Proteinuria-Lowering Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Chronic Kidney Disease Patients: A Real-World Multicentric Study

Control of dyslipidemia in chronic kidney disease (CKD) is not always guaranteed with statins and/or ezetimibe. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have opened up a new era in lipid control, but their effect on renal function and proteinuria in real life have not yet been evaluated. The aim of the present study was to analyze the evolution of renal function and proteinuria in a cohort of CKD patients treated with PCSK9i. This retrospective multicentric cohort study included CKD patients treated with PCSK9i. Baseline epidemiological data, comorbidities and laboratory findings (including estimated glomerular filtration rate [eGFR], proteinuria and lipid profile) …

An Alternative to the Human Hemoglobin Test in the Investigation of Bloodstains Treated with Active Oxygen: The Human Glycophorin A Test

In criminal investigations, there are three stages involved when studying bloodstains: search and orientation, confirmation, and individualization. Confirmatory tests have two aims: to show that the stain contains a human biological fluid and to confirm the type of biological fluid. The need to determine the nature of the evidence is reflected in the latest bibliography, where the possibility of employing mRNA and miRNA markers for this purpose is proposed. While these new proposals are being investigated, the kits for determining human hemoglobin currently provide a simple solution for resolving this issue. With these kits, the possibility of obtaining false positives and false negatives i…

DNA Evidence Uncompromised by Active Oxygen

Currently, forensic sciences can make use of the potential of instrumental analysis techniques to obtain information from the smallest, even invisible, samples. However, as laboratory techniques improve, so too should the procedures applied in the search for and initial testing of clues in order to be equally effective. This requires continuous revision so that those procedures may resolve the problems that samples present. As far as bloodstains are concerned, there are methods available that are recognized as being both highly sensitive and effective. Nevertheless, the marketing of new cleaning products, those that contain active oxygen, has raised doubts about the ability of those procedu…

Saturated fat intake and alcohol consumption modulate the association between the APOE polymorphism and risk of future coronary heart disease: a nested case-control study in the Spanish EPIC cohort

The association is still not clear between the common APOE polymorphism and coronary heart disease (CHD) risk, nor its modulation by diet. Thus, our aim was to study the association between the APOE genotypes and incident CHD and how dietary fat and alcohol consumption modify these effects. We performed a nested case-control study in the Spanish European Prospective Investigation into Cancer and Nutrition cohort. Healthy men and women (41,440, 30-69 years) were followed up over a 10-year period, with the incident CHD cases being identified. We analyzed 534 incident CHD cases and 1123 controls. APOE, dietary intake and plasma lipids were determined at baseline. The APOE polymorphism was sign…

Asociaciones de la concentración de adiponectina sérica con parámetros antropométricos, bioquímicos y presión arterial en población de alto riesgo cardiovascular

Introduccion La adiponectinemia se ha asociado inversamente con obesidad abdominal, un perfil lipidico mas favorable y menor resistencia a la insulina. Sin embargo, recientes estudios en poblacion de alto riesgo cardiovascular, especialmente con funcion renal alterada, muestran que concentraciones elevadas son un indicador desfavorable. Nuestro objetivo ha sido estudiar la asociacion entre adiponectinemia y parametros antropometricos, bioquimicos y presion arterial (PA) en pacientes de alto riesgo cardiovascular. Pacientes y metodos Se estudio a 185 pacientes (133 mujeres y 52 varones), participantes del estudio PREDIMED (edad media de 65,5 ± 4,3 anos). Se obtuvieron datos clinicos, antropo…

Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status (‘healthy population’, HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-va…

Single tube optimisation of APOE genotyping based on melting curve analysis

Objectives: To develop and validate a single-tube protocol for APOE genotyping using fluorescent probes. Design and methods: We have designed and validated a hybrid, single-tube, SimpleProbe/FRET probe protocol that takes advantage of the different probe wavelength emissions. Results: Our method offers high quality outcomes, minimum interferences between probe signals and is 100% concordant with the reference protocol. Conclusions: This method is cheaper, faster and more reliable and versatile than other alternatives proposed. © 2008 Elsevier Inc. All rights reserved.

Chemistry in Crime Investigation: Sodium Percarbonate Effects on Bloodstains Detection

Chemistry plays a leading role in crime investigation. In the study of bloodstains, chemical reactions provide the means for the detection. All these procedures have been thoroughly studied. However, recently, a new source of error has been found: washing stains with "active oxygen" detergents abrogates presumptive and human hemoglobin tests for bloodstains (although visible). The aim of this investigation was to evaluate the ability of pure sodium percarbonate-main component of detergents-to abrogate presumptive and human hemoglobin tests. Then, a solution to this problem could be found. The results demonstrate that pure sodium percarbonate-itself-is able to abrogate all tests, as well as …

The 1258 GA polymorphism in the neuropeptide Y gene is associated with greater alcohol consumption in a Mediterranean population.

Abstract Neuropeptide Y (NPY) is a neurotransmitter widely distributed in the central nervous system. Several studies have demonstrated that increases of NPY are associated with reduced alcohol intake and anxiety manifestations. The Leu7Pro polymorphism in the NPY has been associated with alcohol consumption, but evidence is scarce. In the Spanish Mediterranean population, this variant is not polymorphic. Thus, our aim is to identify novel functional variants in the NPY and to investigate the impact of these markers and others previously described on alcohol consumption in this population. A total of 911 subjects (321 men and 590 women) from the Spanish Mediterranean population were recruit…

Amelogenin test: From forensics to quality control in clinical and biochemical genomics.

Abstract Background The increasing number of samples from the biomedical genetic studies and the number of centers participating in the same involves increasing risk of mistakes in the different sample handling stages. We have evaluated the usefulness of the amelogenin test for quality control in sample identification. Methods Amelogenin test (frequently used in forensics) was undertaken on 1224 individuals participating in a biomedical study. Concordance between referred sex in the database and amelogenin test was estimated. Additional sex-error genetic detecting systems were developed. Results The overall concordance rate was 99.84% (1222/1224). Two samples showed a female amelogenin test…

Validating a Rapid Method for Detecting Common Polymorphisms in the APOA5 Gene by Melting Curve Analysis Using LightTyper

The recently identified apolipoprotein A-V gene (APOA5) has been shown to play an important role in hypertriglyceridemia (1). Genetic variation in APOA5 has been consistently associated with plasma triglyceride concentrations in several studies (2)(3)(4). Moreover, some studies have demonstrated additional associations with lipoprotein subclasses, remnant-like particles, and cardiovascular disease risk (4)(5)(6). Several single-nucleotide polymorphisms (SNPs) in the human APOA5 gene have been detected with differing frequencies depending on the population analyzed (7)(8), and Klos et al.(7) have also suggested context-dependent associations in different populations. Overall, 5 common SNPs, …

PPAR-alpha L162V and PGC-1 G482S gene polymorphisms, but not PPAR-gamma P12A, are associated with alcohol consumption in a Spanish Mediterranean population.

Abstract Background Peroxisome Proliferator-Activated Receptors (PPARs) and its co-activators are regulatory elements of the cellular lipid homeostasis and have been associated with feeding behavior modulation. Animal models suggest that these genes may be involved in alcohol consumption regulation. However, no studies in humans exist. Our aim is to estimate the possible association between polymorphisms in the PPAR-α , PPAR-γ and PPAR-γ co-activator 1A ( PGC-1A ) genes and alcohol consumption in humans. Methods We have conducted a cross-sectional study between the PPAR-α L162V, PPAR-γ P12A and PGC-1A G482S polymorphisms, and alcohol consumption in a general Mediterranean Spanish population…

MicroRNAs and Drinking : Association between the Pre-miR-27a rs895819 Polymorphism and Alcohol Consumption in a Mediterranean Population

Recently, microRNAs (miRNA) have been proposed as regulators in the different processes involved in alcohol intake, and differences have been found in the miRNA expression profile in alcoholics. However, no study has focused on analyzing polymorphisms in genes encoding miRNAs and daily alcohol consumption at the population level. Our aim was to investigate the association between a functional polymorphism in the pre-miR-27a (rs895819 A>G) gene and alcohol consumption in an elderly population. We undertook a cross-sectional study of PREvención con DIeta MEDiterránea (PREDIMED)-Valencia participants (n = 1007, including men and women aged 67 7 years) and measured their alcohol consumption (to…

Modulación de la expresión fenotípica del paciente con cistinuria: influencia de la intervención terapéutica y de la dieta

OBJETIVOS El fenotipo final del paciente con cistinuria depende, por una parte, de la ausencia o defecto molecular mas o menos grave en el transporte de cistina y aminoacidos dibasicos; y por otra parte tambien de factores ambientales. El objetivo del presente estudio es conocer el efecto de la modulacion de diversos factores ambientales (pH urinario, ingesta de liquido, tratamiento farmacologico y en especial la dieta) sobre el fenotipo final del paciente con cistinuria. METODOS Se estudiaron 45 sujetos diagnosticados como pacientes con cistinuria (25 hombres y 20 mujeres), 42 individuos pertenecientes al arbol genealogico de estos pacientes con cistinuria (15 hombres y 27 mujeres) y 90 co…

The effectiveness of the RSID confirmatory test kit for human alpha amylase: the effects of environmental factors and substrate materials

The investment in time and money that DNA analyses involves, provides a justification for forensic laboratories to carry out prior tests to ensure the presence of biological fluid in samples. The RSID kit has already been evaluated for forensic use, but its effectiveness on forensic casework samples is almost impossible to predict. Moreover, forensic reports presented before a court of law must justify the methods used to generate their findings. Consequently, trials to know how factors – such as the characteristics of the donor, the substrate and environmental conditions – can affect the kit’s efficacy are essential. This study evaluates some of these factors. For this aim, samples were ma…

Legume consumption is inversely associated with type 2 diabetes incidence in adults: A prospective assessment from the PREDIMED study

Background & aims: Legumes, a low-energy, nutrient-dense and low glycemic index food, have shown beneficial effects on glycemic control and adiposity. As such, legumes are widely recommended in diabetic diets, even though there is little evidence that their consumption protects against type 2 diabetes. Therefore the aim of the present study was to examine the associations between consumption of total legumes and specific subtypes, and type 2 diabetes risk. We also investigated the effect of theoretically substituting legumes for other protein- or carbohydrate-rich foods. Methods: Prospective assessment of 3349 participants in the PREvención con DIeta MEDiterránea (PREDIMED) study without ty…

Solving underwater crimes: development of latent prints made on submerged objects.

Underwater crime scenes always present a challenge for forensic researchers, as the destructive effect of water considerably complicates the chances of recovering material of evidential value. The aim of this study is to tackle the problem of developing marks that have been left on submerged objects. Fingermark deposition was randomly made on two surfaces - glass and plastic whilst the material was submerged under tap water and then left for one to fifteen days before drying and development. For their later development, various reagents - Black Powder, Silver Metallic Powder, Fluorescent Powder, Sudan Black (powder and solution) and Small Particle Reagent - were used and the effectiveness o…

Association between Opioid Receptor mu 1 (OPRM1) Gene Polymorphisms and Tobacco and Alcohol Consumption in a Spanish Population.

Evidence gained from animals and humans suggests that the encephalic opioid system might be involved in the development of drug addiction through its role in reward. Our aim is to assess the influence of genetic variations in the opioid receptor mu 1 on alcohol and tobacco consumption in a Spanish population. 763 unrelated individuals (465 women, 298 men) aged 18-85 years were recruited between October 2011 and April 2012. Participants were requested to answer a 35-item questionnaire on tobacco and alcohol consumption, as well as to complete the AUDIT and Fagerström tests. Individuals were genotyped for three polymorphisms in the opioid receptor mu 1 (OPRM1) gene, using a TaqMan® protocol. …

El diagnóstico genético del sexo mediante el test de la amelogenina: Métodos y posibles fuentes de error

El diagnóstico del sexo a partir de indicios biológicos es crucial en la ciencia forense en general y en la investigación criminal, en particular. La amelogenina -proteina codificada en los cromosomas sexuales- se viene utilizando con ese fin desde la última década del siglo pasado. Existen divergencias en secuencia y tamaño entre los alelos codificados en el cromosoma X y el cromosoma Y (AMELX y AMELY, respectivamente). Esta es la base que ha permitido su amplia utilización en ciencias forenses para el diagnóstico genético del sexo. No obstante, recientemente se han publicado casos en los cuales el resultado del test de la amelogenina no corresponde con el sexo legal (oficial) del individu…

Comparación de las frecuencias de los alelos factor V Leiden (G1691A) y protrombina-G20210A entre pacientes con trombosis venosa profunda y población general mediterránea española

Background: Factor V leiden and the -G20210A variant of prothrombin gene are associated to a higher risk of deep venous thrombosis. Aim: To assess the frequency of factor V Leiden (G1691A) and prothrombin -G20210A alleles in patients with deep venous thrombosis (DVT) and in the general population from Spain. Material and methods: Factor V Leiden (g1691a) and prothrombin-g20210a alleles were genotyped in 493 individuals from the Spanish general populations and in 131 patients with DVT. The presence of DVT was confirmed by phlebography. Allelic frequencies and the DVT risk associated with these variants were estimated. Results: Allelic frequencies for the factor V Leiden (G1691A) allele were …

Death: the ultimate clinical diagnosis

Arylesterase Activity and Antioxidant Status Depend on PON1-Q192R and PON1-L55M Polymorphisms in Subjects with Increased Risk of Cardiovascular Disease Consuming Walnut-Enriched Meat

Human paraoxonase (PON1) exists in 2 major polymorphic forms and has been shown to protect LDL and HDL against oxidation. The aim of this study was to assess the differences between subjects at increased risk of cardiovascular disease (CVD), taking into account the effects of PON1-Q192R and PON1-L55M polymorphisms on 1) basal serum arylesterase activity, lipid peroxidation (LPO), and LDL-cholesterol (LDL-C), HDL-C, total cholesterol (TC), and oxidized-LDL (ox-LDL) concentrations; 2) the relations between arylesterase activity and lipid variables; and 3) the effect of walnut-enriched meat (WM) consumption on arylesterase activity and lipid variables. Twenty-three Caucasians at increased risk…

Variaciones en el gen SLC7A9: impacto de trece mutaciones frecuentes en la etiología de la cistinuria en población mediterránea española

Fundamento y objetivo Investigar la presencia de mutaciones en el gen SLC7A9, descritas como mas prevalentes en otras poblaciones, en familias con cistinuria en poblacion mediterranea espanolay su asociacion con manifestaciones clinicas de la enfermedad. Pacientes y metodo Se estudio a 20 familias con cistinuria (6 tipo I, 12 tipo no I y 2 de tipo desconocido), incluidos 48 pacientes con cistinuria y 44 familiares. Se aislo el ADN y se realizoel analisis molecular de 13 mutaciones en el gen SLC7A9 (P52L, N58_G79del22, G63R,G105R, T123M, V170M, A182T, V188M, c.614dupA, G259R, L283F, A316V y R333W). Seestudio la asociacion de estas mutaciones con las concentraciones de aminoacidos en orina,fo…

Parte judicial de lesiones: uso y abuso

Sure he's dead? Be wise.

Predisposición genética en el consumo de alcohol: el caso de la Alcohol Deshidrogenasa 1C

Introduccion: El consumo de alcohol se presenta frecuentemente asociado a determinados delitos, siendo en unas ocasiones atenuante o eximente, y en otras una infraccion penal per se. Se han identificado numerosos factores geneticos y ambientales que predisponen al consumo de alcohol. Nuestro objetivo ha sido estudiar la prevalencia del polimorfismo Ile349Val en la alcohol deshidrogenasa 1C que da lugar a la isoforma gamma 2 (metabolizador lento), y estudiar su asociacion con el consumo de alcohol asi como reflexionar sobre la dimension de la implicacion de estas variantes geneticas en la Medicina Legal. Material y Metodos: Se ha genotipado el polimorfismo Ile 349Val en 869 individuos proced…

Bleach interference in forensic luminol tests on porous surfaces: more about the drying time effect.

As criminals try to avoid leaving clues at the scene of a crime, bloodstains are often washed away, but fortunately for investigators, they are difficult to eliminate completely. Porous surfaces easily retain blood traces, which are sometimes invisible to the naked eye. The reagent of choice for detecting latent blood traces on all types of surfaces is luminol, but its main disadvantage is a high degree of sensitivity to oxidising contaminants in the blood sample. If household bleach is used to clean bloodstains, presumptive tests are invalidated. Hypochlorites, however, are known to be unstable and deteriorate over time, and this feature could be of help in preventing household bleach-indu…

The effect of the APOE polymorphism on HDL-C concentrations depends on the cholesterol ester transfer protein gene variation in a Southern European population.

Abstract Background Apolipoprotein E (ApoE) locus has consistently shown a significant association with low-density lipoprotein cholesterol (LDL-C). However, its impact on high-density lipoprotein cholesterol (HDL-C) has been highly controversial suggesting that it may be context-dependent. We examined the gene–gene interaction between the common ApoE and the CETP polymorphisms in determining HDL-C concentrations in men and women from the general population. Methods 550 unrelated Caucasian subjects were randomly selected from a Mediterranean Region in Spain. Plasma lipids, anthropometric, clinical and lifestyle variables were measured. Common ApoE and CETP-TaqIB polymorphisms were determine…

Efecto del polimorfismo +2138InsCAGACC en el gen del receptor 3 de la melanocortina en el riesgo de obesidad en población española

Objetivo El receptor 3 de la melanocortina (MC3R) ha sido implicado en la regulacion de la homeostasis energetica y en el peso corporal. Nuestro objetivo es conocer si el polimorfismo +2138InsCAGACC en dicho gen se asocia con el riesgo de obesidad en poblacion espanola. Material y metodo Se ha realizado un estudio de casos y controles con 303 casos de obesidad y 606 controles apareados por sexo y edad. Se determinaron variables antropometricas y del estilo de vida y el polimorfismo +2138InsCAGACC en el gen del MC3R. Resultados La frecuencia alelica para la variante +2138InsCAGACC para el total de la poblacion fue de 0,29, y resulto ligeramente menos frecuente en el grupo de casos que en el …

Impacto de la apolipoproteína A5 en el riesgo cardiovascular: Modulaciones genéticas y ambientales

Triglyceride concentrations are an independent risk factor for coronary heart disease. Apolipoprotein A5 gene (APOA5) has an important role determining triglyceride metabolism and it is a potential cardiovascular risk. However the mechanisms for these actions are not well-known. Despite the different allelic frequency of its major polymorphisms in different populations, multiple studies have shown consistent associations between these variants and fasting triglycerides. Variations in the APOA5 gene have also been associated with postprandial triglycerides, as well as with different sizes of lipoproteins and other markers. Moreover, some of the APOA5 gene variants have been associated with i…

Dietary inflammatory index and all-cause mortality in large cohorts: The SUN and PREDIMED studies

[Background]: Inflammation is known to be related to the leading causes of death including cardiovascular disease, several types of cancer, obesity, type 2 diabetes, depression-suicide and other chronic diseases. In the context of whole dietary patterns, the Dietary Inflammatory Index (DII®) was developed to appraise the inflammatory potential of the diet. [Objective]: We prospectively assessed the association between DII scores and all-cause mortality in two large Spanish cohorts and valuated the consistency of findings across these two cohorts and results published based on other cohorts.

Bloodstains on Leather: Examination of False Negatives in Presumptive Test and Human Hemoglobin Test.

Presumptive tests for blood are very simple and sensitive tests used in the search for evidence. They also provide initial information on the nature of stains. A second test can confirm their nature. However, these tests can present false–negative results for different reasons. Some of those reasons have been studied, while others, those caused by the substrate material that contains the stain, are less well known. This work studies the effect of one component of a leather substrate—quebracho extract—on presumptive and human hemoglobin blood tests. Assays were performed using samples of blood dilutions contaminated with quebracho extract and others formed on a substrate containing the conta…

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