Towards On-Chip Self-Referenced Frequency-Comb Sources Based on Semiconductor Mode-Locked Lasers.

Miniaturization of frequency-comb sources could open a host of potential applications in spectroscopy, biomedical monitoring, astronomy, microwave signal generation, and distribution of precise time or frequency across networks. This review article places emphasis on an architecture with a semiconductor mode-locked laser at the heart of the system and subsequent supercontinuum generation and carrier-envelope offset detection and stabilization in nonlinear integrated optics

Effect of Natural Polymorphisms in the HIV-1 CRF02_AG Protease on Protease Inhibitor Hypersusceptibility

Hypersusceptibility (HS) to inhibition by different antiretroviral drugs (ARVs) among diverse HIV-infected individuals may be a misnomer because clinical response to treatment is evaluated in relation to subtype B infections while drug susceptibility of the infecting virus, regardless of subtype, is compared to a subtype B HIV-1 laboratory strain (NL4-3 or IIIB). Mounting evidence suggests that HS to different ARVs may result in better treatment outcome just as drug resistance leads to treatment failure. We have identified key amino acid polymorphisms in the protease coding region of a non-B HIV-1 subtype linked to protease inhibitor HS, namely, 17E and 64M in CRF02_AG. These HS-linked polymorphisms were introduced in the BD6-15 CRF02_AG molecular clone and tested for inhibition using a panel of protease inhibitors. in general, suspected HS-linked polymorphisms did increase susceptibility to specific protease inhibitors such as amprenavir and atazanavir, but the combination of the 17E/64M polymorphisms showed greater HS. These two mutations were found at low frequencies but linked in a sequence database of over 700 protease sequences of CRF02_AG. in direct head-to-head virus competitions, CRF02_AG harboring the 17E/64M polymorphisms also had higher replicative fitness than did the 17E or the 64M polymorphism in the CFR02_AG clone. These findings suggest that subtype-specific, linked polymorphisms can result in hypersusceptibility to ARVs. Considering the potential benefit of HS to treatment outcome, screening for potential HS-linked polymorphisms as well as preexisting drug resistance mutations in treatment-naive patients may guide the choice of ARVs for the best treatment outcome.Case Western Reserve Univ, Cleveland, OH 44106 USAUniv Fed Rio de Janeiro, Dept Genet, Lab Virol Humana, Rio de Janeiro, BrazilHosp Egas Moniz, Lisbon, PortugalUniversidade Federal de São Paulo, Lab Retrovirol, São Paulo, BrazilUniv Rostock, Rostock, GermanyInst Nacl Canc, Programa Genet, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Lab Retrovirol, São Paulo, BrazilWeb of Scienc

Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals (AIDS (2015) 29 (2045-2052))

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Pharmacy refill adherence outperforms self-reported methods in predicting HIV therapy outcome in resource-limited settings

BACKGROUND: Optimal adherence to antiretroviral therapy is critical to prevent HIV drug resistance (HIVDR) epidemic. The objective of the study was to investigate the best performing adherence assessment method for predicting virological failure in resource-limited settings (RLS). METHOD: This study was a single-centre prospective cohort, enrolling 220 HIV-infected adult patients attending an HIV/AIDS Care and Treatment Centre in Dar es Salaam, Tanzania, in 2010. Pharmacy refill, self-report (via visual analog scale [VAS] and the Swiss HIV Cohort study-adherence questionnaire), pill count, and appointment keeping adherence measurements were taken. Univariate logistic regression (LR) was done to explore a cut-off that gives a better trade-off between sensitivity and specificity, and a higher area under the curve (AUC) based on receiver operating characteristic curve in predicting virological failure. Additionally, the adherence models were evaluated by fitting multivariate LR with stepwise functions, decision trees, and random forests models, assessing 10-fold multiple cross validation (MCV). Patient factors associated with virological failure were determined using LR. RESULTS: Viral load measurements at baseline and one year after recruitment were available for 162 patients, of whom 55 (34%) had detectable viral load and 17 (10.5%) had immunological failure at one year after recruitment. The optimal cut-off points significantly predictive of virological failure were 95%, 80%, 95% and 90% for VAS, appointment keeping, pharmacy refill, and pill count adherence respectively. The AUC for these methods ranged from 0.52 to 0.61, with pharmacy refill giving the best performance at AUC 0.61. Multivariate logistic regression with boost stepwise MCV had higher AUC (0.64) compared to all univariate adherence models, except pharmacy refill adherence univariate model, which was comparable to the multivariate model (AUC = 0.64). Decision trees and random forests models were inferior to boost stepwise model. Pharmacy refill adherence (<95%) emerged as the best method for predicting virological failure. Other significant predictors in multivariate LR were having a baseline CD4 T lymphocytes count < 200 cells/μl, being unable to recall the diagnosis date, and a higher weight. CONCLUSION: Pharmacy refill has the potential to predict virological failure and to identify patients to be considered for viral load monitoring and HIVDR testing in RLS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-1035) contains supplementary material, which is available to authorized users

Caracterización de las adolescentes gestantes de Bucaramanga, Colombia. Un estudio transversal.

ResumenAntecedentes: El embarazo en adolescentes se ve influenciado por factores sociales, culturales y familiares siendo fundamentales los soportes familiares y antecedentes de embarazo durante la adolescencia.[Ortiz R, Anaya NI, Sep&uacute;lveda C, Torres SJ, Camacho PA. Caracterizaci&oacute;n de las adolescentes gestantes de Bucaramanga, Colombia. Un estudio transversal. MedUNAB 2005; 8:71-77].Palabras clave: Adolescentes, Envarazo en adolescentes, Factores sociales, Culturales y familiares de riesgo

implications for first line treatment recommendations

Introduction: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). Objective: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017. Methods: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression. Results and Discussion: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p < 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p < 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p < 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p < 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p < 0.001). Conclusions: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients.publishersversionpublishe

Efectos del genotipo, tamaño de la camada y el sexo sobre las características de la canal y el perfil de ácidos grasos en corderos de pelo

The effect of the genotype (Pelibuey vs Katahdin), type of lambing (single vs. double) and sex (males vs. females) on the characteristics of the carcass and its cuts, in addition to the fatty acid profile of the loin were evaluated in 66 lambs slaughtered at weaning. The yield of the carcass and ribs were higher (P<0.05) in the Pelibuey breed. Slaughter weight, carcass weight and rib yield were higher (P<0.01) in single-born lambs, while the yield of shoulder and leg were lower (P<0.01) than in double-born lambs. The proportion of soft tissue of the different cuts was higher (P<0.05), but that of bone was lower (P< 0.05) in single-born lambs than in double-born lambs. Females had a higher (P<0.05) proportion of soft tissue and a lower proportion of bone (P<0.01) than males. The concentrations of C18:1n7 and C20:4n-6 were higher (P<0.05) in the Pelibuey breed than in the Katahdin breed, while the C22:5n-3 and C22:6n-3 were lower. The percentage of monounsaturated fatty acids was higher (P<0.05) in the meat of single-born lambs, while that of total polyunsaturated fatty acids and n-3 was higher (P<0.05) in double-born lambs. The characteristics of the carcass, the tissue composition of the commercial cuts and the fatty acid profile in hair sheep slaughtered at weaning varied more due to the type of lambing than due to the genotype or sex.El efecto del genotipo (Pelibuey vs Katahdin), tipo de parto (simple vs dobles) y sexo (machos vs. hembras) sobre las características de la canal y de sus cortes, además del perfil de ácidos grasos del lomo fueron evaluados en 66 corderos sacrificados al destete. El rendimiento de la canal y del costillar fue mayor (P<0.05) en la raza Pelibuey. El peso al sacrificio, peso de canal y rendimiento del costillar fue mayor (P<0.01) en crías de parto simple, mientras que el rendimiento de paleta y pierna fue menor (P< 0.01) que en crías de parto doble. La proporción del tejido blando de los diferentes cortes fue mayor (P<0.05), pero el de hueso fue menor (P< 0.05) en crías de parto simple que las de parto doble. Las hembras tuvieron mayor (P<0.05) proporción de tejido blando y menor proporción de hueso (P<0.01) que los machos. Las concentraciones de C18:1n7 y C20:4n-6 fueron mayores (P< 0.05) en la raza Pelibuey que, en la Katahdin, mientras que los C22:5n-3 y C22:6n-3 fueron menores. El porcentaje de ácidos grasos monoinsaturados fue mayor (P<0.05) en la carne de crías de partos simples, en tanto que el de los ácidos grasos poliinsaturados totales y n-3 fue mayor (P<0.05) en crías de partos dobles. Las características de la canal, la composición tisular de los cortes comerciales y el perfil de ácidos grasos en ovinos de pelo sacrificados al destete mostraron más cambios por el tipo de parto que por el genotipo o el sexo

Sub-epidemics explain localized high prevalence of reduced susceptibility to Rilpivirine in treatment-naive HIV-1-infected patients: subtype and geographic compartmentalization of baseline resistance mutations

This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited."Objective: The latest nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) is indicated for human immunodeficiency virus type-1 (HIV-1) patients initiating antiretroviral treatment, but the extent of genotypic RPV resistance in treatment-naive patients outside clinical trials is poorly defined. Study Design: This retrospective observational study of clinical data from Belgium and Portugal evaluates genotypic information from HIV-1 drug-naive patients obtained for the purpose of drug resistance testing. Rilpivirine resistance-associated mutations (RPV-RAMs) were defined based on clinical trials, phenotypic studies, and expert-based resistance algorithms. Viral susceptibility to RPV alone and to the single-tablet regimen was estimated using expert-based resistance algorithms. Results: In 4,631 HIV-1 treatment-naive patients infected with diverse HIV-1 subtypes, major RPV-RAMs were detected in 4.6%, while complete viral susceptibility to RPV was estimated in 95% of patients. Subtype C- and F1-infected patients displayed the highest levels of reduced viral susceptibility at baseline, respectively 13.2% and 9.3%, mainly due to subtype- and geographic-dependent occurrence of RPV-RAMs E138A and A98G as natural polymorphisms. Strikingly, a founder effect in Portugal resulted in a 138A prevalence of 13.2% in local subtype C-infected treatment-naive patients. The presence of transmitted drug resistance did not impact our estimates. Conclusion: RPV is the first HIV-1 inhibitor for which, in the absence of transmitted drug resistance, intermediate or high-level genotypic resistance can be detected in treatment-naive patients. The extent of RPV susceptibility in treatment-naive patients differs depending on the HIV-1 subtype and dynamics of local compartmentalized epidemics. The highest prevalence of reduced susceptibility was found to be 15.7% in Portuguese subtype C-infected treatment-naive patients. In this context, even in the absence of transmitted HIV-1 drug resistance (TDR), drug resistance testing at baseline should be considered extremely important before starting treatment with this NNRTI.

Molecular epidemiology of hiv-1 infected migrants followed up in Portugal: Trends between 2001-2017

Migration is associated with HIV-1 vulnerability. Objectives: To identify long-term trends in HIV-1 molecular epidemiology and antiretroviral drug resistance (ARV) among migrants followed up in Portugal Methods: 5177 patients were included between 2001 and 2017. Rega, Scuel, Comet, and jPHMM algorithms were used for subtyping. Transmitted drug resistance (TDR) and Acquired drug resistance (ADR) were defined as the presence of surveillance drug resistance mutations (SDRMs) and as mutations of the IAS-USA 2015 algorithm, respectively. Statistical analyses were performed. Results: HIV-1 subtypes infecting migrants were consistent with the ones prevailing in their countries of origin. Over time, overall TDR significantly increased and specifically for Non-nucleoside reverse transcriptase inhibitor (NNRTIs) andNucleoside reverse transcriptase inhibitor (NRTIs). TDR was higher in patients from Mozambique. Country of origin Mozambique and subtype B were independently associated with TDR. Overall, ADR significantly decreased over time and specifically for NRTIs and Protease Inhibitors (PIs). Age, subtype B, and viral load were independently associated with ADR. Conclusions: HIV-1 molecular epidemiology in migrants suggests high levels of connectivity with their country of origin. The increasing levels of TDR in migrants could indicate an increase also in their countries of origin, where more efficient surveillance should occur. © 2020 by the authors

Convergent Deployment of Ancestral Functions During the Evolution of Mammalian Flight Membranes

Lateral flight membranes, or patagia, have evolved repeatedly in diverse mammalian lineages. While little is known about patagium development, its recurrent evolution may suggest a shared molecular basis. By combining transcriptomics, developmental experiments, and mouse transgenics, we demonstrate that lateral Wnt5a expression in the marsupial sugar glider (Petaurus breviceps) promotes the differentiation of its patagium primordium. We further show that this function of Wnt5a reprises ancestral roles in skin morphogenesis predating mammalian flight and has been convergently used during patagium evolution in eutherian bats. Moreover, we find that many genes involved in limb development have been redeployed during patagium outgrowth in both the sugar glider and bat. Together, our findings reveal that deeply conserved genetic toolkits contribute to the evolutionary transition to flight in mammals