)] and triglycerides (164.18 vs 68.12 mg/dL), and a lower value for the BH4/BH2 index (0.7846 vs 1.6117). These results indicate significant metabolic alterations and endothelial dysfunction for the FH-T2D group. This strongly suggests the need to screen individuals with a family history of inherited T2D based on their level of HbA1c, triglycerides and BH4.

Evaluación del área de sección del nervio mediano tras la inyección intraneural o perineural / Cross-sectional area of the median nerve after intraneural vs perineural low volume administration

Introducción: Conocer la relación entre la aguja y el nervio durante el bloqueo de nervio periférico es de interés para evitar el daño neural; sin embargo, los signos de inyección intraneural no se hallan claramente establecidos. Nos propusimos determinar los cambios observados en el nervio periférico tras inyectar 1ml de solución en disposición intraneural o perineural de la aguja. Material y métodos: Se utilizaron 10 cadáveres frescos, a los cuales se les realizó bloqueo de nervio mediano ecoguiado en plano en 60 ocasiones (3 por brazo), realizando una punción intraneural (n=30) o perineural (n=30) según aleatorización previa. Tras el consenso de localización por 7 especialistas, se inyectó 1ml de solución y se evaluó el cambio en el área de sección del nervio y el desplazamiento a lo largo del mismo. Resultados: El área de sección del nervio mediano se aumentó en ambos grupos, sin embargo, el incremento fue significativamente mayor en el grupo intraneural (perineural 0,007+/-0,013 vs. intraneural 0,032+/-0,021cm2, p<0,0001). Un incremento superior al 27% del área de sección asegura una inyección intraneural en el nervio mediano según el análisis de la curva ROC. La difusión proximal y la distal se observó con mayor frecuencia en el grupo intraneural (proximal: 86 vs. 14%; p<0,0001. Distal: 43 vs. 4%; p<0,0001). Conclusiones: En base a nuestro estudio experimental concluimos que la inyección de un pequeño volumen (1ml) permite discriminar la disposición de la aguja intraneural vs. perineural en un porcentaje elevado de casos. Por ello, sugerimos que esta «dosis test» debe de considerarse en los algoritmos de seguridad si queremos reducir la incidencia de inyección intraneural

Introduction: To recognise the relationship between the needle tip and the median nerve during peripheral nerve block is of interest to avoid neural damage. However, signs of intraneural injection are not clearly established. The aim of this study was to define the changes observed in the peripheral nerve after the intraneural or perineural administration of 1ml of solution. Material and methods: Ultrasound guided median nerve blocks were performed in the forearm of 10 fresh cadavers on 60 occasions (3 per forearm). They were randomised into the intraneural (n=30) or perineural (n=30) location of the needle tip, after the consensus of location by 7 specialists. After 1ml of solution was injected an evaluation was made of the changes in the cross-sectional area of the nerve, as well as the displacement along the nerve. Results: The cross-sectional area of the median nerve was increased in both groups, however, the increase was significantly higher in the intraneural group (perineural 0.007+/-0.013cm2 vs. intraneural 0.032+/-0.021cm2, P<.0001). An increase of more than 27% of the area ensures an intraneural injection in the median nerve according to the ROC curve analysis. Both proximal and distal diffusion were observed more frequently in the intraneural group (proximal: 86% vs 14%, P<.0001, Distal: 43% vs 4%, P<.0001). Conclusions: Based on this experimental study, it is concluded that the injection of a small volume (1ml) allows to discriminate the disposition of the intraneural vs perineural needle in a high percentage of cases. Therefore, it is suggested that this "dose test" should be considered in the safety algorithms if it is required to reduce the incidence of intraneural injection

Cross-sectional area of the median nerve after intraneural vs perineural low volume administration. / Evaluación del área de sección del nervio mediano tras la inyección intraneural o perineural.

INTRODUCTION: To recognise the relationship between the needle tip and the median nerve during peripheral nerve block is of interest to avoid neural damage. However, signs of intraneural injection are not clearly established. The aim of this study was to define the changes observed in the peripheral nerve after the intraneural or perineural administration of 1ml of solution. MATERIAL AND METHODS: Ultrasound guided median nerve blocks were performed in the forearm of 10 fresh cadavers on 60 occasions (3 per forearm). They were randomised into the intraneural (n=30) or perineural (n=30) location of the needle tip, after the consensus of location by 7 specialists. After 1ml of solution was injected an evaluation was made of the changes in the cross-sectional area of the nerve, as well as the displacement along the nerve. RESULTS: The cross-sectional area of the median nerve was increased in both groups, however, the increase was significantly higher in the intraneural group (perineural 0.007±0.013cm2 vs. intraneural 0.032±0.021cm2, P<.0001). An increase of more than 27% of the area ensures an intraneural injection in the median nerve according to the ROC curve analysis. Both proximal and distal diffusion were observed more frequently in the intraneural group (proximal: 86% vs 14%, P<.0001, Distal: 43% vs 4%, P<.0001). CONCLUSIONS: Based on this experimental study, it is concluded that the injection of a small volume (1ml) allows to discriminate the disposition of the intraneural vs perineural needle in a high percentage of cases. Therefore, it is suggested that this "dose test" should be considered in the safety algorithms if it is required to reduce the incidence of intraneural injection.

Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

OBJECTIVES: To determine efficacy and safety of withholding antimicrobials in children with cancer, fever and neutropenia (FN) with a demonstrated respiratory viral infection. METHODS: Prospective, multicentre, randomized study in children presenting with FN at five hospitals in Santiago, Chile, evaluated at admission for diagnosis of bacterial and viral pathogens including PCR-microarray for 17 respiratory viruses. Children positive for a respiratory virus, negative for a bacterial pathogen and with a favourable evolution after 48 h of antimicrobial therapy were randomized to either maintain or withhold antimicrobials. Primary endpoint was percentage of episodes with uneventful resolution. Secondary endpoints were days of fever/hospitalization, bacterial infection, sepsis, admission to paediatric intensive care unit (PICU) and death. RESULTS: A total of 319 of 951 children with FN episodes recruited between July 2012 and December 2015 had a respiratory virus as a unique identified microorganism, of which 176 were randomized, 92 to maintain antimicrobials and 84 to withdraw. Median duration of antimicrobial use was 7 days (range 7-9 days) versus 3 days (range 3-4 days), with similar frequency of uneventful resolution (89/92 (97%) and 80/84 (95%), respectively, not significant; OR 1.48; 95% CI 0.32-6.83, p 0.61), and similar number of days of fever (2 versus 1), days of hospitalization (6 versus 6) and bacterial infections throughout the episode (2%-1%), with one case of sepsis requiring admission to PICU in the group that maintained antimicrobials, without any deaths. CONCLUSIONS: The reduction of antimicrobials in children with FN and respiratory viral infections, based on clinical and microbiological/molecular diagnostic criteria, should favour the adoption of evidence-based management strategies in this population.

Caracterización de fonoaudiólogos/as insertos/as en centros comunitarios de rehabilitación / Characterization of speech therapists inserts in communitarian rehabilitation centers

El quehacer fonoaudiológico actualmente se encuentra influenciado por perspectivas de atención en salud que promueven una atención basada en el modelo biopsicosocial, el cual propende a la inclusión social de personas en situación de discapacidad. En este contexto, la presente investigación pretende caracterizar el quehacer profesional de fonoaudiólogos/as insertos en Centros Comunitarios de Rehabilitación (CCR) que utilizan una estrategia comunitaria (Rehabilitación Basada en la Comunidad, RBC) para llevar a cabo sus procesos de evaluación, diagnóstico y rehabilitación. Este estudio cualitativo se enmarca en un enfoque microsociológico relacionado con la exploración de las prácticas profesionales en contextos de salud. La recolección de datos se realizó mediante la técnica de entrevistas en profundidad y observación no participante de las prácticas de dos fonoaudiólogos que fueron registradas en bitácoras. La información obtenida fue procesada mediante análisis de contenido. Los profesionales fonoaudiólogos definieron su rol por medio de diferentes acciones que promueven su incorporación a un equipo multidisciplinario de atención y la participación activa, tanto del usuario como de la familia, en el proceso de rehabilitación. Se discute la suficiencia de las acciones fonoaudiológicas para explicar aspectos específicos del rol y diferencias en las formas de llevar a cabo las prácticas basadas en esta estrategia comunitaria de rehabilitación. Finalmente, la expresión de esta estrategia es parcial y constituye aún un desafío para el/la fonoaudiólogo/a basar la totalidad de su práctica diaria en dicha estrategia.

The speech therapists task is currently influenced by prospects of health care based on biopsychosocial model; which tends to social inclusion of people with disabilities. In this text, this article aims to characterize professional work of speech therapists inserts in Communitarian Rehabilitation Centers (CRC) using community strategy (Community based rehabilitation, RBC) to carry out assessment, diagnosis and rehabilitation processes. This qualitative research is part of a micro sociological approach which explores professional practices in health contexts. Data collection was performed using in-depth interview and nonparticipating technique in observation of two speech therapists practice that were recorded in logbooks. The information obtained was analyzed through content analysis. Speech therapists defined their role through actions that promoted their incorporation to a multidisciplinary health team, and the active participation of both the user/patient and the family in the rehabilitation process. The adequacy of actions to explain role specific aspects and carry out ways differences of speech therapists practice based on this communitarian rehabilitation strategy. Finally, expression of this strategy is partial and is still a challenge for speech therapists to base their daily practice on this strategy.

Neumolaberinto: una complicación atípica en un implante coclear / Pneumolabyrinth: an atypical complication in a cochlear implant

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Aromatase and estrogen receptor alpha mRNA expression as prognostic biomarkers in patients with astrocytomas.

Estrogens are oncogenic hormones at a high level in breast, prostate, endometrial and lung cancer. Estrogens are synthesized by aromatase which has been used as a biomarker both in breast and lung cancer. Estrogen biological activities are executed by their classic receptors (ERα and ERß). ERα has been described as a cancer promoter and ERß, as a possible tumor suppressor. Both receptors are present at low levels in primary multiforme glioblastoma (GBM). The GBM frequency is 50 % higher in men than in women. The GBM patient survival period ranges from 7 to 18 months. The purpose of this pilot study was to evaluate aromatase and estrogen receptor expression, as well as 17ß-estradiol concentration in astrocytoma patients biopsies to obtain a prognosis biomarker for these patients. We analyzed 36 biopsies of astrocytoma patients with a different grade (I-IV) of malignity. Aromatase and estrogen receptor mRNA expression were analyzed by semiquantitative RT-PCR, and the E2 levels, by ELISA. E2 concentration was higher in GBM, compared to grade II or III astrocytomas. The number of cells immunoreactive to aromatase and estrogen receptors decreased as the grade of tumor malignity increased. Aromatase mRNA expression was present in all biopsies, regardless of malignity grade or patient age or gender. The highest expression of aromatase mRNA in GBM patients was associated to the worst survival prognostic (6.28 months). In contrast lowest expression of ERα mRNA in astrocytoma patients had a worst prognosis. In conclusion, aromatase and ERα expression could be used as prognosis biomarkers for astrocytoma patients.

End of life, death and dying in neonatal intensive care units in Latin America.

AIM: Most analyses of end of life decisions in Neonatal Intensive Care Units (NICUs) have come from Europe/English-speaking countries. Would decisions be different in Latin American NICUs? Therefore, we aim to evaluate the approach to dying infants/families in NICUs in Latin America. METHODS: Multinational descriptive study of all deaths in babies born at >22 weeks in eight NICUs in five Latin American countries. Deaths were categorized as: (i) no Cardiopulmonary Resuscitation (CPR) or life support offered; (ii) life support initiated but do not resuscitate (DNR) orders written or no CPR provided; (iii) full life support and CPR; and (iv) unclassifiable. RESULTS: There were 100 deaths, 81% in >27 weeks. Seventeen infants received no CPR/life support at birth, 10 died in DR and seven in NICU. There were 27 infants in group 2, 54 in group three and two in group 4. No baby had care withdrawn or care withdrawn/CPR withheld. Thirty-two infants had 'do not resuscitate' order. Decisions without parents' involvement in 15%, both parents present at death 24% and sedatives/narcotics documented 14%. CONCLUSIONS: Latin American NICUs differ from those in Northern Europe/English-speaking countries. More deaths are accompanied by full life support and CPR. DNR orders are rare. Withdrawal of life support is virtually non-existent. Latin American's doctors are more likely to make decisions without the objections of family about withholding life-sustaining treatment.