Adipose tissue concentrations of persistent organic pollutants and total cancer risk in an adult cohort from Southern Spain: Preliminary data from year 9 of the follow-up

There is an increasing trend in the incidence of cancer worldwide, and it has been accepted that environmental factors account for an important proportion of the global burden. The present paper reports preliminary findings on the influence of the historical exposure to a group of persistent organic pollutants on total cancer risk, at year 9 in the follow-up of a cohort from Southern Spain. A cohort of 368 participants (median age 51 years) was recruited in 2003. Their historical exposure was estimated by analyzing residues of persistent organic pollutants in adipose tissue. Estimation of cancer incidence was based on data from a population-based cancer registry. Statistical analyses were performed using multivariable Cox-regression models. In males, PCB 153 concentrations were positively associated with total cancer risk, with an adjusted hazard ratio (95% confidence interval) of 1.20 (1.01–1.41) for an increment of 100 ng/g lipid. Our preliminary findings suggest a potential relationship between the historical exposure to persistent organic pollutants and the risk of cancer in men. However, these results should be interpreted with caution and require verification during the future follow-up of this cohort.This study was supported in part by research grants from the Spanish Ministry of Health (FIS 02/974, EUS2008-03574), CIBER de Epidemiología; Junta de Andalucía (01/264, P09-CTS-5488 Project of Excellence, PI-0675-2010, and PI-0513-2012), and the Instituto de Salud Carlos III (FIS PI11/0610)

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Myasthenia gravis (MG) in adults from institutions pertaining to the Mexican public health system: An analysis of hospital discharges during 2010 [Miastenia gravis (MG) en adultos de instituciones pertenecientes al sistema público sanitario mexicano: un análisis de egresos hospitalarios durante el año 2010]

Introduction: Epidemiological studies on myasthenia gravis (MG) in Mexico is mainly derived from experiences in referral centers. Objective: To describe the epidemiological characteristics of hospital discharges during 2010 with the diagnosis of MG in adults hospitalized in the Mexican public health system. Methods: We consulted the database of hospital discharges during 2010 of the National Health Information System (Ministry of Health, IMSS, IMSS oportunidades, ISSSTE, PEMEX, and the Ministry of Defense). The MG records were identified by the code G70.0 of the International Classification of Diseases 10th revision. Results: During 2010 there were 5, 314, 132 hospital discharges (4, 254, 312 adults). Among them, 587 (0.01[%]) were adults with MG (median age: 47 years, 60[%] women). Women with MG were significantly younger than men (median age: 37 vs. 54 years, respectively; p < 0.001). The median hospital stay was six days. The case fatality rate was 3.4[%], without gender differences. Age was associated with the probability of death. Conclusions: We confirmed the bimodal age-gender distribution in MG. The in-hospital case fatality rate in Mexico is consistent with recent reports around the world. © 2015, Gaceta Medica de Mexico. All right reserved

[Myasthenia gravis in adults of institutions pertaining to the Mexican public health system: an analysis of hospital discharges during 2010]

INTRODUCTION: Epidemiological studies on myasthenia gravis (MG) in Mexico is mainly derived from experiences in referral centers. OBJECTIVE: To describe the epidemiological characteristics of hospital discharges during 2010 with the diagnosis of MG in adults hospitalized in the Mexican public health system. METHODS: We consulted the database of hospital discharges during 2010 of the National Health Information System (Ministry of Health, IMSS, IMSS oportunidades, ISSSTE, PEMEX, and the Ministry of Defense). The MG records were identified by the code G70.0 of the International Classification of Diseases 10th revision. RESULTS: During 2010 there were 5,314,132 hospital discharges (4,254,312 adults). Among them, 587 (0.01%) were adults with MG (median age: 47 years, 60% women). Women with MG were significantly younger than men (median age: 37 vs. 54 years, respectively; p < 0.001). The median hospital stay was six days. The case fatality rate was 3.4%, without gender differences. Age was associated with the probability of death. CONCLUSIONS: We confirmed the bimodal age-gender distribution in MG. The in-hospital case fatality rate in Mexico is consistent with recent reports around the world

[Myasthenia gravis in adults of institutions pertaining to the Mexican public health system: an analysis of hospital discharges during 2010]

INTRODUCTION: Epidemiological studies on myasthenia gravis (MG) in Mexico is mainly derived from experiences in referral centers. OBJECTIVE: To describe the epidemiological characteristics of hospital discharges during 2010 with the diagnosis of MG in adults hospitalized in the Mexican public health system. METHODS: We consulted the database of hospital discharges during 2010 of the National Health Information System (Ministry of Health, IMSS, IMSS oportunidades, ISSSTE, PEMEX, and the Ministry of Defense). The MG records were identified by the code G70.0 of the International Classification of Diseases 10th revision. RESULTS: During 2010 there were 5,314,132 hospital discharges (4,254,312 adults). Among them, 587 (0.01%) were adults with MG (median age: 47 years, 60% women). Women with MG were significantly younger than men (median age: 37 vs. 54 years, respectively; p < 0.001). The median hospital stay was six days. The case fatality rate was 3.4%, without gender differences. Age was associated with the probability of death. CONCLUSIONS: We confirmed the bimodal age-gender distribution in MG. The in-hospital case fatality rate in Mexico is consistent with recent reports around the world