Treponema pallidum genetic diversity and its implications for targeted vaccine development: A cross-sectional study of early syphilis cases in Southwestern Colombia.

BACKGROUND: Venereal syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (TPA), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of TPA strains circulating within at-risk populations. The aim of this study was to describe the clinical, demographic, and molecular features of early syphilis cases in Cali, Colombia. METHODS AND FINDINGS: We conducted a cross-sectional study to identify individuals with early syphilis (ES) in Cali, Colombia through a city-wide network of public health centers, private sector HIV clinics and laboratory databases from public health institutions. Whole blood (WB), skin biopsies (SB), and genital and oral lesion swabs were obtained for measurement of treponemal burdens by polA quantitative polymerase chain reaction (qPCR) and for whole-genome sequencing (WGS). Among 1,966 individuals screened, 128 participants met enrollment criteria: 112 (87%) with secondary (SS), 15 (12%) with primary (PS) and one with early latent syphilis; 66/128 (52%) self-reported as heterosexual, while 48 (38%) were men who have sex with men (MSM). Genital ulcer swabs had the highest polA copy numbers (67 copies/µl) by qPCR with a positivity rate (PR) of 73%, while SS lesions had 42 polA copies/µl with PR of 62%. WB polA positivity was more frequent in SS than PS (42% vs 7%, respectively; p = 0.009). Isolation of TPA from WB by rabbit infectivity testing (RIT) was achieved in 5 (56%) of 9 ES WB samples tested. WGS from 33 Cali patient samples, along with 10 other genomic sequences from South America (9 from Peru, 1 from Argentina) used as comparators, confirmed that SS14 was the predominant clade, and that half of all samples had mutations associated with macrolide (i.e., azithromycin) resistance. Variability in the outer membrane protein (OMP) and vaccine candidate BamA (TP0326) was mapped onto the protein's predicted structure from AlphaFold. Despite the presence of mutations in several extracellular loops (ECLs), ECL4, an immunodominant loop and proven opsonic target, was highly conserved in this group of Colombian and South American TPA isolates. CONCLUSIONS: This study offers new insights into the sociodemographic and clinical features of venereal syphilis in a highly endemic area of Colombia and illustrates how genomic sequencing of regionally prevalent TPA strains can inform vaccine development.

Presentación de una escala para evaluar actitudes y creencias sobre la sexualidad reproductiva en adolescentes varones de la región Caribe colombiana / Presentation of an Attitudes and Beliefs Scale to Assess Adolescent Sexuality and Reproductive Health of Young Males in the Caribbean Region

Este artículo presenta la construcción y comprobación de la confiabilidad de un instrumento para evaluar las actitudes y normas subjetivas en el comportamiento sexual y reproductivo en varones en dos estudios. La escala fue administrada a 965 estudiantes varones escolarizados, entre 11 a 19 años de edad, en la región Caribe colombiana. En el Estudio 1 (pilotaje) el cuestionario constituido por 150 ítems se redujo a 78 en la prueba final. En la escala de actitud protección (Media = 4.1 y DE = 1.07) se obtuvo un alfa de Cronbach de 0.93 y en la de actitud abstinencia/retardo (Media = 3.6 y DE = 1.26), un alfa de 0.88 y homogeneidad elevada con correlación ítem-total superiores a 0.6. Para la escala de creencias categorizada como normas subjetivas (Media = 3.79 y DE = 1.08) la estimación del alfa de Cronbach fue de 0.98 y homogeneidad adecuada con correlaciones superiores a 0.66. La evaluación de la validez de constructo mediante el análisis factorial exploratorio y análisis de componentes principales con rotación VARIMAX, denota adecuación satisfactoria de los datos a la matriz factorial en el Estudio 2 (escala definitiva). En conclusión el instrumento es confiable, de estructura estable para la medición de actitudes y normas subjetivas en sexualidad reproductiva y contribuirá a establecer acciones específicas en programas, acorde a las expectativas en salud sexual y reproductiva de los adolescentes varones.

This paper presents the construction and testing of the reliability of an instrument to assess attitudes and subjective norms sexual and reproductive behavior of young males. The scale was administered to 965 male students (From of 11 to 19 years) enrolled at school in the Colombian Caribbean region. This work includes two independent studies, in the Study 1 (pilot) the questionnaire consisted of 150 items and it was reduced to 78. In the protective attitude scale (Mean = 4.1 and SD = 1.07) was obtained Cronbach's alpha of 0.93 and for the abstinence / delay attitude (Mean = 3.6 and SD = 1.26) an alpha of 0.88 with high homogeneity. The total correlation item was greater than 0.6 for all the attitude scales. On the scale of beliefs represented by the subjective norms (Mean = 3.79 and SD = 1.08) the estimation of Cronbach's alpha was 0.98 with correlations above 0.66. In Study 2 (final stop), the construct validity assessment using factorial analysis and principal components analysis with VARIMAX rotation reported a satisfactory fit of the data to the array factor. In conclusion, the instrument has a reliable and stable structure for the measurement of attitudes and subjective norms for sexuality and reproductive health, and it is useful to help in the setting of programs.

Stretching single atom contacts at multiple subatomic step-length.

This work describes jump-to-contact STM-break junction experiments leading to novel statistical distribution of last-step length associated with conductance of a single atom contact. Last-step length histograms are observed with up to five for Fe and three for Cu peaks at integral multiples close to 0.075 nm, a subatomic distance. A model is proposed in terms of gliding from a fcc hollow-site to a hcp hollow-site of adjacent atomic planes at 1/3 regular layer spacing along with tip stretching to account for the multiple subatomic step-length behavior.

A Straightforward Approach for the Determination of the Maximum Time Step for the Simulation of Nanometric Metallic Systems.

In the present work, we report on a systematic analysis to determine the maximum time step allowed in molecular dynamics simulations applied to study metal systems of current interest in nanoscience. Using the velocity Verlet integration scheme, we have found that it is possible to use a 20 fs time step for the simulation of gold nanosystems. This is roughly an order of magnitude greater than the usually employed integration step (2 to 5 fs). We also propose a general criterion to select this maximum time step for other metallic nanosystems, even in the case of bimetallic nanosystems.