The present study sought to observe, through online treatments, whether explicit information assists acquisition in a way that has not been measured in previous processing instruction (PI) studies. Two experiments examined learners' behavior while they processed Spanish sentences with object-verb-subject (OVS) word order and Spanish subjunctive under two treatments: with explicit information (the PI group) and without explicit information (the structured input [SI] group). Participants in both groups worked individually with a computer and processed a series of 30 SI items. They received feedback right after each response, and both accuracy and response time were recorded. It was expected that learners in the PI group would start to process both of the linguistic targets sooner in the sequence of input items and would submit their responses faster than learners in the SI group, because explicit information in the PI treatment would help learners notice the target items early in the series. The results showed no difference between the SI group and the PI group when processing OVS sentences, but the PI group processed subjunctive forms sooner and faster than the SI group. The results suggest that the benefits of explicit information might depend on the nature of the task and the processing problem.

Objective: Toll-like receptor 4 (TLR4) signalling participates in the innate immune response against hepatitis C virus (HCV) infection. TLR4 gene polymorphisms may influence the risk of HCV-induced hepatocellular carcinoma (HCC). This is a single-centre-based study designed to analyse the distribution of several TLR4 gene single nucleotide polymorphisms in healthy controls and in patients chronically infected with HCV, with and without HCC. Methods: We have determined three single nucleotide polymorphisms (rs2149356, rs4986791 and rs5030719) at the TLR4 gene in 155 patients with HCV-related HCC, 153 patients with chronic hepatitis C and 390 healthy controls. All were white and most were Spaniards. Results:(1) rs5030719 was monomorphic and was not further analysed; (2) the rs2149356 T allele carrier state was significantly less frequent in patients with HCC than in healthy controls (OR 0.421, 95% CI 0.285–0.625) and in patients with chronic hepatitis C (OR 0.426, 95% CI 0.236–0.767); (3) the proportion of rs2149356 T allele carriers progressively diminished with increasing clinical stage of HCC; (4) no significant differences were observed for the rs4986791 T allele. Conclusion: The TLR4 rs2148356 T allele is associated with a reduced risk of HCC and could slow down its clinical progression in HCV-induced chronic liver disease.

The syndrome of pyrexia of unknown origin (PUO) was first defined in 1961 but remains a clinical challenge for many physicians. Different subgroups with PUO have been suggested, each requiring different investigative strategies: classical, nosocomial, neutropenic and HIV-related. This could be expanded to include the elderly as a fifth group. The causes are broadly divided into four groups: infective, inflammatory, neoplastic and miscellaneous. Increasing early use of positron emission tomography-computed tomography (PET-CT) and the development of new molecular and serological tests for infection have improved diagnostic capability, but up to 50% of patients still have no cause found despite adequate investigations. Reassuringly, the cohort of undiagnosed patients has a good prognosis. In this article we review the possible aetiologies of PUO and present a systematic clinical approach to investigation and management of patients, recommending potential second-line investigations when the aetiology is unclear.

A simple diagnostic method for detecting in clinical routine HAART-associated lipodystrophy in HIV-infected patients is lacking. We studied the relationships between the scores obtained with a subjective lipodystrophy severity grading scale (LSGS) and standard anthropometric and echographic measurements of the subcutaneous and visceral fat thickness of 74 HIV-infected patients. Patients were divided into four groups according to their LSGS score (0, 1-7, 8-14, 15-21). Significant correlations between the LSGS and the anthropometric and echographic measurements of fat thickness, mainly the limb circumferences (brachial: r= -0.43, p < 0.001; thigh: r= -0.41, p < 0.001), and, especially, the echographically assessed perirenal fat diameters either adjusted (r= 0.46, p < 0.001) or nonadjusted to the body mass index (r= 0.35, p < 0.001) were observed. Significant differences in most of these anthropometric parameters between either the lowest (score 0) and the highest (score 15-21) score groups and the remaining groups were found, but not between the two intermediate groups (scores 1-7 vs. 8-14). This suggests that lipodystrophy should be clinically categorized as absent, mild, or marked, and that even minor changes in physical aspect should be considered as indicative of this disorder. The combination of these subjective and objective parameters could be helpful in the early detection of lipodystrophy in clinical practice.

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Purpose: To evaluate the impact of acquired and inherited factors on the development of lipodystrophic syndrome in patients on highly active antiretroviral therapy. Methods: Two hundred forty-three human immunodeficiency virus-infected Caucasians on highly active antiretroviral therapy were prospectively followed-up for 3 years. Eleven were naïve and 232 were on antiretrovirals (mean, 93.0 months Ϯ 43.8 months). Lipodystrophic syndrome was Key Words: lipodystrophy, stavudine, IL-1␤ (ϩ3954C/T), polymorphism, cytokines, nitric oxide synthaseLipodystrophic syndrome (LD) is a frequent medical condition found in human immunodeficiency virus (HIV)-infected patients, characterized by redistribution of body fat (lipoatrophy and fat accumulation) and metabolic abnormalities (hyperlipidemia, insulin resistance, and hyperlactatemia). Different studies have reported a variable prevalence of LD in HIV-infected patients on highly active antiretroviral therapy (HAART), between 17% and 75%, probably due to clinical variability in the diagnosis of LD. 1-8 LD is considered an inflammatory syndrome and is associated with increased serum cytokine levels. 9 -11 High serum levels of cytokines have also been observed in HIV-related wasting syndrome, similar in its adipose tissue alterations to the lipoatrophic form of LD. 12,13 Early reports associated LD with the use of different protease inhibitors, 1,2 while later reports linked LD to thymidine nucleoside analogue use that produced mitochondrial toxicity, hyperlactatemia, and lipoatrophy. 14 -17 LD improves after antiretroviral change, mostly after the switching of protease inhibitors or stavudine to a non-nucleoside reverse transcriptase inhibitor. 18,19 Thus, the association between antiretrovirals and LD seems clear. However, factors other than antiretrovirals could influence the development of LD, for example, sex of the patient. 20 In addition, there is support for a role of a genetic background of patients in the development of LD: (1) there are some congenital syndromes, not related to HIV infection that are associated with LD 21 ; (2) only some of the HIV-infected patients on HAART develop LD, despite receiv-

Echographically measured thicknesses of perirenal and subcutaneous fat, as well as serum metabolic and anthropometric parameters, were evaluated in 74 human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy (HAART), 22 of whom were HAART-naive at baseline, who were followed-up for 27 months to detect predictive factors of lipodystrophy. Perirenal fat diameter (PRFD) at baseline differed in HAART-naive and HAART-experienced patients (P<.001), and it was the best predictor of lipodystrophy changes after 12 months of follow-up in the HAART-naive patients (hazard ratio, 7.34; 95% confidence interval, 1.18-45.49; P=.032). In addition, HAART-experienced patients in whom lipodystrophy improved had thinner baseline perirenal fat than those in whom lipodystrophy did not improve (P=.04). A PRFD of >2.6 mm at baseline or >4.9 mm during receipt of HAART suggested lipodystrophy predisposition. PRFD correlated significantly with other metabolic and anthropometric parameters. Echographically measured PRFD is associated with lipodystrophy and could be used as an early predictor of this syndrome in treatment-naive patients starting HAART.

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