Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals

Background The MPER region of the HIV-1 envelope glycoprotein gp41 is targeted by broadly neutralizing antibodies. However, the localization of this epitope in a hydrophobic environment seems to hamper the elicitation of these antibodies in HIV infected individuals. We have quantified and characterized anti-MPER antibodies by ELISA and by flow cytometry using a collection of mini gp41-derived proteins expressed on the surface of 293T cells. Longitudinal plasma samples from 35 HIV-1 infected individuals were assayed for MPER recognition and MPER-dependent neutralizing capacity using HIV-2 viruses engrafted with HIV-1 MPER sequences. Results Miniproteins devoid of the cysteine loop of gp41 exposed the MPER on 293T cell membrane. Anti-MPER antibodies were identified in most individuals and were stable when analyzed in longitudinal samples. The magnitude of the responses was strongly correlated with the global response to the HIV-1 envelope glycoprotein, suggesting no specific limitation for anti-MPER antibodies. Peptide mapping showed poor recognition of the C-terminal MPER moiety and a wide presence of antibodies against the 2F5 epitope. However, antibody titers failed to correlate with 2F5-blocking activity and, more importantly, with the specific neutralization of HIV-2 chimeric viruses bearing the HIV-1 MPER sequence; suggesting a strong functional heterogeneity in anti-MPER humoral responses. Conclusions Anti-MPER antibodies can be detected in the vast majority of HIV-1 infected individuals and are generated in the context of the global anti-Env response. However, the neutralizing capacity is heterogeneous suggesting that eliciting neutralizing anti-MPER antibodies by immunization might require refinement of immunogens to skip nonneutralizing responses.

Prevalence of Ischemic Heart Disease and Management of Coronary Risk in Daily Clinical Practice: Results from a Mediterranean Cohort of HIV-Infected Patients

There are conflicting data on the prevalence of coronary events and the quality of the management of modifiable cardiovascular risk factors (CVRF) inHIV-infected patients. Methods.We performed a retrospective descriptive study to determine the prevalence of coronary events and to evaluate the management of CVRF in a Mediterranean cohort of 3760 HIV-1-infected patients from April 1983 through June 2011. Results.We identified 81 patients with a history of a coronary event (prevalence 2.15%); 83% of them suffered an acute myocardial infarction. At the time of the coronary event, CVRF were highly prevalent (60.5% hypertension, 48% dyslipidemia, and 16% diabetes mellitus).OtherCVRF, such as smoking, hypertension, lack of exercise, and body mass index, were not routinely assessed. After the coronary event, a significant decrease in total cholesterol ( � = 0.025) and LDLcholesterol ( � = 0.004) was observed. However, the percentage of patients whomaintained LDL-cholesterol > 100mg/dL remained stable (from 46% to 41%, � = 0.103). Patients using protease inhibitors associated with a favorable lipid profile increased over time ( � = 0.028). Conclusions.The prevalence of coronary events in our cohort is low. CVRF prevalence is high and theirmanagement is far from optimal. More aggressive interventions should be implemented to diminish cardiovascular risk in HIV-infected patients.

Clopidogrel Pharmacogenetics, resistance to antiplatelet therapy in ischemic stroke by Epigenome Wide Association Study (EWAS).

Clopidogrel is a widely used antiplatelet drug used in preventing vascular events after suffering a first stoke. Genome-wide association studies (GWAS) has not been able to establish a clear association between polymorphisms and recurrence. Therefore in the present final master project an epigenetic approach is proposed. Using an array based technology, 450.000 CpG sites across all genome were assessed in 48 individuals (21 cases and 21 controls). Looking at differentially methylated levels between cases and controls, 58 CpG sites (DMGs) were found. Although, no clear locus was observed. Looking individually to each 49 genes, two appeared to be important to our study. TRAF3 and ADAMTS2 are gens highly related to platelet aggregation. In orther to confirm these result, a new DNA methylation study will be done in a larger cohort, using Sequenom technology.

Secondhand tobacco smoke exposure in open and semi-open settings: a systematic review

Background: Some countries have recently extended smoke-free policies to particular outdoor settings; however, there is controversy regarding whether this is scientifically and ethically justifiable. Objectives: The objective of the present study was to review research on secondhand smoke (SHS) exposure in outdoor settings. Data sources: We conducted different searches in PubMed for the period prior to September 2012. We checked the references of the identified papers, and conducted a similar search in Google Scholar. Study selection: Our search terms included combinations of"secondhand smoke,""environmental tobacco smoke,""passive smoking" OR"tobacco smoke pollution" AND"outdoors" AND"PM" (particulate matter),"PM2.5" (PM with diameter ≤ 2.5 µm),"respirable suspended particles,""particulate matter,""nicotine,""CO" (carbon monoxide),"cotinine,""marker,""biomarker" OR"airborne marker." In total, 18 articles and reports met the inclusion criteria. Results: Almost all studies used PM2.5 concentration as an SHS marker. Mean PM2.5 concentrations reported for outdoor smoking areas when smokers were present ranged from 8.32 to 124 µg/m3 at hospitality venues, and 4.60 to 17.80 µg/m3 at other locations. Mean PM2.5 concentrations in smoke-free indoor settings near outdoor smoking areas ranged from 4 to 120.51 µg/m3. SHS levels increased when smokers were present, and outdoor and indoor SHS levels were related. Most studies reported a positive association between SHS measures and smoker density, enclosure of outdoor locations, wind conditions, and proximity to smokers. Conclusions: The available evidence indicates high SHS levels at some outdoor smoking areas and at adjacent smoke-free indoor areas. Further research and standardization of methodology is needed to determine whether smoke-free legislation should be extended to outdoor settings.

Non-invasive diagnostic and prognostic evaluation of liver cirrhosis and portal hypertension.

Cirrhosis is the final stage of most of chronic liver diseases, and is almost invariably complicated by portal hypertension, which is the most important cause of morbidity and mortality in these patients. This review will focus on the non-invasive methods currently used in clinical practice for diagnosing liver cirrhosis and portal hypertension. The first-line techniques include physical examination, laboratory parameters, transient elastography and Doppler-US. More sophisticated imaging methods which are less commonly employed are CT scan and MRI, and new technologies which are currently under evaluation are MR elastography and acoustic radiation force imaging (ARFI). Even if none of them can replace the invasive measurement of hepatic venous pressure gradient and the endoscopic screening of gastroesophageal varices, they notably facilitate the clinical management of patients with cirrhosis and portal hypertension, and provide valuable prognostic information.

La Enfermedad a lo largo de la historia. Un punto de mira entre la biología y la simbología

Las enfermedades tienen sus propios ritmos que se van modificando a lo largo de los siglos; cada sociedad construye su forma de pensar y sentir las enfermedades. La interdependencia entre las condiciones biológicas y sociales de la vida civilizada, ha ocasionado que cada momento histórico viva de forma distinta la enfermedad. El objetivo de este artículo es reflexionar sobre la forma de ver y vivir la enfermedad en Occidente, a lo largo de la historia, centrándonos especialmente en la creencia, surgida a partir del siglo XVIII, que el progreso humano erradicaría la enfermedad. Las raíces de la forma de sentir la enfermedad en el Occidente de inicios del siglo XXI deben buscarse en los orígenes griegos y judeo-cristianos, que se continúan a lo largo de la Edad Media, hasta que con la llegada de la Modernidad se produce un giro desde la búsqueda de la eternidad en el otro mundo, hacia un caminar a la inmortalidad en la tierra. En los inicios del siglo XXI, el hombre post-moderno traslada la crisis de pensamiento vigente al campo de la salud, ello plantean tensiones que se hacen patentes en la forma de vivir y atender la enfermedad

Discursos sobre la naturaleza americana: desde el descubrimiento de América hasta la visión ilustrada.

Los siglos del descubrimiento y la conquista parten de una visión providencialista de la historia que incide directamente en el concepto de la naturaleza americana. De este concepto derivan algunas características básicas de la escritura historiográfica de la época. A partir del siglo XVIII desaparece el concepto místico-geográfico que el cristianismo había dado a la geografía. Con respecto a la naturaleza americana, durante el siglo XVIII tanto los naturalistas como los historiadores y los filósofos pretendieron estudiarla partiendo de premisas consideradas más objetivas y como consecuencia de la sistematización del conocimiento. Todo ello repercutirá en el descrédito que sufrirán las crónicas de Indias. Sin embargo, esta nueva manera de leer las crónicas de Indias guarda relación no tan sólo con la búsqueda de formas alternativas de pruebas históricas o el uso de nuevos tipos de pruebas más fidedignas, sino también con determinados intereses políticos y la creación de la leyenda negra.

La Enfermedad a lo largo de la historia. Un punto de mira entre la biología y la simbología

Las enfermedades tienen sus propios ritmos que se van modificando a lo largo de los siglos; cada sociedad construye su forma de pensar y sentir las enfermedades. La interdependencia entre las condiciones biológicas y sociales de la vida civilizada, ha ocasionado que cada momento histórico viva de forma distinta la enfermedad. El objetivo de este artículo es reflexionar sobre la forma de ver y vivir la enfermedad en Occidente, a lo largo de la historia, centrándonos especialmente en la creencia, surgida a partir del siglo XVIII, que el progreso humano erradicaría la enfermedad. Las raíces de la forma de sentir la enfermedad en el Occidente de inicios del siglo XXI deben buscarse en los orígenes griegos y judeo-cristianos, que se continúan a lo largo de la Edad Media, hasta que con la llegada de la Modernidad se produce un giro desde la búsqueda de la eternidad en el otro mundo, hacia un caminar a la inmortalidad en la tierra. En los inicios del siglo XXI, el hombre post-moderno traslada la crisis de pensamiento vigente al campo de la salud, ello plantean tensiones que se hacen patentes en la forma de vivir y atender la enfermedad

Orofacial pain of cardiac origin: review literature and clinical cases

The most common types of orofacial pain originate at the dental or periodontal level or in the musculoskeletal structures. However, the patient may present pain in this region even though the source is located elsewhere in the body. One possible source of heterotopic pain is of cardiac origin. Objectives: Report two cases of orofacial pain of cardiac origin and review the clinical cases described in the literature. Study Design: Description of clinical cases and review of clinical cases. Results and conclusions: Nine cases of atypical pain of cardiac origin are recorded, which include 5 females and 4 males. In craniofacial structures, pain of cardiac origin is usually bilateral. At the craniofacial level, the most frequent location described is in the throat and jaw. Pain of cardiac origin is considered atypical due to its location, although roughly 10% of the cases of cardiac ischemia manifest primarily in craniofacial structures. Finally, the differential diagnosis of pain of odontogenic origin must be taken into account with pain of non-odontogenic origin (muscle, psychogenic, neuronal, cardiac, sinus and neurovascular pain) in order to avoid diagnostic errors in the dental practice as well as unnecessary treatments.

The Rose Bengal test in human brucellosis: a neglected test for the diagnosis of a neglected disease

Brucellosis is a highly contagious zoonosis affecting livestock and human beings. The human disease lacks pathognomonic symptoms and laboratory tests are essential for its diagnosis. However, most tests are difficult to implement in the areas and countries were brucellosis is endemic. Here, we compared the simple and cheap Rose Bengal Test (RBT) with serum agglutination, Coombs, competitive ELISA, Brucellacapt, lateral flow immunochromatography for IgM and IgG detection and immunoprecipitation with Brucella proteins. We tested 208 sera from patients with brucellosis proved by bacteriological isolation, 20 contacts with no brucellosis, and 1559 sera of persons with no recent contact or brucellosis symptoms. RBT was highly sensitive in acute and long evolution brucellosis cases and this related to its ability to detect IgM, IgG and IgA, to the absence of prozones, and to the agglutinating activity of blocking IgA at the pH of the test. RBT was also highly specific in the sera of persons with no contact with Brucella. No test in this study outperformed RBT, and none was fully satisfactory in distinguishing contacts from infected patients. When modified to test serum dilutions, a diagnostic titer >4 in RBT resulted in 87.4% sensitivity (infected patients) and 100% specificity (contacts). We discuss the limitations of serological tests in the diagnosis of human brucellosis, particularly in the more chronic forms, and conclude that simplicity and affordability of RBT make it close to the ideal test for small and understaffed hospitals and laboratories.

CERKL Knockdown Causes Retinal Degeneration in Zebrafish

The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration

Efectos de la primera visita de consejo genético sobre la percepción de riesgo y el malestar emocional

Objetivo: Analizar los efectos que provoca la primera visita de consejo genético para cáncer hereditario sobre la percepción de riesgo, y el malestar emocional en pacientes que acuden por primera vez a la Unidad de Consejo Genético (UCG) por historia familiar de cáncer de mama, ovario o colon hereditario. Método: Se evaluó la percepción de riesgo de padecer cáncer (al año, a 10 años, y a lo largo de toda la vida), y la intensidad del malestar emocional (evaluada como la ansiedad, tristeza y preocupación por la salud experimentadas durante la última semana) en tres ocasiones: inmediatamente antes de la primera visita de consejo genético (CG), inmediatamente después de la misma, y al cabo de 2-3 semanas. Resultados: El malestar emocional previo a la visita se producía en aproximadamente un 30% de los pacientes, siendo mayor en las personas que no realizaban actividad laboral. Si bien la visita de CG reducía el malestar emocional en muchos casos, ocurría lo contrario en algunos pacientes inmediatamente después de la misma (un 34% se sentía más ansioso, un 32% se sentía más triste, y un 23% se sentía más preocupado), y ello guardaba relación con la preocupación por los hijos (tanto si se tenían como si se pretendía tenerlos en el futuro). No obstante, este malestar se reducía en las 2-3 semanas posteriores. La visita de CG reducía la percepción de riesgo de padecer cáncer a lo largo de toda la vida (p< .01), no existiendo diferencias en función del tipo de cáncer. Conclusiones: Esta primera visita reduce la sobreestimación del riesgo de padecer cáncer que los pacientes tienen antes de la misma, pero, en aproximadamente un tercio de los mismos, no reduce los niveles de malestar emocional, observándose, incluso, un incremento de éste que va disminuyendo durante las semanas posteriores a la visita. Son necesarios más estudios que permitan determinar si este incremento es una consecuencia inevitable del inicio del proceso de CG, o si puede reducirse modificando algún aspecto del protocolo que se aplica en la primera visita.

Dendritic Spine Abnormalities in Hippocampal CA1 Pyramidal Neurons Underlying Memory Deficits in the SAMP8 Mouse Model of Alzheimer's Disease

SAMP8 is a strain of mice with accelerated senescence. These mice have recently been the focus of attention as they show several alterations that have also been described in Alzheimer"s disease (AD) patients. The number of dendritic spines, spine plasticity, and morphology are basic to memory formation. In AD, the density of dendritic spines is severely decreased. We studied memory alterations using the object recognition test. We measured levels of synaptophysin as a marker of neurotransmission and used Golgi staining to quantify and characterize the number and morphology of dendritic spines in SAMP8 mice and in SAMR1 as control animals. While there were no memory differences at 3 months of age, the memory of both 6- and 9-month-old SAMP8 mice was impaired in comparison with age-matched SAMR1 mice or young SAMP8 mice. In addition, synaptophysin levels were not altered in young SAMP8 animals, but SAMP8 aged 6 and 9 months had less synaptophysin than SAMR1 controls and also less than 3-month-old SAMP8 mice. Moreover, while spine density remained stable with age in SAMR1 mice, the number of spines started to decrease in SAMP8 animals at 6 months, only to get worse at 9 months. Our results show that from 6 months onwards SAMP8 mice show impaired memory. This age coincides with that at which the levels of synaptophysin and spine density decrease. Thus, we conclude that together with other studies that describe several alterations at similar ages, SAMP8 mice are a very suitable model for studying AD.

Estudio clínico comparativo de la eficacia de azitromicina frente a amoxicilina/Ac. Clavulánico en el tratamiento de infecciones orales.

Fundamentos: el objetivo de este estudio fue comparar la eficacia. seguridad y tolerancia de la azitromicina frente a amoxicilina/ac. clavulánico en el tratamiento de pacientes con infecciones bucales agudas de origen odontogénico. Pacientes y Método: en este estudio abierto, comparativo y multicéntrico, se incluyeron 208 pacientes con infección bucal aguda de origen odontogénico, asignados aleatoriamente a dos grupos; 102 pacientes recibieron azitromicina, y 106 pacientes recibieron amoxicilina/ac. clavulánico. Se realizaron una historia clínica y una exploración física, y se tomaron muestras de sangre y orina. En cada una de las visitas, se recogieron los signos y síntomas característicos de la infección. Resultados: el nivel de respuesta fue similar en ambos grupos terapéuticos, obteniéndose un porcentaje de curación o mejoría superior al 90%. Azitromicina fue mejor tolerada y tuvo mejor cumplimiento que amoxicilina/ac. clavulánico. Los efectos adversos fueron en su mayoría gastrointestinales. Conclusión: Azitromicina y amoxicilina/clavulánico fueron igualmente efectivos en el tratamiento de infecciones agudas de origen odontogénico.

Pronóstico y tratamiento de la boca seca. Revisión sistemática

No existen protocolos claramente establecidos para el tratamiento de la boca seca. El objetivo de este trabajo es realizar una revisión sistemática de la literatura médica de los últimos 10 años. Hemos utilizado las palabras: «dry mouth», «prognosis», «treatment» y «dentistry». En una primera búsqueda hemos encontrado 1.450 entradas. Con la restricción «clinical trials OR randomized controlled trial OR systemic reviews» se han reducido a 522, de las que 145 eran metaanálisis y revisiones sistemáticas. Se han eliminado las que no eran pertinentes al tema y han quedado reducidas a 53. Posteriormente se descartaron 24 (8 no pertinentes, 7 revisiones y 9 opiniones personales). De los 29 artículos analizados, 15 son ensayos clínicos controlados, 2 ensayos no controlados, 4 estudios observacionales, 2 revisiones sistemáticas y 5 revisiones. Los enfermos mejor estudiados son los pacientes con síndrome de Sjögren y los pacientes irradiados. El tratamiento se centra en el etiológico, preventivo, sintomático, de estimulación salival local y sistémicos. Podemos concluir que el tratamiento debe ser individualizado, pudiéndose aplicar sustitutos salivales y diferentes técnicas de estimulación mecánica. There are no clearly established protocols for the treatment of dry mouth. The aim of this paper is a systematic review of the literature of the past 10 years using the words «dry mouth», «prognosis», «treatment» and «dentistry». The initial search found 1,450 entries and within the restriction «clinical trials OR randomized controlled trial OR systemic reviews» it has been reduced to 522, which 145 were meta-analysis and systematic reviews. Papers not relevant to the issue were removed reducing the entries to 53. Twenty-four were dismissed (8 irrelevant, 7 reviews without adequate information and 9 personal opinions). Of the 29 items tested, 15 were controlled trials, 2 uncontrolled trials, 4 observational studies, 2 systematic reviews and 5 non systematic reviews. The most studied patients were Sjögren's syndrome and the irradiated patients. Treatments are focused on the etiology, prevention, symptomatic, local salivary stimulation and systemic treatments. It can be concluded that treatment must be individualized, salivary substitutes and mechanical stimulation techniques can be applied.