Evolution and associated factors of hand hygiene compliance in a pediatric tertiary hospital.

BACKGROUND: The objective is to know the evolution of the Degree of Compliance with Recommendations (DCR) on hand hygiene (HH) and its associated factors in the pediatric care areas (PCAs) of a tertiary hospital. METHODS: Observational, cross-sectional study, repeated over time, with direct observation of the DCR on HH during the daily activity of health care workers. Over 13 years, 9226 HH opportunities were observed. Associations between DCR, PCA and other variables (eg, age, sex, and professional position) were examined using χ² and adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: DCR on HH in 9 PCAs was 64.3% (95% CI, 63.3-65.3), and in the group of non-pediatric areas it was 49.6% (95% CI, 49.1-50.1). The areas with the highest degree of compliance were Oncology 72.8% (95% CI, 69.2-76.4), Neonatology 73.2% (95% CI, 71.3-75.1), and Neonatal intensive care unit 70.0% (95% CI, 67.5-72.6). These were the areas with the strongest association with HH compliance, with aOR:2.8 (95% CI, 2.2-3.6); aOR, 3.0 (95% CI, 2.6-3.6) aOR:2.6 (95% CI, 2.1-3.1), respectively. Other associated factors were the indications "after an activity," aOR, 1.6 (95% CI, 1.5-1.8) and the availability of pocket-size alcohol-based solution, aOR, 2.1(95% CI, 1.9-2.3). CONCLUSIONS: The DCR on HH in PCAs is higher than in other areas, although there is still margin for improvement. We have identified modifiable factors that have an independent association with HH compliance in PCAs. Focusing on modifiable factors will increase compliance with HH with the ultimate goal of reducing healthcare associated infections.

Real World Patient-reported Outcomes in HIV-infected Adults Switching to EVIPLERA®, Because of a Previous Intolerance to cART. PRO-STR Study.

BACKGROUND: To investigate the impact of switching from stable Combined Antiretroviral Therapy (cART) to single-tablet regimen (RPV/FTC/TDF=EVIPLERA® /COMPLERA®) on patient- reported outcomes in HIV-infected adults who cannot tolerate previous cART, in a real-world setting. METHODS: PRO-STR is a 48-week observational, prospective, multicenter study. Presence and magnitude of symptoms (main endpoint), health-related quality-of-life (HRQoL), adherence, satisfaction with treatment and patient preferences were assessed. RESULTS: Three hundred patients with 48-week follow-up, who switched to EVIPLERA® (mean age: 46.6 years; male: 74.0%; 74.7% switched from a non-nucleoside reverse-transcriptase-inhibitor, 25.3% from a protease inhibitor + ritonavir) were included. There was no statistical difference in median CD4+ cell count (baseline: 678.5 cells/mm3; 48-week: 683.0 cells/mm3) neither in virological suppression (≤50 copies/mL) (baseline: 98.3%; 48-week: 95.3%). The most frequent reasons for switching were neuropsychiatric (62.3%), gastrointestinal (19.3%) and biochemical/metabolic (19.3%) events. Only 7.7% of patients permanently discontinued therapy. At 48-week, all outcomes showed an improvement compared to baseline. Overall, there was a significant decrease (pvalue≤ 0.05) in number and magnitude of symptoms, while HRQoL, satisfaction and adherence improved significantly. Most patients prefered EVIPLERA® than previous cART. According to the type of intolerance, HRQoL was improved, but only significantly in patients with neuropsychiatric and gastrointestinal symptoms. Adherence improved significantly in patients with metabolic disturbances and satisfaction with EVIPLERA® was higher in the three groups. CONCLUSION: Switching to EVIPLERA® from non-nucleoside reverse-transcriptase-inhibitor or protease inhibitor-based regimens due to toxicity, improved the presence/magnitude of symptoms, HRQoL, and preference with treatment. EVIPLERA® maintained a virological response, CD4+ cell count and maintained or improved adherence.

Improvement of lipoatrophy by switching from efavirenz to lopinavir/ritonavir.

OBJECTIVE: To assess whether changes in antiretroviral drugs other than thymidine nucleoside reverse transcriptase inhibitors (NRTI) may have a body fat impact in HIV-infected patients with lipoatrophy. METHODS: Ninety-six-week phase IV, open-label, multicentre, pilot randomized trial. HIV-infected patients with moderate/severe lipoatrophy at one or more body sites despite long-term thymidine NRTI-free therapy were randomized to continue their efavirenz (EFV)-based antiretroviral regimen or to switch from EFV to lopinavir/ritonavir (LPV/r). The primary endpoint was the absolute change in limb fat mass measured by dual X-ray absorptiometry from baseline to 96 weeks. Changes in other body fat measurements, subjective perception of lipoatrophy, subcutaneous fat gene expression and plasma lipids were also assessed. RESULTS: Thirty-three patients (73% men, median age 52 years) were recruited. At 96 weeks, absolute limb fat mass increased in the LPV/r arm vs. the EFV arm (estimated difference +1082.1 g; 95% CI +63.7 to +2103.5; P = 0.04); this difference remained significant after adjustment by gender, age, fat mass, body mass index and CD4 cell count at baseline. Subjective lipoatrophy perception scores also improved in the LPV/r arm relative to the EFV arm. Adipogenesis, glucose and lipid metabolism, and mitochondrial gene expression increased in the LPV/r arm compared with the EFV arm at 96 weeks. HDL cholesterol decreased in the LPV/r arm relative to the EFV arm. CONCLUSIONS: Switching from EFV to LPV/r in HIV-infected patients with lipoatrophy may offer further limb fat gain beyond thymidine NRTI discontinuation, although this strategy decreased plasma HDL cholesterol and caused changes in subcutaneous fat gene expression that may be associated with increased insulin resistance.

Tratamiento quirúrgico de las roturas del tendón distal del bíceps con anclajes óseos por abordaje anterior único / Surgical treatment of distal biceps tendon ruptures with bone anchors using a single anterior approach

Objetivo. Valorar los resultados clínicos de la reinserción del tendón distal del bíceps con anclajes óseos por vía anterior. Material y métodos. Estudio retrospectivo de 79 pacientes en los que se realizó la reinserción del tendón distal del bíceps con anclajes metálicos óseos por vía anterior. El promedio de edad fue de 46 años (rango, 32-64). En el 57% de los casos se utilizaron dos anclajes y en el 43% un anclaje. Todos los pacientes realizaron el mismo protocolo postoperatorio. Se hizo una valoración funcional con la escala funcional MEPS. El promedio de tiempo de seguimiento fue de 20 meses (rango: 12-28). Resultados. La puntuación final media de la escala MEPS fue de 95,2 pts (DE 6,8). El 94% de los pacientes tuvieron resultado excelente y bueno y en el 6% el resultado fue aceptable y pobre. No se observaron diferencias al comparar el resultado funcional entre los pacientes en los que se utilizó un anclaje (96 puntos) con aquellos en los que se utilizaron dos anclajes (95 puntos), p = 0,5. El tiempo promedio de baja laboral fue de 14 semanas (rango, 5-56) pudiendo reincorporarse a su trabajo el 100% de los pacientes. La incidencia de complicaciones fue del 13%, siendo la más frecuente la neuroapraxia del nervio cutáneo antebraquial lateral. Conclusiones. La reinserción anatómica del tendón distal del bíceps con anclajes óseos por vía anterior única es una técnica segura que ofrece resultados funcionales excelentes y buenos a mediano plazo (AU)

Purpose. To evaluate the clinical results of reinsertion of the distal biceps tendon with anterior bone anchors. Material and methods. A retrospective study was conducted on 79 patients who underwent reinsertion of the distal biceps tendon with anterior bone anchors. The mean age was 46 years (range, 32-64). Two anchors were used in 57% of cases, and one anchor in 43%. The same postoperative protocol was performed in all patients. Functional assessment was made using a Motor evoked potentials (MEPS) functional scale. The mean of follow-up time was 20 months (range, 12 -28 months). Results. The final mean of MEPS score was 95.2 points (SD 6.8). Almost all (94%) patients had excellent and good results, and 6% a bad result. No differences were observed when comparing functional outcome among patients in whom one anchor was used (96 points) with those in whom two anchors were used (95 points), p = 0.5. The mean time off work was 14 weeks (range, 5-56) and 100% of patients were able to return to work. The incidence of complications was 13%. The most frequent was neuropraxia of the lateral antebrachial cutaneous nerve. Conclusion. The anatomic re-attachment of the distal biceps tendon with bone anchors using a single anterior approach is a safe technique that offers excellent and good functional results in the medium term (AU)

[Surgical treatment of distal biceps tendon ruptures with bone anchors using a single anterior approach]. / Tratamiento quirúrgico de las roturas del tendón distal del bíceps con anclajes óseos por abordaje anterior único.

PURPOSE: To evaluate the clinical results of reinsertion of the distal biceps tendon with anterior bone anchors. MATERIAL AND METHODS: A retrospective study was conducted on 79 patients who underwent reinsertion of the distal biceps tendon with anterior bone anchors. The mean age was 46 years (range, 32-64). Two anchors were used in 57% of cases, and one anchor in 43%. The same postoperative protocol was performed in all patients. Functional assessment was made using a Motor evoked potentials (MEPS) functional scale. The mean of follow-up time was 20 months (range, 12 -28 months). RESULTS: The final mean of MEPS score was 95.2 points (SD 6.8). Almost all (94%) patients had excellent and good results, and 6% a bad result. No differences were observed when comparing functional outcome among patients in whom one anchor was used (96 points) with those in whom two anchors were used (95 points), p=0.5. The mean time off work was 14 weeks (range, 5-56) and 100% of patients were able to return to work. The incidence of complications was 13%. The most frequent was neuropraxia of the lateral antebrachial cutaneous nerve. CONCLUSION: The anatomic re-attachment of the distal biceps tendon with bone anchors using a single anterior approach is a safe technique that offers excellent and good functional results in the medium term.

Documento de consenso sobre el manejo de la patología renal en pacientes con infección por VIH / Consensus document on the management of renal disease in HIV-infected patients

OBJETIVO: Actualizar las recomendaciones sobre la evaluación y el manejo de la afectación renal en pacientes con infección por el virus de la inmunodeficiencia humana (VIH). MÉTODOS: Este documento ha sido consensuado por un panel de expertos del Grupo de Estudio de Sida (GESIDA) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), de la Sociedad Española de Nefrología (S.E.N.) y de la Sociedad Española de Química Clínica y Patología Molecular (SEQC). Para la valoración de la calidad de la evidencia y la graduación de las recomendaciones se ha utilizado el sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTADOS: La evaluación renal debe incluir la medida de la concentración sérica de creatinina, la estimación del filtrado glomerular (ecuación chronic kidney disease epidemiological collaboration [CKD-EPI]), la medida del cociente proteína/creatinina en orina y un sedimento urinario. El estudio básico de la función tubular ha de incluir la concentración sérica de fosfato y la tira reactiva de orina (glucosuria). En ausencia de alteraciones, el cribado será anual. En pacientes tratados con tenofovir o con factores de riesgo para el desarrollo de enfermedad renal crónica (ERC), se recomienda una evaluación más frecuente. Se debe evitar el uso de antirretrovirales potencialmente nefrotóxicos en pacientes con ERC o factores de riesgo para evitar su progresión. En este documento se revisan las indicaciones de derivación del paciente a Nefrología y las de la biopsia renal, así como las indicaciones y la evaluación y el manejo del paciente en diálisis o del trasplante renal. CONCLUSIONES: La función renal debe monitorizarse en todos los pacientes con infección por el VIH y este documento pretende optimizar la evaluación y el manejo de la afectación renal.(AU)

OBJECTIVE: To update the 2010 recommendations on the evaluation and management of renal disease in HIV-infected patients. METHODS: This document was approved by a panel of experts from the AIDS Working Group (GESIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Nephrology (S.E.N.), and the Spanish Society of Clinical Chemistry and Molecular Pathology (SEQC). The quality of evidence and the level of recommendation were evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, Urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glucosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document advises on the optimal time for referral of a patient to the nephrologist and provides indications for renal biopsy. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. CONCLUSIONS: Renal function should be monitored in all HIV-infected patients. The information provided in this document should enable clinicians to optimize the evaluation and management of HIV-infected patients with renal disease.(AU)

Monaural conductive hearing loss alters the expression of the GluA3 AMPA and glycine receptor α1 subunits in bushy and fusiform cells of the cochlear nucleus.

The impact of conductive hearing loss (CHL), the second most common form of hearing loss, on neuronal plasticity in the central auditory pathway is unknown. After short-term (1 day) monaural earplugging, the GluA3 subunits of the AMPA receptor (AMPAR) are upregulated at auditory nerve synapses on the projection neurons of the cochlear nucleus; glycine receptor α1 (GlyRα1) subunits are downregulated at inhibitory synapses in the same neuronal population. These data suggest that CHL affects receptor trafficking at synapses. We examined the impact of 7 days of CHL on the general expression of excitatory and inhibitory receptors by quantitative biochemistry and immunohistochemistry, using specific antibodies to detect AMPAR subunits (GluA1, GluA2, GluA2/3, and GluA4), GlyRα1, and the GABA(A) receptor subunits ß2/3. Following monaural earplugging and an elevation of the hearing threshold by approximately 35 dB, the immunolabeling of the antibody for the GluA2/3 subunits but not the GluA2 subunit increased on bushy cells (BCs) and fusiform cells (FCs) of the ipsilateral ventral and dorsal cochlear nuclei. These same cell types showed a downregulation of the GlyRα1 subunit. Similar results were observed in the contralateral nuclei. The expression levels of GABA(A) ß2/3 were unchanged. These findings suggest that, following longer periods of monaural conductive hearing loss, the synthesis and subsequent composition of specific glutamate and glycine receptors in projection neurons and their synapses are altered; these changes may contribute to abnormal auditory processing.

Mitochondrial DNA (mtDNA) and schizophrenia.

The poorly understood aetiology of schizophrenia is known to involve a major genetic contribution even though the genetic factors remain elusive. Most genetic studies are based on Mendelian rules and focus on the nuclear genome, but current studies indicate that other genetic mechanisms are probably involved. This review focuses on mitochondrial DNA (mtDNA), a maternally inherited, 16.6-Kb molecule crucial for energy production that is implicated in numerous human traits and disorders. The aim of this review is to summarise the studies that have explored mtDNA in schizophrenia patients and those which provide evidence for its implication in this illness. Alterations in mitochondrial morphometry, brain energy metabolism, and enzymatic activity in the mitochondrial respiratory chain suggest a mitochondrial dysfunction in schizophrenia that could be related to the genetic characteristics of mtDNA. Moreover, evidence of maternal inheritance and the presence of schizophrenia symptoms in patients suffering from a mitochondrial disorder related to an mtDNA mutation suggest that mtDNA is involved in schizophrenia. The association of specific variants has been reported at the molecular level; however, additional studies are needed to determine whether the mitochondrial genome is involved in schizophrenia.

Short communication: Biological and genetic characterization of HIV type 1 subtype B and nonsubtype B transmitted viruses: usefulness for vaccine candidate assessment.

Due to the extraordinary degree of genetic diversity of HIV-1 and the structural complexity of its envelope glycoproteins, designing an effective vaccine is difficult, requiring the development of viral reagents to assess vaccine-elicited neutralizing antibodies. The aim of this study was to improve on our previously developed panel of HIV-1 strains of different genetic forms, focusing on strains from acute and recently acquired infections as the most representative of the transmitted viruses. HIV-1 primary isolates were expanded in peripheral blood mononuclear cells. Viral stocks of 40 ml each were produced. Syncytium-inducing (SI) phenotype, coreceptor use, and TCID(50)/ml were determined. Near full-length HIV-1 genomes were amplified by RT-nested PCR in four overlapping segments. Phylogenetic analyses were performed with neighbor-joining trees and bootscanning. Forty-four HIV-1 strains were included in the panel. Twenty-four (54.1%) strains were from early infections (16 acute and 8 recent); of them, 21 (87%) were sexually transmitted. NSI/R5 phenotype was detected in 37 (84.1%) viruses and SI/R5,X4 in another 7 (15.9%). TCID(50)/ml ranged between 10(4) and 10(6.6). Twelve different genetic forms constituted this panel: subtypes A1, B, C, F1, and G; circulating recombinant forms CRF02_AG, CRF14_BG, and CRF24_BG; and unique recombinant forms CRF02_AG/A3, BF1, CRF12_BF/B, and DF1G. In conclusion, in this study, we report the development of a comprehensive and well-characterized panel of HIV-1 isolates for assessing neutralization in HIV vaccine research. This panel is available for distribution through the Programme EVA Centre for AIDS Reagents, National Institute for Biological Standard and Control (NIBSC).

Actividades de aprendizaje y evaluación a través del campus virtual. Experiencia en Fisiología y Fisiopatología I del Grado de Farmacia / A web-based learning platform for activities and assessment. An experiment in teaching physiology and pathophysiology in a degree course in Pharmacy

Nuestro objetivo consiste en fomentar, entre alumnos internos del Departamento de Fisiología, el autoaprendizaje, el trabajo autónomo y en equipo, espíritu crítico y habilidad para buscar y analizar información. A la vez se pretende iniciar a estos alumnos en los sistemas de transferencia de resultados de la investigación básica a la investigación aplicada.Para ello a los alumnos se les proporciona materiales que contienen información sobre las materias objeto de aprendizaje y enlaces a diferentes sitios webs de interés relacionados con el tema. En ellos se promueve la exposición de trabajos y la participación en jornadas especializadas.El uso de estos materiales bajo supervisión del profesorado, ha permitido la mejora del conocimiento en Fisiología y la creación de equipos especializados en diferentes aspectos de la Fisiología. Además, la transferencia de información entre alumnos, ha propiciado que puedan adquirir una visión clara y amplia sobre qué es un trabajo de investigación básica o un trabajo de investigación aplicada, así como la importancia del trabajo en equipo, lo que ha posibilitado que pudieran diseñar pequeños experimentos y estudiar su aplicabilidad.Al final del periodo de formación, los alumnos demostraron haber adquirido las competencias genéricas CG1, CG3, CG5, CG6, CG11, CG13 y CG15 incluidas en la ficha Verifica para el Grado en Farmacia, así como las competencias específicas para el módulo 5 (Medicina y Farmacología) CEM5.8, CEM5.9 y CEM5.11, concluyendo así que la aplicación de métodos de enseñanza basados en el autoaprendizaje (bajo supervisión de equipos docentes) constituye una excelente herramienta para la promoción de la adquisición de competencias generales y específicas en el Grado en Farmacia(AU)

Our goal is to motivate students of physiology in the area of independent study, working alone and in groups, enabling them to develop a critical spirit and skills, and to be capable of seeking and analyzing information. At the same time, we seek to introduce these students to the systems of transferring results from basic to applied research. For this purpose, the students were provided with materials containing information on subjects appropriate for independent study, and links to various websites of interest related to the subject. The teaching staff promoted the presentation of students’ projects, and encouraged them to participate in specialized workshops. The use of these materials, under the teachers’ supervision, has led to the students acquiring greater knowledge of physiology, and to the creation of teams specialized in diverse aspects of the subject. Moreover, the transfer of information among students has made it possible for them to acquire a keen, broad-ranging view of what isinvolved in a basic or applied research project, and to understand the importance of working as part of a team. Thus, the students designed small-scale experiments and studied their applicability.By the end of this training period, the students showed they had acquired the generic skills 1, 3, 5, 6, 11, 13 and 15 required to be awarded a Degree in Pharmacy, as well as the specific skills necessary for Module 5 (Medicine and Pharmacology), numbers 5.8, 5.9 and 5.11. Accordingly, it can be concluded that the application of teaching methods based on independent study (under the supervision of teaching staff) constitutes an excellent tool for promoting students’ acquisition of general and specific skills as part of their studies for the Pharmacy Degree(AU)

Critical role of ribavirin for the achievement of early virological response to HCV therapy in HCV/HIV-coinfected patients.

The response to hepatitis C virus (HCV) therapy seems to be lower in HCV/HIV-coinfected patients than in HCV-monoinfected individuals. Given that most pivotal trials conducted in coinfected patients have used the combination of pegylated interferon (pegIFN) along with fixed low doses (800 mg/day) of ribavirin (RBV), it is unclear whether HIV itself and/or suboptimal RBV exposure could explain this poorer outcome. Two well-defined end points of early virological response were evaluated in Peginterferon Ribavirina España Coinfección (PRESCO), a multicentre trial in which the combination of pegIFN plus RBV (1000 mg if body weight <75 kg and 1200 mg if >75 kg) was prescribed to coinfected patients. For comparisons, we used unpublished data from early kinetics in two other large trials, one performed in HIV-negative patients [Pegasys International Study Group (PISG)] in which RBV 1000-1200 mg/day was used and another [AIDS Pegasys Ribavirin Coinfection Trial (APRICOT)] in which HIV-positive patients received fixed low RBV doses (800 mg/day). A total of 348 HCV/HIV-coinfected patients from the PRESCO trial were analysed as well as all patients treated with pegIFN plus RBV, who completed 12 weeks of therapy in the comparative studies (435 in PISG and 268 in APRICOT). Negative serum HCV-RNA at week 4 (which has the highest positive predictive value of sustained virological response, SVR) was attained in 33.3%, 31.2% and 13% of treated patients with HCV genotype 1, respectively, in PRESCO, PISG and APRICOT. For HCV genotypes 2/3, responses were 83.7%, 84.2% and 37%, respectively. A decline lower than 2 log(10) at week 12 (which has the highest negative predictive value of SVR) was seen in 25.5%, 19.5% and 37% of HCV genotype-1-infected patients, and in 2.1%, 2.9% and 12% of genotypes-2/3-infected patients, respectively. Prescription of high RBV doses enhances the early virological response to HCV therapy in HCV/HIV-coinfected patients, with results approaching those seen in HCV-monoinfected patients.

Recommendations from SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA on nutrition in the HIV-infected patient.

OBJECTIVE: to make recommendations on the approach to nutritional problems (malnutrition, cachexia, micronutrient deficiency, obesity, lipodystrophy) affecting HIV-infected patients. METHODS: these recommendations have been agreed upon by a group of expertes in the nutrition and care of HIV-infected patients, on behalf of the different groups involved in drafting them. Therefore, the latest advances in pathophysiology, epidemiology, and clinical care presented in studies published in medical journals or at scientific meetings were evaluated. RESULTS: there is no single method of evaluating nutrition, and diferent techniques--CT, MRI, and DXA--must be combined. The energy requirements of symptomatic patients increase by 20-30%. There is no evidence to support the increase in protein or fat intake. Micronutrient supplementation in only necessary in special circumstances (vitamin A in children and pregnant woman). Aerobic and resistance excercise is beneficial both for cardiovascular health and for improving lean mass and muscular strength. It is important to follow the rules of food safety at every stage in the chain. Therapeutic intervention in anorexia and cachexia must be tailored, by combining nutritional and pharmacological support (appetite stimulants, anabolic steroids, and, in some cases, testosterone). Artificial nutrition (oral supplementation, enteral or parenteral nutrition) is safe and efficacious, and improves nutritional status and response to therapy. In children, nutritional recommendations must be made early, and are a necessary component of therapy. CONCLUSION: appropriate nutritional evaluation and relevant therapeutic action are an essential part of the care of HIV-infected patients.

Recommendations from SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/ GESIDA on nutrition in the HIV-infected patient / Recomendaciones de SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA sobre nutrición en el paciente con infección por VIH

Objective: to make recommendations on the approach to nutritional problems (malnutrition, cachexia, micronutrient deficiency, obesity, lipodystrophy) affecting HIV-infected patients. Methods: these recommendations have been agreed upon by a group of expertes in the nutrition and care of HIV-infected patients, on behalf of the different groups involved in drafting them. Therefore, the latest advances in pathophysiology, epidemiology, and clinical care presented in studies published in medical journals or at scientific meetings were evaluated. Results: there is no single method of evaluating nutrition, and diferent techniques —CT, MRI, and DXA— must be combined. The energy requirements of symptomatic patients increase by 20-30%. There is no evidence to support the increase in protein or fat intake. Micronutrient supplementation in only necessary in special circumstances (vitamin A in children and pregnant woman). Aerobic and resistance excercise is beneficial both for cardiovascular health and for improving lean mass and muscular strength. It is important to follow the rules of food safety at every stage in the chain. Therapeutic intervention in anorexia and cachexia must be tailored, by combining nutritional and pharmacological support (appetite stimulants, anabolic steroids, and, in some cases, testosterone). Artificial nutrition (oral supplementation, enteral or parenteral nutrition) is safe and efficacious, and improves nutritional status and response to therapy. In children, nutritional recommendations must be made early, and are a necessary component of therapy. Conclusion: appropriate nutritional evaluation and relevant therapeutic action are an essential part of the care of HIV-infected patients

Objetivo: realizar recomendaciones sobre el abordaje de los problemas nutricionales (malnutrición, caquexia, déficit de micronutrientes, obesidad, lipodistrofia) presentes en la infección VIH. Métodos: estas recomendaciones se han consensuado por un grupo de expertos en nutrición y en atención al enfermo VIH, en representación de las distintas sociedades firmantes. Para ello se han revisado los últimos avances fisiopatológicos, epidemiológicos y clínicos recogidos en estudios publicados en revistas médicas o presentados en congresos. Resultados: no existe un único método de valoración nutricional, debiendo combinarse cuestionarios y técnicas como TAC, RNM y DEXA. Los requerimientos energéticos en enfermos sintomáticos aumentan en un 20-30%. No existe evidencia que respalde el incremento del aporte proteico o graso. La suplementación de micronutrientes sólo es necesaria en circunstancias especiales (Vitamina A en niños y embarazadas). El ejercicio aeróbico de resistencia es beneficioso tanto para la salud cardiovascular como para mejorar la masa magra y la fuerza muscular. Es importante seguir normas de seguridad en toda la cadena alimentaria. La intervención terapéutica en la anorexia y caquexia debe ser individualizada, combinando soporte nutricional y farmacológico (estimulantes del apetito, agentes anabolizantes y testosterona en algún caso). La nutrición artificial (suplementación oral, nutrición enteral o parenteral) es segura y eficaz, mejorando el estado nutricional y la respuesta al tratamiento. En niños, las recomendaciones nutricionales deben ser muy precoces, formando necesariamente parte del tratamiento. Conclusión: La adecuada valoración nutricional y la pertinente actuación terapéutica son parte esencial de la asistencia del enfermo VIH

Clustered and non-clustered GABAA receptors in cultured hippocampal neurons.

In cultured hippocampal neurons, gamma2 subunit-containing GABA(A) Rs form large postsynaptic clusters at GABAergic synapses and small clusters outside GABAergic synapses. We now show that a pool of non-clustered gamma2 subunit-containing GABA(A) Rs are also present at the cell surface. We also demonstrate that myc- or EGFP-tagged gamma2, alpha2, beta3 or alpha1 subunits expressed in these neurons assemble with endogenous subunits, forming GABA(A) Rs that target large postsynaptic clusters, small clusters outside GABAergic synapses or a pool of non-clustered surface GABA(A) Rs. In contrast, myc- or EGFP-tagged delta subunits only form non-clustered GABA(A) Rs, which can be induced to form clusters by antibody capping. A myc-tagged chimeric gamma2 subunit possessing the large intracellular loop (IL) of the delta-subunit IL (myc gamma2S/delta-IL) assembled into GABA(A) Rs, but it did not form clusters, therefore behaving like the delta subunit. Thus, the large intracellular loops of gamma2 and delta play an important role in determining the synaptic clustering/non-clustering capacity of the GABA(A) Rs.

Long-term monitoring of genotypic and phenotypic resistance to T20 in treated patients infected with HIV-1.

The aim of this study was to investigate the susceptibility to T20 and the dynamics of amino acid changes in HR1 and HR2 of gp41 of HIV-1 obtained from plasma, peripheral blood mononuclear cells (PBMC), and primary isolates (PI) in four highly antiretroviral-experienced patients. These patients received T20 plus an antiretroviral regimen and were followed-up over a period of 40-72 weeks. In one non-responder patient, N43D substitution was detected at 12 weeks of treatment, in association with a value of T20-IC50 of 10 microg/ml (10-fold increase). Double mutations N42T + N43D were observed in plasma RNA at 32 weeks and remained detectable up to 16 weeks after the withdrawal of the drug. The S138A substitution in HR2 was observed in plasma RNA at 32 weeks, and both in plasma RNA and in PI DNA at 40 weeks, associated with an increase of the T20-IC50 to 25 microg/ml (25-fold increase). Mutations V101G and E137K, not reported previously, were also observed in the HR2 region. Whether these new substitutions play a role in T20 resistance needs to be examined. In three temporary responders, coinciding with viral load rebound, G36D, and N42T substitutions were observed at 12, 24, and 40 weeks. G36D mutation was associated with a value of T20-IC50 of 5 microg/ml. The HR2 S138A mutation was detected after the detection of HR1 substitutions and was associated with an increase in the level of T20-IC50 to 125 microg/ml (125-fold increase) All these data reinforce the role of gp41 amino acids 36-45 and the potential influence of the HR2 S138A mutation in the genotypic/phenotypic resistance to T20.

Biochemical analysis of GABA(A) receptor subunits alpha 1, alpha 5, beta 1, beta 2 in the hippocampus of patients with Alzheimer's disease neuropathology.

Alzheimer's disease (AD) is characterized by selective vulnerability of specific neuronal populations within particular brain regions. For example, hippocampal glutamatergic cell populations within the CA1/subicular pyramidal cell fields have been found to be particularly vulnerable early in AD progression. In contrast, hippocampal GABA-ergic neurons and receptors appear resistant to neurodegeneration. Despite relative sparing of GABA(A) receptors in AD, it is possible that the specific subunit composition of these receptors may undergo alterations with disease progression. In order to address this issue, we employed quantitative Western blot analysis to examine protein levels of GABA(A) receptor subunits alpha 1, alpha 5, beta 1, beta 2 in the hippocampus of subjects displaying increasing severity of AD neuropathology. Subjects were categorized into three groups based upon Braak staging pathologic criteria: pathologically mild (stages I/II, n=9); moderate (stages III/IV, n=8); and severe (stages V/VI, n=7). Across all subject groups, levels of subunit protein were heterogeneously distributed throughout the five hippocampal subregions analyzed (subiculum, CA1-3, dentate gyrus). Statistical analyses revealed differential preservation of GABA(A) receptor subunits in AD. In particular, alpha 1, beta 1, and beta 2 displayed little difference in protein levels among pathologically mild, moderate, and severe subject groups. In contrast, although relatively modest, protein levels of the alpha 5 subunit were significantly reduced between subjects with severe neuropathology compared with pathologically mild subjects (13.5% reduction). Collectively, our data provide evidence for heterogeneous distribution and relative sparing of GABA(A) receptor subunits in the hippocampus of AD patients.

Cancer antigen 125 associated with multiple benign and malignant pathologies.

BACKGROUND: Cancer antigen (CA) 125 tumor-associated antigen is a high molecular glycoprotein used for follow-up of epithelial ovarian cancer. The test is often requested as a differential diagnosis in patients with pleural or peritoneal fluid. This study analyzes the prevalence of CA-125 increases in a population of patients attending a general hospital and discusses the possible clinical implications of increased levels. METHODS: On 4 different days, 380 CA-125 assays were performed in randomly selected patients attending our hospital. Serum CA-125 was measured with a commercial enzyme immunoassay, and clinical records were reviewed for assessment of clinical parameters. RESULTS: Sixty-one patients (16%) had increased CA-125. The pathologies of these patients were heart failure in 9 (14.7%), lung disease 11 (18%), hepatic cirrhosis in 7 (11.4%), malignant tumors in 9 (14.7%), intra-abdominal nonhepatic disease in 6 (10%), previous surgery in 17 (27.8%), and miscellaneous in 2 (3%). Effusions were seen in 34 patients (55.7%). CONCLUSIONS: Our data confirm the variety of benign and malignant pathologies coursing with increased CA-125. Cardiovascular and chronic liver disease were the most frequent diagnoses in patients with increased CA-125; this supports the opinion that CA-125 lacks utility as a marker for malignancy. CA-125 could have a role in the follow-up of cardiovascular, hepatic, and tumoral diseases with serosal involvement.

[Systemic inflammation during exacerbations of chronic obstructive pulmonary disease]. / Inflamación sistémica durante las agudizaciones de la enfermedad pulmonar obstructiva crónica.

OBJECTIVE: The circulating blood levels of several inflammatory cytokines and acute phase proteins are higher in patients with stable chronic obstructive pulmonary disease (COPD). However, whether or not these inflammatory markers increase during COPD exacerbation or are modified by corticosteroid treatment has not been investigated. The objective of this study was therefore 1) to describe changes in several inflammatory markers in systemic circulation during COPD exacerbation, and 2) to assess the potential effects of corticosteroid treatment during exacerbation. METHODS: Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP) were determined for 10 patients (65 2 years old) with severe COPD (FEV1 35 4% reference) who were hospitalized for acute respiratory failure (PaO2 57 2 mm Hg; PaCO2 48 3 mm Hg). Blood samples were obtained in the emergency room (before starting intravenous corticosteroid treatment), during the first 24 hours of admission, upon discharge and two months later. Eight healthy non-smokers of a similar age (54 3 years) were also studied as control subjects. RESULTS: The COPD patients had higher concentrations of IL-6 (5.1 1.6 vs. 1.8 0.5 pg/mL, p < 0.05) and CRP (2.2 0.4 vs. 0.6 0.2 mg/dL, p < 0.005) than did controls, but the concentrations of IL-8 were similar (29 11.3 vs. 34.7 10.3 pg/mL, p = ns). No statistically significant changes were seen either during recovery, in spite of intravenous corticosteroid treatment, or two months after discharge.The ELISA test used was unable to detect TNF-alpha in any of the samples obtained from either patients or controls. CONCLUSION: The results show that 1) there is evidence of systemic inflammation during exacerbation of COPD, and 2) such systemic inflammation does not appear to be influenced significantly by intravenous corticosteroid treatment.