No Need for Lopinavir Dose Adjustment during Pregnancy: a Population Pharmacokinetic and Exposure-Response Analysis in Pregnant and Nonpregnant HIV-Infected Subjects

ABSTRACT Lopinavir-ritonavir is frequently prescribed to HIV-1-infected women during pregnancy. Decreased lopinavir exposure has been reported during pregnancy, but the clinical significance of this reduction is uncertain. This analysis aimed to evaluate the need for lopinavir dose adjustment during pregnancy. We conducted a population pharmacokinetic analysis of lopinavir and ritonavir concentrations collected from 84 pregnant and 595 nonpregnant treatment-naive and -experienced HIV-1-infected subjects enrolled in six clinical studies. Lopinavir-ritonavir doses in the studies ranged between 400/100 and 600/150 mg twice daily. In addition, linear mixed-effect analysis was used to compare the area under the concentration-time curve from 0 to 12 h (AUC 0–12 ) and concentration prior to dosing ( C predose ) in pregnant women and nonpregnant subjects. The relationship between lopinavir exposure and virologic suppression in pregnant women and nonpregnant subjects was evaluated. Population pharmacokinetic analysis estimated 17% higher lopinavir clearance in pregnant women than in nonpregnant subjects. Lopinavir clearance values postpartum were 26.4% and 37.1% lower than in nonpregnant subjects and pregnant women, respectively. As the tablet formulation was estimated to be 20% more bioavailable than the capsule formulation, no statistically significant differences between lopinavir exposure in pregnant women receiving the tablet formulation and nonpregnant subjects receiving the capsule formulation were identified. In the range of lopinavir AUC 0–12 or C predose values observed in the third trimester, there was no correlation between lopinavir exposure and viral load or proportion of subjects with virologic suppression. Similar efficacy was observed between pregnant women and nonpregnant subjects receiving lopinavir-ritonavir at 400/100 mg twice daily. The pharmacokinetic and pharmacodynamic results support the use of a lopinavir-ritonavir 400/100-mg twice-daily dose during pregnancy

Factors affecting the retention efficiency and physicochemical properties of spray dried lipid nanoparticles loaded with lippia sidoides essential oil

Essential oils (EOs) are widely used in various industrial sectors but can present several instability problems when exposed to environmental factors. Encapsulation technologies are effective solutions to improve EOs properties and stability. Currently, the encapsulation in lipid nanoparticles has received significant attention, due to the several recognized advantages over conventional systems. The study aimed to investigate the influence of the lipid matrix composition and spray-drying process on the physicochemical properties of the lipid-based nanoparticles loaded with Lippia sidoides EO and their retention efficiency for the oil. The obtained spray-dried products were characterized by determination of flow properties (Carr Index: from 25.0% to 47.93%, and Hausner ratio: from 1.25 to 1.38), moisture (from 3.78% to 5.20%), water activity (<0.5), and powder morphology. Zeta potential, mean particle size and polydispersity index, of the redispersed dried product, fell between 25.9 mV and 30.9 mV, 525.3 nm and 1143 nm, and 0.425 and 0.652, respectively; showing slight differences with the results obtained prior to spray-drying (from 16.4 mV to 31.6 mV; 147 nm to 1531 nm; and 0.459 to 0.729). Thymol retention in the dried products was significantly lower than the values determined for the liquid formulations and was affected by the drying of nanoparticles.I.B. acknowledges CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for the financial support (88887.368385/2019-00). E.B.S. acknowledges the Portuguese Science and Technology Foundation (FCT) for the funded projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund). WPO acknowledges the São Paulo Research Foundation (FAPESP) for the financial support (Grant N. 2018/26069-0 and 2011/10333-1).info:eu-repo/semantics/publishedVersio

Avaliação de erosão em áreas peri-urbanas no município de Porto Velho-RO.

A pesquisa objetivou identificar na zona periurbana de Porto Velho-RO áreas potenciais para ocorrência de processos erosivos acelerados. Para tal, foram selecionadas 03 áreas em pontos distintos e nelas identificados pontos críticos em função das atividades antrópicas. Estes foram fotografados, identificados o tipo de erosão ocorrente e mensurados quanto as suas dimensões. A área 01 situa-se nas coordenadas geográficas 8º 47? 59&#8214;S e 8&#947;º 48? 01&#8214; O na BR &#947;64 sentido Cuiabá-Porto Velho. A área 02 situa-se nas coordenadas geográficas 8º 48? &#946;9&#8214; S e 6&#947;º 5&#947;?&#946;&#946;&#8214; na avenida Campos Sales ? Bairro Novo Horizonte sentido Cidade do Lobo. A Área 03 está localizada na BR 364 com Avenida Rio Madeira nas coordenadas geográficas 8º 46? &#947;6&#8214;S e 6&#947;º 5&#946;? &#946;&#947;&#8214;O. Os resultados permitiram concluir que há necessidade urgente de práticas conservacionistas nas três áreas estudadas

Cosmological Parameters from the 2003 flight of BOOMERANG

We present the cosmological parameters from the CMB intensity and polarization power spectra of the 2003 Antarctic flight of the BOOMERANG telescope. The BOOMERANG data alone constrains the parameters of the $\Lambda$CDM model remarkably well and is consistent with constraints from a multi-experiment combined CMB data set. We add LSS data from the 2dF and SDSS redshift surveys to the combined CMB data set and test several extensions to the standard model including: running of the spectral index, curvature, tensor modes, the effect of massive neutrinos, and an effective equation of state for dark energy. We also include an analysis of constraints to a model which allows a CDM isocurvature admixture.Comment: 18 pages, 10 figures, submitted to Ap

A Measurement of the Angular Power Spectrum of the CMB Temperature Anisotropy from the 2003 Flight of Boomerang

We report on observations of the Cosmic Microwave Background (CMB) obtained during the January 2003 flight of Boomerang . These results are derived from 195 hours of observation with four 145 GHz Polarization Sensitive Bolometer (PSB) pairs, identical in design to the four 143 GHz Planck HFI polarized pixels. The data include 75 hours of observations distributed over 1.84% of the sky with an additional 120 hours concentrated on the central portion of the field, itself representing 0.22% of the full sky. From these data we derive an estimate of the angular power spectrum of temperature fluctuations of the CMB in 24 bands over the multipole range (50 < l < 1500). A series of features, consistent with those expected from acoustic oscillations in the primordial photon-baryon fluid, are clearly evident in the power spectrum, as is the exponential damping of power on scales smaller than the photon mean free path at the epoch of last scattering (l > 900). As a consistency check, the collaboration has performed two fully independent analyses of the time ordered data, which are found to be in excellent agreement.Comment: 11 pages, 7 figures, 3 tables. High resolution figures and data are available at http://cmb.phys.cwru.edu/boomerang/ and http://oberon.roma1.infn.it/boomerang/b2

Searching for non Gaussian signals in the BOOMERanG 2003 CMB maps

We analyze the BOOMERanG 2003 (B03) 145 GHz temperature map to constrain the amplitude of a non Gaussian, primordial contribution to CMB fluctuations. We perform a pixel space analysis restricted to a portion of the map chosen in view of high sensitivity, very low foreground contamination and tight control of systematic effects. We set up an estimator based on the three Minkowski functionals which relies on high quality simulated data, including non Gaussian CMB maps. We find good agreement with the Gaussian hypothesis and derive the first limits based on BOOMERanG data for the non linear coupling parameter f_NL as -300<f_NL<650 at 68% CL and -800<f_NL<1050 at 95% CL.Comment: accepted for publication in ApJ. Letter

Subdegree Sunyaev-Zel'dovich Signal from Multifrequency BOOMERanG observations

The Sunyaev-Zel'dovich (SZ) effect is the inverse Compton-scattering of cosmic microwave background (CMB) photons by hot electrons in the intervening gas throughout the universe. The effect has a distinct spectral signature that allows its separation from other signals in multifrequency CMB datasets. Using CMB anisotropies measured at three frequencies by the BOOMERanG 2003 flight we constrain SZ fluctuations in the 10 arcmin to 1 deg angular range. Propagating errors and potential systematic effects through simulations, we obtain an overall upper limit of 15.3 uK (2 sigma) for rms SZ fluctuations in a broad bin between multipoles of of 250 and 1200 at the Rayleigh-Jeans (RJ) end of the spectrum. When combined with other CMB anisotropy and SZ measurements, we find that the local universe normalization of the density perturbations is sigma-8(SZ) < 0.96 at the 95% confidence level, consistent with sigma-8 determined from primordial perturbations.Comment: accepted for publication in ApJ. Letter

Polymeric nanoparticles: production, characterization, toxicology and ecotoxicology

Polymeric nanoparticles (NPs) are particles within the size range from 1 to 1000 nm and can be loaded with active compounds entrapped within or surface-adsorbed onto the polymeric core. The term “nanoparticle” stands for both nanocapsules and nanospheres, which are distinguished by the morphological structure. Polymeric NPs have shown great potential for targeted delivery of drugs for the treatment of several diseases. In this review, we discuss the most commonly used methods for the production and characterization of polymeric NPs, the association efficiency of the active compound to the polymeric core, and the in vitro release mechanisms. As the safety of nanoparticles is a high priority, we also discuss the toxicology and ecotoxicology of nanoparticles to humans and to the environment.This research was supported by the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) through the projects M-ERA-NET/0004/2015-PAIRED, UIDB/04469/2020 (strategic fund) and UIDB/04033/2020 (to CITAB), co-financed by FEDER, under the Partnership Agreement PT2020info:eu-repo/semantics/publishedVersio

H1N1pdm09 Adjuvanted Vaccination in HIV-Infected Adults: A Randomized Trial of Two Single versus Two Double Doses

Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses.Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm(3) was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively.Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm(3), to achieve antibody levels that are both higher and more sustained.ClinicalTrials.gov NCT01155037

KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients

Contains fulltext : 96042.pdf (publisher's version ) (Open Access)BACKGROUND: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases. METHODS: Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13. RESULTS: KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation. CONCLUSION: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis