Viral Load Dynamics in Plasma and Semen When Antiretroviral Therapy Is Initiated During Early HIV-1 Infection.

We assessed human immunodeficiency virus (HIV) load in plasma and semen during primary HIV infection using serial samples of semen and plasma during the first 24 weeks after diagnosis in untreated participants and those who started antiretroviral therapy (ART) immediately at diagnosis. In the absence of treatment, semen viral load was >1000 copies/mL in almost all specimens (83%) collected 2-10 weeks after the estimated date of HIV acquisition and remained >1000 copies/mL in 35% of untreated participants at the last observed time point. Thus, in the absence of ART, semen viral load remained at a level consistent with transmissibility throughout primary infection.

Prioritizing cardiovascular disease-associated variants altering NKX2-5 and TBX5 binding through an integrative computational approach.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide and are heavily influenced by genetic factors. Genome-wide association studies have mapped >90% of CVD-associated variants within the noncoding genome, which can alter the function of regulatory proteins, such as transcription factors (TFs). However, due to the overwhelming number of single-nucleotide polymorphisms (SNPs) (>500,000) in genome-wide association studies, prioritizing variants for in vitro analysis remains challenging. In this work, we implemented a computational approach that considers support vector machine (SVM)-based TF binding site classification and cardiac expression quantitative trait loci (eQTL) analysis to identify and prioritize potential CVD-causing SNPs. We identified 1535 CVD-associated SNPs within TF footprints and putative cardiac enhancers plus 14,218 variants in linkage disequilibrium with genotype-dependent gene expression in cardiac tissues. Using ChIP-seq data from two cardiac TFs (NKX2-5 and TBX5) in human-induced pluripotent stem cell-derived cardiomyocytes, we trained a large-scale gapped k-mer SVM model to identify CVD-associated SNPs that altered NKX2-5 and TBX5 binding. The model was tested by scoring human heart TF genomic footprints within putative enhancers and measuring in vitro binding through electrophoretic mobility shift assay. Five variants predicted to alter NKX2-5 (rs59310144, rs6715570, and rs61872084) and TBX5 (rs7612445 and rs7790964) binding were prioritized for in vitro validation based on the magnitude of the predicted change in binding and are in cardiac tissue eQTLs. All five variants altered NKX2-5 and TBX5 DNA binding. We present a bioinformatic approach that considers tissue-specific eQTL analysis and SVM-based TF binding site classification to prioritize CVD-associated variants for in vitro analysis.

Prioritizing Cardiovascular Disease-Associated Variants Altering NKX2-5 Binding through an Integrative Computational Approach.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide and are heavily influenced by genetic factors. Genome-wide association studies (GWAS) have mapped > 90% of CVD-associated variants within the non-coding genome, which can alter the function of regulatory proteins, like transcription factors (TFs). However, due to the overwhelming number of GWAS single nucleotide polymorphisms (SNPs) (>500,000), prioritizing variants for in vitro analysis remains challenging. In this work, we implemented a computational approach that considers support vector machine (SVM)-based TF binding site classification and cardiac expression quantitative trait loci (eQTL) analysis to identify and prioritize potential CVD-causing SNPs. We identified 1,535 CVD-associated SNPs that occur within human heart footprints/enhancers and 9,309 variants in linkage disequilibrium (LD) with differential gene expression profiles in cardiac tissue. Using hiPSC-CM ChIP-seq data from NKX2-5 and TBX5, two cardiac TFs essential for proper heart development, we trained a large-scale gapped k-mer SVM (LS-GKM-SVM) predictive model that can identify binding sites altered by CVD-associated SNPs. The computational predictive model was tested by scoring human heart footprints and enhancers in vitro through electrophoretic mobility shift assay (EMSA). Three variants (rs59310144, rs6715570, and rs61872084) were prioritized for in vitro validation based on their eQTL in cardiac tissue and LS-GKM-SVM prediction to alter NKX2-5 DNA binding. All three variants altered NKX2-5 DNA binding. In summary, we present a bioinformatic approach that considers tissue-specific eQTL analysis and SVM-based TF binding site classification to prioritize CVD-associated variants for in vitro experimental analysis.

Epidemiological Surveillance Reveals the Rise and Establishment of the Omicron SARS-CoV-2 Variant in Brazil.

The introduction of SARS-CoV-2 variants of concern (VOCs) in Brazil has been associated with major impacts on the epidemiological and public health scenario. In this study, 291,571 samples were investigated for SARS-CoV-2 variants from August 2021 to March 2022 (the highest peak of positive cases) in four geographical regions of Brazil. To identify the frequency, introduction, and dispersion of SARS-CoV-2 variants in 12 Brazilian capitals, VOCs defining spike mutations were identified in 35,735 samples through genotyping and viral genome sequencing. Omicron VOC was detected in late November 2021 and replaced the Delta VOC in approximately 3.5 weeks. We estimated viral load differences between SARS-CoV-2 Delta and Omicron through the evaluation of the RT-qPCR cycle threshold (Ct) score in 77,262 samples. The analysis demonstrated that the Omicron VOC has a lower viral load in infected patients than the Delta VOC. Analyses of clinical outcomes in 17,586 patients across the country indicated that individuals infected with Omicron were less likely to need ventilatory support. The results of our study reinforce the importance of surveillance programs at the national level and showed the introduction and faster dispersion of Omicron over Delta VOC in Brazil without increasing the numbers of severe cases of COVID-19.

Disease-associated non-coding variants alter NKX2-5 DNA-binding affinity.

Genome-wide association studies (GWAS) have mapped over 90 % of disease- or trait-associated variants within the non-coding genome, like cis-regulatory elements (CREs). Non-coding single nucleotide polymorphisms (SNPs) are genomic variants that can change how DNA-binding regulatory proteins, like transcription factors (TFs), interact with the genome and regulate gene expression. NKX2-5 is a TF essential for proper heart development, and mutations affecting its function have been associated with congenital heart diseases (CHDs). However, establishing a causal mechanism between non-coding genomic variants and human disease remains challenging. To address this challenge, we identified 8475 SNPs predicted to alter NKX2-5 DNA-binding using a position weight matrix (PWM)-based predictive model. Five variants were prioritized for in vitro validation; four of them are associated with traits and diseases that impact cardiovascular health. The impact of these variants on NKX2-5 binding was evaluated with electrophoretic mobility shift assay (EMSA) using purified recombinant NKX2-5 homeodomain. Binding curves were constructed to determine changes in binding between variant and reference alleles. Variants rs7350789, rs7719885, rs747334, and rs3892630 increased binding affinity, whereas rs61216514 decreased binding by NKX2-5 when compared to the reference genome. Our findings suggest that differential TF-DNA binding affinity can be key in establishing a causal mechanism of pathogenic variants.

Alteraciones del sueño en niños con trastorno del espectro autista y su afectación individual y familiar. Un estudio observacional de centro único en México / Sleep disturbances in children with autism spectrum disorder and their individual and family affectation. A single-center observational study in Mexico

Introducción: Los trastornos del sueño en niños, tienen un impacto en el desarrollo, afecta el comportamiento, el estado de ánimo, las funciones cognitivas, disminuyendo la atención selectiva y la memoria. El objetivo del presente estudio fue determinar las alteraciones del sueño en niños con trastorno del espectro autista (TEA), su afectación individual y familiar en el Centro Regional de Autismo Delicias Chihuahua. Métodos: El presente estudio transversal, incluye niños con TEA en quienes se determinó alguna alteración del sueño y se buscó su relación con la afectación individual y familiar, además se evaluaron, edad, sexo, grado escolar, nivel funcional de TEA, afectaciones familiares. Se aplicó el cuestionario de cribado del sueño en niños con TEA, el cuestionario adaptado para niños con TEA -BRUNI y el cuestionario de satisfacción sobre las actividades de los padres, cuidadores primarios y familiares de primera línea. Se usa estadística descriptiva y en un segundo análisis se usa Razón de Momios de Prevalencia (RMP). Resultados: Se analizan 57 pacientes, 43 (75.4%) hombres, 28 (49.1%) en grado 1 de nivel funcional TEA, 16 (28.1%) tenían mal desempeño individual, 56 (98.2%) sus familiares referían mal desempeño, 43 (75.4%) tenían alteraciones del sueño. Los niños preescolares tienen 2.5 veces riesgo de tener afec-tación individual. Los pacientes en nivel funcional TEA grado 3 tienen 2.15 veces riesgo de tener afectación individual. Los que despiertan cansados tienen 5.93 veces riesgo de tener afectación individual. Conclusión: La afectación familiar del desempeño es mucho mayor a la afectación individual de los niños con TEA, lo cual genera alteraciones en la dinámica familiar.

Introduction: Sleep disorders in children impact development, affecting behavior, mood, and cognitive functions and decreasing selective attention and memory. This study aimed to determine sleep disturbances in children with autism spectrum disorder (ASD) and their individual and family involvement at the Delicias Chihuahua Regional Autism Center. Methods: This cross-sectional study included children with ASD in whom some sleep disturbance was determined, and its relationship with individual and family affectation was sought; in addition, age, sex, school grade, functional level of ASD, and family affectations were evaluated. The sleep screening questionnaire for children with ASD, the adapted questionnaire for children with ASD -BRUNI, and the satisfaction questionnaire on the activities of parents, primary caregivers, and first-line family members were applied. Descriptive statistics were used, and the prevalence odds ratio (MPR) was used in a second analysis. Results: A total of 57 patients were analyzed; 43 (75.4%) were men, 28 (49.1%) were at the grade 1 ASD functional lev-el, 16 (28.1%) had poor individual performance, 56 (98.2%) their relatives reported poor performance, and 43 (75.4%) had sleep disturbances. Preschool children have a 2.5 times higher risk of having individual involvement. Patients in functional level ASD grade 3 have a 2.15 times higher risk of having individual involvement. Those who wake up tired have a 5.93 times higher risk of having individual involvement. Conclusion: The family affectation of performance is much greater than the personal affectation of children with ASD, which generates changes in family dynamics.

Ribosomes: The New Role of Ribosomal Proteins as Natural Antimicrobials.

Moonlighting proteins are those capable of performing more than one biochemical or biophysical function within the same polypeptide chain. They have been a recent focus of research due to their potential applications in the health, pharmacological, and nutritional sciences. Among them, some ribosomal proteins involved in assembly and protein translation have also shown other functionalities, including inhibiting infectious bacteria, viruses, parasites, fungi, and tumor cells. Therefore, they may be considered antimicrobial peptides (AMPs). However, information regarding the mechanism of action of ribosomal proteins as AMPs is not yet fully understood. Researchers have suggested that the antimicrobial activity of ribosomal proteins may be associated with an increase in intracellular reactive oxidative species (ROS) in target cells, which, in turn, could affect membrane integrity and cause their inactivation and death. Moreover, the global overuse of antibiotics has resulted in an increase in pathogenic bacteria resistant to common antibiotics. Therefore, AMPs such as ribosomal proteins may have potential applications in the pharmaceutical and food industries in the place of antibiotics. This article provides an overview of the potential roles of ribosomes and AMP ribosomal proteins in conjunction with their potential applications.

Long-term effects of early antiretroviral initiation on HIV reservoir markers: a longitudinal analysis of the MERLIN clinical study.

BACKGROUND: Early antiretroviral therapy (ART) initiation (ie, within 3 months of infection) limits establishment of the HIV reservoir. However, the effect of early ART initiation on the long-term dynamics of the pool of infected cells remains unclear. METHODS: In this longitudinal analysis, we included cisgender men who have sex with men (MSM) and transgender women (aged 18-54 years) at high risk for HIV infection, enrolled in the ongoing longitudinal MERLIN study in Peru between Oct 28, 2014, and Nov 8, 2018. Participants were eligible if they had been infected with HIV less than 90 days before enrolment, and if they had cryopreserved peripheral blood mononuclear cell (PBMC) samples. Participants were stratified into three groups on the basis of whether they initiated ART at 30 days or less (acute group), at 31-90 days (early group), or more than 24 weeks (deferred group) after the estimated date of detectable infection. PBMC samples were collected before ART initiation and longitudinally for up to 4 years on ART. The main outcomes were to establish the size of the HIV reservoir before ART initiation and to assess the effect of the timing of ART initiation on the decay of the HIV reservoir over 4 years follow-up. We quantified viral load, and isolated CD4 cells to quantify total HIV DNA, integrated HIV DNA and 2-long terminal repeat circles. Longitudinal analysis of active and inducible HIV reservoirs were measured by quantifying the frequency of CD4 cells producing multiply-spliced HIV RNA ex vivo and after in-vitro stimulation with a tat/rev induced limiting dilution assay (TILDA). A mixed-effects model from the time of ART initiation was used to measure longitudinal decays in viral loads and each HIV reservoir measure in each of the three groups. FINDINGS: We included 56 participants in this analysis, all of whom were MSM: 15 were in the acute group, 19 were in the early group, and 22 were in the deferred group. Participants in all three groups had similar levels of all HIV reservoir markers before ART initiation. All participants, including those in the acute group, had a pool of transcriptionally silent HIV-infected cells before ART initiation, as indicated by a substantial increase in TILDA measures upon stimulation. Longitudinal analysis over 4 years of ART revealed a biphasic decay of all HIV persistence markers, with a rapid initial decline followed by a slower decay in all participants. During the first-phase decay, the half-lives of both total and integrated HIV DNA and TILDA measures were significantly shorter in the acute group than in the early and deferred groups. During the second-phase decay, HIV reservoir markers continued to decline only in participants in the acute group. INTERPRETATION: Participants who initiated ART within 30 days or less of HIV infection showed a steeper and more sustained decay in HIV reservoir measures, suggesting long-term benefit of acute ART initiation on reservoir clearance. FUNDING: The US National Institutes of Health and the Canadian Institutes for Health Research.

Long-term effects of early antiretroviral initiation on HIV reservoir markers: a longitudinal analysis of the MERLIN clinical study.

BACKGROUND: Early antiretroviral therapy (ART) initiation (ie, within 3 months of infection) limits establishment of the HIV reservoir. However, the effect of early ART initiation on the long-term dynamics of the pool of infected cells remains unclear. METHODS: In this longitudinal analysis, we included cisgender men who have sex with men (MSM) and transgender women (aged 18-54 years) at high risk for HIV infection, enrolled in the ongoing longitudinal MERLIN study in Peru between Oct 28, 2014, and Nov 8, 2018. Participants were eligible if they had been infected with HIV less than 90 days before enrolment, and if they had cryopreserved peripheral blood mononuclear cell (PBMC) samples. Participants were stratified into three groups on the basis of whether they initiated ART at 30 days or less (acute group), at 31-90 days (early group), or more than 24 weeks (deferred group) after the estimated date of detectable infection. PBMC samples were collected before ART initiation and longitudinally for up to 4 years on ART. The main outcomes were to establish the size of the HIV reservoir before ART initiation and to assess the effect of the timing of ART initiation on the decay of the HIV reservoir over 4 years follow-up. We quantified viral load, and isolated CD4 cells to quantify total HIV DNA, integrated HIV DNA and 2-long terminal repeat circles. Longitudinal analysis of active and inducible HIV reservoirs were measured by quantifying the frequency of CD4 cells producing multiply-spliced HIV RNA ex vivo and after in-vitro stimulation with a tat/rev induced limiting dilution assay (TILDA). A mixed-effects model from the time of ART initiation was used to measure longitudinal decays in viral loads and each HIV reservoir measure in each of the three groups. FINDINGS: We included 56 participants in this analysis, all of whom were MSM: 15 were in the acute group, 19 were in the early group, and 22 were in the deferred group. Participants in all three groups had similar levels of all HIV reservoir markers before ART initiation. All participants, including those in the acute group, had a pool of transcriptionally silent HIV-infected cells before ART initiation, as indicated by a substantial increase in TILDA measures upon stimulation. Longitudinal analysis over 4 years of ART revealed a biphasic decay of all HIV persistence markers, with a rapid initial decline followed by a slower decay in all participants. During the first-phase decay, the half-lives of both total and integrated HIV DNA and TILDA measures were significantly shorter in the acute group than in the early and deferred groups. During the second-phase decay, HIV reservoir markers continued to decline only in participants in the acute group. INTERPRETATION: Participants who initiated ART within 30 days or less of HIV infection showed a steeper and more sustained decay in HIV reservoir measures, suggesting long-term benefit of acute ART initiation on reservoir clearance. FUNDING: The US National Institutes of Health and the Canadian Institutes for Health Research.

Clinical and Immunologic Outcomes After Immediate or Deferred Antiretroviral Therapy Initiation During Primary Human Immunodeficiency Virus Infection: The Sabes Randomized Clinical Study.

BACKGROUND: In addition to demonstrated public health benefits on reducing transmission, it remains unclear how early antiretroviral therapy (ART) must be started after acquisition of human immunodeficiency virus (HIV) to maximize individual benefits. METHODS: We conducted an open-label randomized clinical study in Lima, Peru among adult men who have sex with men and transgender women with acute (HIV-antibody negative/HIV-1 RNA positive) or recent (confirmed negative HIV-antibody or RNA test within 3 months) HIV infection, who were randomized to start ART immediately versus defer by 24 weeks. We evaluated outcomes by treatment arm and immunologic markers by days since estimated date of detectible infection (EDDI). RESULTS: Of 216 participants, 105 were assigned to immediate arm and 111 to deferred arm (median age 26.8 years, 37% with acute HIV). The incidence of non-ART-related adverse events was lower in immediate versus deferred arm (83 vs 123/100 person-years, IRR 0.67 (95% confidence interval [CI] .47, .95; P = .02), the difference dominated by fewer infections in those treated immediately. After 24 weeks of ART, between-group differences in CD4/CD8 cell ratio lessened (P = .09 overall), but differences between those initiating ART ≤ 30 days from EDDI (median 1.03, interquartile range [IQR] 0.84, 1.37), and those initiating > 90 days (0.88, IQR 0.61, 1.11) remained, P = .02. Principal components analysis of 20 immune biomarkers demonstrated distinct patterns between those starting ART > 90 days from EDDI versus those starting within 30 or 90 days (both P < .001). CONCLUSIONS: To our knowledge, this is the only evaluation of randomized ART initiation during primary HIV and provides evidence to explicitly consider acute HIV in World Health Organization recommendations for universal ART. CLINICAL TRIALS REGISTRATION: NCT01815580.

Perceptions Prediagnosis and Social Experiences Postdiagnosis Among a Sample of High-Risk Peruvian Men Who Have Sex With Men.

This pilot study examines associations of perceived stigma pre-diagnosis with experienced stigma and social support post-diagnosis with qualitative data; and quantifies the interplay between pre- and post-diagnosis social factors on depressive symptoms among a sample of newly diagnosed Peruvian men who have sex with men (n = 67 total). Qualitative findings highlight the differences between perceptions of stigma pre-disclosure and actual social experiences post-disclosure for most participants. Perceived stigma pre-diagnosis was significantly related to post-diagnosis social support, B = -0.35, p = 0.03, and marginally associated with experienced stigma, B = 0.29, p = 0.07. Pre-diagnosis perceived stigma was associated with greater depressive symptoms, but only among individuals who reported higher amounts of social support, B = 0.55, p = 0.01. Findings suggest the importance of addressing social perceptions in order to optimize the beneficial effects of social support resources among newly diagnosed individuals.

Traditional and Web-Based Technologies to Improve Partner Notification Following Syphilis Diagnosis Among Men Who Have Sex With Men in Lima, Peru: Pilot Randomized Controlled Trial.

BACKGROUND: Patient-initiated partner notification (PN) following the diagnosis of a sexually transmitted infection is a critical component of disease control in men who have sex with men (MSM) sexual networks. Both printed and internet-based technologies offer potential tools to enhance traditional partner notification approaches among MSM in resource-limited settings. OBJECTIVE: This randomized controlled trial aimed to evaluate the effect of 2 different PN technologies on notification outcomes following syphilis diagnosis among MSM in Peru: a Web-based notification system and patient-delivered partner referral cards. METHODS: During 2012-2014, we screened 1625 MSM from Lima, Peru, for syphilis infection and enrolled 370 MSM with symptomatic primary or secondary syphilis (n=58) or asymptomatic latent syphilis diagnosed by serology (rapid plasma reagin, RPR, and Microhemagglutination assay for Treponema pallidum antibody; n=312). Prior to enrollment, potential participants used a computer-based self-interviewing system to enumerate their recent sexual partnerships and provide details of their 3 most recent partners. Eligible participants were randomly assigned to one of 4 intervention arms: (1) counseling and patient-initiated Web-based PN (n=95), (2) counseling with Web-based partner notification and partner referral cards (n=84), (3) counseling and partner referral cards (n=97), and (4) simple partner notification counseling (control; n=94). Self-reported partner notification was assessed after 14 days among 354 participants who returned for the follow-up assessment. RESULTS: The median age of enrolled participants was 27 (interquartile range, IQR 23-34) years, with a median of 2 partners (IQR 1-5) reported in the past month. Compared with those who received only counseling (arm 4), MSM provided with access to Web-based partner notification (arms 1 and 2) or printed partner referral cards (arms 2 and 3) were more likely to have notified one or more of their sexual partners (odds ratio, OR, 2.18, 95% CI 1.30-3.66; P=.003 and OR 1.68, 95% CI 1.01-2.79; P=.045, respectively). The proportion of partners notified was also higher in both Web-based partner notification (241/421, 57.2%; P<.001) and referral card (240/467, 51.4%; P=.006) arms than in the control arm (82/232, 35.3%). CONCLUSIONS: Both new Web-based technologies and traditional printed materials support patient-directed notification and improve self-reported outcomes among MSM with syphilis. Additional research is needed to refine the use of these partner notification tools in specific partnership contexts. TRIAL REGISTRATION: ClinicalTrials.gov NCT01720641; https://clinicaltrials.gov/ct2/show/NCT01720641 (Archived by WebCite at http://www.webcitation.org/70A89rJL4).

Design Strategy of the Sabes Study: Diagnosis and Treatment of Early HIV Infection Among Men Who Have Sex With Men and Transgender Women in Lima, Peru, 2013-2017.

The Sabes Study evaluated a treatment-as-prevention intervention among cisgender men who have sex with men and transgender women in Lima, Peru-populations disproportionately affected by the human immunodeficiency virus (HIV) epidemic. The intervention was designed to prevent onward transmission of HIV by identifying HIV-negative high-risk individuals, testing them monthly for the presence of HIV, and then rapidly treating those who became HIV-positive. The main outcome of interest was the development of a model predicting the population-level impact of early detection of HIV infection and immediate initiation of antiretroviral therapy in this population. From July 2013 to September 2015, a total of 3,337 subjects were screened for HIV; 2,685 (80.5%) were negative, and 2,109 began monthly testing. We identified 256 individuals shortly after HIV acquisition, 216 of whom were enrolled in the treatment phase of the study. All participants were followed for 48 weeks (follow-up ended in 2017) and were then referred to the Peruvian Ministry of Health to continue receiving free HIV care and treatment. Initial findings from this intervention demonstrate that it is possible to recruit high-risk individuals, screen them for HIV, continue to test those who are initially HIV-negative in order to identify incident cases shortly after acquisition, and then rapidly link them to health care.

Individual and partnership factors associated with anticipated versus actual partner notification following STI diagnosis among men who have sex with men and/or with transgender women in Lima, Peru.

OBJECTIVES: A detailed understanding of intentions and practices related to partner notification (PN) following STI diagnosis can improve control strategies. We assessed participant-level and partner-level factors guiding notification behaviour among men who have sex with men and/or with transgender women (MSM-TW) in Lima, Peru, including discordances between anticipated and actual notification. METHODS: Men newly diagnosed with gonorrhoea, chlamydia and/or syphilis between 2012 and 2014 reported recent partners' characteristics, anticipated PN practices, and actual PN outcomes following diagnosis. Generalised estimating equation Poisson regression analyses assessed factors guiding PN outcomes. RESULTS: Participants (n=150) predominantly identified as homosexual (70%) and moderno (versatile sexual role, 55%); 55% of partners (n=402) were casual. Among all sexual partners, 35% were notified of the STI diagnosis, though only 51% of predicted PN occurred and 26% of actual notifications were unanticipated. 47% of participants notified no partners, while 24% notified all partners. PN was more common with stable versus casual (adjusted prevalence ratio (aPR), 95% CI: 0.53, 0.39 to 0.73) or commercial (aPR, 95% CI: 0.38, 0.12 to 1.21) partners, and among participants who perceived PN as normative among their peers (aPR, 95% CI: 1.96, 1.37 to 2.82). A trend towards greater notification following condom-protected intercourse was observed (aPR, 95% CI: 1.33, 0.98 to 1.81). PN frequency did not differ by type of STI diagnosed.Anticipated notification predicted actual notification (aPR, 95% CI: 1.67, 1.19 to 2.33) only imperfectly: 81 (54%) participants' PN practices did not match their anticipated behaviour. Successful notification despite anticipated silence (40 participants, 63 partners) was associated with stable partnerships and a normative perception of PN. Non-notification despite intention (43 participants, 73 partners) frequently occurred among participants reporting exclusively oral sex with the partner or with partners identified as activo (insertive role). CONCLUSIONS: Anticipated notification imperfectly reflects actual PN behaviour. Future interventions to improve PN among MSM-TW in Peru need to acknowledge partnership contexts.

Expedited Partner Therapy (EPT) increases the frequency of partner notification among MSM in Lima, Peru: a pilot randomized controlled trial.

BACKGROUND: Expedited Partner Therapy (EPT) has been shown to improve treatment outcomes among heterosexual partners of individuals with curable sexually transmitted infections (STIs). Although the use of EPT with men who have sex with men (MSM) has been debated, due to the potential for missed opportunities to diagnose unidentified cases of HIV and syphilis infection in symptomatic partners, increases in partner notification (PN) resulting from use of EPT may promote testing and treatment of otherwise unidentified partners. We assessed the impact of EPT on self-reported PN among MSM in Peru with gonorrheal (GC) and/or chlamydial (CT) infection. METHODS: We enrolled 173 MSM in Lima, Peru with symptomatic or asymptomatic GC and/or CT infection between 2012 and 2014. We enrolled 44 MSM with symptomatic urethritis/proctitis and 129 MSM with asymptomatic GC/CT infection, diagnosed based on nucleic acid testing (Aptima Combo 2 Transcription-Mediated Amplification [TMA]) from urethral, pharyngeal, and rectal sites. Eligible participants were randomly assigned to receive either standard PN counseling (n = 84) or counseling plus EPT (cefixime 400 mg/azithromycin 1 g) for up to five recent partners (n = 89). Self-reported notification was assessed by computer-assisted self-administered survey among 155 participants who returned for 14-day follow-up. RESULTS: The median age of participants was 26 (interquartile range [IQR]: 23-31) with a median of 3 sexual partners (IQR: 2-4) in the previous 30-day period. Among all participants, 111/155 (71.6%) notified at least one partner at 14-day follow-up with a median of 1 partner notified per participant (IQR: 0-2). For participants randomized to receive EPT, 69/83 (83.1%) reported notifying at least one partner, compared with 42/72 (58.3%) of participants in the control arm (odds ratio = 3.52; 95% confidence interval [CI]: 1.68-7.39). The proportion of all recent partners notified was significantly greater in the EPT than in the control arm (53.5%, 95% CI: 45.0-62.0% versus 36.4%, 95% CI: 27.0-47.4%). CONCLUSIONS: Provision of EPT led to significant increases in notification among Peruvian MSM diagnosed with GC/CT infection. Additional research is needed to assess the impact of EPT on biological outcomes, including persistent or recurrent infection, antimicrobial resistance, and HIV/STI transmission, in MSM sexual networks. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01720654 . Registered on 10/29/2012.

Molecular rare earth metal alumosilicates.

The synthesis and stabilization of molecular four-coordinated lanthanide alumosilicates was achieved by the use of a highly encumbered alumosilicate ligand LAl(OH·thf)(µ-O)Si(OH)(OtBu)2 (1, L = HC{C(Me)N(2,6-iPr2C6H3)}2). Reactions between 1 and tris-cyclopentadienyl lanthanides (LnCp3; Ln = Ce, Nd, Sm, Gd, Tb, Dy, Y, Er) derived in the isolation of eight compounds (2-9) where the ligand is observed in three different bonding modes: adducts (2, 3), spirocyclic (4) or cyclic (5-9) coordination compounds. The observed reactivity can be related to the ionic radius of the lanthanide atom and the nature of the oxygen donor-atom from the hydroxide (Al-OH) or hydroxyl (Si-OH) moieties in 1. Compounds 2-9 present general O-Al-O-Si-O-Ln connectivities with different degrees of substitution over the -OH groups in 1 and structural features with only slight variations over the alumosilicate moiety (O-Al-O-Si-O) upon the lanthanide coordination. The spirocyclic samarium derivative presents two tetra-coordinated samarium atoms with a tetrahedral and distorted square planar geometries, respectively, as a result of a highly strained polycyclic architecture.

Knowledge and preferences concerning acute HIV testing programs among both Peruvian men who have sex with men and transgender women.

Immediate antiretroviral therapy (ART) for acute HIV infection (AHI) may decrease HIV transmission in high-risk populations. This study evaluated knowledge of AHI and AHI testing program preferences in Lima, Peru through four semi-structured focus groups with high-risk men who have sex with men (MSM) ( n = 20) and transgender women (TW) ( n = 16). Using content analysis, emergent themes included knowledge of AHI symptoms, AHI transmission potential, and the HIV testing window period, and preferences concerning point of care results. Participants demonstrated low familiarity with the term AHI, but many correctly identified AHI symptoms. However, these symptoms may not motivate testing because they overlap with common viral illnesses and AIDS. Some were aware that infectiousness is highest during AHI, and believe this knowledge would facilitate HIV testing. The shortened window period with AHI testing would encourage testing following high-risk sex. Delayed result notification would not decrease AHI testing demand among MSM, although it might for some TW.

Frecuencia de anticuerpos anti Toxoplasma gondii en gestantes de Cúcuta, Colombia / Frequency of anti Toxoplasma gondii antibodies in pregnant of Cucuta, Colombia

La toxoplasmosis es una infección ocasionada por Toxoplasma gondii, peligrosa durante la gestación. La presencia de anticuerpos IgG específicos implica contacto previo individuo-parásito, mientras que la detección de IgM anti-T. gondii, es considerada marcador de infección aguda, fase en la que se incrementa además el título IgG. Objetivo: Determinar la frecuencia y título de anticuerpos contra Toxoplasma gondii en gestantes. Material y métodos: Estudio transversal, se determinó el título de IgG y la presencia de IgM específicas contra el parásito, mediante técnicas de aglutinación y Enzimoinmunoanálisis, respectivamente, en muestras de suero de mujeres en el primer, segundo o tercer trimestre de embarazo que asistieron a su control prenatal en el Centro de Imagenología y Laboratorio Clínico, durante el segundo semestre del año 2014. Resultados: Se evaluaron 167 pacientes, de las cuales 115 (68,9%) fueron negativas y 52 (31,1%) positivas para IgG anti T. gondii; dentro del último grupo se rastreó IgM específica en 35 pacientes, hallándose solo una positiva (3%). La titulación para IgG anti-T. gondii mostró resultados desde 1:1 a 1:8 diluciones en las 34 pacientes negativas para IgM específica y de 1:16 diluciones, en el caso positivo. Conclusión: Los resultados obtenidos en el presente estudio permiten concluir que una tercera parte de la población gestante presenta anticuerpos asociados a memoria inmunológica contra T.gondii a títulos bajos, y sólo una minoría (inferior al 5%) evidencia concomitantemente huella serológica de infección reciente...

Toxoplasmosis is caused by Toxoplasma gondii and it is especially dangerous during pregnancy. The presence of IgG antibodies against T. gondii indicates past infection, while the presence of IgM indicates acute infection. Objective: To determine the frequency and titers of antibodies against T. gondii in pregnant women in Cucuta, Colombia. Methods: A cross sectional study was carried out in which titers of IgG and IgM to T. gondii were measured using agglutination and immunoassay methods in serum samples of first, second and third trimester pregnant women who attended pre-natal control in the Center for Imagenology and Clinical Laboratory during the second semester of 2014. Results: 167 women were evaluated; 115 (68.9%) were negative for IgG and 52 (31.1%) were positive; specific IgM was search for in 35 of these IgG positive women, only one was positive (3%). IgG titers varied from 1:1 to 1:8 in the 34 IgM seronegative women, but was 1:16 in seropositive women. Conclusions: One third of the population studied was previously infected showing low titers of IgG, the minority showed evidence of acute infection...

Detecting feigned ADHD in later adolescence: an examination of three PAI-A negative distortion indicators.

The validity of various indicators of response distortion on the Personality Assessment Inventory-Adolescent (PAI-A; Morey, 2007a) and its potential usefulness to detect malingering were evaluated by having 17- and 18-year-old students complete the PAI-A attempting to simulate Attention-Deficit/Hyperactivity Disorder (ADHD) under coached or noncoached conditions. Scores for these respondents on the Negative Impression and Positive Impression scales, the Malingering Index, and the Rogers Discriminant Function (RDF) were compared to those of 17- and 18-year-old patients receiving clinical diagnoses of ADHD. Simulating respondents also completed the Conners Adult ADHD Rating Scale (CAARS) to determine if they could successfully simulate self-reported symptoms of ADHD. A total of 45% of simulating participants obtained CAARS scores reflecting clinically significant symptoms of ADHD. All indicators demonstrated the ability to distinguish between actual patients and feigned responses of successful simulators, with the RDF demonstrating the greatest accuracy in distinguishing these groups.