Factores de riesgo y causas de lesión en los accidentes laborales de ocho provincias peruanas / Risk factors and injury causes in occupational accidents in 8 Peruvian provinces

Introducción: Los accidentes laborales en el país se describen, de manera general, mencionando el tipo de trabajo asociado o el lugar donde se produjeron, lo que evidencia un subreporte de esta problemática que aún no se logra solucionar. Objetivo: Determinar los factores de riesgo asociados a la causa de la lesión en accidentes laborales de trabajadores en ocho provincias del Perú en el periodo del 2000-2014. Métodos: Estudio transversal, analítico; de los atendidos por accidentes laborales en la emergencia de Hospitales EsSalud en ocho provincias del Perú. Resultados: De 45 291 accidentes ocupacionales, en el multivariado se encontró que la caída de altura y los golpes estuvieron asociados al sexo (p < 0,001), a la edad (p < 0,001), a lesionarse en la cabeza (p < 0,025), en el tórax (p < 0,003, solo para caída de altura), en los miembros superiores (p < 0,001, solo para caída de altura), a la antigüedad laboral (p = 0,004, solo para caída de altura), a generar una contusión (p < 0,001) o una herida (p < 0,021). Conclusiones: Se encontró múltiples asociaciones de variables sociales y laborales, así como, de las consecuencias que tuvo el haberse accidentado, tanto por algún golpe o por la caída de la altura estructural(AU)

Introduction: The occupational accidents in the country are described in a general way, mentioning the type of associated work or the place where they took place, evidencing a sub report of a problem that is not yet solved. Objective: To determine the risk factors associated with the mechanism of injury in occupational accidents of workers in eight provinces of Peru in the period 2000-2014. Methods: Transversal, analytical study of those treated for occupational accidents in the EsSalud Hospital emergency in eight regions of Peru. Results: Out of 45291 occupational accidents, in the multivariate study it was found that falls from height and blows were associated with sex (p < 0.001), age (p < 0.001), head injury (p < 0.025), and chest injury (p < 0),003, only for fall from height), in the upper limbs (p < 0.001, only for fall from height), to work seniority (p = 0.004, only for fall from height), to generate a contusion (p < 0.001) or an injury (p < 0.021). Conclusions: Multiple associations of social and labor variables were found, as well as, of the consequences of having been injured, by a blow or by a fall from structural height(AU)

Diagnóstico y tratamiento de la retinopatía diabética y edema macular diabético: guía de práctica clínica del Seguro Social de Salud del Perú (EsSalud) / Diagnosis and treatment of diabetic retinopathy and diabetic macular edema: clinical practice guidelines of the Peruvian Health Social Security (EsSalud)

RESUMEN Introducción. El presente artículo resume la guía de práctica clínica (GPC) para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en el Seguro Social de Salud del Perú (EsSalud). Objetivo. Proveer recomendaciones clínicas basadas en evidencia para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en EsSalud. Métodos. Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló 4 preguntas clínicas a ser respondidas por la presente GPC. Para cada una de estas preguntas se realizó búsquedas de revisiones sistemáticas y de estudios primarios (cuando se consideró pertinente) en PubMed durante el 2018. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buena práctica clínica y el flujograma de manejo. Resultados. La presente GPC abordó 4 preguntas clínicas sobre el tamizaje, diagnóstico, tratamiento de elección y tratamiento adyuvante. En base a estas preguntas se formularon 6 recomendaciones (4 fuertes y 2 condicionales), 19 puntos de buena práctica clínica y 1 flujograma de manejo. Conclusión. El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en EsSalud.

ABSTRACT Introduction. This article summarizes the clinical practice guidelines (CPG) for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema of the Health Social Security of Peru (EsSalud). Objective. To provide clinical recommendations based on evidence for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema in EsSalud. Methods. A guidelines elaborating group (GEG) was conformed by medical specialists and methodologists. The GEG formulated 4 clinical questions intended to be answered by this CPG. For each of these questions systematic searches of systematic reviews and primary studies (when considered pertinent) were carried out in PubMed during 2018. Evidence was selected in order to reply each of the proposed clinical questions. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. During periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate the recommendations, points of good clinical practice and the management flowchart. Results. The present CPG addressed 4 clinical questions of four topics: screening, diagnosis, treatment of choice and adjuvant treatment. Based on these questions, 6 recommendations (4 strong and 2 conditional), 19 points of good clinical practice, and 1 management flowchart were formulated. Conclusion. This article summarizes the methodology and conclusions based on evidence from the CPG for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema in EsSalud.

Vivimos más, pero vemos menos / We live more, but we see less

La esperanza de vida mundial en 1990 era 65,45 años, y para 2017 fue 72,25 años de vida al nacer, la población mundial de personas mayores de 50 años casi se dobló de 878 millones en 1990 a 1640 millones en 2015. La degeneración macular relacionada a la edad (DMRE) es la cuarta causa global de ceguera, su prevalencia global es de 8,69%, siendo mayor en europeos (12,33%), seguido de hispanos (10,43%), causando el 4% de discapacidad visual a nivel mundial. En el Perú, es la tercera causa de ceguera y su prevalencia aumenta con la edad, mundialmente pasa de 5,66% entre las personas de 50 a 59 años, a 24,96% en mayores de 80 años; por lo expuesto, se prevé un incremento significativo de su prevalencia,vivimos más, pero vemos menos

There is no doubt that we live longer, that is, the world population is aging; partly thanks to advances in science and technology, and its application to medicine for the prevention, cure, and recovery of different nosological entities previously considered lethal. The world life expectancy in 1990 was 65.45 years; for the dawn of the new millennium, it increased to 67.68, for 2010 to 70.68 and for 2017 to 72.25 years of life at birth. In general terms, the world population of people over 50 almost doubled from 878 million in 1990 to 1,640 million in 2015. As is already known, the fact that the population is living longer brings with it the increase of so-called degenerative diseases, among which is age-related macular degeneration (AMD). We live longer, but we see less.

Effects of Antiangiogenic Drugs on Expression Patterns of Epigenetic Pathway Genes.

BACKGROUND AND OBJECTIVE: To investigate the effects of antiangiogenic drugs on the transcription profile of acetylation genes in immortalized human retinal pigment epithelium cells (ARPE-19) in vitro. MATERIALS AND METHODS: This in vitro study evaluated the effect of antiangiogenic drugs on the expression of histone acetylation genes on immortalized ARPE-19 cell cultures. ARPE-19 cells were cultured, plated, and treated for 24 hours with aflibercept (Eylea; Regeneron, Tarrytown, NY), ranibizumab (Lucentis; Genentech, South San Francisco, CA), or bevacizumab (Avastin; Genentech, South San Francisco, CA) at one (1×) or two times (2×) the concentrations of the clinical intravitreal dose. Untreated cells were used as controls. RNA was isolated, and real-time quantitative reverse transcription polymerase chain reaction analysis was performed on individual samples to quantify expression levels of genes associated with epigenetic acetylation pathways: histone acetyltransferase 1 (HAT1) and histone deacetylases 1, 6, and 11 (HDAC1, HDAC6, and HDAC11). Differences in cycle thresholds (ΔΔCts) were obtained, and folds were calculated using the formula 2^ΔΔCt. Main outcome measures were expression levels of candidate genes in treated versus untreated samples. RESULTS: Compared with untreated cells, 1× ranibizumab-treated cells expressed higher levels of HDAC6, and 2× ranibizumab-treated cells expressed higher HDAC11 levels. Bevacizumab-treated (1×) cells had significant change in HDAC1, HDAC6, and HDAC11. In cultures treated with 2× bevacizumab, only HDAC11 expression levels were significantly affected compared with controls. Aflibercept-treated (1×) cells had changes in expression of HDAC1, HDAC6, and HDAC11. At 2× concentration, only HDAC11 was significantly changed. CONCLUSION: Our results show that antiangiogenic drugs can affect the transcription profile of genes regulating the histone acetylation status in ARPE-19 cells in vitro. This finding may have an implication in differential patient response to anti-vascular endothelial growth factor therapy by means of possible interactions between treatment and patient's epigenomic profile. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S29-S33.].

Increased expression of ApoE and protection from amyloid-beta toxicity in transmitochondrial cybrids with haplogroup K mtDNA.

Mitochondrial (mt) DNA haplogroups, defined by specific single nucleotide polymorphism (SNP) patterns, represent populations of diverse geographic origins and have been associated with increased risk or protection of many diseases. The H haplogroup is the most common European haplogroup while the K haplogroup is highly associated with the Ashkenazi Jewish population. Transmitochondrial cybrids (cell lines with identical nuclei, but mtDNA from either H (n=8) or K (n=8) subjects) were analyzed by the Seahorse flux analyzer, quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC). Cybrids were treated with amyloid-ß peptides and cell viabilities were measured. Other cybrids were demethylated with 5-aza-2'-deoxycytidine (5-aza-dC) and expression levels for APOE and NFkB2 were measured. Results show K cybrids have (a) significantly lower mtDNA copy numbers, (b) higher expression levels for MT-DNA encoded genes critical for oxidative phosphorylation, (c) lower Spare Respiratory Capacity, (d) increased expression of inhibitors of the complement pathway and important inflammasome-related genes; and (e) significantly higher levels of APOE transcription that were independent of methylation status. After exposure to amyloid-ß1-42 peptides (active form), H haplogroup cybrids demonstrated decreased cell viability compared to those treated with amyloid-ß42-1 (inactive form) (p<0.0001), while this was not observed in the K cybrids (p=0.2). K cybrids had significantly higher total global methylation levels and differences in expression levels for two acetylation genes and four methylation genes. Demethylation with 5-aza-dC altered expression levels for NFkB2, while APOE transcription patterns were unchanged. Our findings support the hypothesis that mtDNA-nuclear retrograde signaling may mediate expression levels of APOE, a key factor in many age-related diseases. Future studies will focus on identification of the mitochondrial-nuclear retrograde signaling mechanism(s) contributing to these mtDNA-mediated differences.

Corticosteroids: Triamcinolone, Dexamethasone and Fluocinolone.

Steroids have been extensively used to treat macular edema due to diabetic retinopathy, venous occlusive disease, ocular inflammation and, to a lesser extent, also in some cases of choroidal neovascularization. The various intraocular steroids that have been employed include dexamethasone, triamcinolone and fluocinolone. During the past few years, new drug delivery methods for corticosteroids have been developed and are now part of our therapeutic armamentarium. This chapter provides a brief description of the pharmacology, efficacy and adverse effects associated with the use of steroids in various retinal diseases.

Brimonidine Can Prevent In Vitro Hydroquinone Damage on Retinal Pigment Epithelium Cells and Retinal Müller Cells.

PURPOSE: Brimonidine is a selective alpha-2 adrenergic agonist used to reduce intraocular pressure and it has been shown to have some neuroprotective effects. Hydroquinone (HQ) is a toxicant present in cigarette smoke, and other sources. In this study, we investigated the cyto-protective effects in vitro of Brimonidine on human retinal pigment epithelium cells (ARPE-19) and human retinal Müller cells (MIO-M1) that had been treated with HQ. METHODS: Cells were pretreated for 6 h with different doses of Brimonidine tartrate 0.1% (1/2×, 1×, 5×, 10×), followed by a 24-h exposure to 100 µM of HQ, while the Brimonidine was still present. Assays were used to measure cell viability, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) production, and lactate dehydrogenase (LDH) release. RESULTS: Brimonidine increased the cell viability at all concentrations studied in both cell lines studied. ΔΨm also improved at all Brimonidine doses in ARPE-19 cells and in the 5× and 10× dosages MIO-M1 cells. The ROS levels decreased at 1×, 5×, and 10× doses of Brimonidine in ARPE-19 but only at 10× on MIO-M1 cells. The 10×-Brimonidine ARPE-19 cells had decreased LDH release, but no LDH changes were observed on MIO-M1 cells. CONCLUSION: HQ-induced toxicity is mediated through mitochondrial damaging, oxidative stress-related and necrosis-related pathways; Brimonidine significantly prevented the mitochondrial damaging and oxidative stress-related effects but had little effect on blocking the necrosis component of HQ-toxicity. Brimonidine protective effects differ between the different retinal cell types and high concentrations of Brimonidine (10×) have minimal damaging effects on human retinal cells.

Effects of light on retinal pigment epithelial cells, neurosensory retinal cells and Müller cells treated with Brilliant Blue G.

BACKGROUND: The aim of this study is to evaluate the safety profile of Brilliant Blue G (BBG) with and without exposure to light (L) on three different retinal cell lines. METHOD: ARPE-19, R28 and MIO-M1 cells were treated with BBG: 0.125 mg/mL (0.5x clinical concentration), 0.25 mg/mL (1x) or 0.5 mg/mL (2x) with or without surgical illumination of halogen light exposure for 10 min, 15 min or 30 min. Cells were further cultured after 24 h and then analysed for cell viability, late stages of apoptosis and mitochondrial damage associated with early apoptosis using assays that measure trypan blue dye exclusion, increases in caspase-3/7 activity or changes in mitochondrial membrane potential (ΔΨm), respectively. RESULT: All three cell lines that were exposed to BBG in the presence or absence of light exposure for 30 min were found to have cell viability and caspase-3/7 activity levels similar to the untreated cultures. The mitochondrial membrane potential (ΔΨm) was decreased significantly at the 2x + L dose and 2x dose in all three retinal cell lines compared to their respective untreated control cells. At the lower doses of BBG, with or without exposure to light, the ΔΨm values were similar to the untreated control cultures. CONCLUSION: Exposure to BBG dye concentrations that are used clinically (0.125 mg/mL and 0.25 mg/mL) in the presence up to 30 min of surgically equivalent light intensity is safe for retinal cells.

Mitochondrial DNA variants can mediate methylation status of inflammation, angiogenesis and signaling genes.

Mitochondrial (mt) DNA can be classified into haplogroups representing different geographic and/or racial origins of populations. The H haplogroup is protective against age-related macular degeneration (AMD), while the J haplogroup is high risk for AMD. In the present study, we performed comparison analyses of human retinal cell cybrids, which possess identical nuclei, but mtDNA from subjects with either the H or J haplogroups, and demonstrate differences in total global methylation, and expression patterns for two genes related to acetylation and five genes related to methylation. Analyses revealed that untreated-H and -J cybrids have different expression levels for nuclear genes (CFH, EFEMP1, VEGFA and NFkB2). However, expression levels for these genes become equivalent after treatment with a methylation inhibitor, 5-aza-2'-deoxycytidine. Moreover, sequencing of the entire mtDNA suggests that differences in epigenetic status found in cybrids are likely due to single nucleotide polymorphisms (SNPs) within the haplogroup profiles rather than rare variants or private SNPs. In conclusion, our findings indicate that mtDNA variants can mediate methylation profiles and transcription for inflammation, angiogenesis and various signaling pathways, which are important in several common diseases.

Human retinal transmitochondrial cybrids with J or H mtDNA haplogroups respond differently to ultraviolet radiation: implications for retinal diseases.

BACKGROUND: It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation. METHODOLOGY/PRINCIPAL FINDINGS: Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids. CONCLUSION/SIGNIFICANCE: In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be important to consider.

Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture.

PURPOSE: To compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture. METHODS: Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death. RESULTS: Cell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses. CONCLUSIONS: At clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses.

Inherited mitochondrial DNA variants can affect complement, inflammation and apoptosis pathways: insights into mitochondrial-nuclear interactions.

Age-related macular degeneration (AMD) is the leading cause of vision loss in developed countries. While linked to genetic polymorphisms in the complement pathway, there are many individuals with high risk alleles that do not develop AMD, suggesting that other 'modifiers' may be involved. Mitochondrial (mt) haplogroups, defined by accumulations of specific mtDNA single nucleotide polymorphisms (SNPs) which represent population origins, may be one such modifier. J haplogroup has been associated with high risk for AMD while the H haplogroup is protective. It has been difficult to assign biological consequences for haplogroups so we created human ARPE-19 cybrids (cytoplasmic hybrids), which have identical nuclei but mitochondria of either J or H haplogroups, to investigate their effects upon bioenergetics and molecular pathways. J cybrids have altered bioenergetic profiles compared with H cybrids. Q-PCR analyses show significantly lower expression levels for seven respiratory complex genes encoded by mtDNA. J and H cybrids have significantly altered expression of eight nuclear genes of the alternative complement, inflammation and apoptosis pathways. Sequencing of the entire mtDNA was carried out for all the cybrids to identify haplogroup and non-haplogroup defining SNPs. mtDNA can mediate cellular bioenergetics and expression levels of nuclear genes related to complement, inflammation and apoptosis. Sequencing data suggest that observed effects are not due to rare mtDNA variants but rather the combination of SNPs representing the J versus H haplogroups. These findings represent a paradigm shift in our concepts of mt-nuclear interactions.