PLoS One

Compared to the general population, HIV-infected patients are at higher risk of developing non-AIDS-defining cancers. Chronic HCV infection has also been associated with a higher risk than that of the general population of developing cancers other than hepatocarcinoma. Evaluation of the impact of HCV-related factors on non-AIDS-defining and non HCV-liver (NANL) related cancers among HIV/HCV co-infected patients are scarce. The aim of this study was to identify the impact of HIV/HCV clinical characteristics on NANL related cancers in a large cohort of HIV/HCV-coinfected patients followed from 2005 to 2017. Cox proportional hazards models with delayed entry were used to estimate factors associated with NANL related cancer. Among 1391 patients followed for a median of 5 years, 60 patients developed NANL related cancers, yielding an incidence rate of 8.9 per 1000 person-years (95% CI, [6.6-11.1]). By final multivariable analysis, after adjustment for sex, tobacco or alcohol consumption, baseline CD4 cell count and HCV sustained viral response (SVR), age and a longer duration since HIV diagnosis were independently associated with a higher risk of NANL related cancer (aHR for each additional year 1.10, 95% CI 1.06-1.14, p<0.0001 and 1.06, 95% CI 1.01-1.11, p = 0.02, respectively). Duration of HCV infection, cirrhosis, HCV viral load, genotype and SVR were not associated with the occurrence of NANL related cancer. Among HIV/HCV-coinfected patients, age and the duration of HIV infection were the only characteristics found to be associated with the occurrence of NANL related cancer. In contrast, no association was observed with any HCV-related variables

DETECÇÃO DE SARS-CoV-2 EM CONTATOS ESTREITOS ASSIMTOMÁTICOS DE CASOS CONFIRMADOS POR DIAGNÓSTICO MOLECULAR, PROVÍNCIA DE BUENOS AIRES, ARGENTINA

The detection of SARS-CoV-2 and its implication in the diagnosis of COVID-19 have been highly debated in the pandemic. Access to molecular diagnosis and its target population was essential in the public policy. The objective of this study was to evaluate the cost / benefit of detecting SARS-CoV-2 in asymptomatic close contacts using different molecular diagnostic tests. 51 close contacts of people with a diagnosis of SARS-CoV-2 confirmed by RTqPCR, classified by Ct (&lt;20, between 20 and 30 and&gt; 30), were studied in public hospitals in Province of Buenos Aires. Of all contacts studied, 15.7% were confirmed for SARS-CoV-2, there were no contacts of cases with Ct&gt; 30 positive. The number of positive contacts of cases with Ct &lt;20 was significantly higher than that of cases with Cts&gt; 20. Samples with Cts &lt;20 were associated with an estimated viral load of 1 to 4 orders of magnitude difference with Ct ranges&gt; 20. 13.7% of positive close contacts were from cases with Ct &lt;20. When studying positive samples with confirmed diagnosis by PCR, corresponding to EW1 of 2021, only 19.35% corresponded to samples with Cts &lt;20 and 50.7% with Cts between 20 and 30. From these data it is shown that with the close contact test we could detect only 3.7% of cases. The effort by the public health system for this strategy, with low predictive power, may have a negative effect on the fulfillment of the isolation of contacts and could generate a delay in the results of suspected cases, without contributing significantly to controlling the pandemic.La detección de SARS-CoV-2 y su implicancia en el diagnóstico de COVID-19 han sido muy debatidos en la pandemia. El acceso al diagnóstico molecular y su población destinataria fue parte esencial de las políticas públicas. El objetivo de este estudio fue evaluar el costo/beneficio de la detección de SARS-CoV-2 en contactos estrechos asintomáticos mediante el uso de distintas pruebas de diagnóstico molecular. Se estudiaron 51 contactos estrechos de personas con diagnóstico de SARS-CoV-2 confirmado por RTqPCR, clasificadas por Ct (&lt;20, entre 20 y 30 y &gt;30) en hospitales públicos de la Provincia de Buenos Aires. Del total de contactos estudiados el 15,7% resultó confirmado para SARS-CoV-2, no hubo contactos de casos con Ct&gt;30 positivos. La cantidad de contactos positivos de casos con Ct&lt;20 fue significativamente mayor que la de casos con Cts&gt;20. Las muestras con Cts&lt;20 se asociaron a una carga viral estimada de entre 1 a 4 órdenes de magnitud de diferencia con los rangos de Ct &gt;20. Un 13,7% de contactos estrechos positivos fueron de casos con Ct&lt;20. Al estudiar muestras positivas con diagnóstico confirmado por PCR, correspondientes a la SE1 del 2021, sólo un 19,35% correspondían a muestras con Cts&lt;20 y un 50,7% con Cts entre 20 y 30. A partir de estos datos se muestra que con el testeo de contactos estrechos podríamos detectar sólo un 3,7% de casos. El esfuerzo por parte del sistema de salud pública para esta estrategia, con bajo poder predictivo, puede tener un efecto negativo para el cumplimiento del aislamiento de los contactos y podría generar una demora en los resultados de los casos sospechosos, sin aportar significativamente a controlar la pandemia.A detecção de SARS-CoV-2 e sua implicação no diagnóstico de COVID-19 têm sido altamente debatidos na pandemia. O acesso ao diagnóstico molecular e à sua população-alvo era parte essencial das políticas públicas. O objetivo deste estudo foi avaliar o custo / benefício da detecção da SARS-CoV-2 em contatos próximos assintomáticos usando diferentes testes de diagnóstico molecular. 51 contatos próximos de pessoas com diagnóstico de SARS-CoV-2 confirmado pelo RTqPCR, classificados pelo Ct (&lt;20, entre 20 e 30 e&gt; 30), foram estudados em hospitais públicos da Província de Buenos Aires. Do total de contatos estudados, 15,7% foram confirmados para SARS-CoV-2, não houve contato de casos com Ct&gt; 30 positivo. O número de contatos positivos de casos com Ct &lt;20 foi significativamente maior que o de casos com Ct&gt; 20. As amostras com Cts &lt;20 foram associadas a uma carga viral estimada de 1 a 4 ordens de diferença de magnitude com intervalos de Ct&gt; 20. 13,7% dos contatos próximos positivos eram de casos com Ct &lt;20. Ao estudar amostras positivas com diagnóstico confirmado por PCR, correspondentes a EW1 de 2021, apenas 19,35% corresponderam a amostras com Cts &lt;20 e 50,7% com Cts entre 20 e 30. A partir desses dados, mostra-se que com o teste de contato próximo poderíamos detectar apenas 3,7% dos casos. O esforço do sistema público de saúde por essa estratégia, com baixo poder preditivo, pode repercutir negativamente no cumprimento do isolamento dos contatos e pode gerar atraso nos resultados dos casos suspeitos, sem contribuir significativamente para o controle da pandemia

Monitoring lactoferrin iron levels by fluorescence resonance energy transfer: A combined chemical and computational study

Three forms of lactoferrin (Lf) that differed in their levels of iron loading (Lf, LfFe, and LfFe2) were simultaneously labeled with the fluorophores AF350 and AF430. All three resulting fluorescent lactoferrins exhibited fluorescence resonance energy transfer (FRET), but they all presented different FRET patterns. Whereas only partial FRET was observed for Lf and LfFe, practically complete FRET was seen for the holo form (LfFe2). For each form of metal-loaded lactoferrin, the AF350–AF430 distance varied depending on the protein conformation, which in turn depended on the level of iron loading. Thus, the FRET patterns of these lactoferrins were found to correlate with their iron loading levels. In order to gain greater insight into the number of fluorophores and the different FRET patterns observed (i.e., their iron levels), a computational analysis was performed. The results highlighted a number of lysines that have the greatest influence on the FRET profile. Moreover, despite the lack of an X-ray structure for any LfFe species, our study also showed that this species presents modified subdomain organization of the N-lobe, which narrows its iron-binding site. Complete domain rearrangement occurs during the LfFe to LfFe2 transition. Finally, as an example of the possible applications of the results of this study, we made use of the FRET fingerprints of these fluorescent lactoferrins to monitor the interaction of lactoferrin with a healthy bacterium, namely Bifidobacterium breve. This latter study demonstrated that lactoferrin supplies iron to this bacterium, and suggested that this process occurs with no protein internalization.This work was supported by MINECO and FEDER (projects CTQ2012-32236, CTQ2011-23336, and BIO2012-39682-C02-02) and BIOSEARCH SA. F.C. and V.M.R. are grateful to the Spanish MINECO for FPI fellowships

Binding of the chemokine CXCL12α to its natural extracellular matrix ligand heparan sulfate enables myoblast adhesion and facilitates cell motility

The chemokine CXCL12α is a potent chemoattractant that guides the migration of muscle precursor cells (myoblasts) during myogenesis and muscle regeneration. To study how the molecular presentation of chemokines influences myoblast adhesion and motility, we designed multifunctional biomimetic surfaces as a tuneable signalling platform that enabled the response of myoblasts to selected extracellular cues to be studied in a well-defined environment. Using this platform, we demonstrate that CXCL12α, when presented by its natural extracellular matrix ligand heparan sulfate (HS), enables the adhesion and spreading of myoblasts and facilitates their active migration. In contrast, myoblasts also adhered and spread on CXCL12α that was quasi-irreversibly surface-bound in the absence of HS, but were essentially immotile. Moreover, co-presentation of the cyclic RGD peptide as integrin ligand along with HS-bound CXCL12α led to enhanced spreading and motility, in a way that indicates cooperation between CXCR4 (the CXCL12α receptor) and integrins (the RGD receptors). Our findings reveal the critical role of HS in CXCL12α induced myoblast adhesion and migration. The biomimetic surfaces developed here hold promise for mechanistic studies of cellular responses to different presentations of biomolecules. They may be broadly applicable for dissecting the signalling pathways underlying receptor cross-talks, and thus may guide the development of novel biomaterials that promote highly specific cellular responses

The coming of the Greeks to Provence and Corsica: Y-chromosome models of archaic Greek colonization of the western Mediterranean

<p>Abstract</p> <p>Background</p> <p>The process of Greek colonization of the central and western Mediterranean during the Archaic and Classical Eras has been understudied from the perspective of population genetics. To investigate the Y chromosomal demography of Greek colonization in the western Mediterranean, Y-chromosome data consisting of 29 YSNPs and 37 YSTRs were compared from 51 subjects from Provence, 58 subjects from Smyrna and 31 subjects whose paternal ancestry derives from Asia Minor Phokaia, the ancestral embarkation port to the 6^thcentury BCE Greek colonies of Massalia (Marseilles) and Alalie (Aleria, Corsica).</p> <p>Results</p> <p>19% of the Phokaian and 12% of the Smyrnian representatives were derived for haplogroup E-V13, characteristic of the Greek and Balkan mainland, while 4% of the Provencal, 4.6% of East Corsican and 1.6% of West Corsican samples were derived for E-V13. An admixture analysis estimated that 17% of the Y-chromosomes of Provence may be attributed to Greek colonization. Using the following putative Neolithic Anatolian lineages: J2a-DYS445 = 6, G2a-M406 and J2a1b1-M92, the data predict a 0% Neolithic contribution to Provence from Anatolia. Estimates of colonial Greek vs. indigenous Celto-Ligurian demography predict a maximum of a 10% Greek contribution, suggesting a Greek male elite-dominant input into the Iron Age Provence population.</p> <p>Conclusions</p> <p>Given the origin of viniculture in Provence is ascribed to Massalia, these results suggest that E-V13 may trace the demographic and socio-cultural impact of Greek colonization in Mediterranean Europe, a contribution that appears to be considerably larger than that of a Neolithic pioneer colonization.</p