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IntroductionTight junctions (TJs) serve as permeability filters between the internal and external cellular environment. A large number of proteins have been identified to be localized at the TJs. Due to limitations in tissue collection, TJs in the male genital tract have been understudied.MethodsWe analysed the transcriptomics of 132 TJ genes in foreskin tissue of men requesting voluntary medical male circumcision (VMMC) and enrolled in the Combined HIV Adolescent Prevention Study (CHAPS) trial conducted in South Africa and Uganda (NCT03986970). The trial evaluated the dose requirements for event-driven HIV pre-exposure prophylaxis (PrEP) with emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during insertive sex. A total of 144 participants were randomized to either control arm or one of 8 PrEP arms (n=16/arm), receiving oral FTC-TDF or FTC-TAF over one or two days. Following in vivo oral PrEP dosing and VMMC, the expression level of three important TJ proteins (CLDN-1, OCN and ZO-1) was measured ex vivo in foreskin tissue by Western blot. The expression of cytokine genes implicated in TJ regulation was determined. Non-parametric Kruskal-Wallis tests were used to compare TJ gene expression and protein levels by type of PrEP received, and Spearman’s correlation coefficients were calculated to assess whether TJ gene expression levels were related to cytokine gene levels or to PrEP drug concentrations and their active intracellularly phosphorylated metabolites.ResultsA high level of expression in foreskin tissue was found for 118 (of 132) TJ genes analysed; this finding contributed to create a map of TJ components within the male genital tract. Importantly, PrEP regimens tested in the CHAPS trial did not affect the expression of TJ genes and the analysed proteins in the foreskin; thus, further supporting the safety of this prevention strategy against HIV-1 transmission during insertive sex. Additionally, we identified the level of several cytokines’ genes to be correlated to TJ gene expression: among them, IL-18, IL-33 and VEGF.DiscussionTJs can limit viral entry into target cells; to affect this biological function viruses can reduce the expression of TJ proteins. Our study, on the expression and regulation of TJs in the foreskin, contribute important knowledge for PrEP safety and further design of HIV-1 prophylaxis.

ObjectiveThis study aims to provide rapid and up-to-date evidence on the effectiveness of Health at Every Size (HAES) interventions compared to controls or other conventional approaches in individuals with overweight or obesity, with the goal of developing more effective and body-diverse respectful strategies.MethodsA review of literature was carried out using the following databases: PubMed, Scopus, Embase, Web of Science, and SciELO. Research articles were selected based on predefined inclusion and exclusion criteria. Extracted data included study characteristics (design, setting, population demographics, sample size, intervention characteristics, study duration, and follow-up period) and health-related outcomes.ResultsThe search yielded 324 articles, of which 20 articles met the inclusion and exclusion criteria. The majority of studies focused on lifestyle improvement, particularly in nutrition, body image, and relationships with food, utilizing a HAES approach. Additionally, other studies examined outcomes such as general well-being, body weight, body composition, cardiovascular risk, and changes in physical activity. Long-term results were particularly noted in studies incorporating physical activity interventions.ConclusionHAES interventions appear to be a feasible strategy for promoting overall health and wellness, regardless of body size or shape. However, further evaluation is needed to assess the sustainability of these changes and their long-term impact, as current evidence suggest a they may not be maintained over time.

Este artículo tiene como objetivo comprender, mediante el análisis de 16 entrevistas semiestructuradas, las implicancias teórico-clínicas del posicionamiento con perspectiva de género o feminista en la práctica psicoterapéutica contemporánea en Chile, desde la perspectiva de consultantes y psicoterapeutas. Como resultados, se observa que el valor de esta psicoterapia radica en entregar una lectura sociocultural del malestar generizado. Sin embargo, quienes consultan reproducen estereotipos de género al elegir este enfoque a propósito del género femenino de la psicoterapeuta, pues consideran que habría un mayor entendimiento “por ser mujer”, lo cual les garantizaría un espacio seguro, libre de juicios y revictimización. Se destaca que las intervenciones de este enfoque tienen un componente político que favorece el trabajo de la desculpabilización de las consultantes. Esto resulta favorable en ciertos casos, pero podría obstaculizar el abordaje y reconocimiento de aquellas características singulares del sujeto que inciden en el sufrimiento y trascienden la certeza ideológica.

Transition period is a critical time for dairy cows because a large proportion of clinical and subclinical diseases are observed in the first month after parturition. Occurrence of negative energy balance is associated with depressed immunity and these conditions can affect oocyte quality and further embryonic development. The aim of this study was to assess the effects of negative energy balance-associated disorders on in vitro embryo production (IVP) in dairy cattle. We hypothesized that subclinical metabolic and/or inflammatory disorders have a negative effect on oocyte developmental competence and morphokinetic parameters of the resulting embryos. The study was conducted on 30 lactating Holstein-Friesian cows which were assigned into four groups: healthy (HEAL, n = 6), metabolic disease (META, n = 8), inflammatory disease (INFL, n = 8), or combined metabolic and inflammatory disease (COMB, n = 8). Ovum pick-up (OPU) was performed twice weekly on all cows over a period of four weeks (n = 8 OPU sessions/cow) starting on the fifth week postpartum, and the collected oocytes were subjected to routine IVP. Donor’s health status did not affect the number of oocytes/OPU or the recovery rate (p > 0.05). The number of quality 1 oocytes collected from INFL and COMB cows was lower compared to HEAL cows (p 0.05). Presence of disease did not affect the time required by zygotes to reach specific developmental stages, as recorded by means of time-lapse monitoring. Nevertheless, there was a higher probability of direct cleavage after IVF in oocytes of COMB cows compared to those of HEAL cows (p

The penile epithelial microbiome remains underexplored. We sequenced human RNA and a segment of the bacterial 16S rRNA gene from the foreskin tissue of 144 adolescents from South Africa and Uganda collected during penile circumcision after receipt of 1–2 doses of placebo, emtricitabine + tenofovir disoproxil fumarate, or emtricitabine + tenofovir alafenamide to investigate the microbiome of foreskin tissue and its potential changes with antiretroviral use. We identified a large number of anaerobic species, including Corynebacterium acnes, which was detected more frequently in participants from South Africa than Uganda. Bacterial populations did not differ by treatment received, and no differentially abundant taxa were identified between placebo versus active drug recipients. The relative abundance of specific bacterial taxa was negatively correlated with expression of genes downstream of the innate immune response to bacteria and regulation of inflammation. Our results show no difference in the tissue microbiome of the foreskin with short-course antiretroviral use but that bacterial taxa were largely inversely correlated with inflammatory gene expression, consistent with commensal colonization.

Abstract Life-threatening bacterial infections in women after childbirth, known as puerperal sepsis, resulted in classical epidemics and remain a global health problem. While outbreaks of puerperal sepsis have been ascribed to Streptococcus pyogenes, little is known about disease mechanisms. Here, we show that the bacterial R28 protein, which is epidemiologically associated with outbreaks of puerperal sepsis, specifically targets the human receptor CEACAM1. This interaction triggers events that would favor the development of puerperal sepsis, including adhesion to cervical cells, suppression of epithelial wound repair and subversion of innate immune responses. High-resolution structural analysis showed that an R28 domain with IgI3-like fold binds to the N-terminal domain of CEACAM1. Together, these findings demonstrate that a single adhesin-receptor interaction can drive the pathogenesis of bacterial sepsis and provide molecular insights into the pathogenesis of one of the most important infectious diseases in medical history.

Summary: Background: The efficacy of on-demand HIV pre-exposure prophylaxis (PrEP) for men in sub-Saharan Africa has not been evaluated, and the on-demand PrEP dosing requirement for insertive sex remains unknown. Methods: HIV-negative males 13–24 years, requesting voluntary medical male circumcision (VMMC), were enrolled into an open-label randomised controlled trial (NCT03986970), and randomised 1:1:1:1:1:1:1:1:1 to control arm or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) over one or two days, and circumcised 5 or 21 h thereafter. The primary outcome was foreskin p24 concentrations following ex vivo HIV-1BaL challenge. Secondary outcomes included peripheral blood mononuclear cell (PBMC) p24 concentration, and drug concentrations in foreskin tissue, PBMCs, plasma and foreskin CD4+/CD4-cells. In the control arm, post-exposure prophylaxis (PEP) activity of non-formulated tenofovir-emtricitabine (TFV-FTC) or TAF-FTC was assessed with ex vivo dosing 1, 24, 48 or 72 h post-HIV-1 challenge. Findings: 144 participants were analysed. PrEP with F/TDF or F/TAF prevented ex vivo infection of foreskins and PBMCs both 5 and 21 h after PrEP dosing. There was no difference between F/TDF and F/TAF (p24day15 geometric mean ratio 1.06, 95% confidence interval: 0.65–1.74). Additional ex vivo dosing did not further increase inhibition. In the control arm, PEP ex vivo dosing was effective up to 48 post-exposure diminishing thereafter, with TAF-FTC showing prolonged protection compared to TFV-FTC. Participants receiving F/TAF had higher TFV-DP concentrations in foreskin tissue and PBMCs compared with F/TDF, irrespective of dose and sampling interval; but F/TAF did not confer preferential TFV-DP distribution into foreskin HIV target cells. FTC-TP concentrations with both drug regimens were equivalent and ∼1 log higher than TFV-DP in foreskin. Interpretation: A double dose of either F/TDF or F/TAF given once either 5 or 21 h before ex vivo HIV-challenge provided protection across foreskin tissue. Further clinical evaluation of pre-coital PrEP for insertive sex is warranted. Funding: EDCTP2, Gilead Sciences, Vetenskapsrådet.

With a growing interest in the study of urban life and health, evidence indicates that the quality of the environment in which we live can have implications for our subjective well-being and health. This study assesses the potential impacts of perceptions of visual air pollution, olfactory air pollution, and noise pollution on self-perceived health, self-perceived happiness, and satisfaction with life, through the calculation of ordinal logistic regressions, using the information of an online survey carried out in Quito, Ecuador. We found that perceptions of unpleasant odors and noise pollution influence self-perceived health, self-perceived happiness, and satisfaction with life. The obtained results may support the incorporation of citizens’ perspectives to better understand environmental pollution and to enrich local planning for urban sustainability.

Pangenomes have a number of advantages over linear reference assemblies. Here the authors use bovine haplotype-resolved assemblies to show that structural variant-based pangenomes are consistent regardless of sequence platform, assembler, or coverage, suggesting that rigid protocols may not be required.

Background: Different antiretroviral therapies (ARTs) may have differing effects on central nervous system (CNS) function. We assessed CNS pharmacodynamic effects of switching integrase inhibitors in people-with-HIV (PWH). Methods: PWH on tenofovir-DF/emtricitabine plus raltegravir 400 mg twice daily with suppressed plasma HIV RNA and without overt neuropsychiatric symptoms were randomly allocated on a 1:2 basis to remain on raltegravir or switch to dolutegravir 50 mg once daily for 120 days. Pharmacodynamic parameters assessed included cognitive function (z-score of 7 domains), patient-reported outcome measures (PROMs; PHQ-9 and Beck’s depression questionnaires), cerebral metabolite ratios measured by proton magnetic resonance spectroscopy (H1-MRS) and plasma and cerebrospinal fluid (CSF) HIV RNA. Pharmacokinetic parameters were also assessed in plasma and CSF. Changes and factors associated with changes in pharmacodynamics parameters were assessed. Results:In 20 subjects (19 male, 14 white ethnicity, median age 43 years (IQR: 11.5) and CD4 + count 717 (SD: 298) cells/µL), over 120 days there were no statistically significant changes in cognitive function [mean z-score difference (95%CI) −0.004 (−0.38/0.37); p = 0.98], PROMs [PHQ-9 median score change: 0 in control arm, −0.5 switch arm (p = 0.57); Beck’s depression questionnaire: −1.5 control arm, −1.0 switch arm (p = 0.38)], nor cerebral metabolite ratios between study arms. CSF HIV RNA was

Preventing new HIV infections remains a global challenge. Young women continue to bear a disproportionate burden of infection. Oral pre-exposure prophylaxis (PrEP), offers a novel women-initiated prevention technology and PrEP trials completed to date underscore the importance of their inclusion early in trials evaluating new HIV PrEP technologies. Data from completed topical and systemic PrEP trials highlight the role of gender specific physiological and social factors that impact PrEP uptake, adherence and efficacy. Here we review the past and current developments of HIV-1 prevention options for women with special focus on PrEP considering the diverse factors that can impact PrEP efficacy. Furthermore, we highlight the importance of inclusion of female scientists, clinicians, and community advocates in scientific efforts to further improve HIV prevention strategies.

Whilst short-term oral pre-exposure prophylaxis (PrEP) with antiretroviral drugs in men who have sex with men has shown protection against HIV-1 infection, the impact of this regimen on the in vivo foreskin transcriptome is unknown. We collected foreskin tissue after voluntary medical male circumcision from 144 young men (72 from Uganda and 72 from South Africa) randomized to one to two doses of either oral tenofovir (TFV) disoproxil fumarate (FTC-TDF) or tenofovir alafenamide (FTC-TAF) or no drug (untreated controls). This novel approach allowed us to examine the impact of short-term oral PrEP on transcriptome of the male genital tract. A single dose of FTC-TDF did not affect the foreskin transcriptome in relation to control arm, however one dose of FTC-TAF induced upregulation of four genes AKAP8, KIAA0141, HSCB and METTL17. Following two doses of either FTC-TDF or FTC-TAF, there was an increase in 34 differentially expressed genes for FTC-TDF and 15 for FTC-TAF, with nine DEGs in common: KIAA0141, SAFB2, CACTIN, FXR2, AKAP8, HSCB, CLNS1A, DDX27 and DCAF15. Functional analysis of differentially expressed genes revealed modulation of biological processes related to mitochondrial stress (KIAA0141, HSCB and METTL17), anti-viral and anti-inflammatory pathways (CACTIN and AKAP8). Our results show that short-course on-demand oral PrEP in men modulates genes in foreskin tissue which are likely unfavorable to HIV acquisition and replication. We also describe an upregulated expression of genes involved in diverse mitochondria biology which may potentially result in worsened mitochondria-related. These results warrant further studies to assess the role of short-course and prolonged oral PrEP on biological processes of the foreskin mucosa.

Previous studies on highly HIV-1-exposed, yet persistently seronegative women from the Punwami Sex Worker cohort in Kenya, have shed light on putative protective mechanisms, suggesting that mucosal immunological factors, such as antiproteases, could be mediating resistance to HIV-1 transmission in the female reproductive tract. Nine protease inhibitors were selected for this study: serpin B4, serpin A1, serpin A3, serpin C1, cystatin A, cystatin B, serpin B13, serpin B1 and α-2-macroglobulin-like-protein 1. We assessed in a pilot study, the activity of these antiproteases with cellular assays and an ex vivo HIV-1 challenge model of human ecto-cervical tissue explants. Preliminary findings with both models, cellular and tissue explants, established an order of inhibitory potency for the mucosal proteins as candidates for pre-exposure prophylaxis when mimicking pre-coital use. Combination of all antiproteases considered in this study was more active than any of the individual mucosal proteins. Furthermore, the migration of cells out of ecto-cervical explants was blocked indicating potential prevention of viral dissemination following amplification of the founder population. These findings constitute the base for further development of these mucosal protease inhibitors for prevention strategies.

Improving the availability of new sources of probiotics is essential to continue implementing alternative solutions to improve coral health; one such source is urban corals. However, little is known about urban coral’s health status and whether they can harbor bacteria exhibiting probiotic traits. Here, we explored the status of the urban coral Madracis auretenra and the presence of probiotic traits in its associated culturable bacteria. After assessing ecological attributes, we observed a similar abundance (cover %) when comparing patches of M. auretenra occurring in both an urban site and a marine protected area. The urban patch also exhibited a high abundance of vibrios in coral tissues and signs of ecosystem deterioration. However, this patch showed a “good” health index condition; so, we hypothesized the presence of beneficial bacteria. We isolated 132 bacterial strains from this healthy urban M. auretenra. These bacteria were affiliated with 11 genera, including Vibrio, Shewanella, Bacillus, Exiguobacterium, Priestia, and Niallia, among others. Screenings revealed the predominant presence of potential probiotic traits such as catalase, antiQS, and the production of siderophores activities among the bacterial isolates. We proposed a list of 24 bacterial isolates as probiotic precandidates that jointly exhibited three or more of these traits, among which the Vibrio and Bacilli strains stand out. We provide insights into the health status of this urban coral and its potential as a source of bacteria exhibiting potential probiotic traits.

This study aimed to optimize the 3D printing parameters of salmon gelatin gels (SGG) using artificial neural networks with the genetic algorithm (ANN-GA) and response surface methodology (RSM). In addition, the influence of the optimal parameters obtained using the two different methodologies was evaluated for the physicochemical and digestibility properties of the printed SGG (PSGG). The ANN-GA had a better fit (R2 = 99.98%) with the experimental conditions of the 3D printing process than the RSM (R2 = 93.99%). The extrusion speed was the most influential parameter according to both methodologies. The optimal values of the printing parameters for the SGG were 0.70 mm for the nozzle diameter, 0.5 mm for the nozzle height, and 24 mm/s for the extrusion speed. Gel thermal properties showed that the optimal 3D printing conditions affected denaturation temperature and enthalpy, improving digestibility from 46.93% (SGG) to 51.52% (PSGG). The secondary gel structures showed that the β-turn structure was the most resistant to enzymatic hydrolysis, while the intermolecular β-sheet was the most labile. This study validated two optimization methodologies to achieve optimal 3D printing parameters of salmon gelatin gels, with improved physicochemical and digestibility properties for use as transporters to incorporate high value nutrients to the body.

The extent of oxidative damage transferred by the damaged sperm to the progeny is likely to be limited by the oocyte’s repair and antioxidative capacity. We aimed to assess the association between Brilliant Cresyl Blue (BCB) staining in oocytes and their competence for embryo development after in vitro fertilisation (IVF) with damaged sperm. For this purpose, bovine sperm were incubated without (non-oxidised sperm, NOX S) or with 100 µM H2O2 (oxidised sperm, OX S) and were used to fertilise in-vitro-matured bovine oocytes (BCB-pos./BCB-neg.). Unstained oocytes served as controls (US). Development was assessed at 30, 46, 60 h and on Days (D) 7 and 8 after IVF. Total cell number and apoptotic index were analysed in D7 blastocysts. BCB-neg. oocytes showed lower cleavage rates and blastocyst rates than unstained oocytes after IVF with NOX S (p < 0.05). They showed the highest reduction in D7 blastocyst rate upon fertilisation with OX S and showed a delayed embryo development at 46 and 60 h after IVF compared to embryos produced with NOX S (p < 0.05). Total cell number in blastocysts produced with BCB-neg. oocytes was lower (p < 0.05) in the embryos produced with OX S than in embryos after IVF with NOX S. In conclusion, BCB-neg. oocytes have a lower competence to support embryo development after in vitro fertilisation with oxidised sperm.

HIV-1 pre-exposure prophylaxis (PrEP) relies on inhibition of HIV-1 replication steps. To understand how PrEP modulates the immunological environment, we derived the plasma proteomic profile of men receiving emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during the CHAPS trial in South Africa and Uganda (NCT03986970). The CHAPS trial randomized 144 participants to one control and 8 PrEP arms, differing by drug type, number of PrEP doses and timing from final PrEP dose to sampling. Blood was collected pre- and post-PrEP. The inflammatory profile of plasma samples was analyzed using Olink (N=92 proteins) and Luminex (N=33) and associated with plasma drug concentrations using mass spectrometry. The proteins whose levels changed most significantly from pre- to post-PrEP were CCL4, CCL3 and TNF-α; CCL4 was the key discriminator between pre- and post-PrEP samples. CCL4 and CCL3 levels were significantly increased in post-PrEP samples compared to control specimens. CCL4 was significantly correlated with FTC drug levels in plasma. Production of inflammatory chemokines CCL4 and CCL3 in response to short-term PrEP indicates the mobilization of ligands which potentially block virus attachment to CCR5 HIV-1 co-receptor. The significant correlation between CCL4 and FTC levels suggests that CCL4 increase is modulated as an inflammatory response to PrEP.

Objective. Determine the psychometric characteristics of DASS-21 and identify its advantages as an aid in the diagnosis and screening of mental health disorders (depression, anxiety and stress). Materials and methods. Descriptive and cross-sectional study. The sample was non-probabilistic of 964 university students from different regions of Colombia who met the selection criteria and answered the questionnaire. Using Cronbach's Alfa, the internal consistency of the questionnaire was measured and exploratory factor analysis was applied for the validation of the construct, using a methodology of main axes with varimax factor rotation. To establish the number of factors to be conserved, the Kaiser criterion was used. It was considered significant with p value

Summary: Non-human primates (NHP) are widely used for the pre-clinical assessment of antiretrovirals (ARVs) for HIV treatment and prevention. However, the utility of these models is questionable given the differences in ARV pharmacology between humans and macaques. Here, we report a model based on ex vivo ARV exposure and the challenge of mucosal tissue explants to define pharmacological differences between NHPs and humans. For colorectal and cervicovaginal explants in both species, high concentrations of tenofovir (TFV) and maraviroc were predictive of anti-viral efficacy. However, their combinations resulted in increased inhibitory potency in NHP when compared to human explants. In NHPs, higher TFV concentrations were measured in colorectal versus cervicovaginal explants (p = 0.042). In humans, this relationship was inverted with lower levels in colorectal tissue (p = 0.027). TFV-resistance caused greater loss of viral fitness for HIV-1 than SIV. This, tissue explants provide an important bridge to refine and appropriately interpret NHP studies.

Colocar en el mercado un producto o servicio y que sea acogido por el target no es nada sencillo. Uno de los problemas de los emprendimientos de bajo presupuesto es que el emprendedor carece del conocimiento para promocionarse y venderse con mayores posibilidades de éxito. La presente investigación se enfoca en las estrategias de marketing para fortalecer la imagen de servicio de “Helados Artesanales del Charra” en la ciudad de Bahía de Caráquez, provincia de Manabí. El objetivo del estudio se orientó en la imagen comercial e influencia en la decisión de compra de los clientes. La metodología utilizada fue de tipo cualitativa y cuantitativa. Entre los resultados obtenidos está que un 67,7% de los encuestado sostiene que la imagen comercial si influye al momento de adquirir el producto, considerando que el 78,1% consume frecuentemente helados artesanales, además, se hizo el diseño de imagen para el logo del negocio que se utilizará en la camiseta, gorra y la carreta.

The mucosal environment of the upper respiratory tract is the first barrier of protection against SARS-CoV-2 transmission. However, the mucosal factors involved in viral transmission and potentially modulating the capacity to prevent such transmission have not fully been identified. In this pilot proteomics study, we compared mucosal and systemic compartments in a South African cohort of vaccinated and unvaccinated individuals undergoing maxillofacial surgery with previous history of COVID-19 or not. Inflammatory profiles were analyzed in plasma, nasopharyngeal swabs, and nasal and oral tissue explant cultures, using Olink and Luminex technologies. SARS-CoV-2-specific antibody levels were measured in serum and tissue explants. An increased pro-inflammatory proteomic profile was measured in the nasal compartment compared to plasma. However, IP-10 and MIG levels were higher in secretions than in nasal tissue, and the opposite was observed for TGF-β. Nasal anti-SARS-CoV-2 spike IgG correlated with mucosal MIG expression for all participants. A further positive correlation was found with IP-10 in BioNTech/Pfizer-vaccinated individuals. Systemic levels of anti-SARS-CoV-2 spike IgG elicited by this vaccine correlated with plasma IL-10, IL-6 and HBD4. Proteomic profiles measured in mucosal tissues and secretions using combined technologies could reveal correlates of protection at the mucosal portals of viral entry.

La ingeniería de tejidos es una ciencia que busca desarrollar sustitutos de tejido y órganos para mantener, restaurar o aumentar las funciones de sus contrapartes heridas o enfermas in vivo. El órgano cutáneo es el tejido que constituye la mayor extensión en el cuerpo humano, y a la vez es el órgano más externo, lo cual, consecuentemente, hace que sea el órgano más propenso a herirse. Debido a esta problemática las investigaciones y esfuerzos con fines de solucionar este problema son constantes. El enfoque de la revisión es el de presentar métodos recientes a través de los cuales la ingeniería de tejidos, utilizando compuestos biocompatibles, ha logrado una satisfactoria regeneración del órgano cutáneo, esto incluirá la revisión del uso de métodos para la regeneración de tejidos, tales como la impresión 3D y el uso de andamios poliméricos, apósitos biodiseñados y células madre.

Como una forma pedagógica de aprendizaje activo, se relacionaron temas desarrollados en clase de biología molecular con la pandemia del coronavirus COVID-19 que en este momento avanza en casi la totalidad del planeta. Contar con un método eficiente para diagnosticar la infección durante el inicio de esta infección respiratoria aguda es importante para detectar tanto los pacientes sintomáticos como los asintomáticos. Por este motivo, se retó a los estudiantes de séptimo semestre de las carreras de biología marina y ambiental que cursan la materia biología molecular en la Universidad de Bogotá Jorge Tadeo Lozano a diseñar un método diagnóstico para el virus COVID 19 basado en RT PCR y qPCR. El objetivo de este ejercicio académico consistió en incentivar a los estudiantes para que propusieran un método efectivo que permita detectar el virus COVID 19 a través de los conocimientos adquiridos durante el curso. Se realizó una revisión de la literatura previa para identificar los métodos existentes para la detección del virus y con ayuda de herramientas bioinformáticas se realizó el análisis de las secuencias de los genomas del COVID 19, el SARS humano y el SARS de murciélago disponibles en GenBank.

As festividades à Virgem de Andacollo são realizadas duas vezes por ano no Chile, segundo as celebrações indígenas ancestrais. A primeira, denominada “chica”, acontece no equinócio de primavera ao longo do primeiro domingo de outubro. A segunda, designada “festa grande”, ocorre no solstício de verão, no período de 23 a 27 de dezembro. Atualmente, essas festas foram assimiladas pelas celebrações católicas e atraem centenas de pessoas à pequena Andacollo, na região de Coquimbo. A praça principal é tomada pelo som de caixas, tambores e flautas, as ruas ganham cor e brilho com as vestimentas e estandartes dos devotos. As igrejas tornam-se cúpulas vivas do ir e vir de homens, mulheres e crianças que renovam a cada ano o íntimo propósito de se colocarem diante da imagem de Nossa Senhora de Andacollo.

Abstract Background Area-level deprivation is associated with multiple adverse birth outcomes. Few studies have examined the mediating pathways through which area-level deprivation affects these outcomes. The objective of this study was to investigate the association between area-level deprivation and preterm birth, and examine the mediating effects of maternal medical, behavioural, and psychosocial factors. Methods We conducted a retrospective cohort study using national, commercial health insurance claims data from 2011, obtained from the Health Care Cost Institute. Area-level deprivation was derived from principal components methods using ZIP code-level data. Multilevel structural equation modeling was used to examine mediating effects. Results In total, 138,487 women with a live singleton birth residing in 14,577 ZIP codes throughout the United States were included. Overall, 5.7% of women had a preterm birth. In fully adjusted generalized estimation equation models, compared to women in the lowest quartile of area-level deprivation, odds of preterm birth increased by 9.6% among women in the second highest quartile (odds ratio (OR) 1.096; 95% confidence interval (CI) 1.021, 1.176), by 11.3% in the third highest quartile (OR 1.113; 95% CI 1.035, 1.195), and by 24.9% in the highest quartile (OR 1.249; 95% CI 1.165, 1.339). Hypertension and infection moderately mediated this association. Conclusions Even among commercially-insured women, area-level deprivation was associated with increased risk of preterm birth. Similar to individual socioeconomic status, area-level deprivation does not have a threshold effect. Implementation of policies to reduce area-level deprivation, and the screening and treatment of maternal mediators may be associated with a lower risk of preterm birth.

Zika virus (ZIKV) cases continue to be reported, and no vaccine or specific antiviral agent has been approved for the prevention or treatment of infection. Though ZIKV is primarily transmitted by mosquitos, cases of sexual transmission and prolonged viral RNA presence in semen have been reported. In this observational study, we report the mucosal responses to sub-cutaneous and mucosal ZIKV exposure in cynomolgus macaques during acute and late chronic infection. Subcutaneous challenge induced a decrease in the growth factor VEGF in colorectal and cervicovaginal tissues 100 days post-challenge, in contrast to the observed increase in these tissues following vaginal infection. This different pattern was not observed in the uterus, where VEGF was upregulated independently of the challenge route. Vaginal challenge induced a pro-inflammatory profile in all mucosal tissues during late chronic infection. Similar responses were already observed during acute infection in a vaginal tissue explant model of ex vivo challenge. Non-productive and productive infection 100 days post-in vivo vaginal challenge induced distinct proteomic profiles which were characterized by further VEGF increase and IL-10 decrease in non-infected animals. Ex vivo challenge of mucosal explants revealed tissue-specific modulation of cytokine levels during the acute phase of infection. Mucosal cytokine profiles could represent biosignatures of persistent ZIKV infection.

Background: HIV-1 pre-exposure prophylaxis (PrEP) has focused predominantly on protective efficacy in receptive sex, with limited research on the dosing requirements for insertive sex. We pre-clinically assessed the ex vivo pharmacokinetic–pharmacodynamic (PK–PD) profile of tenofovir (TFV) and tenofovir alafenamide (TAF) in foreskin tissue. Methods: Inner and outer foreskin explants were exposed to serial dilutions of TFV or TAF prior to addition of HIV-1BaL at a high (HVT) or a low viral titer (LVT). Infection was assessed by measurement of p24 in foreskin culture supernatants. TFV, TAF and TFV–diphosphate (TFV–DP) concentrations were measured in tissues, culture supernatants and dosing and washing solutions. Results: Dose–response curves were obtained for both drugs, with greater potency observed against LVT. Inhibitory equivalency mimicking oral dosing was defined between 1 mg/mL of TFV and 15 µg/mL of TAF against HVT challenge. Concentrations of TFV–DP in foreskin explants were approximately six-fold higher after ex vivo dosing with TAF than with TFV. Statistically significant negative linear correlations were observed between explant levels of TFV or TFV–DP and p24 concentrations following HVT. Conclusions: Pre-clinical evaluation of TAF in foreskin explants revealed greater potency than TFV against penile HIV transmission. Clinical evaluation is underway to support this finding.

Summary: Background: Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of-care real time RT-PCR CovidNudge test, which requires no laboratory handling or sample pre-processing. Methods: Between April and May, 2020, we obtained two nasopharyngeal swab samples from individuals in three hospitals in London and Oxford (UK). Samples were collected from three groups: self-referred health-care workers with suspected COVID-19; patients attending emergency departments with suspected COVID-19; and hospital inpatient admissions with or without suspected COVID-19. For the CovidNudge test, nasopharyngeal swabs were inserted directly into a cartridge which contains all reagents and components required for RT-PCR reactions, including multiple technical replicates of seven SARS-CoV-2 gene targets (rdrp1, rdrp2, e-gene, n-gene, n1, n2 and n3) and human ribonuclease P (RNaseP) as sample adequacy control. Swab samples were tested in parallel using the CovidNudge platform, and with standard laboratory RT-PCR using swabs in viral transport medium for processing in a central laboratory. The primary analysis was to compare the sensitivity and specificity of the point-of-care CovidNudge test with laboratory-based testing. Findings: We obtained 386 paired samples: 280 (73%) from self-referred health-care workers, 15 (4%) from patients in the emergency department, and 91 (23%) hospital inpatient admissions. Of the 386 paired samples, 67 tested positive on the CovidNudge point-of-care platform and 71 with standard laboratory RT-PCR. The overall sensitivity of the point-of-care test compared with laboratory-based testing was 94% (95% CI 86–98) with an overall specificity of 100% (99–100). The sensitivity of the test varied by group (self-referred healthcare workers 94% [95% CI 85–98]; patients in the emergency department 100% [48–100]; and hospital inpatient admissions 100% [29–100]). Specificity was consistent between groups (self-referred health-care workers 100% [95% CI 98–100]; patients in the emergency department 100% [69–100]; and hospital inpatient admissions 100% [96–100]). Point of care testing performance was similar during a period of high background prevalence of laboratory positive tests (25% [95% 20–31] in April, 2020) and low prevalence (3% [95% 1–9] in inpatient screening). Amplification of viral nucleocapsid (n1, n2, and n3) and envelope protein gene (e-gene) were most sensitive for detection of spiked SARS-CoV-2 RNA. Interpretation: The CovidNudge platform was a sensitive, specific, and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. The device, which has been implemented in UK hospitals since May, 2020, could enable rapid decisions for clinical care and testing programmes. Funding: National Institute of Health Research (NIHR) Imperial Biomedical Research Centre, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England, NIHR Biomedical Research Centre Oxford, and DnaNudge.

Abstract Background Reactive oxygen species (ROS)-induced oxidative stress is well known to play a major role in male infertility. Sperm are sensitive to ROS damaging effects because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. However, how oxidative DNA lesions in sperm affect early embryonic development remains elusive. Results Using cattle as model, we show that fertilization using sperm exposed to oxidative stress caused a major developmental arrest at the time of embryonic genome activation. The levels of DNA damage response did not directly correlate with the degree of developmental defects. The early cellular response for DNA damage, γH2AX, is already present at high levels in zygotes that progress normally in development and did not significantly increase at the paternal genome containing oxidative DNA lesions. Moreover, XRCC1, a factor implicated in the last step of base excision repair (BER) pathway, was recruited to the damaged paternal genome, indicating that the maternal BER machinery can repair these DNA lesions induced in sperm. Remarkably, the paternal genome with oxidative DNA lesions showed an impairment of zygotic active DNA demethylation, a process that previous studies linked to BER. Quantitative immunofluorescence analysis and ultrasensitive LC–MS-based measurements revealed that oxidative DNA lesions in sperm impair active DNA demethylation at paternal pronuclei, without affecting 5-hydroxymethylcytosine (5hmC), a 5-methylcytosine modification that has been implicated in paternal active DNA demethylation in mouse zygotes. Thus, other 5hmC-independent processes are implicated in active DNA demethylation in bovine embryos. The recruitment of XRCC1 to damaged paternal pronuclei indicates that oxidative DNA lesions drive BER to repair DNA at the expense of DNA demethylation. Finally, this study highlighted striking differences in DNA methylation dynamics between bovine and mouse zygotes that will facilitate the understanding of the dynamics of DNA methylation in early development. Conclusions The data demonstrate that oxidative stress in sperm has an impact not only on DNA integrity but also on the dynamics of epigenetic reprogramming, which may harm the paternal genetic and epigenetic contribution to the developing embryo and affect embryo development and embryo quality.

Objective: To analyse the internationalisation of SMEs from the perspective of the entrepreneur and the special characteristics and traits that influence internationalisation while dealing with parsimony of financial assets, country of origin liability and other institutional voids. Research Design & Methods: 11 Colombian SMEs were observed and studied on a case-by-case basis, using a methodology inspired by the phenomenological interpretative analysis (IPA). Findings: The coding and analysis of the collected empirical data highlighted five main features that positively influence the internationalisation of the observed SMEs: technical expertise of an entrepreneur, opportunistic behaviour towards internationalisation, international focus from inception, an ability to build networks and value creation based on personal traits of the entrepreneur. Implications & Recommendations: The findings of this study contribute to a more comprehensive understanding of the behaviour, rationality and distinctive entrepreneur’ traits that influence the internationalisation of service SMEs. Contribution & Value Added: This study observes the internationalisation of SMEs from a region that is underrepresented in the literature, furthermore, it uses an entrepreneur-level approach and IPA methodology that is novel in international entrepreneurship studies.

Non-human primates (NHPs) remain the most relevant challenge model for the evaluation of HIV vaccine candidates; however, discrepancies with clinical trial results have emphasized the need to further refine the NHP model. Furthermore, classical evaluation of vaccine candidates is based on endpoints measured systemically. We assessed the mucosal responses elicited upon vaccination with ALVAC and AIDSVAX using ex vivo Rhesus macaque mucosal tissue explant models. Following booster immunization with ALVAC/AIDSVAX, anti-gp120 HIV-1CM244-specific IgG and IgA were detected in culture supernatant cervicovaginal and colorectal tissue explants, as well as systemically. Despite protection from ex vivo viral challenge, no neutralization was observed with tissue explant culture supernatants. Priming with ALVAC induced distinct cytokine profiles in cervical and rectal tissue. However, ALVAC/AIDSVAX boosts resulted in similar modulations in both mucosal tissues with a statistically significant decrease in cytokines linked to inflammatory responses and lymphocyte differentiation. With ALVAC/AIDSVAX boosts, significant correlations were observed between cytokine levels and specific IgA in cervical explants and specific IgG and IgA in rectal tissue. The cytokine secretome revealed differences between vaccination with ALVAC and ALVAC/AIDSVAX not previously observed in mucosal tissues and distinct from the systemic response, which could represent a biosignature of the vaccine combination.

El estudio pretendió el diseño y validación de contenido de un programa de intervención biopsicosocial para mejorar la adherencia al tratamiento (at) en pacientes en rehabilitación cardíaca (rc) durante la fase no supervisada por profesionales de la salud. El diseño incluyó la revisión de literatura científica y la información de tres grupos focales: expertos (5), pacientes (6) y familiares y/o cuidadores (5). El programa está sustentado en el concepto de autorregulación y basado en el modelo hapa (Health Action Process Approach); la estructura contiene sesiones educativas y psicológicas, así como ejercicios transversales y actividades de seguimiento. La validación se realizó con seis jueces expertos, quienes calificaron los componentes: objetivos, actividades, metodología y recursos. Esta evaluación reveló índices de validación de contenido (ivc) excelentes (1) y buenos (.83), según parámetros de Lynn (1986). Se concluyó que es una intervención clara, pertinente, suficiente y coherente, útil para el psicólogo que integra los equipos interdisciplinarios sanitarios, lo cual mejora el beneficio para los pacientes.

Prevention strategies against sexual transmission of human immunodeficiency virus (HIV) are essential to curb the rate of new infections. In the absence of a correlate of protection against HIV infection, pre-clinical evaluation is fundamental to facilitate and accelerate prioritization of prevention candidates and their formulations in a rapidly evolving clinical landscape. Characterization of pharmacokinetic (PK) and pharmacodynamic (PD) properties for candidate inhibitors is the main objective of pre-clinical evaluation. in vitro and ex vivo systems for pharmacological assessment allow experimental flexibility and adaptability at a relatively low cost without raising as significant ethical concerns as in vivo models. Applications and limitations of pre-clinical PK/PD models and future alternatives are reviewed in the context of HIV prevention.

The current paradigm in the field of mammalian iron biology states that body iron levels are determined by dietary iron absorption, not by iron excretion. Iron absorption is a highly regulated process influenced by iron levels and other factors. Iron excretion is believed to occur at a basal rate irrespective of iron levels and is associated with processes such as turnover of intestinal epithelium, blood loss, and exfoliation of dead skin. Here we explore iron excretion in a mouse model of iron excess due to inherited transferrin deficiency. Iron excess in this model is attributed to impaired regulation of iron absorption leading to excessive dietary iron uptake. Pharmacological correction of transferrin deficiency not only normalized iron absorption rates and halted progression of iron excess but also reversed body iron excess. Transferrin treatment did not alter the half-life of 59Fe in mutant mice. 59Fe-based studies indicated that most iron was excreted via the gastrointestinal tract and suggested that iron-loaded mutant mice had increased rates of iron excretion. Direct measurement of urinary iron levels agreed with 59Fe-based predictions that urinary iron levels were increased in untreated mutant mice. Fecal ferritin levels were also increased in mutant mice relative to wild-type mice. Overall, these data suggest that mice have a significant capacity for iron excretion. We propose that further investigation into iron excretion is warranted in this and other models of perturbed iron homeostasis, as pharmacological targeting of iron excretion may represent a novel means of treatment for diseases of iron excess.

Macroalgae belong to a diverse group of organisms that could be exploited for biomolecule application. Among the biocompounds found in this group, mycosporine-like amino acids (MAAs) are highlighted mainly due to their photoprotection, antioxidant properties, and high photo and thermo-stability, which are attractive characteristics for the development of cosmeceutical products. Therefore, here we revise published data about MAAs, including their biosynthesis, biomass production, extraction, characterization, identification, purification, and bioactivities. MAAs can be found in many algae species, but the highest concentrations are found in red macroalgae, mainly in the order Bangiales, as Porphyra spp. In addition to the species, the content of MAAs can vary depending on environmental factors, of which solar radiation and nitrogen availability are the most influential. MAAs can confer photoprotection due to their capacity to absorb ultraviolet radiation or reduce the impact of free radicals on cells, among other properties. To extract these compounds, different approaches can be used. The efficiency of these methods can be evaluated with characterization and identification using high performance liquid chromatography (HPLC), associated with other apparatus such as mass spectrometry (MS) and nuclear magnetic resonance (NMR). Therefore, the data presented in this review allow a broad comprehension of MAAs and show perspectives for their inclusion in cosmeceutical products.

Innate responses during acute HIV infection correlate with disease progression and pathogenesis. However, limited information is available about the events occurring during the first hours of infection in the mucosal sites of transmission. With an ex vivo HIV-1 challenge model of human colorectal tissue we assessed the mucosal responses induced by R5- and X4-tropic HIV-1 isolates in the first 24 h of exposure. Microscopy studies demonstrated virus penetration of up to 39 μm into the lamina propia within 6 h of inoculation. A rapid, 6 h post-challenge, increase in the level of secretion of inflammatory cytokines, chemokines, interferon- γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed following exposure to R5- or X4-tropic isolates. This profile persisted at the later time point measured of 24 h. However, exposure to the X4-tropic isolate tested induced greater changes at the proteomic and transcriptomic levels than the R5-tropic. The X4-isolate induced greater levels of CCR5 ligands (RANTES, MIP-1α and MIP-1β) secretion than R5-HIV-1. Potential drugs candidates for colorectal microbicides, including entry, fusion or reverse transcriptase inhibitors demonstrated differential capacity to modulate these responses. Our findings indicate that in colorectal tissue, inflammatory responses and a Th1 cytokine profile are induced in the first 24 h following viral exposure.

The purpose of this paper is to show the importance of business education in Disaster Risk Manage-ment (DRM). This paper aims to evaluate the awareness level of the Master in Business Administra-tion’s (MBA) students regarding the importance disaster risk management (DRM) plays. This paper develops a literature review concerning the concept of disasters, Disaster Risk Management, Disaster Risk Reduction, and the role of MBA programs. Furthermore, a survey at Universidad EAFIT (Medellin, Colombia) was designed and implemented as primary source information with the purpose of showing the DRM awareness level of MBA’s students. Finally, a case study connecting DRM with entrepre-neurship formation is described. This paper identified a limited formal education in DRM Latin Ameri-can MBA programs, and specifically at Universidad EAFIT. Additionally, a lack of awareness in MBA’s students about the importance of DRM was identified. In this sense, the paper proposes a DRM edu-cation model that uses a Corporate Social Responsibility (CSR) and entrepreneurial formation in busi-ness education. This study aims to show the importance of the inclusion of disaster risk reduction and management knowledge as part of the courses in: Corporate Social Responsibility (CSR), Sustainabili-ty, and Entrepreneurship content in Masters in Business Administration (MBA) programs.

Here we present data on liver metal levels and expression of genes related to iron homeostasis in rhesus monkeys after inhalational manganese exposure. Archived liver samples from rhesus monkeys exposed to 0 (n=6), 0.06 (n=6), 0.3 (n=4) and 1.5 (n=4) mg/m3 manganese inhalation for 65 days were obtained from a published study (“Tissue manganese concentrations in young male rhesus monkeys following subchronic manganese sulfate inhalation” [1]). Samples were analyzed by spectroscopy, immunoblotting and quantitative PCR to assess metal levels and gene expression. Liver manganese and iron levels were linearly correlated although only the intermediate manganese exposure level (0.3 mg Mn/m3) led to a statistically significant increase in liver iron levels. Keywords: Iron, Manganese, Inhalation, Monkey

This study focused on applying different high hydrostatic pressure + carbon dioxide (HHP + CO2) processing conditions on refrigerated (4 °C, 25 days) farmed coho salmon (Oncorhynchus kisutch) to inactivate endogenous enzymes (protease, lipase, collagenase), physicochemical properties (texture, color, lipid oxidation), and microbial shelf life. Salmon fillets were subjected to combined HHP (150 MPa/5 min) and CO2 (50%, 70%, 100%). Protease and lipase inactivation was achieved with combined HHP + CO2 treatments in which lipase activity remained low as opposed to protease activity during storage. Collagenase activity decreased approximately 90% during storage when applying HHP + CO2. Combined treatments limited the increase in spoilage indicators, such as total volatile amines and trimethylamine. The 150 MPa + 100% CO2 treatment was the most effective at maintaining hardness after 10 days of storage. Combined treatments limited HHP-induced color change and reduced the extent of changes caused by storage compared with the untreated sample. Microbial shelf life was extended by the CO2 content and not by the HHP treatments; this result was related to an increased lag phase and decreased growth rate. It can be concluded that combining HHP and CO2 could be an effective method of inactivating endogenous enzymes and extend salmon shelf life.

This article makes a review of the legislation in force in Colombia on peace processes that we have had, recommending to the Colombian State, take into account the main settings for the current negotiation, from the perspective of the right to peace embodied in our Constitution and the legal framework for the peace established in the Legislative Act 1 of 2012.

Trace metals are essential for health but toxic when present in excess. The maintenance of trace metals at physiologic levels reflects both import and export by cells and absorption and excretion by organs. The mechanism by which this maintenance is achieved in vertebrate organisms is incompletely understood. To explore this, we chose zebrafish as our model organism, as they are amenable to both pharmacologic and genetic manipulation and comprise an ideal system for genetic screens and toxicological studies. To characterize trace metal content in developing zebrafish, we measured levels of three trace elements, copper, zinc, and manganese, from the oocyte stage to 30 days post-fertilization using inductively coupled plasma mass spectrometry. Our results indicate that metal levels are stable until zebrafish can acquire metals from the environment and imply that the early embryo relies on maternal contribution of metals to the oocyte. We also measured metal levels in bodies and yolks of embryos reared in presence and absence of the copper chelator neocuproine. All three metals exhibited different relative abundances between yolks and bodies of embryos. While neocuproine treatment led to an expected phenotype of copper deficiency, total copper levels were unaffected, indicating that measurement of total metal levels does not equate with measurement of biologically active metal levels. Overall, our data not only can be used in the design and execution of genetic, physiologic, and toxicologic studies but also has implications for the understanding of vertebrate metal homeostasis.

En América Latina solo el 2% de libros son accesibles a la población con discapacidad visual, fenómeno que incide en su desarrollo inclusivo, por esta razón, se está estudiando la ratificación del Tratado de Marrakech, para que las leyes de derechos de autor incluyan excepciones, que permitan que las entidades que promueven los derechos de las personas con discapacidad visual puedan producir dichas obras sin tener que solicitar permisos o pagar derechos para ponerla a disposición de esta población.

This research aims to analyze the changes on the Multinational Corporations capacity of action over the States, in order to illustrate the economic and political panorama that arose since the 2008 economic and financial crisis. This is analyzed taking into account the dynamic relation between States and Multinationals and the use of an approach that combines historical and contemporary aspects. Both provide a thesis which harmonizes the variables (such as employment, impact on GDP, mobility and capital international markets) that modify the incidence on companies and, that appear as the main sources of liability of Multinational Corporations in their negotiating processes with the States. Finally, this study reviews the State capitalism as a phenomenon that values the existent role of current economies and, presents the relations between specific cases and their performance.Con el ánimo de ilustrar el panorama económico y político que surge a partir de la crisiseconómica y financiera que tuvo lugar en 2008, la presente investigación tuvo porobjeto analizar el cambio que ha tenido la capacidad de acción de las CorporacionesMultinacionales sobre los Estados.Teniendo en cuenta el dinamismo de esta relación, ha sido útil el uso de un enfoqueque combina aspectos históricos y contemporáneos para una lectura de la crisis queprovee una tesis en la que se armonizan variables que modifican (según el contexto) laincidencia de estas empresas. Dichas variables se resumen en el empleo, el impactoen el PIB, la movilidad y el acceso al mercado internacional de capitales; que aparecen,entonces, como las principales fuentes de apalancamiento de las CMN en sus procesos denegociación con los Estados.Por último se hace una revisión del capitalismo estatal como fenómeno que es precisono dejar de lado, al valorar el rol que ocupa en las economías actuales, y se presentan-aunque en otra medida- las relaciones existentes entre varios casos específicos y sucorrecto desempeño.

Soluble cervicovaginal biomarkers of inflammation, immune activation and risk of HIV acquisition are needed to reliably assess the safety of new biomedical prevention strategies including vaccines and microbicides. However, a fuller understanding of expression profiles in women at high risk for HIV infection is crucial to the effective use of these potential biomarkers in Phase 3 trial settings. We have measured 45 soluble proteins and peptides in cervicovaginal lavage samples from 100 HIV negative women at high risk for HIV infection. Women were followed over one menstrual cycle to investigate modulation by hormonal contraception, menstrual cycle phase, recent sexual exposure and intravaginal practices. Women using injectable DMPA had increased concentration of several soluble proteins of the innate and adaptive immune system, including IL-1α, IL-1β, IL-2, MIP-1β, IP-10, IL-8, TGF-β, HBD4, IgA, IgG1, and IgG2. Women using combined oral contraceptives had a similar signature. There were differences in concentrations among samples from post-ovulation compared to pre-ovulation, notably increased immunoglobulins. Increased prostate-specific antigen, indicative of recent sexual exposure, was correlated with increased IL-6, MCP-1, and SLPI, and decreased GM-CSF and HBD3. The identified signature profiles may prove critical in evaluating the potential safety and impact on risk of HIV acquisition of different biomedical intervention strategies.

Teniendo en cuenta la calidad del empleo como parte del concepto integral de sostenibilidad empresarial, el presente artículo demuestra a través del análisis de datos oficiales, que en Colombia se presentan diferencias considerables en cuanto a la inclusión social de los empleados de su sistema productivo. Las conclusiones obtenidas evidencian que los más excluidos poseen empleos de inferior calidad, como muestra de la precariedad laboral presente en el país. Esta situación indica que la revisión sistemática de sus políticas de sostenibilidad constituye una necesidad para el empresariado colombiano, particularmente en lo relacionado con el tipo de empleo que está brindando, considerando que el trabajo es un aspecto altamente influyente en la vida de los individuos.

Mice have been essential for distinguishing the role of hepcidin in iron homeostasis. Currently, investigators monitor levels of murine hepatic hepcidin-1 mRNA as a surrogate marker for the bioactive hepcidin protein itself. Here, we describe and validate a competitive, enzyme-linked immunosorbent assay that quantifies hepcidin-1 in mouse serum and urine. The assay exhibits a biologically relevant lower limit of detection, high precision, and excellent linearity and recovery. We also demonstrate correlation between serum and urine hepcidin-1 values and validate the competitive enzyme-linked immunosorbent assay by analyzing plasma hepcidin response of mice to physiological challenges, including iron deficiency, iron overload, acute blood loss, and inflammation. Furthermore, we analyze multiple murine genetic models of iron dysregulation, including β-thalassemia intermedia (Hbbth3/+), hereditary hemochromatosis (Hfe−/−, Hjv−/−, and Tfr2Y245X/Y245X), hypotransferrinemia (Trfhpx/hpx), heterozygous transferrin receptor 1 deficiency (Tfrc+/−) and iron refractory iron deficiency anemia (Tmprss6−/− and Tmprss6hem8/hem8). Novel compound iron metabolism mutants were also phenotypically characterized here for the first time. We demonstrate that serum hepcidin concentrations correlate with liver hepcidin mRNA expression, transferrin saturation and non-heme liver iron. In some circumstances, serum hepcidin-1 more accurately predicts iron parameters than hepcidin mRNA, and distinguishes smaller, statistically significant differences between experimental groups.