Search

HIV-associated lipodystrophy syndrome (HALS) contributes to the increased cardiovascular risk connoting people living with HIV (PLHIV). HALS recognition, based on clinical ground, may be inaccurate urging an objective instrumental diagnosis. The aim of this study is to search for the DXA-derived fat mass ratio (FMR) threshold, among those suggested for the diagnosis of HALS, able to identify PLHIV at high cardiovascular risk.In a cross-sectional analysis of 101 PLHIV (age 53 ± 11 years, men 55%) and 101 age- and sex-matched uninfected controls, DXA-derived FMR and anthropometric as well as cardio-metabolic parameters were assessed. PLHIV showed a higher FMR (1.15 ± 0.42 vs 0.95 ± 0.18, p 0.01) together with a greater cardio-metabolic derangement than controls, in spite of lower BMI (24.3 ± 4.3 vs 26.9 ± 4.0 kg/mSex-specific FMR thresholds, proposed for diagnosis of HALS, could represent new indices of cardio-metabolic derangement in PLHIV.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in people living with HIV (PLWH) despite successful treatment with combination antiretroviral therapy (cART). HAND pathogenesis is complex and definitive surrogate biomarkers are not clearly defined. Brain function has been assessed through the evaluation of cortical source rhythms with delta waves associated with neurological impairment. The aim of this study was to assess the correlation between EEG cortical sources, cerebrospinal fluid (CSF) biomarkers, and neurocognitive tests in PLWH with HAND. PLWH with HAND without significant comorbidities were enrolled. Baseline rsEEG-LORETA waves, CSF biomarkers (t-tau, p-tau, β-amiloid

We compared the performance of several deformable mirrors and deformable lenses as regard their capability of correcting static and dynamic aberrations both in open- and closed- loop. These tests highlighted notable differences between the devices as regards the performance in different cases, as well as their ease to use.

Since the introduction of combined antiretroviral therapy, human immunodeficiency virus (HIV) infection is no longer a contraindication for solid organ transplantation. In HIV/hepatitis C virus (HCV)-coinfected patients undergoing liver transplantation, HCV-related cirrhosis, drug-drug interactions, and calcineurin inhibitors-related toxicity affect clinical outcomes. Therapeutic drug monitoring can be useful to assess antiretroviral over- or underexposure in this cohort. We report the clinical characteristics along with antiretroviral trough levels of maraviroc, darunavir, and etravirine in 3 HIV/HCV-coinfected liver transplant recipients who developed post-transplant liver cirrhosis.

Objectives: The DUAL study is a phase III, randomized, open-label, multicenter, 96 weeks-long pilot study in virologically suppressed HIV-1+ patients with the aim of evaluating the efficacy and the impact on non-HIV related morbidity of switching to a dual therapy with darunavir-ritonavir (DRV/r) and rilpivirine (RPV). Methods: We recruited patients who received a PI/r-containing HAART for >=6 months, HIV-RNA< 50 cp/mL for >=3 months, eGFR>60 mL/min/1,73m2, without DRV or RPV RAMs. We randomized patients in arm A: RPV+DRV/r QD or arm B: triple therapy. Primary endpoint: percentage of patients with HIV-RNA< 50 cp/mL at week 48 (ITT). VACS index, Framingham CVD risk (FRS) and urinary RBP were calculated. We used Chi-square or Fisher statistics for categorical variables and Mann-Whitney U for continuous ones. Results: Forty-two patients were enrolled (23 in arm A, 14 in arm B, plus 5 screening failures): 26 patients reached 48 weeks: 17/17 had HIV-RNA< 50 cp/mL in arm A versus 8/9 in arm B (Figure). One patient in arm A showed detectable HIV-RNA at baseline (955 cp/mL), reported scarce adherence and was discontinued at week 4. Similar changes were observed in median CD4/mL between baseline and week 48 (-14 versus -116, p n.s.). Thirty-one in arm A and 20 in arm B adverse events took place, whereas only 1 serious (arm A, unrelated to HAART). Among the 7 discontinuations (4 in A, 3 in B), only 1 was related to adverse event (arm A: G3 depression, insomnia, weakness). The tolerability parameters (FRS, VACS index, uRBP) did not vary from baseline to week 48.

Using vibrational (Fourier transform IR and Raman) spectroscopy, ascorbic acid/dimethyl- and diethylsulfoxide solutions have been studied. Noticeable changes obwerved in the range of S=O-groups vibrations can be explained by the presence of hydrogen bond between ascorbic acid and sulfoxides. Based on spectral analysis data, various types of ascorbic acid/sulfoxide hydrogen-bonded complexes were revealed. As the results of studies show, the ascorbic acid/dimethylsulfoxide system has predominantly complexes of one type whereas the ascorbic acid/diethylsulfoxide system can contain complexes of three types.

In this paper we present a Deformable Mirror (DM) based on the continuous voltage distribution over a resistive layer. This DM can correct the low order aberrations (defocus, astigmatism, coma and spherical aberration) using three electrodes with nine contacts leading to an ideal device for sensorless applications. We present a mathematical description of the mirror, a comparison between the simulations and the experimental results. In order to demonstrate the effectiveness of the device we compared its performance with the one of a multiactuator DM of similar properties in the correction of an aberration statistics. At the end of the paper an example of sensorless correction is shown.

We present the first study of atomic clusters irradiated by ultra-short pulses. A weak prepulse has been shown to allow energetic coupling with the clusters enhancing the electron yield.

Non-conventional strategies with nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimens in antiretroviral naive human immunodeficiency virus (HIV) -infected patients have been explored in clinical trials. A prospective, open-label, randomized (1:1), multicentre, proof-of-concept trial (VEMAN study, EUDRACT number 2008-006287-11) was conducted assigning HIV-infected naive patients to once-daily maraviroc plus lopinavir/ritonavir (MVC group) or to tenofovir/emtricitabine plus lopinavir/ritonavir (TDF/FTC group). Clinical and laboratory data were collected at baseline, and after 4, 12, 24, 36 and 48 weeks with the objective to evaluate the 48-week virological and immunological efficacy. HIV-1 DNA load and CD4(+) T-cell subsets were analysed on frozen peripheral blood mononuclear cells collected at baseline, 4 and 48 weeks to explore the trend in HIV reservoirs. Fifty patients were randomized and included in the analysis. During follow up, HIV-1 RNA decreased similarly in both groups and, at week 48, all patients in the MVC group and 22/24 (96%) in the TDF/FTC group had < 50 copies/ml of HIV-1 RNA. CD4(+) trend during follow up was higher in maraviroc-treated patients (MVC group: 286 (183-343) versus TDF/FTC group: 199 (125-285); Mann-Whitney U-test: p 0.033). A significant 48-week increase of CCR5(+) CD4(+) T cells and CD4(+) effector memory cells was observed among maraviroc-treated patients (Wilcoxon signed rank test: p 0.016 and p 0.007, respectively). No significant variations were found in naive and central memory CD4(+) T cells. Among naive patients with an R5 virus, treatment with maraviroc and lopinavir/ritonavir was shown to provide a virological response compared to a triple therapy and a greater immunological benefit.

Options for antiretroviral therapy in patients infected with HIV continue to expand as new drugs are integrated into treatment regimens. Nucleoside/nucleotide reverse transcriptase inhibitors (Nt/NRTIs) remain the backbone of highly active antiretroviral therapy (HAART). Although this is the oldest class of antiretrovirals, pharmacokinetic and pharmacodynamic properties have been less studied as compare to protease inhibotors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). The aim of this article is to review the current status of clinical pharmacology onf Nt/NRTIs, highlighting the issues with clinical interest. Therefore, implications of intracellular pharmacokinetics on dosing schedule, potential for drug-drug interaction and pharmacodynamics is discussed.

The development of new medical tools for minimal-invasive surgery is essential for the reduction of pain, side-effects and hospitalisation costs. The benefits of using optical methods in some procedures are now well recognised. In this context semiconductor optical sources offer the advantages of high efficiency, compactness, low cost, long lifetime, low power consumption and high reliability. The optical source presented in this paper comprises a phase-locked, high-power laser diode array and beam shaping optics designed to optimise the coupling to small-diameter optical fibres. The high-power, index-guided laser array used in this work has been developed to achieve high-brightness by adopting a specially designed optical cavity based on the parabolic taper for each individual element in the array. With this design the individual elements are phase-coherent and the fundamental mode of the array is dominant, thus achieving quasi-diffraction-limited operation without the use of external lenses. Compared to other high-brightness laser arrays, the parabolic bow-tie laser array used here offers the advantages of simple device fabrication, reduced costs and compactness. In this work, specially designed lenses are used to circularise the beam and, therefore, to focus the beam to a small spot-size to improve coupling to single mode fibres. Details of the device characteristics, with emphasis on beam quality and phase front, and of the design of anamorphic optics for beam shaping and focusing will be presented in the context of the integration of the high-brightness laser array with the specially design optics to achieve optical power delivery exclusively where necessary via small-diameter optical fibres.

Sym-dialchylsulfoxides (DASO), with both the hydrophilic and hydrophobic character, are able to destabilize the native structure of proteins by weakening hydrophobic interactions between non-polar residues as well by perturbing the structure of water surrounding the protein molecule. They showed effective cryoprotective effect on living system, more enhanced in the presence of diethylsulfoxide (DESO) than of dimethylsulfoxide (DMSO) or di-n-propylsulfoxide (DnPSO) (1). The knowledge of the influence of DASO on the thermal denaturation and to the structural stability of protein is essential to understand their role in the cryoprotective effect and we approached this problem by studying the thermal denaturation of lysozyme by means of Differential Scanning Calorimetry (DSC).

Digital European cordless telephone (DECT) is a second generation wireless network standard released by the European Telecommunications Standard Institute (ETSI). DECT services are offered to cordless portable parts (CPP), and include wireless PABX, telepoint, and data. Low cost, low power consumption, and hand held CPPs are the standard target. These features pose challenging demands on some CPP functional modules and require components specifically designed and intended for use in DECT systems. The authors have been involved in the design and realization of a prototype DECT endpoint in order to verify how close it is possible to get to the target results with currently available (noncustom) low cost components, and to investigate related technology trends. The DECT standard, the endpoint architecture and modules are described. Measurement results are displayed and compared with standard specifications. Cost, size, and power consumption considerations are given. A view of the CPP evolution due to the use of announced components is then shown. >

Aggressive treatment has been advocated for the management of primary HIV infection (PHI), but the composition and the optimal duration of therapy are still to be determined. In addition, time to undetectable viral load (VL), rate and duration of VL suppression as well as subsequent therapeutic choices remain issues widely debated. We evaluated the rate and duration of VL suppression in 12 consecutive patients with PHI given triple-drug treatment with zidovudine, lamivudine and indinavir (highly active antiretroviral therapy, HAART) at onset of the acute illness and subsequently switched to a simplified 2-NRTI-based regimen once VL suppression was maintained for at least 6 months. Throughout the study, no patient discontinued treatment because of symptoms attributed to the study medications. In the study population, undetectable VL was achieved after a median of 84 days (range: 67-135) on HAART and was maintained for a median of 194 days (range: 179-205) before simplification. After switching to simplified maintenace, undetectable VL was maintained in all patients for at least 6 months. Only one patient experienced virological failure, plasma HIV-RNA remaining suppressed for a median foliow-up of 33 months (15-54) and T-CD4+ being steadily higher than 500/mL in the remaining patients. Our results suggest that simplification of HAART in patients promptly treated during PHI and maintaining undetectable VL for at least 6 months before simplification may be a valid option capable of controlling viral replication and maintaining an optimal immunological profile for a prolonged time.

The advances in the use of the Global Positioning System (GPS) and the dramatic price reduction which has been experienced by GPS products has turned GPS into an affordable and effective technology for the design of public transport fleet management solutions. An in-depth analysis of GPS-based fleet location systems in five European sites and the additional experiences outside Europe have shown that GPS has all it needs to become the automatic vehicle location technology for public transport fleets. It does not introduce propagating errors (like dead reckoning) and does not require distributed infrastructure on the ground (like signposts). The main drawbacks, limited availability and accuracy, can be solved by integrating a dead reckoning system and adopting differential GPS (DGPS), respectively. Since these add-ons have a clear influence on first time costs, system design must be tightly driven by application requirements and by an up-to-date view on the rapidly evolving world of location and communication solutions.

Divalent cationic bipyridilium derivatives (Paraquat) have been widely used in agriculture; the primary target of these chemicals has been considered to be the phospholipids, and their effects could be modulated by the presence of bivalent cations. A study of paraquat (PQ)-phospholipid (PL), with different charge at pH 7, has been carried out by means of some different chemico-physical techniques. The systems PQ-dipalmitoylphosphatidic acid (DPPA) and PQ-dipalmitoylphosphatidylcholine (DPPC) water suspensions at pH 7 have been investigated. The experimental results demonstrate that the interaction between PQ and PL is mainly electrostatic; PQ strongly binds DPPA, which bears one negative charge at pH 7, but only weakly DPPC. The small changes in the DSC curves of DPPC can be explained by a small penetration into PL bilayer of the hydrophobic tail of PQ molecules. The presence of calcium ions, in an amount sufficient to bind completely the lipid, strongly alters the DPPA-PQ interactions, thus inhibiting the binding of PQ to lipid. On the contrary, the DPPC-PQ interactions are not modified by the presence of calcium ions. The behaviour of PQ is different from that of other polycations as polyamines, due to the steric effects present in the PQ molecule. Our results confirm that the negatively charged PL could be the possible molecular target of PQ. The electrostatic interactions are strongly modulated by the presence of cations with a great affinity for the phosphate group, such as calcium ions. © 1995 Elsevier Science Ireland Ltd. All rights reserved.

The stability of cefodizime in five intravenous infusion fluids (0.9% sodium chloride, 5% dextrose in water, 10% dextrose in water, 5% amino acid injection, 3% polygeline) was studied at room temperature and at 4 degrees C. The compatibility of cefodizime with commonly used injectable drugs (ranitidine, metoclopramide, folinic acid, furosemide, aminophilline, methylprednisolone, betamethasone, hydrocortisone, dexamethasone, ketoprofen, noramidopyrine, acetylcysteine, digoxin, diazepam, acetylsalicylic acid, chlorpromazine, clonidine, clomipramine) was studied in 0.9% sodium chloride and 5% dextrose at room temperature. At intervals during the storage periods (up to 24 hrs at room temperature; up to 6 days at 4 degrees C) color, clarity and solution pH were examined; cefodizime content was determined by a microbiological method. Cefodizime concentrations remained greater than 90% of the initial concentrations in all infusion fluids for at least 24 hrs at room temperature and 6 days at 4 degrees C. No visual changes or appreciable changes in pH were observed for any of the solutions. Immediate clouding was observed when chlorpromazine was combined with the solution of cefodizime. A color change was observed when acetylcysteine was mixed with cefodizime. An increase in pH was noted when aminophilline was added to the solution of cefodizime. However, cefodizime concentrations remained greater than 90% of the initial concentrations of the solutions after mixture with all the tested drugs for at least 24 hrs at room temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

A 45 year-old nurse reported a needlestick injury from an unknown source. A three-drug anti-HIV post-exposure prophylaxis (PEP) regimen with Combivir (azidotimidine/lamivudine) 1 pill plus nelfinavir (250 mg) 5 pills twice daily was prescribed, but efavirenz pills (200 mg) were erroneously supplied instead of nelfinavir; consequently she took 5 pills (1000 mg) of efavirenz. Shortly thereafter she experienced dizziness, lightheadedness, irritability, impaired concentration, anxiety and insomnia. Nevertheless, the morning after she continued to take all the medications at breakfast. Her central nervous system (CNS) symptoms worsened and she also experienced mental confusion and had an unsteady gait. She then returned to the Infectious Disease consultant and soon it was realized that she had ingested an overdose of efavirenz. The nurse was admitted to the hospital for observation. On admission, she was in an erethismic state with altered mental state and unsteady gait. The physical examination was otherwise normal as were laboratory tests. Efavirenz blood levels showed a concentration of 9926 ng/ml 3 hours after the second dose (1000 mg) had been ingested, 4242 ng/ml after 24 hours, and 2508 ng/ml after 48 hours. The patient’s CNS symptoms improved and resolved within the next 24 hours. Meanwhile, PEP prophylaxis was continued with Combivir and nelfinavir to complete the 4-week period without further complications. She tested HIV negative at 9 months of follow-up. Journal of Chemotherapy Vol. 19 n. 1 (110) 2007

Dimyristoylphosphatidylcholine (DMPC) – polylysine and DMPC–histones systems have been studied by Raman spectroscopy and differential scanning calorimetry. The results of both techniques indicate that the interactions are mainly confined to the lipid–water interface. The protein fraction of histones giving rise to a partial penetration into the bilayer is not the lysine-rich fraction but rather the non-polar component of the proteins. On the basis of the results obtained, the formation of lipoprotein complexes between histones and DMPC appears to be ruled out.

Background The aim of this study was to investigate the impact of anti-HBc (HBcAb) positivity on the progression of liver fibrosis (Fibrosis-4 score >3.25) in the Italian cohort of HIV-infected individuals naïve to antiretroviral treatment (ICONA). Methods All patients with FIB-4 Results Patients who were HBcAb+/HCV-/HBs antigen (HBsAg)- and HCV+/HBcAb+/HBsAg- or HBsAg+/HBcAb+/HCV- had CD4+ cell counts below the nadir and significantly higher prevalence of AIDS diagnosis at baseline than the other groups (P < .0001). A Cox regression model adjusted for age, HIV transmission mode, country of birth, and alcohol consumption showed a higher relative risk (HR) of progression to FIB-4 >3.25 in HCV+/HBcAb+/HBsAg- patients (HR, 7.2; 95% CI, 3 8–13.64). Conclusions HBcAb+ contributes to liver damage in HIV+/HCV+/HBcAb+/HBsAg- subjects. A careful monitoring for signs of previous HBV infection is needed in this kind of patients.