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We aimed to assess the reported rate of flu vaccination in the 2019/2020 season for respondents to the Italian nationwide online EPICOVID 19 survey. A national convenience sample of volunteers aged 18 or older was assessed between 13 April and 2 June 2020. Flu vaccine rates were calculated for all classes of age. The association between the independent variables and the flu vaccine was assessed by applying a multivariable binary logistic regression model. Of the 198,822 respondents, 41,818 (21.0%) reported having received a flu vaccination shot during the last influenza season. In particular, 15,009 (53.4%) subjects aged 65 years or older received a flu vaccination shot. Being 65 years aged or older (Adjusted Odds Ratios (aOR) 3.06, 95% Confidence Interval (CI) 2.92&ndash, 3.20) and having a high education level (aOR 1.34. 95%CI 1.28&ndash, 1.41) were independently associated to flu vaccination. Heart and lung diseases were the morbidities associated with the higher odds of being vaccinated (aOR 1.97 (95%CI 1.86&ndash, 2.09) and aOR 1.92 (95%CI 1.84&ndash, 2.01), respectively). Nursing home residents aged &ge, 65 years showed lower odds of being vaccinated (aOR 0.39 (95%CI 0.28&ndash, 0.54)). Our data indicate the need for an urgent public heath effort to fill the gap of missed vaccination opportunities reported in the past flu seasons.

Often life-threatening pulmonary fungal infections (PFIs) can occur in patients with rheumatoid arthritis (RA) receiving disease-modifying anti-rheumatic drugs (DMARDs). Most of the data concerning PFIs in RA patients come from case reports and retrospective case series. Of the five most widely described PFIs, Pneumocystis jirovecii pneumonia (PJP) has rarely been seen outside Japan, pulmonary cryptococcosis has been diagnosed in only a small number of patients worldwide, pulmonary coccidioidomycosis has almost only been observed in endemic areas, the limited number of cases of pulmonary histoplasmosis have mainly occurred in the USA, and the rare cases of invasive pulmonary aspergillosis have only been encountered in leukopenic patients. Many aspects of the prophylaxis, diagnosis and treatment of PFIs in RA patients remain to be defined, as does the role of each DMARD in increasing the risk of infection, and the possibility of resuming biological and non-biological DMARD treatment after the infection has been cured. The recommendations for the management of PFIs described in this paper are the product of a consensus procedure promoted by the Italian group for the Study and Management of Infections in Patients with Rheumatic Diseases (the ISMIR group).

Background: Respiratory Syncytial Virus (RSV) is one of the main causes of respiratory infections during the first year of life. Very premature infants may contract more severe diseases and 'late preterm infants' may also be more susceptible to the infection. The aim of this study is to evaluate the risk factors for hospitalization during the first year of life in children born at different gestational ages in Italy. Methods: A cohort of 33-34 weeks gestational age (wGA) newborns matched by sex and age with two cohort of newborns born at 35-37 wGA and >37 wGA were enrolled in this study for a three-year period (2009-2012). Hospitalization for bronchiolitis (ICD-9 code 466.1) during the first year of life was assessed through phone interview at the end of the RSV season (November-March) and at the completion of the first year of life. Results: The study enrolled 2314 newborns, of which 2210 (95.5 %) had a one year follow-up and were included in the analysis; 120 (5.4 %) were hospitalized during the first year of life for bronchiolitis. Children born at 33-34 wGA had a higher hospitalization rate compared to the two other groups. The multivariate analysis carried out on the entire population associated the following factors with higher rates for bronchiolitis hospitalization: male gender; prenatal treatment with corticosteroids; prenatal exposure to maternal smoking; singleton delivery; respiratory diseases in neonatal period; surfactant therapy; lack of breastfeeding; siblings

Background Tobacco smoke exposure (TSE) is a worldwide health problem and it is considered a risk factor for pregnant women’s and children’s health, particularly for respiratory morbidity during the first year of life. Few significant birth cohort studies on the effect of prenatal TSE via passive and active maternal smoking on the development of severe bronchiolitis in early childhood have been carried out worldwide. Methods From November 2009 to December 2012, newborns born at ≥33 weeks of gestational age (wGA) were recruited in a longitudinal multi-center cohort study in Italy to investigate the effects of prenatal and postnatal TSE, among other risk factors, on bronchiolitis hospitalization and/or death during the first year of life. Results Two thousand two hundred ten newborns enrolled at birth were followed-up during their first year of life. Of these, 120 (5.4 %) were hospitalized for bronchiolitis. No enrolled infants died during the study period. Prenatal passive TSE and maternal active smoking of more than 15 cigarettes/daily are associated to a significant increase of the risk of offspring children hospitalization for bronchiolitis, with an adjHR of 3.5 (CI 1.5–8.1) and of 1.7 (CI 1.1–2.6) respectively. Conclusions These results confirm the detrimental effects of passive TSE and active heavy smoke during pregnancy for infants’ respiratory health, since the exposure significantly increases the risk of hospitalization for bronchiolitis in the first year of life. Electronic supplementary material The online version of this article (doi:10.1186/s12931-015-0312-5) contains supplementary material, which is available to authorized users.

Objectives: A high caloric intake has been associated with an increased risk of cognitive decline. Macronutrients are the main determinants of total caloric intake, thus aim of this study was to investigate the association between daily energy intake derived from carbohydrates, proteins and fats in relation to the risk of dementia. Materials and Methods: This is a prospective cohort study on a population of residents (n = 1604) in two districts of Northern Italy aged 40-74 years old who were examined about dietary habits and other lifestyles during the period 1991-5. Dietary habits were assessed by means of a 158-item food frequency questionnaire at baseline. Occurrence of Alzheimer' Disease (AD) and Vascular/other forms of Dementia (VaOD) were ascertained using Regional Health Registries. The proportion of daily energy intake (calories) derived from carbohydrates (%), proteins (%) and fats (%) was calculated and participants were ranked as "low" and "high" intake. Cox models were used to assess the associations between % macronutrients and incident AD and VaOD adjusting for potential confounders. Results: During a median of 18.6 years of followup, 73 incident dementia cases had occurred (39 AD and 34 VaOD). In the fully adjusted models the risk of AD was signifi cantly increased in people with high % carbohydrates (HR 2.45, 95%CI 1.08-5.57) but was reduced in those with high % fats (HR 0.34, 95%CI 0.16-0.71) and high % proteins (HR 0.78, 95%CI 0.38-1.60). The risk of VaOD was elevated in subjects with high % fats (HR 1.77, 0.79-3.95) but was decreased in persons with high % protein intake (HR 0.49, 95%CI 0.22-1.08) even though the estimates did not reach the signifi cance. No association with % carbohydrates was observed. Discussion: High % carbohydrates and low % proteins and fats were associated with an increased risk of AD whereas low % proteins and high % fats increased the risk of VaOD in our cohort. A possible explanation might reside in the food sources. Olive oil, rich in monounsaturated fatty acids, was the main source of fats in AD subjects. Persons who developed VaOD had a high intake of lard and margarine, rich in saturated and trans-unsaturated fatty acids. Regarding carbohydrates, subjects with AD had a higher intake of foods with high glycemic index than individuals with VaOD. Conclusion: Our data suggest that certain dietary choices and habits in adulthood can play a key role in the prevention of AD and dementia in old age.

Health Informative Systems constitute a powerful resource to produce epidemiological results from large scale population-based studies. Scientifi c literature reports an increasing number of studies investigating through their use different health outcomes. Aim of this study was to evaluate the reliability of an algorithm in identifying Dementia cases from Health Information System of ASLMi1 (HIS-Mi1) by comparing the observed incidence with the expected in the general European population (EuroDem)

The aim of the present analysis was to evaluate the association of the Mediterranean diet (MeDi), smoking habits and physical activity with all-cause mortality in an Italian population during a 20-year follow-up study. A total of 1693 subjects aged 40-74 who enrolled in the study in 1991-5 were asked about dietary and other lifestyle information at baseline. Adherence to the MeDi was evaluated by the Mediterranean dietary score (MedDietScore). A healthy lifestyle score was computed by assigning 1 point each for a medium or high adherence to the MedDietScore, non-smoking and physical activity. Cox models were used to assess the associations between lifestyle factors and healthy lifestyle scores and all-cause mortality, adjusting for potential confounders. The final sample included 974 subjects with complete data and without chronic disease at baseline. During a median of 17·4 years of follow-up, 193 people died. Subjects with high adherence to the MedDietScore (hazard ratio (HR) 0·62, 95 % CI 0·43, 0·89)), non-smokers (HR 0·71, 95 % CI 0·51, 0·98) and physically active subjects (HR 0·55, 95 % CI 0·36, 0·82) were at low risk of death. Each point increase in the MedDietScore was associated with a significant 5 % reduction of death risk. Subjects with 1, 2 or 3 healthy lifestyle behaviours had a significantly 39, 56, and 73 % reduced risk of death, respectively. A high adherence to MeDi, non-smoking and physical activity were strongly associated with a reduced risk of all-cause mortality in healthy subjects after long-term follow-up. This reduction was even stronger when the healthy lifestyle behaviours were combined. Copyright © The Authors 2015.

Background Respiratory syncytial virus (RSV) causes respiratory infections during the first year of life. Very premature infants have more severe diseases and also ‘late preterm infants’ may be more susceptible to the infection. Aim of the study To evaluate in an Italian cohort the incidence and risk factors of severe hospitalized lower respiratory tract infection (LRTI) induced or not by RSV during the first year of life. Methods A cohort of 33 + 0d –34 + 6d wGA newborns paired with two sex- and age-matched 35 + 0d –37 + 6d wGA and ≥ 38 + 0d wGA newborns were enrolled. Hospitalization for LRTI induced or not by RSV during the first year of life was assessed through phone interview at the end of the RSV season (November–March) and at the completion of the first year of life. The parents were asked to report hospitalization for any reason. Results 1064 neonates were enrolled (November 2009–October 2010), 697 had at least one phone follow-up by September 2010. Babies of 33 + 0d –34 + 6d wGA were more frequently conceived through assisted fertilization technologies, born from cesarean delivery had more frequently acute perinatal risk factors and were more frequently twins. After a mean 6 month-follow-up, we registered 29 hospitalizations for LRTI induced or not by RSV. Hospitalizations were slightly and non-significantly more frequent in 33 + 0d –37 + 6d wGA infants. The risk of hospitalization was significantly 60% reduced in breastfed babies and four folds significantly increased during the RSV season. Conclusion The very preliminary data of this ongoing study suggest that in ‘late-preterm’ infants some individual/environmental characteristics of the infants play a relevant role in determining the risk of severe RSV infection.

Introduction Lower incidence of cancer in persons with Alzheimer disease and vice-versa has been previously reported, however this might be due to an under-diagnosis of the second disease after the occurrence of the first. Aim of this study was to estimate the unbiased co-occurrence of the two diseases in a population of about one million persons, using administrative health data (AHD). Materials and Methods In AHD we identified incident Cancer and AD cases over a period of five years. To control for under-diagnosis of the second disease three analyses were carried-out: for times preceding or following the index diagnosis, for surviving or not the follow-up period and for different types and sites of cancer. The relative risks (RRs) of AD in persons with cancer and vice-versa, relative to general population, were estimated as observed timed expected cases. Results The RRs of cancer in persons with AD and of AD in persons with cancer were both reduced. The inverse relationship of occurrence was independent from the temporal order of appearance of the diseases, from life-expectancy reduction and from different cancer types. Discussion Administrative data represent a valid source for the conduction of cohort studies on the co-occurrence of diseases.

Introduction In a cohort of 115,524 person-years we observed a 40% risk reduction for the occurrence of Alzheimer's disease (AD) in persons with cancer and vice-versa. A relevant concern about these findings is about the potential effect of misclassification in biasing the results. Materials and Methods All cancer cases were identified from a population Tumor Registry. AD cases were traced from registries of drug prescriptions, hospitalizations and payment exemptions by a classification algorithm that had high specificity but lacked in sensitivity. In the co-occurrence study misclassification of "exposure" (cancer occurrence in the AD cohort) and of disease (AD in cancer cohort), might be alternatively differential (DM) or non-differential (NDM). A sensitivity analysis was performed in this cohort. Results An exposure or disease NDM had the only effect to overestimate the relative risks (RR), weakening the strength of the inverse association. The effect of a DM, unlikely to have occurred, was dependent from levels of sensitivity/specificity in the subgroups of exposure and of disease, and led to biased RR estimates only when classification performances were highly differential. Discussion Large population-based studies on administrative data allow to obtain epidemiological results accounting for possible misclassifications.

Background: Alzheimer's disease (AD) and cancer increase their frequency with age and can be considered main negative consequences of senescence. Few previous studies reported a lower incidence of cancers in persons with Alzheimer's disease (AD) and lower incidence of AD in persons with cancers. This result needs to be confirmed in different sets and with different study designs since it might be due to confounding due to underreporting and/or shortening of life expectancy of persons with cancer or AD. Methods: This was a prospective/retrospective cohort study. Persons living in the geographical area of the local health authority (ASL) of Milano 1 (Mi1) of 60 or more year from 2004 to 2009 with a first diagnosis of AD or cancer were recruited in their specific diagnostic cohort. Diagnoses were retrieved from the ASL Mi1 informative health system. Based on the person-years of observation during the time period from 2004 to 2009 we calculated the incidences of AD in the cohort of cancers and the incidence of cancers in the AD cohort in the period preceding and following the index diagnosis. The incidence of AD and cancers were calculated also for the general population of ASL Mi1 and observed cases in the two cohorts with respect to those expected from the general population were compared. Separate comparisons were made for the period preceding and following the diagnosis of AD or Cancer, for AD occurrence in smoking and non smoking related cancers and for persons surviving or dying during the period 2004-2009. Results: In the whole population of ASL Mi1 we registered 21451 (12225 men) newly diagnosed cancers and 2832 AD (947 men) giving respectively a crude incidence rate per 10000 p-y of 175.1 and of 22.1. The cohort of persons with AD contributed a total of 15063.0 p-y of observation and the corresponding figure for the cancer cohort was 101317.9 p-y. In 161 cases cancer and AD were diagnosed to the same person with AD preceding cancer in 68 cases. In persons with cancer 246 cases of AD were expected from the incidence observed in the whole population of 60 years or older; the risk of AD occurrence, relative to that of the general population of the same age and gender was therefore significantly reduced (observed/expected = 0.65 95% Confidence Interval [CI] 0.56-0.76). The corresponding figure for the cohort of AD were 241.2 cancer expected with a relative risk (RR) of 0, 57 (95% CI 0.49-0.67). No significant differences in the estimates were observed for the follow-up periods preceding and following the diagnosis, for smoking related cancers or for members of the cohort not surviving for the entire period of follow-up. Conclusion(s): Cancer and AD are negative manifestation of senescence and have an inverse relationship of occurrence. This result might be interpreted as a confirmation for the theory of pleiotropic genes for aging and senescence.

Osteoarthritis is linked to a reduced risk of femoral fracture despite osteoporosis. Different bone distribution in the femoral neck in osteoarthritis and fracture was revealed using a peripheral quantitative computed tomography (pQCT) comparative analysis. Our findings sustain the presence of an adaptive mechanism of bone structure providing fracture protection in osteoarthritis. INTRODUCTION: Although osteoarthritis is associated with reduced femoral fracture risk, it does not protect from bone loss. We investigated whether adaptive mechanisms are present at the arthritic joint, leading to reduced fracture risk, despite the presence of low bone mass density. METHODS: We performed pQCT comparative analyses of human femoral neck specimens derived from 32 postmenopausal women who received hip prostheses for osteoarthritis (n=19) or femoral fracture (n=13) by applying an in-house automated software to extract bone structure descriptors, characterize trabecular and cortical bone distribution, and evaluate their mutual relationships. RESULTS: The cortical bone volume and trabecular thickness were significantly (p

Objectives. Raltegravir (RAL) is the only licensed HIV integrase inhibitor. The determinants of virological response to RAL-containing regimens and the prevalence of integrase mutations associated to RAL failure deserve further investigation. Methods. From the Italian database ARCA, we selected 3-class experienced subjects failing their current treatment with complete treatment history available. Selection criteria included HIVRNA, CD4 count and HIV genotype within 3 months prior to RAL initiation. Predictors of 24- week response were analyzed and genotypic sensitivity scores (GSS) and weighted-GSS were evaluated. Results. Virological response was achieved in 74.3% of 105 subjects. Mutations associated to RAL failure were detected in 12/24 subjects with an IN genotype, with the prevalence of Q148H+G140S. Each extra unit of GSS (p=.039) and weighted-GSS (p=.034) predicted virological response. A significant increase in the probability of response appeared for GSS 1- 1.49 (p=.030), GSS>1.5 (p=.044) and weighted-GSS>=1.5 (p=.037). GSS>=1 showed the highest sensitivity, 82.6%. ROC curves depicted the widest AUC (0.663, p=.054) of GSS >=1. Conclusions. Unresponsiveness to RAL-containing regimens among 3-class experienced subjects was low. The activity of the background regimen was a major predictor of response. Although few IN genotypes were available at failure, half of these were without IN resistance mutations Finding IN mutations in approximately half of the successfully genotyped subjects has been very common in most RAL trials, both in naïve and experienced subjects.

Background: HIV-infected pts failing immune recovery on virologically- suppressive HAART maintain a highly activated/ differentiated peripheral CD4 pool. We hypothesized that MVC, by specifically targeting terminally-differentiated CCR5+CD4, might preserve the naive/central memory CD4 pool in these pts. Methods: Pts on HAART with CD4\200/lL and HIV-RNA\50 cp/ mL were randomized to: HAART+MVC (A) or continuing HAART (B). Na?¨ve CD45RA+62L+, memory CD45RA-, central-memory CD127+, activated/proliferating HLA-DR+CD38+Ki67+CD4/CD8, plasma IL-7 were quantified. HIV-RNA was quantified via Amplicor HIV-1 Monitor Kit v1.5, followed by RT-PCR. Results: 66/100 pts were analyzed at week 12 (W12): 39 in A; 27 in B. At baseline, comparable total CD4 and immune-phenotypes were shown between arms. By W12, both study groups displayed a significant increase in CD4 (A: 184-230, p\.001; B: 165-190, p = .037). A statistically significant change in mean CD8 (p = .002) was observed between pts in arm A and B. HIV-RNA remained \50 cp/mL with no difference between arms. The immunephenotype of reconstituting CD4 was different between arms. Whereas HAARTcontrols displayed a rise in memory CD4 (53-70%, p = .05) with a contraction of naive T-cells (CD4, 24-9%, p = .02; CD8, 20-9%, p = .028), MVC-receiving patients maintained stable memory T-cells (CD4, 35-45%, p = .14; CD8, 35-38%, p = .08) with a non-significant rise in naive CD4 (17-37%, p = .3) and CD8 (11-36%, p = .3). Interestingly, MCV resulted in a significantly higher proportion of na?¨ve CD4 compared to controls (p = .03), whereas controls tended to have higher memory CD4 (p = . 08). Both MVC and HAART resulted in the decline of activated HLA-DR+CD38+ T-cells (A: p = .03, p = .03; B: p = .009, p = .038 for CD4 and CD8, respectively). Despite no changes in Ki67+CD4/CD8 in both groups, MVCreceiving pts displayed significantly lower proliferating Ki67+CD4 at W12 (18 vs. 23% p = .04). As for the IL-7/IL-7R, only MVCreceiving patients presented an increasing trend in central-memory CD127+CD4 by W12 (56-60%, p = .058), with no change in CD127 + CD8 and circulating IL-7. Conclusions: In HIV-infected subjects with inefficient immune reconstitution on virologically-suppressive HAART, intensification with MVC results in a significant expansion of na?¨ve CD4 pool that proliferates less actively. This suggests a reduction in peripheral T-cell death and preserved T-cell production, with possible improvement in immune competence.

Background: Under HAART, 7-39% of HIV-infected patients (pts) fail to exhibit a recovery in CD4 cells despite full suppression of viral replication. In MOTIVATE trials, MVC was superior to OBT in increasing CD4 cells in ARV-experienced pts. This study evaluated the clinical efficacy of MVC in terms of CD4 cells recovery, viral replication and tolerability in INR pts. Methods: Randomised, multicentre, proof of concept study enrolling 100 pts divided into 2 arms: A HAART+MVC, B HAART. Planned F-U is 1 year. Ultrasensitive HIV-RNA was quantified via Amplicor HIV-1 Monitor Kit v1.5, followed by RT-PCR for quantifying 1-50 cp/mL. Naive CDRA+62L+, memory CD45RA-, activated HLADR+ CD38+, proliferating Ki67+ were measured by flow cytometry. T-test was used for intra and inter-group comparisons. ANCOVA was used to adjust the baseline values. Results: 100 pts have been randomized (50 pts/arm). 59 pts reached week 12: 30 in arm A and 29 in arm B. 2 HIV-unrelated clinical events were registered in arm B and 2 in arm A (not known the correlation with MVC administration) as well as 9 drop-outs at baseline (withdrawal of the informed consent). No grade 3-4 lab toxicity were reported. At baseline, CD4/CD8 and immune-phenotype was comparable in arm A and B. At week 12, no significant changes in mean CD4 recovery were seen between pts in arm A and B (+41,2 vs -11,6/?l; p=.12). A statistically significant change was observed in mean CD8+ count between pts in arm A and B (+99,3 vs -126,1/?l, p=.025) At baseline and week 12 an immunological study performed by flow cytometry was carried out in 24 out of 61 pts (13 in arm A, 11 in arm B): at week 12, while B pts experienced a progressive contraction of naive CD4 (81 to 67%, p=.02) and CD8 (81 to 77%, p=.04) with a parallel rise in memory CD4 (16 to 30%, p=.02) and CD8 (13 to 17%, p=.06), no significant loss of naive CD4 (70 to 57%, p=.18) and CD8 (69 to 66%, p=.42) was displayed by A pts with a tendency to higher gain in memory CD4 (24 to 40%, p=.06) and CD8 (11 to 25%, p=.008). By week 12, a similar reduction in activated HLA-DR+CD38+ CD8 and CD4 was shown in B (p=.05) and A pts (p=.03 and p=.02 for CD8 and CD4). No changes were shown in proliferating Ki67+CD4 in A (p=.42) and B pts (p=.47), while a tendency to Ki67+CD8 reduction was shown in A (p=.06) and not in B pts (p=.45). HIV-RNA quantification evidenced a trend to higher median values (BL vs week 12) in B pts: 2 vs 5 cp/mL (p=.37). No changes occurred in arm A. Conclusions: we can consider the use of MVC as intensification strategy that seems to impact T-cell peripheral immune-phenotype after examining the significant change in CD8* cells count and the evidence of not significant CD4 gain in arm A.Our findings of reduced loss of naive T-cells with a parallel robust rise in the memory pool suggest a role of MVC in reducing peripheral antigen-driven T-cell death, possibly preserving new T-cell production. However, further data are needed to confirm our results.

Purpose: To compare the safety of conventional and nonconventional antipsychotics in older persons. Specific aims included to i) compare the risk of all-cause mortality among users of conventional versus atypical antipsychotic drugs, ii) investigate whether any increased mortality risk was limited to specific causes of death, and was still present after adjusting for comorbidities and, iii) examine mortality risks among users of conventional versus atypical antipsychotic in people with Alzheimer's Disease (AD). Method: The study included a retrospective cohort study of residents in Milan, Italy, aged 60+ who were prescribed an antipsychotic drug for the first time during April 1, 2002 to June 15, 2005. Data were obtained from the health authorities' information systems. 7739 persons using antipsychotic drugs (n = 2908 conventional, n = 4831 atypical) were included. Overall and cause-specific mortality over six months following first prescription of an antipsychotic drug was investigated. Covariates included, age, sex, and comorbities (cancer, cardio/cerebrovascular and other diseases). Mortality was assessed both in the whole cohort, and a subset of people with AD who were prescribed cholinesterase inhibitors. Results: People prescribed atypical antipsychotics had 65% lower all-cause mortality (HR 0.35, 95% CI 0.31-0.39) than those prescribed conventional antipsychotics. This mortality risk was explained by cancer deaths, with no differences within deaths for other conditions. Among people using cholinesterase inhibitors, no statistically significant difference in mortality was observed for users of conventional versus atypical antipsychotics. Conclusion: The characteristics of the observed differences in mortality suggest that there might be a preferential prescription of conventional drugs in terminally ill cancer patients. There is no evidence of a differential survival in AD patients using conventional or atypical antipsychotics.

BACKGROUND AND AIM: Factor analysis is a multivariate correlation technique that is frequently employed to characterise the clustering of intercorrelated abnormalities, which underlie the metabolic syndrome in cohorts of individuals with different characteristics. To our knowledge, it has never been used to identify the components of this syndrome in obese subjects. The purpose of this study was to use factor analysis to investigate the clustering of features, which characterise the metabolic syndrome, in a cohort of 552 obese women aged 18-83years (mean body mass index: 43.0kg/m(2)+/-5.7 SD). METHODS AND RESULTS: Principal component analysis reduced ten correlated physiological variables, to four uncorrelated factors that explained 72.2% of the variance in the original parameters. These factors were interpreted as: (1) an insulin resistance factor, with positive loading of fasting serum insulin and homeostatic model assessment of insulin resistance; (2) a metabolic glucose/lipid factor, with positive loading of fasting plasma glucose, triglycerides, waist-to-hip ratio, and inverse loading of high density lipoprotein cholesterol; (3) a body mass factor, with positive loading of body mass and waist circumference; and (4) a blood pressure factor, with positive loading of systolic and diastolic blood pressure. CONCLUSION: The identification of four independent factors is consistent with previous findings among samples of different populations and may also support, in obese women, the hypothesis that multiple physiological determinants are responsible for the abnormalities underlying the metabolic syndrome. Nonetheless, findings in this cohort of obese women suggest that the absolute degree of adiposity is not correlated with any tested component of the metabolic syndrome, but that the relative fat distribution is highly correlated with the development of hyperglycaemic and dyslipidaemic phenomena. Furthermore, insulin resistance appears to be a major factor in obese individuals, independent of other metabolic and anthropometic abnormalities.

Frontotemporal dementia regards a group of presenile progressive neurodegenerative form of dementias which includes Pick's disease, corticobasal degeneration, frontotemporal dementia with motor neuron disease, frontal lobe degeneration, dementia-parkinsonism-amyotrophy complex, familial non-specific dementia mapping to chromosome 3, non-Alzheimer degenerative dementia lacking distinctive histological features as well as a number other infrequent syndromes with dementia and focal neurological signs. The aim of this study was to investigate the regional distribution of metallothionein-I-II, an ubiquitary group of buffering proteins, in cases of frontotemporal dementia. The aim of the present study was to study the metallothionein-I-II expression in relationship to the expression in astrocytes of glial fibrillary acidic protein (GFAP) as we have already done in previous studies of Alzheimer's and Binswanger's diseases [31, 32]. Our findings indicate that metallothionein-I-II expression in the most affected areas is likely to be regionally distinct and layer-dependent, in that it is highest in the deep layers of the frontotemporal cortex and the allocortex (hippocampus) while insignificantly immunopositive in the occipital cortex. In addition, the potential use of metallothionein-I-II as a new pharmacological approach to contrast some deleterious aspects of this disease has been also discussed. © 2005 - IOS Press and the authors. All rights reserved.

We evaluated the virological outcome of lopinavir/ritonavir (LPV/RTV) in 224 HIV-1-infected and protease inhibitor (PI)-experienced patients showing virological failure to a highly active antiretroviral therapy (HAART) regimen and followed up for at least 3 months. At baseline, the median level of plasma viraemia was 4.61 log(10) copies/ml (range 3-6.48) and the median CD4 cell count was 219 cells/mm(3) (range 1-836). During a median follow-up of 272 days (range 92-635), we observed an increase in the number of CD4 cells (P=0.02) and a dramatic decrease in plasma viraemia levels (P=0.0001), which became undetectable in 122 patients (54.5%). The closely related predictive factors were baseline plasma viraemia levels and the number of mutations known to reduce susceptibility to LPV/RTV. Thirty-one patients (13.8%) discontinued LPV/RTV during the follow-up, and one AIDS event and three deaths were recorded. Of the 134 patients (59.8%) who underwent a baseline genotype resistance test, 22 (16.4%) had greater than or equal to 6 mutations known to reduce LPV/RTV susceptibility; plasma viraemia became undetectable in 76 patients (56.7%), only five of whom harboured greater than or equal to 6 mutations at baseline (P=0.0001). The independent predictive factors related to virological success were plasma viraemia levels and the number of mutations reducing susceptibility to LPV/RTV at baseline; each additional log(10) copies/ml of HIV RNA reduced the probability of virological success by 34.0% and each extra mutation by 14.5%.

Background: Cross-sectional and retrospective surveys suggest that nucleoside reverse transcriptase inhibitors (NRTIs) contribute to the metabolic and morphologic alterations observed in patients on antiretroviral therapy (ART). Objectives: To assess the risk of developing body habitus changes (BHCs) and metabolic abnormalities in protease inhibitor (PI)-naive HIV-1-infected patients treated with two NRTIs, and the risk associated with each of these drugs. Design: Prospective cohort study. Patients and Methods: The BHCs occurring in 335 patients treated with two NRTIs were evaluated every 3 months. The laboratory tests included determination of CD4 cell counts and the measurement of HIV RNA, serum glucose, cholesterol, and triglyceride levels. Cox proportional hazard models were used to describe the factors associated with the development of BHCs. Results: During a median exposure of 747.5 days, 46 patients (13.7%) developed BHCs: nine fat accumulation alone, 12 fat loss alone, and 25 combined fat loss and accumulation in different body regions. Fat loss alone occurred after a significantly longer median duration of treatment than the other two forms (p = .004). The risk of developing any BHC was significantly higher in female patients (p < .0001). Fat loss was the prevalent alteration in males. Hypertriglyceridemia was observed in 76 patients (22.7%), hypercholesterolemia in 35 (10.5%), and hyperglycemia in 48 (14.3%). The adjusted risk of developing hypertriglyceridemia was higher in the stavudine-treated patients (p = .04) and in those who had previously received ART (p = .02). The only independent factor associated with the development of hypercholesterolemia was to be ART experienced at baseline (p = .02), whereas age was associated with the development of hyperglycemia (p = .0096). Conclusions: Treatment with NRTIs may be responsible for the same morphologic alterations as those observed in patients treated with PIs. Moreover, altered triglyceride levels are also frequently observed. The different timing of presentation and gender distribution of BHCs suggest that multiple pathogenetic mechanisms are involved.

The aim of our study was to investigate the possible correlation of in vitro antibody production (IVAP) directed to the gp160 protein of HIV-1 with CD4(+) slopes, plasma viremia, and disease progression in long-term nonprogressors (LTNPs). Nineteen subjects with a long-term nonprogressive HIV-1 infection were studied and followed for 2 years, During the follow-up, in vitro anti-gp160 producers showed negative CD4(+) slopes in the majority of cases (9 of 12), whereas 5 of 7 nonproducers showed positive CD4(+) slopes. Plasma viremia values, which were not significantly different in the two groups at baseline, became significantly higher in anti-gp160 producers when compared with nonproducers during the follow-up (p = 0.012). Finally, a trend toward progression was observed in the group of producers but not in nonproducers, These findings suggest that the in vitro production of anti-gp160 antibodies by peripheral B cells is not a correlate of protection, and may represent an early predictor of progression in LTNPs.