Impact of monotherapy on HIV-1 reservoir, immune activation, and co-infection with Epstein-Barr virus

Abstract Objectives Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear. Methods This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study. Markers of HIV-1 reservoir (HIV-1 DNA and intracellular HIV-1 RNA) were quantified by real-time PCR. Markers of T-(CD3(+)CD8(+)CD38(+)) and B-(CD19(+)CD80/86(+) and CD19(+)CD10-CD21(low)CD27(+)) cell activation were evaluated by flow cytometry. Plasma levels of microbial translocation markers were quantified by real-time PCR (16S ribosomal DNA and mitochondrial [mt] DNA) or by ELISA (LPS and sCD14). EBV was typed and quantified by multiplex real-time PCR. Results At baseline, no differences were found between mART and cART groups. Three (10%) mART-treated patients had a virological failure vs none in the cART group. Levels of HIV-1 DNA, intracellular HIV-1 RNA and EBV-DNA remained stable in the mART group, while decreased significantly in the cART group. Percentages of T-and B-activated cells significantly increased in the mART-treated patients, while remained at low levels in the cART-treated ones (p = 0.014 and p<0.001, respectively). Notably, levels of mtDNA remained stable in the cART group, but significantly rose in the mART one (p<0.001). Conclusions Long-term mART is associated with higher levels of T-and B-cell activation and, conversely to cART, does not reduce the size of HIV-1 reservoir and EBV co-infection

Induction of angiogenesis using VEGF releasing genipin-crosslinked electrospun gelatin mats

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Atlas of marine bony fish otoliths (Sagittae) of Southeastern - Southern Brazil Part I: Gadiformes (Macrouridae, Moridae, Bregmacerotidae, Phycidae and Merlucciidae); Part II: Perciformes (Carangidae, Sciaenidae, Scombridae and Serranidae)

The drawings, detailed pictures, precise descriptions and measurements that characterize otoliths must be made available for studies in various areas, including taxonomy, phylogeny, ecology, fisheries, paleontology, diversity, predator-prey relationships and modeling. The Collection of Teleostei Fish Otoliths of Southeastern-Southern Brazil (COSS-Brasil) of IOUSP contains 45,000 pairs of otoliths from 210 species. This publication is the first in a series that will constitute an atlas of Teleostei otoliths for southeastern-southern Brazil and presents the results of the morphologic and morphometric analyses of 11 Gadiformes and 36 Perciformes species by means of the most commonly used features, measurements and indices. Three otoliths of each species were illustrated and photographed whenever possible. The frequency of occurrence was calculated for each characteristic by total length classes (TL), and the ontogenetic differences were analyzed (multiple χ2 test; significance 0.05). Morphometric analyses were conducted for each characteristic per total length (TL) class and for the whole sample, and the ontogenetic differences were analyzed.A disponibilidade de desenhos, fotos detalhadas, descrições precisas e medidas que caracterizem os otólitos são ferramentas imprescindíveis para diversas áreas: taxonomia, filogenia, ecologia, pesca, paleontologia, diversidade, relações presa/predador e modelagem. Da Coleção de Otólitos de Peixes Teleósteos da Região Sudeste-Sul do Brasil (COSS-Brasil), IOUSP, constam quarenta e cinco mil pares relativos a 210 espécies. Esta publicação é a primeira de uma série que constituirá um atlas de otólitos para Teleostei da região sudeste-sul brasileira e apresenta os resultados de análises morfológicas e morfométricas de 11 espécies de Gadiformes e 36 de Perciformes das medidas e índices usualmente realizados. Foram desenhados e fotografados três otólitos de cada espécie sempre que possível. A frequência de ocorrência foi calculada por classes de comprimento total (TL) e para toda a amostra, e diferenças ontogenéticas foram analisadas

TERT Promoter Mutations Differently Correlate with the Clinical Outcome of MAPK Inhibitor-Treated Melanoma Patients

Resistance is a major challenge in the management of mitogen-activated protein kinase inhibitor (MAPKi)-treated metastatic melanoma. Tumor genetic alterations can cause MAPK pathway reactivation, leading to lack of response and poor outcome. Characterization of the mutational profile in patients with melanoma might be crucial for patient-tailored treatment choices. Mutations in the promoter region of the telomerase reverse transcriptase gene (TERTprom) lead to increased TERT expression and telomerase activity and are frequent in BRAFV600 mutant melanoma. Reportedly, TERTprom, and BRAFV600 mutations cooperate in driving cancer progression and aggressiveness. We evaluated the effect of the TERTprom status on the clinical outcome in 97 MAPKi-treated melanoma patients. We observed that patients with the c.-146C > T mutation showed a significantly worse progression-free survival (PFS) compared to those carrying the c.-124C > T mutation and a two-fold increased risk of progression (median 5.4 vs. 9.5 months; hazard ratio (HR) 1.9; 95% confidence interval (CI) 1.2-3.2; p = 0.013). This trend was also observed for the overall survival (OS); melanoma patients with the c.-146C > T mutation showed a poorer prognosis compared to those with the c.-124C > T mutation (median 13.3 vs. 25.5 months; HR 1.9, 95% CI 1.1-3.3, p = 0.023). Our results disclose a different correlation of the two TERTprom mutations with MAPKi-treated melanoma patient outcome, highlighting a different impact of the pathway blockade

3D imaging lipidometry in single cell by in-flow holographic tomography

The most recent discoveries in the biochemical field are highlighting the increasingly important role of lipid droplets (LDs) in several regulatory mechanisms in living cells. LDs are dynamic organelles and therefore their complete characteriza- tion in terms of number, size, spatial positioning and relative distribution in the cell volume can shed light on the roles played by LDs. Until now, fluorescence microscopy and transmission electron microscopy are assessed as the gold standard methods for identifying LDs due to their high sensitivity and specificity. However, such methods generally only provide 2D assays and partial measurements. Furthermore, both can be destructive and with low productivity, thus limit- ing analysis of large cell numbers in a sample. Here we demonstrate for the first time the capability of 3D visualization and the full LD characterization in high-throughput with a tomographic phase-contrast flow-cytometer, by using ovarian cancer cells and monocyte cell lines as models. A strategy for retrieving significant parameters on spatial correlations and LD 3D positioning inside each cell volume is reported. The information gathered by this new method could allow more in depth understanding and lead to new discoveries on how LDs are correlated to cellular functions

The Far-Infrared Radiation Mobile Observation System (FIRMOS) for spectral characterization of the atmospheric emission

The Far-Infrared Radiation Mobile Observation System (FIRMOS) is a Fourier transform spectroradiometer developed to support the Far-infrared Outgoing Radiation Understanding and Monitoring (FORUM) satellite mission by validating measurement methods and instrument design concepts, both in the laboratory and in field campaigns. FIRMOS is capable of measuring the downwelling spectral radiance emitted by the atmosphere in the spectral band from 100 to 1000 cm$^{−1}$ (10–100 µm in wavelength), with a maximum spectral resolution of 0.25 cm$^{−1}$. We describe the instrument design and its characterization and discuss the geophysical products obtained by inverting the atmospheric spectral radiance measured during a campaign from the high-altitude location of Mount Zugspitze in Germany, beside the Extended-range Atmospheric Emitted Radiance Interferometer (E-AERI), which is permanently installed at the site. Following the selection of clear-sky scenes, using a specific algorithm, the water vapour and temperature profiles were retrieved from the FIRMOS spectra by applying the Kyoto protocol and Informed Management of the Adaptation (KLIMA) code. The profiles were found in very good agreement with those provided by radiosondes and by the Raman lidar operating from the Zugspitze Schneefernerhaus station. In addition, the retrieval products were validated by comparing the retrieved integrated water vapour values with those obtained from the E-AERI spectra

Microbial deterioration of lamb meat from European local breeds as affected by its intrinsic properties

Although sheep meat has a small share of 1.5 % of the total meat production in the EU, sheep farming is of great importance to rural development and the environment. Enhancing the quality of lamb meat of local breeds is essential to ensure both profitability for sheep producers and the conservation of endangered breeds. This study aimed to (i) characterise the evolution of spoilage microorganisms in refrigerated vacuum-packed lamb meat from a total of 10 farms housing 8 local breeds of Portuguese, Spanish, Italian and Slovenian origin raised in intensive, extensive or semi-extensive regime; and (ii) elucidate how intrinsic properties of meat can affect its microbial spoilage. Cold carcass weight (CCW), ultimate pH (pH24) and proximate analysis were quantified on carcass/meat from each of the 285 animals raised and slaughtered for this purpose; while mesophiles, lactic acid bacteria, Pseudomonas spp. and psychrotrophic bacteria were enumerated during 15-day storage at 4 °C. Substantial variability in all attributes were found between the ten farms. CCW of intensively-raised lambs (21.4 kg; 95 % CI: 20.6–22.1 kg) were higher (p lt 0.05) than the ones in semi-extensive regime (14.9 kg; 95 % CI: 14.4–15.4 kg), and in turn these were heavier (p lt 0.05) than the extensively raised lambs (12.4 kg; 95 % CI: 12.0–12.7). Mean contents of protein (76.5–87.4% db), fat (3.78–13.1% db) and ashes (4.62–5.65% db) in lamb meat were highly dependent on the farm. Although meat from some farms was associated to higher microbial levels, in general, microbial growth was found to be modulated by intrinsic properties of meat. Higher pH24 (p lt 0.05), moisture (p lt 0.05), protein content (p lt 0.05) and ashes content (p lt 0.01) accelerated spoilage rate; whereas meat from heavier carcasses (p lt 0.001) and of higher fat content (p lt 0.01) presented slower growth of spoilage bacteria. In order to improve the microbial quality of lamb meat, animal handling must be enhanced to minimise pre-slaughter stress; slaughtering practices and hygiene must be improved; and a carcass classification system could be adopted towards the selection of fatter animals and chilled carcasses of optimal pH24.The authors are grateful to EU ERA-NET programme and the Portuguese Foundation for Science and Technology (FCT) for funding the project “EcoLamb–Holistic Production to Reduce the Ecological Footprint of Meat (SusAn/0002/2016). CIMO authors are grateful to FCT and FEDER under Programme PT2020 for financial support to CIMO (UIDB/00690/2020). Dr. Gonzales-Barron acknowledges the national funding by FCT, P.I., through the Institutional Scientific Employment Programme contract. José M. Lorenzo is member of the HealthyMeat network, funded by CYTED (ref. 119RT0568). The authors would like to acknowledge also Elena Saccà and Angela Sepulcri for providing technical support in laboratory analyses.info:eu-repo/semantics/publishedVersio