Liver-related mortality and hospitalizations attributable to chronic hepatitis C virus coinfection in persons living with HIV.

OBJECTIVES: The aim of this study was to compare liver-related mortality and liver-related hospitalizations for persons living with HIV (PLWH) with and without hepatitis C virus (HCV) exposure, and to estimate the fraction of liver disease attributable to chronic HCV coinfection. METHODS: An ambispective cohort study followed PLWH between 1993 and 2014. PLWH were classified into three groups: those who were HIV-monoinfected, those who cleared HCV spontaneously and those with chronic HCV coinfection. Liver-related mortality was estimated for the three groups and compared with the adjusted standardized mortality ratio. RESULTS: Data for 2379 PLWH were included in the study (1390 monoinfected individuals, 146 spontaneous HCV resolvers and 843 with chronic HCV coinfection). Global mortality was 33.8%, 21.4% of which was liver-related. Patients who died from liver-related causes were mostly on antiretroviral therapy and had an undetectable HIV viral load when they died. The liver-related mortality rate in those with chronic HCV coinfection was 10.01 per 1000 patient-years vs. 3.84 per 1000 patient-years in the HIV-monoinfected group (P < 0.001). The adjusted standardized mortality ratio in the chronically HCV-coinfected group was 4.52 (95% confidence interval 2.98-5.86). The fractions of liver-related mortality and liver-related hospitalizations attributable to chronic HCV coinfection were 0.61 and 0.74, respectively. There were no differences in liver-related events between HIV-monoinfected individuals and those who spontaneously cleared HCV. CONCLUSIONS: Chronic HCV infection increases the risk of liver-related mortality and liver-related hospitalizations in PLWH, despite good control of HIV infection. Sixty per cent of liver-related mortality in chronically HCV-coinfected PLWH could be attributable to chronic HCV infection. The effect of mass HCV eradication with new therapies should be evaluated.

Genotypic tropism testing of proviral DNA to guide maraviroc initiation in aviraemic subjects: 48-week analysis of results from the PROTEST study.

OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL. RESULTS: Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty-four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow-up, one developed an adverse event (rash), two died from non-study-related causes, and five developed protocol-defined virological failure. CONCLUSIONS: Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.

Trends on epidemiological, virological, and clinical features among newly diagnosed HIV-1 persons in Northwest Spain over the last 10 years.

To describe temporal trend and characteristics of newly HIV-diagnosed patients in a medical care area in Northwest Spain over the last 10 years. All newly diagnosed patients for HIV-infection from 2004 to 2013 at a reference medical care area in Northwest of Spain were identified. Epidemiological, virological, immunological, and clinical data, as well as HIV genotype and drug resistance information were recorded. A total of 565 newly HIV-diagnosed patients were identified. The number of new cases increased in the last 5 years (66 cases/year). Overall, 53.1% had a median CD4 counts < 350 cells/µl and 33.6% had an AIDS defining criteria. Non-B variants were found in 34.4% of patients being subtype F (25.8%) the most common non-B subtype. The rate of transmitted drug resistance (TDR) over the study period was 3.7%, but a decreased to 2.6% was observed in the last 5 years. The most prevalent TDR mutations were: T215 revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M (0.3%), for PIs. Overall, 73.2% of patients started antiretroviral treatment and 9.9% of patients died during follow-up. The number of newly HIV diagnosed patients increased since year 2009. There is a high prevalence of late diagnosis (53%) and 33% had an AIDS defining criteria. Interestingly, the most prevalent non-B subtype in our population was F (25.8%). These findings support the need to facilitate the access for HIV testing to reduce the rate of late HIV diagnosis, improve the clinical outcome and prevent HIV transmission.

Suero lácteo, generalidades y potencial uso como fuente de calcio de alta biodisponibilidad / Whey, generalities and potential use as source of calcium from high bioavailability

The whey is defined as a dairy product obtained during the manufacturing of cheese. It is not a substitute for cow's milk because it is a fraction of it. However, the whey contains nutrients and compounds with potential nutritional and functional benefits. Approximately 90% of calcium from milk is present in whey. Some scientific evidence suggests that calcium from whey is more bioavailable, even overpassing the mineral salts that are used for food fortification or nutritional supplements. The enhanced bioavailability is associated with the nutrients present within, especially proteins and lactose. It has also been shown that the technology used for the processing of whey can involve greater or lesser concentration and bioavailability of calcium. Human Investigations are needed to confirm these hypotheses.

El lactosuero o suero de leche se define como un subproducto lácteo obtenido durante la fabricación del queso que aunque no constituye un sustituto integral de la leche de vaca por ser una fracción de la misma, contiene nutrientes y compuestos con potenciales beneficios nutricionales y funcionales. El calcio es uno de los nutrientes que puede estar en cantidades considerables, alcanzando hasta el 90% de la concentración inicial del mineral en la leche. Existe evidencia que el calcio del suero lácteo es de mayor biodisponibilidad, incluso superando a las sales minerales que se utilizan para fortificación de alimentos o como suplementos nutricionales. La mayor biodisponibilidad se asocia con el contenido de nutrientes presente en el mismo, especialmente proteínas y lactosa. También se ha demostrado que la tecnología utilizada para el procesamiento del suero puede implicar mayor o menor concentración y biodisponibilidad de calcio en suero. Se requieren investigaciones en humanos para confirmar estas hipótesis.

Efectos clínicos de los probióticos: qué dice la evidencia / Clinical effects of probiotics: what does the evidence says

The scientific advances related to healthy properties of the probiotics have increased in a significant form. It is evident the positive effects on physiological functions. Considering the relevance in these advances, this review presents a summary of the scientific evidence supporting the principal biological effects of the probiotics in digestive function, systemic immune reply and lipid profile, pathologies relevant in the functional food development.

Los avances científicos en relación a las propiedades saludables de los probióticos han aumentado significativamente, mostrando grandes avances en su efecto sobre diferentes funciones fisiológicas. Los hallazgos demuestran que las acciones a nivel fisiológico o clínico son cepa específicos, aspecto que toma cada día mayor relevancia en el desarrollo de alimentos funcionales asociados a probióticos. Teniendo en cuenta la importancia de estos avances, este artículo presenta de forma resumida evidencia que sustenta los principales efectos clínicos atribuidos a los probióticos en enfermedades relacionadas con el sistema digestivo, función inmune y metabolismo lipídico, patologías en las cuales el desarrollo de alimentos funcionales se ha venido enfocando.

[Family impact of rotavirus gastroenteritis in children under two years]. / Impacto familiar de la gastroenteritis por rotavirus en menores de dos años.

INTRODUCTION: Acute gastroenteritis (AGE) in infants has a significant impact on the quality of life of their parents. MATERIAL AND METHODS: Cross-sectional study on the sociological family impact related to rotavirus AGE in children under 2 years. The study was carried out in 25 hospitals and 5 primary care centres in Spain. Sociodemographic, epidemiological and clinical data were recorded, as well as the symptomatology of AGE and its severity measured by the Clark scale. Stool samples were tested to determine rotavirus positive (RV+) or negative (RV-). The parents were asked to complete a a family impact questionnaire. RESULTS: Stool specimens were tested in 1087 AGE cases (584 RV+ vs 503 RV-). The 99.5 % of parents whose children were RV+ reported more worries vs. the 97.7 % of RV-, and RV+ had a higher importance score (p < 0.05). A higher percentage of RV+ parents and those with a high importance score reported more time dedicated to dehydration treatment (p < 0.05). The 82.5 % vs. 73.9 % had disruption of their household tasks, with more importance scores (p < 0.05). RV+ had a higher percentage and importance score than RV- ones in all aspects of their child's AGE symptoms, except loss of appetite. CONCLUSION: AGE produces important dysfunctional experiences in daily family life. According to parental perceptions, RV+ produces greater worries and dysfunctions in child behaviour.

The inferior colliculus of the rat: quantitative immunocytochemical study of GABA and glycine.

Both GABA and glycine (Gly) containing neurons send inhibitory projections to the inferior colliculus (IC), whereas inhibitory neurons within the IC are primarily GABAergic. To date, however, a quantitative description of the topographic distribution of GABAergic neurons in the rat's IC and their GABAergic or glycinergic inputs is lacking. Accordingly, here we present detailed maps of GABAergic and glycinergic neurons and terminals in the rat's IC. Semithin serial sections of the IC were obtained and stained for GABA and Gly. Images of the tissue were digitized and used for a quantitative densitometric analysis of GABA immunostaining. The optical density, perimeter, and number of GABA- and Gly immunoreactive boutons apposed to the somata were measured. Data analysis included comparisons across IC subdivisions and across frequency regions within the central nucleus of the IC. The results show that: 1) 25% of the IC neurons are GABAergic; 2) there are more GABAergic neurons in the central nucleus of the IC than previously estimated; 3) GABAergic neurons are larger than non-GABAergic; 4) GABAergic neurons receive less GABA and glycine puncta than non-GABAergic; 5) differences across frequency regions are minor, except that the non-GABAergic neurons from high frequency regions are larger than their counterparts in low frequency regions; 6) differences within the laminae are greater along the dorsomedial-ventrolateral axis than along the rostrocaudal axis; 7) GABA and non-GABAergic neurons receive different numbers of puncta in different IC subdivisions; and 8) GABAergic puncta are both apposed to the somata and in the neuropil, glycinergic puncta are mostly confined to the neuropil.

Trichostatin A effects in different drug-resistant tumor cell lines

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A computational algorithm for computing nonlinear auditory frequency selectivity.

Computational algorithms that mimic the response of the basilar membrane must be capable of reproducing a range of complex features that are characteristic of the animal observations. These include complex input output functions that are nonlinear near the site's best frequency, but linear elsewhere. This nonlinearity is critical when using the output of the algorithm as the input to models of inner hair cell function and subsequent auditory-nerve models of low- and high-spontaneous rate fibers. We present an algorithm that uses two processing units operating in parallel: one linear and the other compressively nonlinear. The output from the algorithm is the sum of the outputs of the linear and nonlinear processing units. Input to the algorithm is stapes motion and output represents basilar membrane motion. The algorithm is evaluated against published chinchilla and guinea pig observations of basilar membrane and Reissner's membrane motion made using laser velocimetry. The algorithm simulates both quantitatively and qualitatively, differences in input/output functions among three different sites along the cochlear partition. It also simulates quantitatively and qualitatively a range of phenomena including isovelocity functions, phase response, two-tone suppression, impulse response, and distortion products. The algorithm is potentially suitable for development as a bank of filters, for use in more comprehensive models of the peripheral auditory system.

A human nonlinear cochlear filterbank.

Some published cochlear filterbanks are nonlinear but are fitted to animal basilar membrane (BM) responses. Others, like the gammatone, are based on human psychophysical data, but are linear. In this article, a human nonlinear filterbank is constructed by adapting a computational model of animal BM physiology to simulate human BM nonlinearity as measured by psychophysical pulsation-threshold experiments. The approach is based on a dual-resonance nonlinear type of filter whose basic structure was modeled using animal observations. In modeling the pulsation threshold data, the main assumption is that pulsation threshold occurs when the signal and the masker produce comparable excitation, that is the same filter output, at the place of the BM best tuned to the signal frequency. The filter is fitted at a discrete number of best frequencies (BFs) for which psychophysical data are available for a single listener and for an average response of six listeners. The filterbank is then created by linear regression of the resulting parameters to intermediate BFs. The strengths and limitations of the resulting filterbank are discussed. Its suitability for simulating hearing-impaired cochlear responses is also discussed.

Effect of the nature of exogenous organic matter on pesticide sorption by the soil.

A study was carried out on the sorption of two sparingly water-soluble pesticides (diazinon and linuron) by a sandy loam soil modified with different exogenous organic materials (EOMs) containing humic-like substances: city refuse compost (CRC), peat (P), commercial "humic" acid (HA), liquid "humic" acid (LHA), and two (nonhumic) model compounds (surfactants), tetradecyltrimethylammonium bromide (TDTMA) and sodium dodecyl sulphate (SDS), before and after 2- and 8-month incubation periods with the soil. In all cases, the isotherms fitted the Freundlich sorption equation (x/m = KCen), generally with r2 values greater than 0.99. The value of the sorption constant K for the natural soil was 8.81 for diazinon and 2.29 for linuron. These values increased significantly for EOM modified soils with respect to natural soil, with the exception of the samples modified with SDS and LHA, in which cases they decreased, possibly due to the micellar properties of these compounds. Incubation of EOMs with soil increased their sorption capacity: the Koc values were increased proportionally to the incubation time for both pesticides and for all treatments carried out. Accordingly, the sorption capacity of hydrophobic pesticides increases with the degree of evolution in the soil of EOMs with "humic"-type compounds, possibly due, among other causes, to the increase in the EOMs' colloidal properties and the modifications occurring in the hydrophobic-hydrophilic characteristics of the soil surfaces. The main conclusion is that application to the soil of carbon-rich wastes, especially those with a high degree of maturity, may offer an important strategy for reducing pesticide leaching and for eliminating pesticide residues from soil with the use of anionic surfactants.

A physical model of sound diffraction and reflections in the human concha.

An approximated physical model of the frequency transfer function of the human concha is developed in this paper. This formulation includes diffraction, reflection, and interference phenomena in the concha cavity. The performance of the proposed diffraction/ reflection model is compared with that of the single-delay-and-add approximation by checking their predictions against the experimental transfer function of a metal spiral-shaped diffracting/reflecting system. Results show that the diffraction/reflection model performs considerably better at predicting both the absolute center frequency of spectral minima and the relative frequency spacing between them. The diffraction/reflection model is then applied to a realistic concha shape and its predictions are compared with experimental head-related transfer functions for azimuth- and elevation-varying sound sources. In this case, the model predicts the elevation-dependent spectral features related to the transverse dimensions of the concha. Additionally, the diffraction/reflection model predicts that, because of sound diffraction, similar spectral features must be generated in the concha for sources at all azimuths within the frontal part of the ipsilateral hemisphere. Experimental and theoretical evidence supporting this prediction is presented.

[Referral and family therapy. A systemic analysis]. / Derivación y terapia familiar. Un análisis sistémico.

OBJECTIVE: To describe the characteristics of demand, family structure and the referral process for families attended at a Family Therapy Unit over a two-year period. DESIGN: A retrospective, observational study. SETTING: A Family Therapy Unit in the Public Health System. PARTICIPANTS: A randomised sample of 80 families out of the 136 referred to the Family Therapy Unit during 1990 and 1991, with a 95% C.I. and 0.05 alpha error. MEASUREMENTS AND MAIN RESULTS: The family 'referrer' (the person who requests help) was the mother of the Patient Identified (PI) in more than half the cases, whereas it was the father in only 10%. The PI was a son or daughter in 56.25% of cases, usually a son. The family dysfunction was identified in the couple in 71 of 80 cases (88.75%). The most common symptoms of the PI were psychotic disorders (23.75%) and behavioural disturbances (22.5%). Families were referred from Mental Health Teams (MHT) in 80% of cases; in more than 75%, the MHT's demand did not coincide with the family's. 70% of these families had previously visited more than one therapist. CONCLUSIONS: The structure of relationships within the families in our study is of a hypofunctioning peripheral father and a mother over-involved with a symptomatic son. On most occasions, a non-explicit parent-spouse conflict underlies the symptomatology expressed by the PI. The severity of the basic conflict and resistance to change affect the intensity of the expressed symptom and the appearance of new Pls, which means further referrals to progressively more specialised care levels.