[Drug Consumption Rooms : Opinion and willingness among people who inject drugs in Marseille, France]. / Salles de consommation à moindre risque : opinion et volonté d'utilisation des personnes injectrices de substances psychoactives à Marseille, France.

BACKGROUND: In France, people who inject drugs (PWID) are still one of the most at risk population for contracting hepatitis C virus (HCV). Drug consumption rooms (DCR) have shown their effectiveness on HCV risk behaviors abroad and in France, where they have been recently evaluated with the COSINUS study. In France, two DCRs opened in 2016, one in Paris and another in Strasbourg. The objective of this sub-analysis was to explore the willingness to use a DCR in PWID living in Marseille, where no DCR is opened. METHODS: The COSINUS study is a prospective multicenter cohort that included 665 PWID recruited in Bordeaux, Marseille, Paris and Strasbourg between 2016 and 2019. Investigators administered questionnaires face-to-face at regular intervals at baseline, 3 months, 6 months and 12 months. In Marseille, 199 PWID were recruited. A multivariable logistic regression model was performed to assess factors associated with willingness to use DCR among this population. RESULTS: Among 545 observations corresponding to 195 distinct participants selected for analyses, 57% declared they were willing to attend a DCR. The main reason given was "to consume more cleanly". Receiving allowances (OR = 2.38; 95% confidence interval (CI) (95% CI) = 1.17-4.81), not having health insurance (OR = 3.61; 95% CI = 1.49-8.75), injecting daily (OR = 1.97; 95% CI = 1.05-3.70) and in a public space (OR = 2.66; 95% CI = 1.29-5.47) were all positively associated with willingness to use a DCR. CONCLUSIONS: DCR are devices that target PWID exposed to high sanitary or social risks, i.e. people living in precarious conditions, who have to inject in public spaces, in deleterious sanitary environments and with rapid gestures in order not to be seen. These analyzes highlight that the people who most want to attend a DCR are aware of the harms associated with their practices and show a desire to seek protection from street-based drug scenes.

Phylogeographic review of Y chromosome haplogroups in Europe.

The Y chromosome has been widely explored for the study of human migrations. Due to its paternal inheritance, the Y chromosome polymorphisms are helpful tools for understanding the geographical distribution of populations all over the world and for inferring their origin, which is really useful in forensics. The remarkable historical context of Europe, with numerous migrations and invasions, has turned this continent into a melting pot. For this reason, it is interesting to study the Y chromosome variability and how it has contributed to improving our knowledge of the distribution and development of European male genetic pool as it is today. The analysis of Y lineages in Europe shows the predominance of four haplogroups, R1b-M269, I1-M253, I2-M438 and R1a-M420. However, other haplogroups have been identified which, although less frequent, provide significant evidence about the paternal origin of the populations. In addition, the study of the Y chromosome in Europe is a valuable tool for revealing the genetic trace of the different European colonizations, mainly in several American countries, where the European ancestry is mostly detected by the presence of the R1b-M269 haplogroup. Therefore, the objective of this review is to compile the studies of the Y chromosome haplogroups in current European populations, in order to provide an outline of these haplogroups which facilitate their use in forensic studies.

Chemotherapy and PARP inhibitors in heavily pretreated BRCA1/2 mutation ovarian cancer (BMOC) patients.

OBJECTIVES: The hallmarks of germline(g) and/or somatic(s) BRCA1/2 mutation ovarian cancer (BMOC) patients are increased sensitivity to platinum-based chemotherapy (PCT) and PARP inhibitors (PARPi). There is little information on the effectiveness of chemotherapy in heavily pretreated (≥3 CT lines) g/sBMOC patients. METHODS: g/sBMOC patients who received CT from 2006 to 2016 at 4 cancer centers in Spain were selected. Overall survival (OS) and time to progression (TTP) were calculated with Kaplan Meier and Cox models. RESULTS: 135 g/sBMOC patients were identified (6% sBRCA1/2 mutations). The median number of chemotherapy lines was 2 (1-7). The 6-years OS rate was 69.4% and 71% in BRCA1 or BRCA2 mutation carriers (p = 0.98). A total of 57 (42%) patients had ≥3 CT lines (3-7), which encompassed a total of 155 treatments. The median overall TTP across all treatment lines beyond 2nd line was 10.2 months (CI 95% 8.4-11.9 months). In the platinum-sensitive setting, TTP was improved with PCT plus PARPi (17.1 m), PCT (12.6 m) or PARPi (12.4 m) versus non-PCT (4.9 m; p < 0.001 all comparisons). In the platinum-resistant setting, these differences in TTP were not statistically significant. A multivariate model confirmed that primary platinum-free interval (PFI) > 12 months and exposure to PCT and PARPi associated with improved outcomes. PARPi exposure did not compromise benefit of subsequent CT beyond 2nd relapse. CONCLUSIONS: Heavily pretreated g/sBMOC demonstrated CT sensitivity, including for non-PCT choices. Primary platinum-free interval (PFI) >12 months and exposure to both platinum-based chemotherapy and PARPi associate with improved prognosis in heavily pretreated g/sBMOC patients.

Two ovine mitochondrial DNAs harboring a fifth 75/76 bp repeat motif without altered gene expression in Northern Spain.

The Basque Country is home to the Latxa sheep breed, which is divided in several varieties such as Latxa Black Face (LBKF) and Latxa Blonde Face (LBLF). Mitochondrial DNA control region analysis of 174 male sheep (97 LBKF and 77 LBLF) was performed with the objective of characterizing the maternal lineages of these two varieties that are the basis to produce the cheese with Idiazabal quality label. The percentage of unique haplotypes was 77.32% in LBKF and 67.53% in LBLF. Most of the individuals were classified into B haplogroup (98.85%), while A haplogroup was much less frequent. Two Latxa individuals (one LBKF and one LBLF), both belonging to B haplogroup, displayed an additional 75/76 bp tandem repeat motif. Only 33 other sequences with this repeat motif were found among 11 061 sheep sequences included in the GenBank database. Gene expression was analyzed in peripheral blood leukocytes since the additional 75/76 bp repeat motif falls within ETAS1, a domain with a possible function in regulation of replication and transcription. The mRNA expression from four mitochondrial genes (COI, cyt b, ND1, and ND2) was analyzed in the two individuals of this study with a fifth repeat motif and in four without it. Although lower transcription was observed when the additional 75/76 bp repeat motif was present, no statistically significant differences were observed. Therefore, the variation in the number of the 75/76 repeat motif does not seem to modify the gene expression rate in mitochondrial genes.

Impact of drug consumption rooms on non-fatal overdoses, abscesses and emergency department visits in people who inject drugs in France: results from the COSINUS cohort.

BACKGROUND: The effectiveness of drug consumption rooms (DCRs) for people who inject drugs (PWID) has been demonstrated for HIV and hepatitis C virus risk practices, and access to care for substance use disorders. However, data on other health-related complications are scarce. Using data from the French COSINUS cohort, we investigated the impact of DCR exposure on non-fatal overdoses, abscesses and emergency department (ED) visits, all in the previous 6 months. METHODS: COSINUS is a 12-month prospective cohort study of 665 PWID in France studying DCR effectiveness on health. We collected data from face-to-face interviews at enrolment, and at 6 and 12 months of follow-up. After adjusting for other correlates (P-value < 0.05), the impact of DCR exposure on each outcome was assessed using a two-step Heckman mixed-effects probit model, allowing us to adjust for potential non-randomization bias due to differences between DCR-exposed and DCR-unexposed participants, while taking into account the correlation between repeated measures. RESULTS: At enrolment, 21%, 6% and 38% of the 665 participants reported overdoses, abscesses and ED visits, respectively. Multivariable models found that DCR-exposed participants were less likely to report overdoses [adjusted coefficient (95% CI): -0.47 (-0.88; -0.07), P = 0.023], abscesses [-0.74 (-1.11; -0.37), P < 0.001] and ED visits [-0.74 (-1.27; -0.20), P = 0.007]. CONCLUSION: This is the first study to show the positive impact of DCR exposure on abscesses and ED visits, and confirms DCR effectiveness in reducing overdoses, when adjusting for potential non-randomization bias. Our findings strengthen the argument to expand DCR implementation to improve PWID injection environment and health.

NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia.

MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair of damaged tissue. The transcription factor nuclear factor kappa B (NF-kappaB) is activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal muscle wasting in cachexia. Here, the role of NF-kappaB in cytokine-induced muscle degeneration was explored. In differentiating C2C12 myocytes, TNF-induced activation of NF-kappaB inhibited SMD by suppressing MyoD mRNA at the posttranscriptional level. In contrast, in differentiated myotubes, TNF plus interferon-gamma (IFN-gamma) signaling was required for NF-kappaB-dependent down-regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-regulated by TNF and IFN-gamma expression in mouse muscle in vivo. These data elucidate a possible mechanism that may underlie the skeletal muscle decay in cachexia.

Metals in particle-size fractions of the soils of five European cities.

Soils from Aveiro, Glasgow, Ljubljana, Sevilla and Torino have been investigated in view of their potential for translocation of potentially toxic elements (PTE) to the atmosphere. Soils were partitioned into five size fractions and Cr, Cu, Ni, Pb and Zn were measured in the fractions and the whole soil. All PTE concentrated in the <10 microm fraction. Cr and Ni concentrated also in the coarse fraction, indicating a lithogenic contribution. An accumulation factor (AF) was calculated for the <2 and <10 microm fraction. The AF values indicate that the accumulation in the finer fractions is higher where the overall contamination is lower. AF for Cr and Ni are particularly low in Glasgow and Torino. An inverse relationship was found between the AF of some metals and the percentage of <10 microm particles that could be of use in risk assessment or remediation practices.

Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF-kappaB.

It is well established that cell survival signals stimulated by growth factors, cytokines, and oncoproteins are initiated by phosphoinositide 3-kinase (PI3K)- and Akt-dependent signal transduction pathways. Oncogenic Ras, an upstream activator of Akt, requires NF-kappaB to initiate transformation, at least partially through the ability of NF-kappaB to suppress transformation-associated apoptosis. In this study, we show that oncogenic H-Ras requires PI3K and Akt to stimulate the transcriptional activity of NF-kappaB. Activated forms of H-Ras and MEKK stimulate signals that result in nuclear translocation and DNA binding of NF-kappaB as well as stimulation of the NF-kappaB transactivation potential. In contrast, activated PI3K or Akt stimulates NF-kappaB-dependent transcription by stimulating transactivation domain 1 of the p65 subunit rather than inducing NF-kappaB nuclear translocation via IkappaB degradation. Inhibition of IkappaB kinase (IKK), using an IKKbeta dominant negative protein, demonstrated that activated Akt requires IKK to efficiently stimulate the transactivation domain of the p65 subunit of NF-kappaB. Inhibition of endogenous Akt activity sensitized cells to H-Ras(V12)-induced apoptosis, which was associated with a loss of NF-kappaB transcriptional activity. Finally, Akt-transformed cells were shown to require NF-kappaB to suppress the ability of etoposide to induce apoptosis. Our work demonstrates that, unlike activated Ras, which can stimulate parallel pathways to activate both DNA binding and the transcriptional activity of NF-kappaB, Akt stimulates NF-kappaB predominantly by upregulating of the transactivation potential of p65.

Estimating the extractability of potentially toxic metals in urban soils: a comparison of several extracting solutions.

Metals released by the extraction with aqua regia, EDTA, dilute HCl and sequential extraction (SE) by the BCR protocol were studied in urban soils of Sevilla, Torino, and Glasgow. By multivariate analysis, the amounts of Cu, Pb and Zn liberated by any method were statistically associated with one another, whereas other metals were not. The mean amounts of all metals extracted by HCl and by SE were well correlated, but SE was clearly underestimated by HCl. Individual data for Cu, Pb and Zn by both methods were correlated only if each city was considered separately. Other metals gave poorer relationships. Similar conclusions were reached comparing EDTA and HCl, with much lower values for EDTA. Dilute HCl extraction cannot thus be recommended for general use as alternative to BCR SE in urban soils.

High prevalence of Pneumocystis jirovecii pneumonia among Mozambican children <5 years of age admitted to hospital with clinical severe pneumonia.

We aimed to describe Pneumocystis jirovecii pneumonia (PCP) prevalence and features in children from sub-Saharan Africa and to investigate PCP-associated risk factors. During 2006-2007 we used molecular methods to test children younger than 5 years old admitted with severe pneumonia to a hospital in southern Mozambique for Pneumocystis infection. We recruited 834 children. PCP prevalence was 6.8% and HIV prevalence was 25.7%. The in-hospital and delayed mortality were significantly higher among children with PCP (20.8% vs. 10.2%, p 0.021, and 11.5% vs. 3.6%, p 0.044, respectively). Clinical features were mostly overlapping between the two groups. Independent risk factors for PCP were age less than a year (odds ratio (OR) 6.34, 95% confidence interval (CI) 1.86-21.65), HIV infection (OR 2.99, 95% CI 1.16-7.70), grunting (OR 2.64, 95% CI 1.04-6.73) and digital clubbing (OR 10.75, 95% CI 1.21-95.56). PCP is a common and life-threatening cause of severe pneumonia in Mozambican children. Mother-to-child HIV transmission prevention should be strengthened. Better diagnostic tools are needed.

Inhibition of NF-kappaB sensitizes non-small cell lung cancer cells to chemotherapy-induced apoptosis.

BACKGROUND: Most non-small cell lung cancers (NSCLC) are chemoresistant. Identification and modulation of chemoresistance cell-signaling pathways may sensitize NSCLC to chemotherapy and improve patient outcome. The purpose of this study was to determine if chemotherapy induces nuclear factor-kappa B (NF-kappaB) activation in NSCLC in vitro and whether inhibition of NF-kappaB would sensitize tumor cells to undergo chemotherapy-induced apoptosis. METHODS: Non-small cell lung cancer cells were treated with gemcitabine, harvested, and nuclear extracts analyzed for NF-kappaB DNA binding by electrophoretic mobility shift assays. Additionally, NSCLC cells that stably expressed a plasmid encoding the superrepressor IkappaBalpha protein (H157I) or a vector control (H157V) were generated. These cells were then treated with gemcitabine and apoptosis determined by terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS: Chemotherapy induced NF-kappaB nuclear translocation and DNA binding in all NSCLC cell lines. H157I cells had enhanced cell death compared with H157V cells, suggesting that NF-kappaB is required for cell survival after chemotherapy. The observed cell death following the loss of NF-kappaB occurred by apoptosis. CONCLUSIONS: Inhibition of chemotherapy-induced NF-kappaB activation sensitizes NSCLC to chemotherapy-induced apoptosis in vitro. Novel treatment strategies for patients with advanced NSCLC may involve chemotherapy combined with inhibition of NF-kappaB-dependent cell-survival pathways.

Release of metals from homogeneous soil columns by wastewater from an agricultural industry.

The effect of discharging olive mill wastewater (OMW) in soils on the release of metals previously retained by them is simulated by leaching homogeneous soil columns with a solution of the residue after passing solutions of Cu or Zn through the columns. The effect of other residues, previously added to the soil as composts in field experiments, on the behaviour observed in the laboratory is also discussed. OMW shows a strong power for releasing the metals retained. Previous addition of a compost made from olive mill sludge and plant refuse to the soil causes a significant reduction of the release of retained metal by liquid OMW. Previous addition of concentrated sugarbeet vinasse causes much less significant effects.

Copper and zinc retention by an organically amended soil.

This paper describes changes in retention of Cu and Zn in laboratory experiments by a sandy soil that had been amended in the field with different composted wastes. The amounts of the metals retained increased as a result of the amendments, especially after two years. Desorption of the sorbed metals was always negligible, regardless of the treatment. The proportion of Cu retained was considerably higher than that of Zn, suggesting a higher affinity of the soil for the former. The greater sorption in the amended soils indicates a build-up of fresh sites for metal retention. The use of 'log(activity) vs. pH' plots showed that the nature of the surfaces retaining metals on the untreated and amended soils is different. At comparable pH values, the amended soils gave higher solution metal concentrations. Some of the possible environmental consequences of the use of these amendments for remediation purposes are discussed.

[Nutritional status and body composition of a group of non-institutionalized elderly in the State of Zulia, Venezuela]. / Estado nutricional y composición corporal de un grupo de adultos mayores no institucionalizados del Estado Zulia, Venezuela.

To assess the nutritional status and body composition of an elderly free-living population from the State of Zulia, Venezuela, ninety-four persons (47 male and 47 female), ages ranging from 60 to 88 years (mean age 69.55 +/- 6.60) (X +/- SD) were studied. Anthropometric measurements, and a dietary study by means of 24-hour recall and a Food Frequency were performed. Significant statistical differences (p < 0.001, and p < 0.05) were observed among female and male groups in all measures and indices except weight, waist, arm area, and arm muscle area. Significant differences (p < 0.05) were also observed among age groups in weight, Quetelet index, percentage ideal weight (% IW), and triceps skinfold thickness. The means of anthropometric measures and nutritional indicators were higher than the results obtained in other studies. The percentage of elderly obese with Quetelet greater than 30 kg/m < or = was 42.6% (females) and 6.4% (males). In contrast, when utilizing % IW it was observed that 4.3% of the men and 48.9% of the women were obese. Body fat distribution index (waist/hip) shows abdominal fat distribution in 21.3% males and 68.1% females. We found sex-based significant differences in dietary intake of energy, total fat, carbohydrates, iron, vitamin A, and thiamin. The results indicate that the intake of protein, total fat, calcium, phosphorus, iron, thiamin, and niacin is high among males y females, when compared with the present Recommended Dietary Allowance (RDA) values of Venezuela. The intake of carbohydrate, fiber, vitamin A, riboflavin, zinc, and copper is low among males and females according RDA values, as well as the intake of riboflavin in males. The study indicates a high frequency of men and women obese, and with overweight among females as a consequence of the inadequacy of dietary intake. The present findings emphasizes the need to study in depth the different factors that affect nutritional status of elderly individuals in our country.

Efecto del nivel de complementación con metionina-colina en vacas Holstein durante el periodo de transición sobre las concentraciones hepáticas de triglicéridos, colina y carnitina / Effect of the level of complementation with methionine-coline in Holstein cows during the transitional period on the hepatic concentrations of triglycerides, choline and carnitine

RESUMEN Con el objetivo de evaluar el potencial lipotropics de metionina-colina en vacas lecheras durante el periodo de transición, dosis de 20 g/d de una Fuente Comercial Protegida de la Degradación Ruminal (FCPDR) de metionina y sus combinaciones con una FCPDR de colina en dosis de 60 y 120 g/d se suministraron a vacas entre el día 260 de gestación y el día 20 posparto. Estas pastoreaban kikuyo (Cenchrus clamdestinus) y recibieron un complemento alimenticio. En los días 270 de gestación y 10 y 20 posparto se cuantificaron las concentraciones plasmáticas de ácidos grasos no esterificados (AGNES), β-Hidroxibutirato (BHB) y triglicéridos (TG), así como las concentraciones hepáticas de triacilglicéridos, de colina, carnitina total, carnitina libre y acil carnitina. Durante el preparto se presentaron los valores significativamente más altos (p < 0.05) de TG plasmáticos y los significativamente más bajos (p < 0.05) de AGNES y BHB. Las concentraciones hepáticas de TG, de colina y de las diferentes formas de carnitina no difirieron significativamente entre periodos de muestreo y no se vieron afectadas por la suplementación con metionina-colina. Por su parte, las concentraciones plasmáticas de BHB aumentaron significativamente (p < 0.05) con la suplementación conjunta de metionina y colina, lo que sugiere un aumento en la oxidación de ácidos grasos. Se concluye que con concentraciones bajas de AGNES la metionina y colina no son nutrientes limitantes para la exportación de TG desde el hígado a la sangre. Bajo esta condición no se observó lipidosis hepática y como consecuencia la suplementación con metionina-colina no ocasionó efectos significativos sobre las concentraciones hepáticas de TG.

ABSTRACT In order to evaluate the lipotropic potential of methionine-coline in dairy cows during the transition period, the effect of supplementation with 20 g / d of a Ruminal Degradation Protected Commercial Source (FCPDR) of methionine was evaluated, and their combinations with a choline FCPDR in doses of 60 and 120 g / day. Cows grazed kikuyo (Cenchrus clandestinus) and received a nutritional supplement between day 260 of gestation and day 20 postpartum. On day 270 of gestation and on days 10 and 20 postpartum blood samples and liver biopsy were taken, in which were quantified: Non-esterified Fatty Acids (NEFAS), β-Hydroxybutyrate (BHB) and Triglycerides; And hepatic concentrations of triacylglycerides, choline, total carnitine, free carnitine and acyl carnitine. The highest values (p < 0.05) of plasma triglycerides and the significantly lower values (p < 0.05) of AGNES and BHB were presented during the prepartum. Hepatic concentrations of triglycerides, choline and different forms of carnitine did not differ significantly between sampling periods, and were unaffected by methionine-choline supplementation. Plasma concentrations of BHB increased significantly (p < 0.05) with co-supplementation with methionine and choline, suggesting an increase in fatty acid oxidation. At relatively low concentrations of AGNES, methionine and choline are not limiting nutrients for the exportation of triglycerides from the liver to the blood, therefore under this condition no hepatic lipidosis was observed and consequently methionine-choline supplementation did not cause significant effects on hepatic triglyceride concentrations.

Availability and bio-accessibility of metals in the clay fraction of urban soils of Sevilla.

The availability of Cd, Cr, Cu, Ni, Mn, Pb and Zn present in the finest size particles of urban soils is studied by comparing the concentrations in the clay fraction with those extracted from the whole soil by either single-extraction or sequential extraction method. Many metals are preferentially present in the finest particles as compared to coarser fractions. This is true for most metals studied, except Mn and, perhaps, Cd. Those metals present in the clay fraction are often in easily bio-accessible forms, especially Cu, Pb and Zn. The results suggest that bio-accessible forms of these three metals are distributed among the three sequential fractions, and even the fraction considered as 'residual' is also bio-accessible to a significant extent. The statistical analysis shows some distinctions among metals that are compared to the 'urban', 'natural', or intermediate behaviour of the various metals as proposed earlier in the literature.

Soil pollution by PAHs in urban soils: a comparison of three European cities.

The purpose of this study was to determine the degree of contamination with polycyclic aromatic hydrocarbons (PAHs) in samples of urban soil from three European cities: Glasgow (UK), Torino (Italy) and Ljubljana (Slovenia). Fifteen PAHs (naphthalene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenzo[a,h]anthracene, benzo[g,h,i]perylene, indeno[1,2,3-c,d]pyrene) were measured in urban soil samples, using harmonised sampling, sample extraction and analyte quantification methods. Although the mean concentration of each PAH in urban soils of each city showed a wide range of values, high levels of contamination were only evident in Glasgow, where the sum of concentrations of 15 PAHs was in the range 1487-51,822 microg kg(-1), cf. ranges in the other two cities were about ten-fold lower (89.5-4488 microg kg(-1)). The three predominant PAHs were phenanthrene, fluoranthene and pyrene, with the sum of these compounds about 40% of the total PAH content. These data, together with some special molecular indices based on ratios of selected PAHs, suggest pyrogenic origins, especially motor vehicle exhausts, to be the major sources of PAHs in urban soils of the three cities. The largest concentrations for PAHs were often found in sites close to the historic quarters of the cities. Overall, the different climatic conditions, the organic carbon contents of soil, and the source apportionment were the dominant factors affecting accumulation of PAHs in soil.