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This is because bio-naïve patients are candidates for biological treatment with a higher PASI than bio-experienced patients who have taken risankizumab following initial secondary inefficacy. Bio-experienced patients achieved PASI90 less than bio-naïve (40.41% vs. 55%, I P i = 0.041) at 16 weeks, differences was also detected in PASI90, 75 and PASI < 3 at week 28 between the two populations (65% vs. 84%, 77% vs. 93% and 78% vs. 91%, I P i = 0.003, I P i = 0.001 and I P i = 0.011 respectively). Effect of Risankizumab on patient-reported outcomes in moderate to severe psoriasis: the UltIMMa-1 and UltIMMa-2 randomized clinical trials. [Extracted from the article]

HCV infection has been hypothesized as a contributor of poor CD4+ recovery in patients living with HIV (PLWHIV). Aim of this study was to evaluate CD4+, CD8+ cells and CD4/CD8 ratio trends before and after HCV treatment with direct acting agents (DAA) in PLWHIV. HIV/HCV patients enrolled in ICONA and HepaICONA cohorts with HIV‐RNA≤50 copies/ml who achieved a sustained viral response after DAA treatment were studied. A linear regression model was used to investigate CD4+, CD8+ and CD4/CD8 changes 12 months before and after DAA treatment. A total of 939 HIV/HCV patients were included, 225 (24.0%) female, median age: 53 years (IQR 50–56). At DAA initiation, CD4+ T cell count was <350 cells/mm3 in 164 patients (17.5%), and 246 patients (26.2%) had liver stiffness>12.5 kPa. Trends of CD4+ and CD4/CD8 ratio were similar before and after DAA in all study populations (CD4+ change +17.6 cells/mm3 (95%CI −33.5; 69.4, p = 0.494); CD4/CD8 change 0.013 (95%CI −0.061; 0.036, p = 0.611). However, patients treated with ribavirin (RBV)‐free DAA showed a significant decrease in CD8+ cells (−204.3 cells/mm3, 95%CI −375.0;‐33.4, p = 0.019), while patients treated with RBV experienced CD8+ cell increase (+141.2 cells/mm3, 95%CI 40.3; 242.1, p = 0.006). In conclusion, HCV eradication following DAA treatment does not seem to have an impact on CD4+ T cell recovery in PLWHIV. However, a fast decline of CD8+T cells has been observed in patients treated without RBV, suggesting a favourable effect of HCV clearance on the general state of immune activation. [ABSTRACT FROM AUTHOR]

Objectives: The management of HIV disease is complicated by the incidence of a new spectrum of comorbid noncommunicable diseases (NCDs). It is important to document changes in the prevalence of NCDs over time. The aim of the study was to describe the impact of ageing on HIV markers and on the prevalence of NCDs in people living with HIV (PLWHIV) in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) seen for care in 2004–2014. Methods: Analyses were conducted separately for a closed cohort (same people seen at both times) and an open cohort (all people under follow‐up). We used the χ2 test for categorical factors and the Wilcoxon test for quantitative factors to compare profiles over time. Results: The closed cohort included 1517 participants and the open cohort 3668 under follow‐up in 2004 and 6679 in 2014. The median age of the open cohort was 41 [interquartile range (IQR) 37–46] years in 2004 and 44 (IQR 36–52) years in 2014. Analysis of the closed cohort showed an increase in the prevalence of some NCDs [the prevalence of dyslipidaemia increased from 75% in 2004 to 91% in 2014, that of hypertension from 67 to 84%, and that of cardiovascular disease (CVD) from 18 to 32%] and a decrease in renal function (5% with eGFR < 60 mL/min per 1.73 m2 in 2004 versus 30% in 2014); the percentage of people in the high‐risk group for the Framingham CHD score more than tripled (from 13 to 45%). Results in the open cohort were similar. Conclusions: The burden of NCDs in our PLWHIV population markedly worsened over a 10‐year time‐span, which is likely to be a result of the effects of both ageing and HIV infection as well as their interaction. Special attention must be given to the management and prevention of NCDs. [ABSTRACT FROM AUTHOR]

Introduction: Concerns about dolutegravir (DTG) tolerability in the real‐life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG‐based regimens from a large cohort of HIV‐infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)‐naïve and virologically suppressed treatment‐experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG‐based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART‐naïve, 747 TE) were included. The one‐ and two‐year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART‐naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART‐naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART‐naïve (2.1%) and TE (1.7%) patients. In ART‐naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG‐based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC‐based triple‐therapies, aHR = 3.56, p = 0.012 for tenofovir‐based) and for toxicity (aHR = 5.26, p = 0.030 for ABC‐based, aHR = 6.60, p = 0.024 for tenofovir‐based). The one‐ and two‐year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first‐line and switching ART. The low risk of treatment‐limiting toxicities in ART‐naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Flood risk assessment is a crucial step for flood risk management purposes, thus answering the requirements of the European Flood Directive 60/2007/EC (European Commission). In this work, a census data scale, which has been considered as a good compromise between spatial resolution and availability of open socio-economic data, is adopted for risk analysis. The damage categories included are structures, household contents and the most representative economic activities in the city of Florence (Italy). Moreover, since Florence is an important art city, a preliminary evaluation of risk to cultural heritage is carried out. Data from hydraulic simulations, historical reports of the devastating 1966 flood and the cultural heritage recognition sheets allow estimating and mapping the annual expected number of works of art lost in the absence of risk mitigation strategies. [ABSTRACT FROM AUTHOR]

Remotely sensed Land Surface Temperature (LST) and Fraction of Photosynthetically Active Radiation absorbed by vegetation (FPAR) are assimilated, respectively, into the Surface Energy Balance (SEB) equation and a Vegetation Dynamics Model (VDM) in order to estimate surface fluxes and vegetation dynamics. The problem is posed in terms of three unknown and dimensionless parameters: (1) neutral bulk heat transfer coefficient, which scales the sum of turbulent heat fluxes, (2) soil and canopy evaporative fractions that characterize partitioning among the turbulent heat fluxes over soil and vegetation, and (3) specific leaf area, which captures seasonal phenology and vegetation dynamics. The model is applied over the Gourma site in Mali, the northern region of the West African Monsoon (WAM) domain. The application of the model over the Gourma site shows that spaceborne LST observations can be used to constrain the SEB equation and obtain its key two unknown parameters (i.e., neutral bulk heat transfer coefficient and evaporative fraction). We demonstrate that the spatial patterns of estimated neutral bulk heat transfer coefficient and evaporative fraction resemble, respectively, those of independently observed vegetation index and soil moisture. The framework also yields estimates of surface energy balance components. The daily sensible, latent, and ground heat flux estimates at the Agoufou site that is located in the south of the Gourma region have, respectively, a root-mean-square error (RMSE) of 53.6, 34.4, and 45.1 Wm−2. The daily sensible heat flux estimates at the Bamba site, which is located in the north of the Gourma domain, have a RMSE of 42.6 Wm−2. The results also show that remotely sensed FPAR observations can constrain the VDM and retrieve its main unknown parameter (specific leaf area) over large-scale domains without costly in situ measurements. The results indicate that the estimated specific leaf area values vary reasonably with the expected influential environmental variables such as precipitation, air temperature, and solar radiation. Assimilating FPAR observations into the VDM can also provide an estimate of Leaf Area Index (LAI) dynamics. The estimated LAI values are comparable in magnitude, spatial pattern and temporal evolution with satellite retrievals. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to investigate the incidence of AIDS-defining cancers ( ADCs) and virus-related and non-virus-related non- AIDS-defining cancers ( NADCs) in HIV-infected patients compared with the general population, and to assess the risk factors associated with these malignancies. Methods We performed a retrospective cohort study for the period from 1999 to 2009 of HIV-infected patients residing in the Local Health Authority of Brescia (northern Italy). Observed cancers in patients with HIV infection were compared with expected cancers in the population living in the same area using standardized incidence ratios ( SIRs). Risk factors were assessed using Poisson regression analysis. Results A total of 5090 HIV-infected patients were included in the study, with 32 390 person-years of follow-up. We recorded 416 tumours in 390 HIV-infected patients. Two hundred of these (48.1%) were ADCs, 138 (33.2%) were non-virus-related NADCs and 78 (18.7%) were virus-related NADCs. An increased risk ( SIR = 4.2) of cancers overall was found in HIV-infected patients. A large excess of ADCs ( SIR = 31.0) and virus-related NADCs ( SIR = 12.3) was observed in HIV-infected patients, while the excess risk for non-virus-related NADCs was small ( SIR = 1.6). The highest SIRs were observed for Kaposi sarcoma among ADCs and for Hodgkin lymphoma among virus-related NADCs. Conversely, among non-virus-related NADCs, SIRs for a broad range of malignancies were close to unity. In multivariate analysis, increasing age and CD4 cell count < 50 cells/μL were the only factors independently associated with all cancers. Conclusions Among HIV-infected people there was an excess of ADCs and also of NADCs, particularly those related to viral infections. Ageing and severe immunodeficiency were the strongest predictors. [ABSTRACT FROM AUTHOR]

A variational data assimilation model is developed to estimate surface energy fluxes from remotely sensed land surface temperature (LST). Components of the surface energy balance (sensible, latent, and ground heat fluxes) have different degrees of efficiency in dissipating available energy. LST is the state variable of the surface energy balance (SEB). Land surface models that capture the exchange and storage of energy in the soil and vegetation media use LST as a prognostic variable. Sequences of LST measurements implicitly contain information on partitioning of available energy among the components of SEB. In this study, we focus on the estimation of the sum of the turbulent fluxes as well as the partitioning among them. Two dimensionless parameters are used to characterize the sum and the partitioning. Using LST observations from a constellation of satellites, these parameters are mapped over a large region. The remotely sensed LST is assimilated to the heat diffusion equation within the SEB framework. In addition, a model error term is added to the SEB equation such that the variational data assimilation scheme includes model uncertainty as well as observation error. The framework is tested over the Southern Great Plains region. The mapped results of the surface evaporation estimation are used to study the surface control on evaporation. Independent mapped soil moisture estimates from an airborne microwave campaign are used. The dependence of the evaporation control-soil moisture relationship on vegetation cover and plant functional types over large regions is examined in this first and exploratory study. [ABSTRACT FROM AUTHOR]

A novel paradigm investigates the ability to understand an agent's intended goal in children with autism (N=25), typically developing children (N=46), and adults (N=16+12) by watching a non-human agent's kinematic properties alone. Computer animations depict a circle at the bottom of a U-shaped valley rolling up and down its slopes and getting closer to a target resting at the top of either side of the valley. The circle's persistent motion and improving attempts evoke the attribution of the intention to reach the target, regardless of whether the circle fails or attains its goal. Children with autism are as able as controls to infer an agent's intended-goal, disregarding its failure to reach the target. In addition, the study showed that the perception of persistent motion is a sufficient but not a necessary cue for very young children and children with autisn to attribute intention to an agent, whereas adults consider the persistent motion cue as a sufficient and necessary cue to attribute intention to an agent. [ABSTRACT FROM AUTHOR]

Objectives To assess prevalence and predictive factors of viro-immunological discordant trends in a cohort of heavily pretreated patients. Methods Factors associated with viro-immunological discordant trends either as categorical or continuous measures have been studied in 159 heavily pretreated HIV-positive patients from a multicentre prospective study of real- vs. virtual-phenotype. Univariate and multivariate logistic regressions were used to assess risk factors for categorical discordant responses, ceasing follow-up at week 32 since enough patients had been on the original drug combination for a sufficient amount of time to evaluate their immune response. Complementary linear regression analysis was performed over the entire 48 weeks' follow-up considering CD4 and plasma viral load (pVL) as continuous measures. Results Among 58 virological responder patients (≥1 log10 HIV-1 RNA copies/mL decrease) and 101 virologically non-responders, immunological discordances (increase in CD4 count of8 months on treatment (HR 41.64, 95%CI 19.27–64.01; P <0.001) correlated with highly significant immune recovery. Conclusions These data confirm that therapy, possibly including PIs, should be continued in heavily pretreated patients and that hard-to-reach pVL undetectability is not essential to obtain immunologic recovery; however, this is strongly increased by the degree of pVL reduction that should be achieved. [ABSTRACT FROM AUTHOR]

Soil-transmitted helminth (STH) infections represent a major public health problem in poor and developing countries. During the period September-October 1998 we conducted an epidemiological survey of STH infections in schoolchildren of an urban area (group A) and an indigenous reserve (group B), in the Municipality of Ortigueira, State of Paranà, Brazil, to assess potential benefits of mass treatment. Stool samples were examined for helminth eggs by quantitative (Kato-Katz) technique to determine the prevalence and intensity of intestinal parasitic infection. Moreover, we examined the relationship between prevalence and intensity of STH infections and housing/hygienic factors (by means of a 7-item questionnaire). 236 schoolchildren aged 5-15 years were enrolled, 136 in group A and 100 in group B. The prevalence of STH infections was significantly higher in group B (93%) than in group A (22%) (P < 0.001). Detected parasites were: A. lumbricoides (16.1% prevalence in group A, 88% in group B, P < 0.001), hookworms (5.8% in group A, 52% in group B, P < 0.001) and T. trichiura (5.1% in group A, 2% in group B, P = 0.2). Heavy infections were detected in 2.9% and 23% of the children in group A and B, respectively (P < 0.001). Housing/hygienic indicators were significantly poorer in group B. A statistically significant correlation was observed between total prevalence of STH infections and prevalence of high-intensity infections with most housing/hygienic variables. On the basis of these results, mass treatment and educational interventions were suggested for the indigenous community, whereas target treatment and educational interventions were suggested for the urban community. Even in a geographically homogeneous area different epidemiological realities can be found, which in turn can influence infection levels and control programmes. [ABSTRACT FROM AUTHOR]

We report the results of a retrospective analysis of the clinical charts of imported malaria cases notified during the period 1991-95 in the Lombardy region of northern Italy. We analysed 694 admissions related to 683 individuals. The proportion of immigrants increased during the observation period from 34.4% in 1991 to 59.9% in 1995 (P = 0.002). P. falciparum was the causative species in 534 cases (78. 2%), and 591 (90.1%) of 656 cases with a full travel history had travelled to Africa. Information on chemoprophylaxis was available in 604 cases: 429 (71.0%) reported no drug intake, 140 (23.2%) an incomplete, and 35 (5.8%) a complete chemoprophylactic course. The proportion of subjects who had initiated malaria chemoprophylaxis was significantly lower among immigrants (7.4%) than nonimmigrants (50.2%) (P < 0.001). Severe disease was diagnosed in 26 (4.7%) of 551 cases of falciparum malaria, with a significantly lower incidence among immigrants (1.3% vs. 9.2%; P < 0.001). Eight deaths were recorded, all among nonimmigrants, whose fatality rate was significantly higher (P = 0.02). Mefloquine treatment of cases of uncomplicated falciparum malaria was associated with a significantly shorter fever clearance time (2.8 days +/- 1.5 vs. 3.5 days +/- 1.9; P < 0.001) and mean hospital stay (5.9 days +/- 4.4 vs. 8.3 days +/- 5.1; P < 0.001) compared to quinine treatment. [ABSTRACT FROM AUTHOR]

A recent non-destructive technique allows estimation of leaf chlorophyll content using the portable SPAD-502 chlorophyll meter. Measurements were taken on four species (winter wheat, maize, soyabean and tobacco) subjected to different nitrogen regimes or senescence status and the non-destructive readings were compared with analytical results obtained by solvent extraction. In general, the relationship between the SPAD measurement and the analytical result was not linear and species was a factor in three out of four crops. Linear, quadratic and exponential curve fitting are presented; only the interpolation with a polynomial exponential function adequately describes the whole data set. The presence of statistically non-significant differences between the estimated values of wheat and maize on the one hand and significant points of difference between those of tobacco and soyabean on the other suggests distinct behaviour patterns for monocots and dicots. This type of response may be explained by differences in the optical properties of pigments with differing spatial distributions (sieve effect) and therefore by in vivo and in vitro different procedures and the structural diversity of leaves belonging to the two subclasses. [ABSTRACT FROM AUTHOR]

Nine Budey tobacco cultivars were tested in three locations of the Veneto region during 3 years in order to single out the ones most suitable for the target environment. Differences among cultivars were found for plant development indicators, yield and visual quality of the cured leaf, but not for physical and chemical properties of the leaf, even if most characters varied widely among the environments. High yields combined well with high scores of Quality Index. F1 hybrids CAS 83-1E and C. 03-6 resulted on average the best performing cultivars, both for yield and quality, confirming the findings of previous trials. [ABSTRACT FROM AUTHOR]

From 1985 to 1987, eight varieties of domestic and foreign Burley tobacco were studied in some Northern Italy locations (Veneto Region), as an alternative to the air-cured light and dark tobacco presently grown in that area. An average 3-year yield equal to or higher than 3 t ha-1 of cured leaf was obtained for all the tested varieties, which indicates a general adaptation to the environment. Early-flowering types were more productive than late-flowering ones; the qualitative leaf traits (alkaloid content, combustibility and specific leaf weight) were mainly related to the growing seasons. The yield stability test and the mean leaf yields highlighted the CAS 83-1A and CAS 83-1E cultivars as high-yielding and stable genotypes, and Virginia 528 as a medium to high yielding genotype adapted to less favourable conditions. [ABSTRACT FROM AUTHOR]

The HAART reduces the risk of HIV-related renal disease but the incidence of end-stage renal disease (ESRD). Therefore, efficacy and safety of renal transplantation (Tx) is an important resource in the HIV-infected population. We reported the results of kidney Tx in HIV+patients from deceased donors from June 2007 to March 2012 at our institution. The patients had to have CD4+T-cell counts≥200/mm3 and undetectable plasma HIV-RNA if on HAART. The induction immunosuppressive therapy consisted of metilprednisolone and basilixmab; tacrolimus and/or mycofenolic acid were used for maintenance therapy. The therapeutic drug monitoring (TDM) has been performed for the adjusting of both their doses []. A total of 14 patients underwent kidney Tx. They were on dialysis (haemodialysis=13, 92.9%; peritoneal=1, 7.1%) for 5±3.1 years and they were included on the Tx waiting list for 10±8 months. The baseline characteristics are showed in Table 1. [ABSTRACT FROM AUTHOR]

Atripla is a fixed-dose drug combining FTC/TDF/EFV into a single pill and may increase adherence. To our knowledge, there is little data comparing the durability of Atripla vs. other regimens. Our first aim was to compare the durability of Truvada (TVD)/EFV or TVD/PIr or Atripla started when ART-naïve, in terms of time to virological failure (VF first of 2 consecutive values>50 and>200 copies/mL), time to discontinuation of any drug in the regimens, or both. Then, we aimed to compare the incidence of virological rebound (VR)>200 copies/mL in patients (pts) currently receiving these same regimens after achieving a viral load (VL)≤80 copies/mL. Pts in the Icona Foundation Study who started for the first time a cART regimen with TVD/EFV or TVD/PIr or Atripla, either while ART-naïve (analysis 1) or while with a VL≤80 (analysis 2) were included. In analysis 1, pts' follow-up accrued from cART initiation to the date of the event (VF or discontinuation of any drug in the regimen) or to the date of last available visit/VL. In the TVD/EFV group a switch to Atripla was not counted as an event. Survival analysis employing KM curves and Cox regression model was used. In analysis 2, follow-up accrued from the date of first VL≤80 (which could be achieved with any cART) to VR or last VL and only person years (PY) on the regimens of interest were considered. Rates were calculated as number of VR per 1000 PY and relative rates (RR) compared using a Poisson regression model. In analysis 1, 515 pts starting TVD/EFV, 1001 TVD/PIr and 160 Atripla when ART-naïve on average in 2010 (IQR: 2008-2011) were included. PI/r were LPV (33%), ATV (38%) fos-APV (4%) and DRV (24%). Median age was 38 years, 19% females, 40% heterosexuals. Pts starting Atripla were younger, less likely to be female, IDU, HCV co-infected, to have AIDS and they had higher CD4 count (334 vs. 280). By 2 years, 48% (95% CI: 43-53) of those initiating TVD/PIr experienced the composite endpoint of VF or drug discontinuation vs. 20% in the other groups (p=0.0001). Median time to switch from TVD to Atripla in the EFV group was 17 months (95% CI: 12-23). The table shows the results of the Cox regression analysis. In analysis 2 (n=1,425), the rates of VR were 16.8 per 1000 PY for TVD/PIr, 11.17 for TVD/EFV and 5.3 for Atripla (adjusted RR vs. TVD/PIr=0.51, 95% CI: 0.19-1.34). Durability of Atripla was comparable to that of TVD/EFV and potentially longer than that of TVD/PIr. Unmeasured confounding cannot be ruled out. [ABSTRACT FROM AUTHOR]

An abstract of the article "Kidney transplantation in HIV-positive patients: a report of 14 cases," by S. Casari and colleagues is presented.

Purpose of the study Although HIV infection impacts the proportion and phenotype of regulatory T-cells (Tregs), discrepant results have been reported depending on the surface markers employed to characterize them and on the patient populations. In addition, the effects of a long-term combined antiretroviral therapy (cART) on Treg cells have not been thoroughly documented. Our study investigated the frequency and number of Tregs and their phenotype in two different groups of HIV-infected patients: one aviremic undergoing long-term cART and one viremic naïve to cART showing a similar CD4+ cell count. Methods Thirty-six HIV+ patients with sustained suppression of plasma viremia (<37 copies/mL) on effective cART for more than 6 years and 22 HIV+patients naïve to cART and without clinical signs of opportunistic infections or tumors at the time of study (untreated group) were included in the study. Healthy donors (HD) were used as control. Flow cytometry on fresh whole blood was used to quantify total Tregs (defined as CD25+CD127low/-CD4+ cells) and the following Treg subsets: naïve (CD45RA+CCR7+) Tregs, central-memory like Tregs (CD45RA-CCR7+, TregCM), effector-memory like Tregs (CD45RA-CCR7−, TregEM) Statistical comparisons of the percentages and number of Tregs and Treg subpopulations were performed by ANOVA or Kruskal-Wallis test. Analysis of covariance was employed in order to adjust for the effect of the age. The Spearman's test was used to assess correlations. Summary of results In viremic untreated and aviremic long-term cART-treated patients the percentage and number of the total Treg cells were not different from those of HD. However, the analysis of Treg phenotype showed a marked redistribution of the Treg subpopulations: in the untreated viremic patients, both the percentage and number of the TregCM subset decreased compared to HD and cART-treated patients, whereas only the percentage of naïve Tregs increased. In particular, the percentage of TregCM was inversely correlated with the viral load (r=−0.51; p=0.016). Conclusions In our aviremic long-term cART-treated and viremic untreated patients, the total Treg cell population seems to be unaffected by HIV infection. However, our results showed that the analysis of the naïve and memory-like Treg subsets may provide a better understanding of the real contribution of Tregs in HIV disease and therapy. [ABSTRACT FROM AUTHOR]

Background: Food allergy (FA) is an inappropriate immunological response to food proteins resulting from an impaired induction of oral tolerance. Various early environmental factors can affect the establishment of intestinal homeostasis, predisposing to FA in early life. In this context, we aimed to assess the effect of chronic perinatal exposure to food-grade titanium dioxide (fg-TiO 2 ), a common food additive., Methods: Dams were fed a control versus fg-TiO 2 -enriched diet from preconception to weaning, and their progeny received the same diet at weaning. A comprehensive analysis of baseline intestinal and systemic homeostasis was performed in offspring 1 week after weaning by assessing gut barrier maturation and microbiota composition, and local and systemic immune system and metabolome. The effect of fg-TiO 2 on the susceptibility of progeny to develop oral tolerance versus FA to cow's milk proteins (CMP) was performed starting at the same baseline time-point, using established models. Sensitization to CMP was investigated by measuring β-lactoglobulin and casein-specific IgG1 and IgE antibodies, and elicitation of the allergic reaction by measuring mouse mast cell protease (mMCP1) in plasma collected after an oral food challenge., Results: Perinatal exposure to fg-TiO 2 at realistic human doses led to an increased propensity to develop FA and an impaired induction of oral tolerance only in young males, which could be related to global baseline alterations in intestinal barrier, gut microbiota composition, local and systemic immunity, and metabolism., Conclusions: Long-term perinatal exposure to fg-TiO 2 alters intestinal homeostasis establishment and predisposes to food allergy, with a clear gender effect., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background and Aims: Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF-associated glomerular and/or tubular dysfunction., Methods: A total of 103 TDF-treated patients were included as follows: age 64 years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV-R) and 71% previously treated with adefovir. Twenty-nine (28%) were switched to ETV because estimated glomerular filtration rate (eGFR MDRD ) was <60 mL/min, 37 (36%) because blood phosphate (P) levels were <2.5 mg/dL and 37 (36%) for both reasons. Kidney, liver and virological parameters were recorded every 4 months thereafter., Results: During 46 (4-115) months of ETV treatment, all patients' renal parameters significantly improved as follows: creatinine from 1.30 to 1.10 mg/dL (P < 0.0001), eGFR MDRD from 54 to 65 mL/min (P = 0.002), P from 2.2 to 2.6 mg/dL (P < 0.0001) and maximal tubule phosphate reabsorption (TmPO4/eGFR) from 0.47 to 0.62 mmol/L (P < 0.0001). Thirteen patients (52%) improved their eGFR MDRD class, P levels were normalised in 13 (35%), and eight (22%) showed improvements in both parameters. Viral suppression was maintained in all but five patients (5%), all of whom had been LMV-R. The 5-year cumulative probability of ETV-R was 0% in LMV-naïve patients, and 11% in LMV-R patients (P = 0.018)., Conclusions: Entecavir is an effective and safe rescue strategy for CHB patients who develop renal dysfunction during long-term TDF treatment., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: To define the pharmacokinetic profile of efavirenz (EFV) in HIV-1 infected patients, when administered alone or with nelfinavir (NFV)., Methods: Eleven HIV-positive patients, in steady-state treatment with EFV and 11 patients in steady-state treatment with EFV+NFV, were evaluated. Blood samples for pharmacokinetic analysis were obtained during a dosage interval. Plasma concentrations of EFV were determined by h.p.l.c., Results: No significant difference was found between the principal pharmacokinetic parameters of EFV when administered alone or in combination with NFV (mean AUC: 57.1-7727.3 vs 60.9+/-12.3 microg ml-1 h; mean CL/F: 0.18+/-0.072 vs 0.16+/-0.04 l h-1 kg-1; mean Cmax: 4.0+/-1.7 vs 4.3+/-1.2 microg ml-1, and mean tmax: 4.1+/-1.7 vs 3.5+/-0.5 h) Mean trough plasma concentrations (C0) of EFV were 1.64+/-0.93 microg ml-1, with and without NFV. A good correlation was found between C0 and AUC(0,24h) (r=0.96; P<0. 01)., Conclusions: Despite the common metabolic pathway, there was no significant influence of NFV on the pharmacokinetics of EFV. EFV exhibits a relatively low interindividual variability and a dosing regimen of 600 mg day-1 assures plasma concentrations that are adequate for inhibition of viral replication.