MicroRNAs as biomarkers of atrophic scarring in acne: a cross-sectional analysis of 41 patients.

BACKGROUND: Acne is the commonest inflammatory dermatosis seen worldwide. Atrophic acne scarring is a frequent complication, which can arise from acne of any severity. Micro (mi)RNAs are noncoding RNA molecules of 19-25 nucleotides that function as post-transcriptomic mediators of gene expression. They have demonstrated differential expression in various pathologies, such as eczema and psoriasis, allowing for a unique miRNA 'signature' profile to be established for different disease states. AIM: To establish a miRNA signature for acne, and acne-associated atrophic scarring and to identify if a pattern of circulating miRNA is evident in patients who are prone to scarring. METHODS: In total, 41 participants were consecutively recruited to this study. Circulating miRNA was quantified from plasma samples in all 41 patients, while in 8 patients, and in a further validation cohort of 9 patients, whole miRNAome was undertaken from tissue specimens, which included lesional, normal and where present, scarred skin. RESULTS: Three miRNAs, miR-223, miR-21 and miR-150, were statistically significantly overexpressed in acne lesions, and notably, in clinically uninvolved skin in participants prone to scarring. In this subgroup, we also found statistically significantly elevated levels of circulating miRNA-21 and miRNA-150. CONCLUSION: The presence of elevated levels of these specific miRNAs in the serum of patients with acne raises the potential of a blood test to identify those at risk of scarring, allowing for earlier intervention with effective therapy.

Efecto de los leucocitos sobre la lesión por almacenamiento en plaquetas de aferesis / Effect of leukocytes on the storage lesion in apheresis platelet

En el Banco de Sangre , las plaquetas sufren una serie de cambios físicos, metabólicos y fisiológicos que se denominan "lesión por almacenamiento" (LA), que depende de varios factores: métodos de preparación del concentrado, tipo de bolsa utilizada, concentración de plaquetas, número de leucocitos presentes en la unidad y acumulación de citoquinas. Todos ellos podrían producir activación plaquetaria y así afectar la calidad del producto, lo cual se reflejaría en una menor sobrevida de las plaquetas transfundidas. Basándose en lo anterior, se plantea que la remoción precoz de leucocitos aminoraría la LA en los concentrados plaquetarios (CPs) obtenidos por aféresis. Se estudiaron veinte CPs obtenidos mediante dos métodos de aféresis que difieren en el número de leucocitos residuales que permanecen en el producto final; un CP leucoreducido (Cobe Spectra) y otro estándar (Baxter CS 3000 plus). Las determinaciones se realizaron el día cero (prealmacenamiento) y al quinto día de almacenamiento. La evaluación de la LA incluyó marcadores de menbrana plaquetaria: p-selectina (CD62-P), glicoproteína Ib (CD42b), fosfatidilserina (Ax V.), factor tisular (CD142), formación de micropartículas (MPs), los cuales se analizaron por citometría de flujo, y citoquinas liberadas por los leucocitos y/o plaquetas activadas (IL-1. IL-6,FNT y RANTES), las cuales se analizaron por ELISA. El principal marcador de activación de las plaquetas (p-selectina) se encontró significativamente aumentado en los CP leucorreducidos (P: 0.001) y en los obtenidos en forma estándar (p: 0.02). La expresión de GPIb disminuyó significativamente solo en las plaquetas no leucorreducidas (p: 0.01). En relación a la actividad procoagulante de las plaquetas, se observó un aumento significativo en la expresión de fosfatidilserina sobre la cara externa de la membrana (p: 0.019) y de MPs plasmáticas (p: 0.025) solo en las plaquetas leucorreducidas y un muy leve aumento de la expresión de factor tisular...

Under Blood Bank storage conditions, platelet undergo a series of physical, metabolic and physiological changes that are denominated "platelet storage lesion" (PSL). This condition depends on several factors: the platelets number and the methodology used for the preparations of platelet concentrates (PC), type of storage bag, the number of leukocytes present in the cell unit, cytokines release, among others. All these factors may produce platelet activation and thus affect the quality of the product, which would be reflected in a shorter survival of the transfused platelets. Based on the previous knowledge, we hypothesized that early removal of leukocytes from the apheresis concentrate will diminish platelets "activation/lesion" during storage. We studied twenty PC obtained by two methods of apheresis that differed in the number of residual leukoreduced PC (Cobe Spectra) and a standard PC (3000 Baxter CS extra). The determinations were made at day zero (pre-storage) and at the fifth day of storage. The evaluation included markers present in platelets membrane, such as, p-selectin (CD62-P), glycoprotein Ib (CD42b), phosphatydilserine expression (PS). Tissue Factor (CD142) and microparticles (MPs) generation, that were analyzed by flow cytometry. Cytokines released by leucocytes or activated platelet (IL-1). IL-6, TNF and RANTES), were analysed by the ELISA technique. The most important marker of platelets activation, CD62-P, was significantly more increased in leukoreduced CP (P: 0.001) than in the standard method (p: 0.02). The expression of GPIb diminished significantly only in non-leukoreduced platelets (p: 0.01). With regard to the procoagulant activity of platelets, a significant increase in the PS expression was observed on the external face of the platelet membranes (p: 0.019) and on MPs (p: 0.025) only in leukoreduced preparations, changes that were accompanied by a very slight increase of tissue factor expression (p: 0.055). The determinations...

The transformer gene in Bactrocera oleae: the genetic switch that determines its sex fate.

Transformer (tra) is the second gene of a regulatory cascade based on RNA splicing that determines sex in Drosophila melanogaster. Splicing of tra transcripts is regulated by the master gene Sex lethal and tra itself regulates splicing of the transcriptional regulator doublesex (dsx). We present the isolation and characterization of Botra, the olive fruit fly Bactrocera oleae orthologue to the Drosophila gene transformer. As in Drosophila, Botra transcripts are spliced in a sex-specific manner so that only females encode a functional polypeptide of 422 amino acids, whereas males encode presumably nonfunctional peptide(s). The identification of multiple TRA/TRA-2 binding sites within the Botra male-specific exons, suggests an autoregulation mechanism of tra, through TRA/TRA2 activities. The fundamental role of the TRA protein in sex determination of Bactrocera was investigated by RNA interference, where the introduction of Botra dsRNA into embryos resulted in complete transformation of XX flies into fertile males.

A prospective study of Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus in adults with human immunodeficiency virus-1.

Antibody titres against Kaposi's sarcoma associated herpesvirus (KSHV or human herpesvirus 8 (HHV-8)) and Epstein-Barr virus (EBV) were examined in people who subsequently developed Kaposi's sarcoma and non-Hodgkin's lymphoma, within randomised controlled trials of antiretroviral therapy in adults infected with the human immunodeficiency virus-1 (HIV). For each case of Kaposi's sarcoma (n=189) and each case of non-Hodgkin's lymphoma (n=67), which developed after randomisation, one control was randomly selected from other trial participants, after matching for age, sex, ethnicity, mode of HIV transmission, type of treatment received and period of follow-up. Using sera taken an average of two and a half years before the diagnosis of cancer, titres of antibodies against KSHV latent (LANA) and lytic (K8.1) antigens and against EBV (VCA) antigens were investigated in relation to subsequent risks of cancer by calculating odds ratios (OR) using conditional logistic regression. Latent antibodies against KSHV were detectable among 38% (72 out of 189) of Kaposi's sarcoma cases and 12% (23 out of 189) of their controls (OR=4.4, 95% confidence intervals (CI) 2.3-8.3, P<0.001). The OR for Kaposi's sarcoma increased with increasing antilatent KSHV antibody titre (chi(2)(1) for trend=32.2, P<0.001). Lytic antibodies against KSHV were detectable among 33% (61 out of 187) of Kaposi's sarcoma cases and 19% (36 out of 187) of their controls (OR=2.0, 95% CI 1.2-3.4, P=0.003) and the OR for Kaposi's sarcoma increased with increasing antilytic KSHV antibody titre (chi(2)(1) for trend=6.2, P=0.02). Virtually, all cases and controls had anti-EBV antibodies detected and the OR for non-Hodgkin's lymphoma associated with a doubling of the anti-EBV antibody titre was estimated to increase by a multiplicative factor of 1.3 (95% CI 0.9-1.7, P=0.1). Kaposi's sarcoma was not associated with antibody levels against EBV (P=0.4) and non-Hodgkin's lymphoma was not associated with antibodies against KSHV (latent P=0.3; lytic P=0.5). Adjustment for CD4 count at the time of sample collection made no material difference to any of the results. In conclusion, among human immunodeficiency virus infected people, high levels of antibodies against KSHV latent and lytic antigens are strongly associated with subsequent risk of Kaposi's sarcoma but not non-Hodgkin's lymphoma. Antibody titre to EBV does not appear to be strongly associated with subsequent risk of Kaposi's sarcoma or non-Hodgkin's lymphoma in HIV infected people.

Subdiagnóstico de delirium en adultos mayores hospitalizados / Delirium in Chilean elderly inpatients: an overlooked problem

Background: Delirium is a common underdiagnosed and undertreated problem in elderly inpatients, associated to higher morbidity, mortality and health cost. Aim: To evaluate the prevalence of delirium at hospital admission in medically ill elderly patients and the attending physician's diagnosis and treatment of delirium. Patients and methods: In a prospective and descriptive study, consecutive patients aged 65 years or more, admitted to an internal medicine ward were evaluated by independent physicians, during the first 48 h of admission, to asses the presence of delirium. Diagnosis of delirium was based on the Confusion Assessment Method. Medical and nurse records were reviewed. Family was interviewed when necessary. Results: One hundred eight patients (52% women, age range 65-94 years) with an APACHE II score of 11.6±5, were evaluated. Fifty seven patients (53%) had delirium (32% hyperactive, 72% hypoactive and 5% mixed). Delirium prevalence was significantly higher in older patients (66% among those aged 75 years or older versus 30% in younger, p <0.05) and among patients with more severe conditions (88% among those with an APACHE score over 16 versus 47% below that value, p <0.05). Medical records of patients with delirium showed that this diagnosis was present only in 32% and cognitive deficit was described in 73%. Ten percent of patients with delirium received sedative medication and 38% were physically restricted. There were no environmental interventions to prevent or control delirium. Conclusions: Delirium in elderly inpatients at this unit is an extraordinarily prevalent problem, seriously under diagnosed (68%) and under treated. This study should alerts our medical community to improve the diagnosis and management of delirium in elderly inpatients.

Situación clínico-epidemiológica del cáncer gástrico: provincias de Quillota y Petorca: V región / Clinical-epidemiological situation of gastric cancer: Quillota and Petorca provincies: V region

Se comunica la experiencia del Hospital San Martín de Quillota en el diagnóstico y tratamiento de cáncer gástrico desde marzo de 1988 hasta julio de 1992. Se revisó las 4.310 endoscopías realizadas en el período pesquisándose 139 tumores malignos (3,2 por ciento ). Sólo un 2,8 por ciento de los pacientes tuvo un cáncer incipiente. Fueron sometidos a estudio clínico 100 pacientes, de los cuales se intervino quirúrgicamente a 48, pudiendo efectuar resecciones curativas en 16 de ellos. Hubo 39 pacientes que abandonaron el control después del diagnóstico. La distribución geográfica de los pacientes mostró una notable concentración en la comuna de Quillota, situación que debe ser investigada a futuro

Cirugía del quiste hidatídico / Hidatid cyst surgery

Se presenta la experiencia local en la pesquisa y tratamiento del quiste hidatídico (QH) desde mayo de 1986 a julio de 1988, así como de la prevalencia de esta parasitosis en animales sacrificados en mataderos de la zona. Se han detectado 50 QH en diversas localizaciones, de los cuales se operaron 24. Se menciona la importancia de la ecografía en la detección de los QH hepáticos. La quistectomía parcial fue la operación que se realizó con mayor frecuencia (83,3%). De acuerdo a este estudio se concluye que en la VI Región la prevalencia de la hidatosis es tan importante como en aquéllas tradicionalmente consideradas como áreas en que esta enfermedad es endémica

Quantum chemical approach to the relationship between molecular structure and serotonin receptor binding affinity.

We have analyzed the dependence of the serotonin receptor binding affinity on the atomic net charges, superdelocalizabilities, mass, and moment of inertia in a group of indole derivatives. The approaches employed are a new nonempirical quantitative structure-activity relationship (QSAR) method and multiple regression analyses. The results suggest that the indole derivatives interact with the receptor through a charge transfer between the phenyl ring and a counterpart in the receptor, plus some localized electrostatic interactions. Also, the fit of the equation obtained suggests that the indole derivatives have the aromatic ring placed in the same relative position during the interaction with the receptor.