Análisis de serie de tiempo de patrones estacionales en defunciones por neumonía en el Perú, periodo 2003-2017

Introducción. Es un concepto generalizado que las infecciones respiratorias son estacionales, pero pocas veces se precisan localmente estos períodos de alta frecuencia en un país con diversidad de climas. Anticipar la temporada de neumonía a nivel local puede proveer de un mejor uso de recursos críticos. Objetivo. Examinar la variabilidad estacional en defunciones mensuales por neumonía en el Perú. Métodos. Estudio observacional retrospectivo de análisis de serie de tiempo para identificar períodos de alta mortalidad por neumonía en siete ciudades del Perú. Se revisaron registros administrativos del Ministerio de Salud sobre defunciones por neumonía durante los años 2003-2017. Se calcularon estadísticas descriptivas y se analizó mediante una serie de tiempo a escala mensual la frecuencia de defunciones por neumonía, precipitación acumulada, y la temperatura ambiental máxima y mínima. Resultados. El 94,4% de las defunciones por neumonía (N = 166 844) reportaron como causa "organismo no especificado", y el 75,6% eran adultos mayores de 65 años. En Tarma, Arequipa y Cusco la temperatura mínima tiene una correlación negativa con las defunciones por neumonía en todas las edades y al menos uno de los grupos de riesgo. En Iquitos la temperatura mínima tiene una correlación positiva con las defunciones en menores de 5 años. Pucallpa y Cajamarca no tuvieron correlaciones significativas. El clima de Lima es un caso particular. La distribución durante el año de las muertes por neumonía sugiere una secuencia norte-sur, mientras que el análisis espaciotemporal del clima sugiere un patrón que va de sur-norte. Conclusión. Existen diferentes patrones estacionales en diferentes ciudades y grupos de riesgo.

Introduction. It is generally accepted that respiratory infections are seasonal, but high-frequency periods are rarely identified at the local level in a country with diverse climates. Anticipating the pneumonia season locally can provide a better use of critical resources. Objective. The aim of the study was to examine seasonal variability in monthly deaths due to pneumonia in Peru. Methods. Observational retrospective study using time series analysis to identify periods of high pneumonia mortality in seven cities in Peru. We reviewed administrative reports from the Ministry of Health for pneumonia deaths during 2003-2017. Descriptive statistics were calculated and a time series analysis at a monthly scale was performed on the frequency of deaths due to pneumonia, cumulative rainfall, and maximum and minimum environmental temperatures. Results. 94.4% of pneumonia deaths (N = 166,844) were reported as pneumonia due to "unspecified organism", and 75.6% were adults older than 65 years. In the cities of Tarma, Arequipa and Cusco, minimum ambient temperature is negatively correlated to pneumonia deaths in all age groups and at least one risk group. In Iquitos, minimum temperature is positively correlated with deaths among children under 5 years of age. The cities of Pucallpa and Cajamarca reported no statistically significant correlation. The climate in Lima is a peculiar case. The distribution of pneumonia deaths throughout the year suggests a north-south sequence, while the climate space-time analysis suggests a south-north pattern. Conclusion. Results show different seasonal patterns for pneumonia deaths in different cities and risk groups.

Trends in children's exposure to second-hand smoke in the INMA-Granada cohort: an evaluation of the Spanish anti-smoking law.

The smoke-free legislation implemented in Spain in 2006 imposed a partial ban on smoking in public and work places, but the result did not meet expectations. Therefore, a more restrictive anti-smoking law was passed five years later in 2011 prohibiting smoking in all public places, on public transport, and the workplace. With the objective of assessing the impact of the latter anti-smoking legislation on children's exposure to second-hand smoke (SHS), we assessed parent's smoking habits and children's urine cotinine (UC) concentrations in 118 boys before (2005-2006) and after (2011-2012) the introduction of this law. Repeated cross-sectional follow-ups of the "Environment and Childhood Research Network" (INMA-Granada), a Spanish population-based birth cohort study, at 4-5 years old (2005-2006) and 10-11 years old (2011-2012), were designed. Data were gathered by ad-hoc questionnaire, and median UC levels recorded as an objective indicator of overall SHS exposure. Multivariable logistic regression was used to examine the association between parent's smoking habits at home and SHS exposure, among other potential predictors. An increase was observed in the prevalence of families with at least one smoker (39.0% vs. 50.8%) and in the prevalence of smoking mothers (20.3% vs. 29.7%) and fathers (33.9% vs. 39.0%). Median UC concentration was 8.0ng/mL (interquartile range [IQR]: 2.0-21.8) before legislation onset and 8.7ng/mL (IQR: 2.0-24.3) afterwards. In the multivariable analysis, the smoking status of parents and smoking habits at home were statistically associated with the risk of SHS exposure and with UC concentrations in children. These findings indicate that the recent prohibition of smoking in enclosed public and workplaces in Spain has not been accompanied by a decline in the exposure to SHS among children, who continue to be adversely affected. There is a need to target smoking at home in order to avoid future adverse health effects in a population that has no choice in the acceptance or not of SHS exposure-derived risk.

Bevacizumab in the treatment of metastatic breast cancer: three case reports.

Case reports are presented for three patients with metastatic breast cancer who received first-line treatment with bevacizumab in combination with taxanes in clinical trials. Two patients showed peak reductions in lesion size of 49 and 70%, respectively. In one patient, subsequent treatment with bevacizumab in combination with capecitabine [Xeloda (after discontinuation of paclitaxel due to asthenia)] yielded peak reductions in target lesion size of 78%. One patient experienced a progression-free survival time of 16 months. In all three patients, bevacizumab was well tolerated and mostly displayed only mild toxicities.

Fluorescence studies of the replication initiator protein RepA in complex with operator and iteron sequences and free in solution.

RepA, the replication initiator protein from the Pseudomonas plasmid pPS10, regulates plasmid replication and copy number. It is capable of autorepression, in which case it binds as a dimer to the inverted repeat operator sequence preceding its own gene. RepA initiates plasmid replication by binding as a monomer to a series of four adjacent iterons, which contain the same half-repeat as found in the operator sequence. RepA contains two domains, one of which binds specifically to the half-repeat. The other is the dimerization domain, which is involved in protein-protein interactions in the dimeric RepA-operon complex, but which actually binds DNA in the monomeric RepA-iteron complex. Here, detailed fluorescence studies on RepA and an N-(iodoacetyl)aminoethyl-8-naphthylamine-1-sulfonic acid-labeled single-cysteine mutant of RepA (Cys160) are described. Using time-resolved fluorescence depolarization measurements, the global rotational correlation times of RepA free in solution and bound to the operator and to two distinct iteron dsDNA oligonucleotides were determined. These provide indications that, in addition to the monomeric RepA-iteron complex, a stable dimeric RepA-iteron complex can also exist. Further, Förster resonance energy transfer between Trp94, located in the dimerization domain, and N-(iodoacetyl)aminoethyl-8-naphthylamine-1-sulfonic acid-Cys160, located on the DNA-binding domain, is observed and used to estimate the distance between the two fluorophores. This distance may serve as an indicator of the orientation between both domains in the unbound protein and RepA bound to the various cognate DNA sequences. No major change in distance is observed and this is taken as evidence for little to no re-orientation of both domains upon complex formation.