Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients, followed-up a median of 9 years

[Abstract] OBJECTIVE: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/μL, 19% CD4 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability

On the characterization of materials and masonry walls of historical buildings: Use of optical system to obtain displacement maps in double-flat jack tests

Among the testing techniques aiming at the mechanical characterization of masonry, the double flat-jack testing method is widely adopted to identify the local value of significant parameters needed to perform structural analyses, such as elastic modulus, Poisson’s ratio and compressive strength. The experience gained from many applications has allowed not only to collect experimental data concerning different types of masonry, but also to highlight the difficulty in the interpretation of the results and the limitations of both single and double flat-jack tests. Although the accuracy of the flat-jack technique in detecting strength and deformability behavior of masonry is still debated in the technical literature and practical activities, changes in the testing procedure aiming at ascertaining the validity of the test results have not been formally defined yet. After a brief description of the standard test procedure and its uncertainties, the present paper proposes an upgrade of the test procedure for improving the level of reliability of the test results. In particular, an experimental case study related to a historical brick masonry building located in Italy is presented to point out the additional information necessary to validate the results of the testing process

Surveillance of Candida spp Bloodstream Infections: Epidemiological Trends and Risk Factors of Death in Two Mexican Tertiary Care Hospitals

Introduction: Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI).Objective: To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City.Design: Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010.Methods: All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis.Results: CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score >= 16 (OR = 6.94, CI95% = 2.34-20.58, p<0.0001), and liver disease (OR = 186.11, CI95% = 7.61-4550.20, p = 0.001). Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed.Conclusions: the cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI.Pfizer Inc.Salvador Zubiran Natl Inst Med Sci & Nutr, Dept Med, Mexico City, DF, MexicoHosp Escuela Tegucigalpa, Tegucigalpa, HondurasUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilNatl Canc Inst, Div Infect Dis, Mexico City, DF, MexicoUniv Nacl Colombia, Dept Internal Med, Bogota, ColombiaUniv Peruana Cayetano Heredia, Dept Med, Lima, PeruHosp Vargas Caracas, Caracas, VenezuelaCtr Med Caracas, Caracas, VenezuelaUniv Fed Rio de Janeiro, Univ Hosp, Rio de Janeiro, BrazilUniv Texas Med Sch Houston, Mem Hermann Texas Med Ctr, Dept Med, Houston, TX USAUniv Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, BrazilUniv Chile, Fac Med, Hosp Luis Calvo Mackenna, Dept Pediat, Santiago 7, ChileUniv Desarrollo, Clin Alemana, Dept Med, Santiago, ChileHosp Clin Jose San Martin, Infect Dis Unit, Buenos Aires, DF, ArgentinaPontificia Univ Catolica Ecuador, Fac Med, Hosp Vozandes, Quito, EcuadorUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilPfizer Inc.: INF-168Web of Scienc

Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: A cross-sectional analysis

Background: Frontotemporal dementia is a highly heritable neurodegenerative disorder. In about a third of patients, the disease is caused by autosomal dominant genetic mutations usually in one of three genes: progranulin (. GRN), microtubule-associated protein tau (. MAPT), or chromosome 9 open reading frame 72 (. C9orf72). Findings from studies of other genetic dementias have shown neuroimaging and cognitive changes before symptoms onset, and we aimed to identify whether such changes could be shown in frontotemporal dementia. Methods: We recruited participants to this multicentre study who either were known carriers of a pathogenic mutation in GRN, MAPT, or C9orf72, or were at risk of carrying a mutation because a first-degree relative was a known symptomatic carrier. We calculated time to expected onset as the difference between age at assessment and mean age at onset within the family. Participants underwent a standardised clinical assessment and neuropsychological battery. We did MRI and generated cortical and subcortical volumes using a parcellation of the volumetric T1-weighted scan. We used linear mixed-effects models to examine whether the association of neuropsychology and imaging measures with time to expected onset of symptoms differed between mutation carriers and non-carriers. Findings: Between Jan 30, 2012, and Sept 15, 2013, we recruited participants from 11 research sites in the UK, Italy, the Netherlands, Sweden, and Canada. We analysed data from 220 participants: 118 mutation carriers (40 symptomatic and 78 asymptomatic) and 102 non-carriers. For neuropsychology measures, we noted the earliest significant differences between mutation carriers and non-carriers 5 years before expected onset, when differences were significant for all measures except for tests of immediate recall and verbal fluency. We noted the largest Z score differences between carriers and non-carriers 5 years before expected onset in tests of naming (Boston Naming Test -0·7; SE 0·3) and executive function (Trail Making Test Part B, Digit Span backwards, and Digit Symbol Task, all -0·5, SE 0·2). For imaging measures, we noted differences earliest for the insula (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume was 0·80% in mutation carriers and 0·84% in non-carriers; difference -0·04, SE 0·02) followed by the temporal lobe (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume 8·1% in mutation carriers and 8·3% in non-carriers; difference -0·2, SE 0·1). Interpretation: Structural imaging and cognitive changes can be identified 5-10 years before expected onset of symptoms in asymptomatic adults at risk of genetic frontotemporal dementia. These findings could help to define biomarkers that can stage presymptomatic disease and track disease progression, which will be important for future therapeutic trials. Funding: Centres of Excellence in Neurodegenerati

Peripheral administration of lactate produces antidepressant-like effects.

In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression

Geosmin suppresses defensive behaviour and elicits unusual neural responses in honey bees.

Geosmin is an odorant produced by bacteria in moist soil. It has been found to be extraordinarily relevant to some insects, but the reasons for this are not yet fully understood. Here we report the first tests of the effect of geosmin on honey bees. A stinging assay showed that the defensive behaviour elicited by the bee's alarm pheromone component isoamyl acetate (IAA) is strongly suppressed by geosmin. Surprisingly, the suppression is, however, only present at very low geosmin concentrations, and disappears at higher concentrations. We investigated the underlying mechanisms at the level of the olfactory receptor neurons by means of electroantennography, finding the responses to mixtures of geosmin and IAA to be lower than to pure IAA, suggesting an interaction of both compounds at the olfactory receptor level. Calcium imaging of the antennal lobe (AL) revealed that neuronal responses to geosmin decreased with increasing concentration, correlating well with the observed behaviour. Computational modelling of odour transduction and coding in the AL suggests that a broader activation of olfactory receptor types by geosmin in combination with lateral inhibition could lead to the observed non-monotonic increasing-decreasing responses to geosmin and thus underlie the specificity of the behavioural response to low geosmin concentrations

Subducted organic matter buffered by marine carbonate rules the carbon isotopic signature of arc emissions

Ocean sediments consist mainly of calcium carbonate and organic matter (phytoplankton debris). Once subducted, some carbon is removed from the slab and returns to the atmo- sphere as CO2 in arc magmas. Its isotopic signature is thought to reflect the bulk fraction of inorganic (carbonate) and organic (graphitic) carbon in the sedimentary source. Here we challenge this assumption by experimentally investigating model sediments composed of 13C-CaCO3 + 12C-graphite interacting with water at pressure, temperature and redox con- ditions of an average slab–mantle interface beneath arcs. We show that oxidative dissolution of graphite is the main process controlling the production of CO2, and its isotopic compo- sition reflects the CO2/CaCO3 rather than the bulk graphite/CaCO3 (i.e., organic/inorganic carbon) fraction. We provide a mathematical model to relate the arc CO2 isotopic signature with the fluid–rock ratios and the redox state in force in its subarc source