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The Mediterranean Sea's biodiversity is declining due to climate change and human activities, with plastics and emerging contaminants (ECs) posing significant threats. This study assessed phthalic acid esters (PAEs) and active pharmaceutical ingredients (APIs) occurrence in four anthozoan species (Cladocora caespitosa, Eunicella cavolini, Madracis pharensis, Parazoanthus axinellae) using solid phase microextraction (SPME) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). All specimens were contaminated with at least one contaminant, reaching maximum values of 57.3 ng/g for the ∑PAEs and 64.2 ng/g (wet weight) for ∑APIs, with dibutyl phthalate and Ketoprofen being the most abundant. P. axinellae was the most contaminated species, indicating higher susceptibility to bioaccumulation, while the other three species showed two-fold lower concentrations. Moreover, the potential adverse effects of these contaminants on anthozoans have been discussed. Investigating the impact of PAEs and APIs on these species is crucial, given their key role in the Mediterranean benthic communities.

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OBJECTIVE: Vorinostat is a drug used to treat cutaneous T cell lymphoma whose action mechanism is based on Histone Deacetylase inhibition. Histone Deacetylases are a family of enzymes that remove acetyl groups from histone and non-histone proteins that control many crucial processes, such as gene regulation, cell cycle progression, differentiation, and apoptosis. Histone Deacetylase homologues are also expressed in parasites of the genus Plasmodium, Leishmania, Cryptosporidium, Schistosoma, Entamoeba, and others. In this way, antiparasitic properties of Vorinostat have been explored. The aim of this review is to report the current state knowledge of Vorinostat as antiparasitic drug against Plasmodium, Leishmania, Cryptosporidium, Schistosoma and Entamoeba in order to support future investigation in this field. MATERIALS AND METHODS: The authors revised the recent and relevant literature concerning the topic and discussed advances and limitations of studies on Vorinostat as potential drug to treat human parasitic diseases. RESULTS: Vorinostat has been efficient in vitro and, in some cases, in vivo, against parasites that cause parasitic diseases, such as malaria, leishmaniasis, cryptosporidiosis, amoebiasis, and schistosomiasis. CONCLUSIONS: In vitro and in vivo models have demonstrated the antiparasitic activity of Vorinostat, however, the challenge is to assay its activity in animal models and to evaluate if Vorinostat is safe for humans as new alternative to treat human parasitic infections.

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NPC1 is a 25-exon gene located on the long arm of chromosome 18q11.2 and encodes NPC1, a transmembrane protein comprising 1278 amino acid residues. Mutations in the NPC1 gene can cause Niemann-Pick disease type C (NP-C), a rare autosomal-recessive neurovisceral disease. We assessed mutant protein folding using computer-based molecular dynamics (MD) simulations and molecular docking of the three most common NPC1 mutations, all of which result in changes in a cysteine-rich luminal loop region of the protein: a) I1061T is the most commonly detected variant in patients with NP-C worldwide; b) P1007A is the second most common variant, frequently detected in Portuguese, British and German patients; c) G992W occurs most often in patients of Acadian descent. Analyses of molecular structural information and related cellular physiological processes revealed that mutant NPC1 proteins exhibited altered function despite being far from the N-terminal domain cholesterol binding. MD simulations revealed that mutant I1061T protein shows remarkable instability in comparison the WT and also de other mutants, and interestingly this mutant has been identified as the most common variant. In the case of the mutant P1007A, it is presumed that this substitution promotes larger structural changes than proline due to their greater hydrophobic properties.Structural changes related to the G992W mutation may affect the physicochemical space of G992W variant protein because tryptophan induces hydrophobic interactions. Cholesterol docking studies focused on binding recognition showed differences in the binding positions of variants versus the wild-type protein that go some way to explaining the molecular pathogenesis.Communicated by Ramaswamy H. Sarma.

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AbbreviationsSAHAsuberoylanilide hydroxamic acidEhHDACHistone Deacetylase from Entamoeba histolyticaRgRadius of gyrationRMSDroot-mean-square deviationRMSFroot-mean-square fluctuationMDSmolecular dynamics simulationVMDVisual Molecular DynamicsNAMDNanoscale Molecular DynamicsPBCperiodic boundary conditionsPMEParticle Mesh Ewald3Dthree-dimensionalCαalpha carbonFDAFood and Drug AdministrationnsnanosecondsGPU CUDAGraphics Processing Unit Compute Unified Device ArchitectureCommunicated by Ramaswamy H. Sarma.

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Before weaning, breast milk is the physiological form of neonatal nutrition, providing pups with all nutrient requirements. Maternal low-protein diet (LPD) during pregnancy and lactation induces adverse changes in key maternal organs, which have negative effects on pup development. We studied the effects of maternal LPD on liver weight, mammary gland (MG) cell differentiation, milk composition and production and pup development throughout lactation. We fed rats with control (C) or LPD (R) during pregnancy and lactation. At 7 d early, 14 d mid and 21 d late lactation stages, maternal biochemical parameters, body, liver and MG weights were analysed. MG cell differentiation was analysed by haematoxylin and eosin staining; milk nutrient composition and production were studied; pup body, liver and brain weights, hippocampal arachidonic acid (AA) and DHA were quantified. Results showed lower body and liver weights, minor MG cell differentiation and lower serum insulin and TAG in R compared with C. R milk contained less protein and higher AA at early and mid stages compared with C. R pup milk and fat intake were lower at all stages. R protein intake at early and mid stages and DHA intake at mid and late stages were lower compared with C. In R pups, lower body, liver and brain weights were associated with decreased hippocampal AA and DHA. We conclude that maternal LPD impairs liver and MG function and induces significant changes in maternal milk composition, pup milk intake and organ development.

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Limitations on interplanetary communications create operations latencies and slow progress in planetary surface missions, with particular challenges to narrow-field-of-view science instruments requiring precise targeting. The AEGIS (Autonomous Exploration for Gathering Increased Science) autonomous targeting system has been in routine use on NASA's Curiosity Mars rover since May 2016, selecting targets for the ChemCam remote geochemical spectrometer instrument. AEGIS operates in two modes; in autonomous target selection, it identifies geological targets in images from the rover's navigation cameras, choosing for itself targets that match the parameters specified by mission scientists the most, and immediately measures them with ChemCam, without Earth in the loop. In autonomous pointing refinement, the system corrects small pointing errors on the order of a few milliradians in observations targeted by operators on Earth, allowing very small features to be observed reliably on the first attempt. AEGIS consistently recognizes and selects the geological materials requested of it, parsing and interpreting geological scenes in tens to hundreds of seconds with very limited computing resources. Performance in autonomously selecting the most desired target material over the last 2.5 kilometers of driving into previously unexplored terrain exceeds 93% (where ~24% is expected without intelligent targeting), and all observations resulted in a successful geochemical observation. The system has substantially reduced lost time on the mission and markedly increased the pace of data collection with ChemCam. AEGIS autonomy has rapidly been adopted as an exploration tool by the mission scientists and has influenced their strategy for exploring the rover's environment.

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Boiling is the most common method of household water treatment in developing countries; however, it is not always effectively practised. We conducted a randomized controlled trial among 210 households to assess the effectiveness of water pasteurization and safe-storage interventions in reducing Escherichia coli contamination of household drinking water in a water-boiling population in rural Peru. Households were randomized to receive either a safe-storage container or a safe-storage container plus water pasteurization indicator or to a control group. During a 13-week follow-up period, households that received a safe-storage container and water pasteurization indicator did not have a significantly different prevalence of stored drinking-water contamination relative to the control group [prevalence ratio (PR) 1·18, 95% confidence interval (CI) 0·92-1·52]. Similarly, receipt of a safe-storage container alone had no effect on prevalence of contamination (PR 1·02, 95% CI 0·79-1·31). Although use of water pasteurization indicators and locally available storage containers did not increase the safety of household drinking water in this study, future research could illuminate factors that facilitate the effective use of these interventions to improve water quality and reduce the risk of waterborne disease in populations that boil drinking water.

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Herpes simplex virus (HSV) is one of the most commonly identified infectious aetiologies of encephalitis in North America and Europe. The epidemiology of encephalitis beyond these regions, however, is poorly defined. During 2009-2012 we enrolled 313 patients in a multicentre prospective study of encephalitis in Peru, 45 (14·4%) of whom had confirmed HSV infection. Of 38 patients with known HSV type, 84% had HSV-1 and 16% had HSV-2. Patients with HSV infection were significantly more likely to present in the summer months (44·4% vs. 20·0%, P = 0·003) and have nausea (60·0% vs. 39·8%, P = 0·01) and rash (15·6% vs. 5·3%, P = 0·01) compared to patients without HSV infection. These findings highlight differences in the epidemiology and clinical presentation of HSV encephalitis outside of the Northern Hemisphere that warrant further investigation. Furthermore, there is an urgent need for improved HSV diagnostic capacity and availability of intravenous acyclovir in Peru.

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Infrastructure for conducting neurological research in resource-limited settings (RLS) is limited. The lack of neurological and neuropsychological (NP) assessment and normative data needed for clinical interpretation impedes research and clinical care. Here, we report on ACTG 5271, which provided neurological training of clinical site personnel and collected neurocognitive normative comparison data in diverse settings. At ten sites in seven RLS countries, we provided training for NP assessments. We collected normative comparison data on HIV- participants from Brazil (n = 240), India (n = 480), Malawi (n = 481), Peru (n = 239), South Africa (480), Thailand (n = 240), and Zimbabwe (n = 240). Participants had a negative HIV test within 30 days before standardized NP exams were administered at baseline and 770 at 6 months. Participants were enrolled in eight strata, gender (female and male), education (<10 and ≥10 years), and age (<35 and ≥35 years). Of 2400 enrolled, 770 completed the 6-month follow-up. As expected, significant between-country differences were evident in all the neurocognitive test scores (p < 0.0001). There was variation between the age, gender, and education strata on the neurocognitive tests. Age and education were important variables for all tests; older participants had poorer performance, and those with higher education had better performance. Women had better performance on verbal learning/memory and speed of processing tests, while men performed better on motor tests. This study provides the necessary neurocognitive normative data needed to build infrastructure for future neurological and neurocognitive studies in diverse RLS. These normative data are a much-needed resource for both clinicians and researchers.

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We profiled the humoral response in the penis, an area that has been minimally explored but may be relevant for protecting insertive men against HIV and other sexually acquired infections. Comparing paired tissue samples from 20 men at risk of HIV infection, foreskin contains less immunoglobulin A (IgA) and more IgG2 than colon. Using foreskin dermal and epidermal explants and paired plasma from 17 men, we examined Ig accumulation by normalizing Ig to human serum albumin (HSA) transudation. Dermal IgM, IgG2, IgA, and IgE ratios were greater than that in plasma, suggesting there is local antibody secretion at the dermis. Local Ig transcription was concentrated at the inner rather than the outer foreskin, and inner foreskin Ig ratios did not correlate with blood, indicating that localized production can contribute to the foreskin response. IgM, IgG1, IgG3, and IgA have preferential access to the foreskin epidermis, whereas IgG2, IgG4, and IgE are restricted to the dermis. Lastly, Ad5-specific IgA was selectively present in the colon, whereas foreskin Ad5 IgG was mainly derived from blood, and reached the inner epidermis at higher ratios than the outer (P<0.002). In summary, the foreskin antibody response combines local and systemic sources, and there is selective isotype accumulation in the epidermis.

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Maternal obesity programmes offspring development. We addressed maternal obesity effects induced by high-fat diets on maternal mammary gland (MG) structure and function and offspring brain, liver and fat outcomes. Mothers were fed control (C, n 5) or obesogenic (MO, n 5) diet from the time they were weaned through pregnancy beginning at 120 d, through lactation. At offspring postnatal day (PND) 20, milk leptin and nutrients were determined. At the end of lactation, maternal liver and MG fatty acid profile were measured. Desaturase (Δ6D and Δ5D) and elongase (ELOVL 5 and ELOVL 2) protein was measured by immunohistochemistry and Western blotting (WB) in the liver and WB in the MG. In mothers, liver, MG and milk fat content were higher in MO than in C. Liver arachidonic acid (AA) and EPA and MG EPA were lower in MO than in C. Liver desaturases were higher in MO. The MG was heavier in MO than in C, with decreased Δ5D expression in MO. Desaturases and elongases were immunolocalised in parenchymal cells of both groups. Milk yield, water, carbohydrate content, EPA and DHA were lower, whereas milk leptin and AA were higher in MO than in C. At PND 21 and 36, brain weight was less and fat depots were greater in MO offspring than in C. MO decreased male absolute brain weight but not female absolute brain weight. In conclusion, maternal obesity induced by an obesogenic diet negatively affects maternal liver and MG function with the production of significant changes in milk composition. Maternal obesity adversely affects offspring metabolism and development.

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Particles in the upper troposphere and lower stratosphere (UT/LS) consist mostly of concentrated sulfuric acid (40-80 wt %) in water. However, airborne measurements have shown that these particles also contain a significant fraction of organic compounds of unknown chemical composition. Acid-catalyzed reactions of carbonyl species are believed to be responsible for significant transfer of gas phase organic species into tropospheric aerosols and are potentially more important at the high acidities characteristic of UT/LS particles. In this study, experiments combining sulfuric acid (H2SO4) with propanal and with mixtures of propanal with glyoxal and/or methylglyoxal at acidities typical of UT/LS aerosols produced highly colored surface films (and solutions) that may have implications for aerosol properties. In order to identify the chemical processes responsible for the formation of the surface films, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and 1H nuclear magnetic resonance (NMR) spectroscopies were used to analyze the chemical composition of the films. Films formed from propanal were a complex mixture of aldol condensation products, acetals and propanal itself. The major aldol condensation products were the dimer (2-methyl-2-pentenal) and 1,3,5-trimethylbenzene that was formed by cyclization of the linear aldol condensation trimer. Additionally, the strong visible absorption of the films indicates that higher-order aldol condensation products must also be present as minor species. The major acetal species were 2,4,6-triethyl-1,3,5-trioxane and longer-chain linear polyacetals which are likely to separate from the aqueous phase. Films formed on mixtures of propanal with glyoxal and/or methylglyoxal also showed evidence of products of cross-reactions. Since cross-reactions would be more likely than self-reactions under atmospheric conditions, similar reactions of aldehydes like propanal with common aerosol organic species like glyoxal and methylglyoxal have the potential to produce significant organic aerosol mass and therefore could potentially impact chemical, optical and/or cloud-forming properties of aerosols, especially if the products partition to the aerosol surface.

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Apparent ileal digestibility (AID) of diets containing sesame expeller (SE) and soya bean meal (SBM) was determined using 15 piglets (Genetiporc(®)), weaned at 17 ± 0.4 days with average body weight of 6.4 ± 0.7 kg (Fertilis 20 × G Performance, Genetiporc(®), PIC México, Querétaro, México). Piglets were randomly assigned to three treatments: (i) a reference diet with casein as the sole protein source; (ii) a mixed diet of casein-SE; and (iii) a mixed diet of casein-SBM. The chemical composition of SE and SBM was determined, and AID and standardized ileal digestibility (SID) of crude protein (CP) and amino acids (AAs) were determined for each protein source. SE contained greater quantities of ether extract, neutral detergent fibre, phytic acid, methionine and arginine than SBM. Lysine and proline contents and trypsin inhibitor activity were higher in SBM than in SE. The AID and SID of CP and AA (except for lysine and proline) were similar in SE and SBM. The AID of lysine and proline was higher in SBM than in SE (p < 0.05), and the SID of proline was higher in SE than in SBM (p < 0.05). These findings indicate that SE is an appropriate alternative protein source for early weaned pigs.

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OBJECTIVE: To determine the extent and socio-demographic determinants of burden of care of caregivers of adult schizophrenic patients. DESIGN AND METHODS: Cross-sectional study of 115 dyads of schizophrenic patients-caregivers attending public mental health clinics, March 24 – April 4, 2014 were consecutively recruited. Burden of care was evaluated using the 22-item Zarit Burden Scale (maximum score, 88). Multiple linear regression model explored factors associated with caregiver burden. RESULTS. Caregivers were predominantly females (75.7%) and were on average 50.8 ñ 15.0 years. Most schizophrenic patients were males (65.2%) and were on average 43.6 ñ 17.2 years old. Caregivers showed on average, mild to moderate burden (score, 30.0 ñ 14.7; median, 28.0). There was a tendency for caregivers of patients who were parents or spouses to have higher levels of burden. In multivariable analyses, higher burden of caregiving was associated with inability to perform self-care, closer kinship and higher numbers of psychotic episodes in the previous year. CONCLUSIONS: Functional and social factors were important determinants of caregiver burden. Further investigations are needed which consider factors such as health status and health expenditures as predictor variables of caregiver burden.

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Modalities of questionnaire administration may affect data quality, particularly when conducting Biological and Behavioral Surveillance Surveys (BBSS) of uniformed personnel. We aimed to examine differences in administration, reporting and data quality across several common modalities of administration for BBSS endeavors. Prior to a large-scale BBSS endeavor with the uniformed services of Peru, we pilot tested three modes of questionnaire administration among personnel engaged in internal combat: face-to-face interview (FFI), self-administered paper-based interview (SAPI), and audio computer-assisted self-interview (ACASI). Individuals who took the survey using ACASI were less likely to have missing data on measures of sexual risk and alcohol abuse and were more likely to report sexual risk behaviours and symptoms of alcohol abuse; however, more individuals took the survey using SAPI given inadequate time to devote to sitting through an entire FFI or ACASI. Sexually transmitted infections did not vary significantly across modes of questionnaire administration. While more logistically complicated for BBSS efforts in resource-constrained settings, we recommend the use of ACASI in collecting BBSS data from uniformed personnel if conditions are permissible.

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BACKGROUND: AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. METHODS: Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. RESULTS: The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). CONCLUSIONS: The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization -recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. CLINICAL TRIALS REGISTRATION: NCT00096824.

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This study assessed lubricant use during receptive anal intercourse (RAI) among Peruvian men who have sex with men (MSM) and willingness to use a hypothetical rectal microbicide (RM) formulated as a lubricant to prevent HIV infection. Data were collected from 843 Peruvian MSM for the 2008 HIV Sentinel Surveillance using a computerized self-interview. Half of the participants reported using a lubricant with their last sex partner during RAI, while 77% were willing to use a lubricant to prevent HIV transmission. Lubricant use with last sex partner was significantly associated with unprotected RAI (odds ratio [OR] 1.59, 95% confidence interval [CI], 1.23, 2.05; P < 0.001) and willingness to use a future lubricant RM (OR 1.56, 95% CI: 1.24, 1.95; P < 0.001). This study provides information on the behaviours associated with lubricant use and non-use among MSM practicing RAI in Peru that should inform future RM studies in Peru and other Latin American countries.

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In Peru, there is a lack of information on molecular analysis in pediatric human immunodeficiency virus (HIV) infection. At present, the mother-to-child transmission rate is estimated at approximately 2-4%. The objective of this study was to assess the molecular epidemiology of HIV-1 in infected children. Children with suspected or confirmed pulmonary tuberculosis were evaluated at two public hospitals between 2002 and 2007. Whole blood samples were obtained from 90 HIV-positive children, who were confirmed to be positive by enzyme-linked immunosorbent assay and Western blot. The specimens were subjected to envelope heteroduplex mobility assay (env HMA) followed by gag and pol gene region sequence analysis. Subtype B was found in 88 (98%) of 90 children and 2 (2%) children were subtype BF recombinants. This is the first report of recombinant HIV strains in HIV-infected children in Peru. Understanding the origin, diversity, and spread of HIV strains worldwide will be necessary for the development of an effective vaccine that targets pediatric populations throughout the world.

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Human T-lymphotropic virus type 1 (HTLV-1) infections are associated with varying degrees of HTLV-1 viral load and spasticity. Increased viral load is associated with higher risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The authors performed a cross-sectional study of 24 people with HAM/TSP in Lima, Perú, to determine if higher HTLV-1 viral load was correlated with increased muscle tone, measured with a device providing quantitative spasticity assessment (QSA). Median HTLV-1 viral load was 17.0 copies/100 peripheral blood mononuclear cells and QSA value was 39.9 Newton-meters/radian. HTLV-1 viral load was significantly correlated with QSA value (Spearman rho = .48, P = .02), suggesting viral load may play a role in expression of symptomatic neurologic disease. Longitudinal studies are needed to determine if treatments that reduce viral load will reduce muscle tone.

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OBJECTIVE: Assessment of HIV prevalence and associated risk behaviours among female commercial sex workers (FCSW) across major cities in South America. METHODS: Seroepidemiological, cross sectional studies of 13 600 FCSW were conducted in nine countries of South America during the years 1999-2002. Participants were recruited in brothels, massage parlours, hotels, and streets where anonymous questionnaires and blood samples were collected. HIV infection was determined by enzyme linked immunosorbent assay (ELISA) screening and western blot confirmatory tests. RESULTS: The overall HIV seroprevalence was 1.2% (range 0.0%-4.5%). The highest HIV seroprevalences were reported in Argentina (4.5%) and Paraguay (2.6%); no HIV infected FCSW were detected in Venezuela and Chile. Consistent predictors of HIV seropositivity were: (1) a previous history of sexually transmitted infections (STI, AORs = 3.8-8.3), and (2) 10 years or more in commercial sex work (AORs = 2.2-24.8). In addition, multiple (> or =3) sexual contacts (AOR = 5.0), sex with foreigners (AOR = 6.9), use of illegal drugs (AOR = 3.2), and marijuana use (AOR = 8.2) were associated with HIV seropositivity in Southern Cone countries. CONCLUSIONS: Consistently low HIV seroprevalences were detected among FCSW in South America, particularly in the Andean region. Predictors of HIV infection across the continent were STI and length of commercial sex work; however, use of illegal drugs, especially marijuana, and sexual contacts with foreigners were also found to be associated risk factors in the Southern Cone region. Interventions for the control of HIV and other STI need to be region and country specific; drug use appears to have an ever increasing role in the spread of HIV among heterosexually active populations.

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