Progress towards the elimination of hepatitis B in children in Colombia: A novel two-phase study approach.

The World Health Organization (WHO) has established a target to eliminate mother-to-child-transmission (EMTCT) of hepatitis B virus (HBV), defined as a prevalence of hepatitis B surface antigen (HBsAg) of ≤0.1% among children, by 2030. Using nationally representative serosurveys to verify achievement of this target requires large sample sizes and significant resources. We assessed the feasibility of a potentially more efficient two-phase method to verify EMTCT of HBV in Colombia. In the first phase, we conducted a risk assessment to identify municipalities at the highest risk of ongoing HBV transmission. We ranked the 1122 municipalities of Colombia based on the reports of HBV infection in pregnant women per 1000 population. Municipalities with ≥0.3 reports per 1000 persons (equating to the top quartile) were further assessed based on health facility birth rates, coverage with three doses of hepatitis B vaccine (HepB3) and seroprevalence data. Hepatitis B risk was considered to be further increased for municipalities with HepB3 coverage or health facility birth rate <90%. In the second phase, we conducted a multistage household serosurvey of children aged 5-10 years in 36 municipalities with the highest assessed HBV risk. HBsAg was not detected in any of 3203 children tested, yielding a 90% upper confidence bound of <0.1% prevalence. Coverage with HepB3 and hepatitis B birth dose was high at 97.5% and 95.6%, respectively. These results support the conclusion that Colombia has likely achieved EMTCT of HBV.

Supervivencia en las personas que viven con VIH en el marco del sistema de salud colombiano 2011-2018 / Survival in people living with HIV in the framework the Colombian health system: 2011-2018

Resumen Objetivo: Describir la supervivencia a siete años y los principales factores asociados a esta, en las personas con VIH que fueron atendidas en el sistema de salud colombiano entre 2011 a 2018. Métodos: Análisis de supervivencia de una cohorte de 64 039 personas diagnosticadas con VIH en Colombia. Se aplicó el método de Kaplan-Meier para estimar la probabilidad de supervivencia a partir de la fecha del diagnóstico. Se ajustó un modelo de supervivencia paramétrico flexible de Royston Parmar. Resultados: La estimación de la supervivencia global a 7 años fue de 94,8% (IC 95%: 94,5-95,2). El mayor riesgo de muerte se presentó en los hombres (HR: 1,2; IC 95%: 1,1-1,4; p: 0,010); en personas ≥50 años de edad (HR: 3,1; IC 95%: 1,6-6,3; p: 0,002); en el régimen subsidiado (HR: 2,2; IC 95%: 1,9-2,5; p: <0,001); en la etapa sida (HR: 2,8; IC 95%: 2,1-3,7; p: <0,001); en quienes presentaron la última carga viral detectable (HR: 7,1; IC 95%: 6,0-8,3; p: <0,001); y en quienes mostraron conteo de linfocitos T CD4+ <350 células/μL (HR: 1,9; IC 95%: 1,4-2,4; p: <0,001). Conclusión: La probabilidad de la supervivencia de las personas que viven con VIH aumenta al ser diagnosticados en edades jóvenes, en quienes presenten un recuento de linfocitos T CD4+ ≥350 células/μL, una carga viral indetectable (< 50 copias/mL) y no se encuentren en etapa sida.

Summary Objective: to describe the seven-year survival and predictors of mortality among people with HIV who were treated in the Colombian health system between 2011 and 2018. Methods: 64 039 people diagnosed with HIV in Colombia were included. Kaplan-Meier analysis estimated the probability of survival from the date of diagnosis. A Royston Parmar flexible parametric survival model was fitted. Results: The overall survival at 7 years was 94.8% (95% CI: 94.5-95.2). Survival was related to sex (men, HR: 1.2; 95% CI: 1.1-1.4; p: 0.010); people ≥50 years of age (HR: 3.1; 95% CI: 1.6-6.3; p: 0.002); subsidized regime (HR: 2.2; 95% CI: 1.9-2.5; p: <0.001); AIDS stage (HR: 2.8; 95% CI: 2.1-3.7; p: <0.001); a detectable viral load (HR: 7.1; 95% CI: 6.0-8.3; p: <0.001); and a CD4+ Lymphocyte count <350 cells/μL (HR: 1.9; 95% CI: 1.4-2.4; p: <0.001). Conclusion: The probability of survival of people living with HIV increases when they are diagnosed at a young age, in those with a CD4+ T Lymphocyte count ≥350 cells/μL, an undetectable viral load (<50 copies/mL) and are not in the AIDS stage.

Optimizing HIV retesting during pregnancy and postpartum in four countries: a cost-effectiveness analysis.

INTRODUCTION: HIV retesting during late pregnancy and breastfeeding can help detect new maternal infections and prevent mother-to-child HIV transmission (MTCT), but the optimal timing and cost-effectiveness of maternal retesting remain uncertain. METHODS: We constructed deterministic models to assess the health and economic impact of maternal HIV retesting on a hypothetical population of pregnant women, following initial testing in pregnancy, on MTCT in four countries: South Africa and Kenya (high/intermediate HIV prevalence), and Colombia and Ukraine (low HIV prevalence). We evaluated six scenarios with varying retesting frequencies from late in antenatal care (ANC) through nine months postpartum. We compared strategies using incremental cost-effectiveness ratios (ICERs) over a 20-year time horizon using country-specific thresholds. RESULTS: We found maternal retesting once in late ANC with catch-up testing through six weeks postpartum was cost-effective in Kenya (ICER = $166 per DALY averted) and South Africa (ICER=$289 per DALY averted). This strategy prevented 19% (Kenya) and 12% (South Africa) of infant HIV infections. Adding one or two additional retests postpartum provided smaller benefits (1 to 2 percentage point increase in infections averted versus one retest). Adding three retests during the postpartum period averted additional infections (1 to 3 percentage point increase in infections averted versus one retest) but ICERs ($7639 and in Kenya and $11 985 in South Africa) greatly exceeded the cost-effectiveness thresholds. In Colombia and Ukraine, all retesting strategies exceeded the cost-effectiveness threshold and prevented few infant infections (up to 31 and 5 infections, respectively). CONCLUSIONS: In high HIV burden settings with MTCT rates similar to those seen in Kenya and South Africa, HIV retesting once in late ANC, with subsequent intervention, is the most cost-effective strategy for preventing infant HIV infections. In these settings, two HIV retests postpartum marginally reduced MTCT and were less costly than adding three retests. Retesting in low-burden settings with MTCT rates similar to Colombia and Ukraine was not cost-effective at any time point due to very low HIV prevalence and limited breastfeeding.

Cost-effectiveness of dual maternal HIV and syphilis testing strategies in high and low HIV prevalence countries: a modelling study.

BACKGROUND: Dual HIV and syphilis testing might help to prevent mother-to-child transmission (MTCT) of HIV and syphilis through increased case detection and treatment. We aimed to model and assess the cost-effectiveness of dual testing during antenatal care in four countries with varying HIV and syphilis prevalence. METHODS: In this modelling study, we developed Markov models of HIV and syphilis in pregnant women to estimate costs and infant health outcomes of maternal testing at the first antenatal care visit with individual HIV and syphilis tests (base case) and at the first antenatal care visit with a dual rapid diagnostic test (scenario one). We additionally evaluated retesting during late antenatal care and at delivery with either individual tests (scenario two) or a dual rapid diagnosis test (scenario three). We modelled four countries: South Africa, Kenya, Colombia, and Ukraine. Strategies with an incremental cost-effectiveness ratio (ICER) less than the country-specific cost-effectiveness threshold (US$500 in Kenya, $750 in South Africa, $3000 in Colombia, and $1000 in Ukraine) per disability-adjusted life-year averted were considered cost-effective. FINDINGS: Routinely offering testing at the first antenatal care visit with a dual rapid diagnosis test was cost-saving compared with the base case in all four countries (ICER: -$26 in Kenya,-$559 in South Africa, -$844 in Colombia, and -$454 in Ukraine). Retesting during late antenatal care with a dual rapid diagnostic test (scenario three) was cost-effective compared with scenario one in all four countries (ICER: $270 in Kenya, $260 in South Africa, $2207 in Colombia, and $205 in Ukraine). INTERPRETATION: Incorporating dual rapid diagnostic tests in antenatal care can be cost-saving across countries with varying HIV prevalence. Countries should consider incorporating dual HIV and syphilis rapid diagnostic tests as the first test in antenatal care to support efforts to eliminate MTCT of HIV and syphilis. FUNDING: WHO, US Agency for International Development, and the Bill & Melinda Gates Foundation.

Prevalence and incidence estimates for syphilis, chlamydia, gonorrhea, and congenital syphilis in Colombia, 1995–2016

[ABSTRACT]. Objectives. To estimate adult (15–49 years old) prevalence and incidence of active syphilis, gonorrhea, and chlamydia, and incidence of congenital syphilis (CS) and adverse birth outcomes (ABOs) in Colombia, over 1995–2016. Methods. The Spectrum-STI epidemiological model tool estimated gonorrhea and chlamydia prevalences as moving averages across prevalences observed in representative general population surveys. For adult syphilis, Spectrum-STI applied segmented polynomial regression through prevalence data from antenatal care (ANC) surveys, routine ANC-based screening, and general population surveys. CS cases and ABOs were estimated from Spectrum’s maternal syphilis estimates and proportions of women screened and treated for syphilis, applying World Health Organization case definitions and risk probabilities. Results. The Spectrum model estimated prevalences in 2016 of 0.70% (95% confidence interval (CI): 0.15%-1.9%) in women and 0.60% (0.1%-1.9%) in men for gonorrhea and of 9.2% (4.4%-15.4%) in women and 7.4% (3.5%-14.7%) in men for chlamydia, without evidence for trends over 1995–2016. The prevalence of active syphilis in 2016 was 1.25% (1.22–1.29%) in women and 1.25% (1.1%-1.4%) in men, decreasing from 2.6% (2.1%-3.2%) in women in 1995. Corresponding CS cases in 2016 (including cases without clinical symptoms) totaled 3 851, of which 2 245 were ABOs. Annual CS and ABO estimates decreased over 2008–2016, reflecting decreasing maternal prevalence and increasing cases averted through ANC-based screening and treatment. Conclusions. The available surveillance and monitoring data synthesized in Spectrum-STI—and the resulting first-ever national STI estimates for Colombia—highlighted Colombia’s persistently high STI burden. Adult syphilis and congenital syphilis are estimated to be falling, reflecting improving screening efforts. Strengthened surveillance, including with periodic screening in low-risk populations and future refined Spectrum estimations, should support planning and implementation of STI prevention and control, including CS elimination.

[RESUMEN]. Objetivos. Estimar la prevalencia e incidencia en los adultos (de 15 a 49 años de edad) de sífilis activa, gonorrea y clamidiasis, así como la incidencia de sífilis congénita y resultados adversos del embarazo en Colombia durante el período de 1995 al 2016. Métodos. Usando las herramientas del modelo epidemiológico Spectrum-STI se estimó la prevalencia de gonorrea y clamidiasis como promedios móviles entre las distintas prevalencias observadas en encuestas representativas de la población general. En cuanto a la sífilis en los adultos, Spectrum-STI aplicó la regresión polinomial segmentada a los datos sobre prevalencia recopilados en encuestas de atención prenatal, el tamizaje sistemático en la atención prenatal y encuestas a la población general. Los casos de sífilis congénita y de resultados adversos del embarazo se estimaron a partir de las cifras de Spectrum sobre sífilis materna y proporciones de mujeres examinadas y tratadas por sífilis, aplicando las definiciones de casos y probabilidades de riesgo de la Organización Mundial de la Salud. Resultados. El modelo Spectrum estimó que en el 2016 la prevalencia de la gonorrea fue de 0,70% (intervalo de confianza de 95% [IC]: 0,15%-1,9%) en las mujeres y de 0,60% (0,1%-1,9%) en los hombres, y que la prevalencia de la clamidiasis fue de 9,2% (4,4%-15,4%) en las mujeres y de 7,4% (3,5%-14,7%) en los hombres, sin datos científicos acerca de las tendencias durante el período 1995-2016. La prevalencia de la sífilis activa en el 2016 fue de 1,25% (1,22-1,29%) en las mujeres y de 1,25% (1,1%-1,4%) en los hombres, con una reducción de 2,6% (2,1%-3,2%) en las mujeres con respecto a 1995. Los casos correspondientes de sífilis congénita en el 2016 (incluidos los asintomáticos) sumaron en total 3 851, de los cuales 2 245 fueron resultados adversos del embarazo. Las cifras anuales estimadas de sífilis congénita y resultados adversos del embarazo disminuyeron entre el 2008 y el 2016, lo que reflejó un descenso en la prevalencia materna y un aumento de casos evitados mediante el tamizaje y el tratamiento durante la atención prenatal. Conclusiones. Los datos disponibles sobre vigilancia y seguimiento sintetizados en Spectrum‑STI, así como los consiguientes estimados nacionales de infecciones de transmisión sexual (ITS) hechos por primera vez en Colombia, pusieron de relieve la carga de morbilidad por ITS persistentemente alta en ese país. Se estima que la sífilis en los adultos y la sífilis congénita van en descenso, lo que refleja mejoras en las actividades de tamizaje. Un fortalecimiento de la vigilancia, incluso con tamizaje periódico en las poblaciones de bajo riesgo, y estimaciones más refinadas con Spectrum en el futuro deberían brindar apoyo a la planificación y la ejecución de medidas para la prevención y el control de las infecciones de transmisión sexual, incluida la eliminación de la sífilis congénita.

[RESUMO]. Objetivos. Estimar a incidência e a prevalência na população adulta (com idade de 15–49 anos) de sífilis ativa, gonorreia e clamídia e a incidência de sífilis congênita (SC) e desfechos adversos congênitos na Colômbia no período de 1995 a 2016. Métodos. O modelo epidemiológico Spectrum-STI foi o instrumento usado para estimar a prevalência de gonorreia e clamídia como médias móveis nas prevalências observadas em pesquisas representativas da população geral. A sífilis em adultos foi estimada com a regressão polinomial segmentada aplicada ao modelo Spectrum-STI com dados de prevalência obtidos de pesquisas da atenção pré-natal, exames pré-natais de rotina de detecção precoce e pesquisas da população geral. Casos de SC e desfechos adversos congênitos foram estimados a partir das estimativas de sífilis materna do modelo Spectrum e percentuais de mulheres que fizeram testes de detecção e foram tratadas para sífilis, segundo as definições de casos da Organização Mundial da Saúde (OMS) e probabilidades de risco. Resultados. O modelo Spectrum estimou, para 2016, uma prevalência de gonorreia de 0,70% (intervalo de confiança de 95% [IC 95%] 0,15%–1,9%) no sexo feminino e 0,60% (0,1%–1,9%) no sexo masculino e uma prevalência de clamídia de 9,2% (4,4%–15,4%) no sexo feminino e 7,4% (3,5%–14.7%) no sexo masculino, sem evidência de tendências no período 1995–2016. A prevalência de sífilis ativa em 2016 foi de 1,25% (1,22–1,29%) no sexo feminino e 1,25% (1,1%–1,4%) no sexo masculino, demonstrando um declínio da prevalência de 2,6% (2,1%–3,2%) observada em 1995 para o sexo feminino. Houve, ao todo, 3.851 casos correspondentes de SC em 2016 (incluindo casos assintomáticos), dos quais 2.245 foram desfechos adversos congênitos. Observou-se uma redução nas estimativas anuais de SC e desfechos adversos congênitos em 2008–2016, refletindo a diminuição da prevalência materna e o número crescente de casos evitados com exames pré-natais de detecção e tratamento. Conclusões. Os dados disponíveis de vigilância e monitoramento condensados no modelo Spectrum-STI, e as resultantes estimativas nacionais de infeções sexualmente transmissíveis (IST) obtidas pela primeira vez na Colômbia, evidenciam a alta carga persistente de IST no país. Estima-se que a ocorrência de sífilis do adulto e sífilis congénita esteja diminuindo em decorrência da melhoria nos esforços de detecção precoce. A vigilância reforçada, consistindo também de exames periódicos de detecção precoce nas populações de baixo risco e estimavas futuras aprimoradas do instrumento Spectrum, deve sustentar o planejamento e a implementação de controle e prevenção de IST e a eliminação da SC.

Prevalence and incidence estimates for syphilis, chlamydia, gonorrhea, and congenital syphilis in Colombia, 1995-2016.

OBJECTIVES: To estimate adult (15-49 years old) prevalence and incidence of active syphilis, gonorrhea, and chlamydia, and incidence of congenital syphilis (CS) and adverse birth outcomes (ABOs) in Colombia, over 1995-2016. METHODS: The Spectrum-STI epidemiological model tool estimated gonorrhea and chlamydia prevalences as moving averages across prevalences observed in representative general population surveys. For adult syphilis, Spectrum-STI applied segmented polynomial regression through prevalence data from antenatal care (ANC) surveys, routine ANC-based screening, and general population surveys. CS cases and ABOs were estimated from Spectrum's maternal syphilis estimates and proportions of women screened and treated for syphilis, applying World Health Organization case definitions and risk probabilities. RESULTS: The Spectrum model estimated prevalences in 2016 of 0.70% (95% confidence interval (CI): 0.15%-1.9%) in women and 0.60% (0.1%-1.9%) in men for gonorrhea and of 9.2% (4.4%-15.4%) in women and 7.4% (3.5%-14.7%) in men for chlamydia, without evidence for trends over 1995-2016. The prevalence of active syphilis in 2016 was 1.25% (1.22-1.29%) in women and 1.25% (1.1%-1.4%) in men, decreasing from 2.6% (2.1%-3.2%) in women in 1995. Corresponding CS cases in 2016 (including cases without clinical symptoms) totaled 3 851, of which 2 245 were ABOs. Annual CS and ABO estimates decreased over 2008-2016, reflecting decreasing maternal prevalence and increasing cases averted through ANC-based screening and treatment. CONCLUSIONS: The available surveillance and monitoring data synthesized in Spectrum-STI- and the resulting first-ever national STI estimates for Colombia-highlighted Colombia's persistently high STI burden. Adult syphilis and congenital syphilis are estimated to be falling, reflecting improving screening efforts. Strengthened surveillance, including with periodic screening in low-risk populations and future refined Spectrum estimations, should support planning and implementation of STI prevention and control, including CS elimination.

Prevalence and incidence estimates for syphilis, chlamydia, gonorrhea, and congenital syphilis in Colombia, 1995-2016 / Estimaciones sobre la prevalencia y la incidencia de sífilis, clamidiasis, gonorrea y sífilis congénita en Colombia, 1995-2016 / Estimativas da incidência e prevalência de sífilis, clamídia, gonorreia e sífilis congênita na Colômbia, 1995-2016

ABSTRACT Objectives To estimate adult (15-49 years old) prevalence and incidence of active syphilis, gonorrhea, and chlamydia, and incidence of congenital syphilis (CS) and adverse birth outcomes (ABOs) in Colombia, over 1995-2016. Methods The Spectrum-STI epidemiological model tool estimated gonorrhea and chlamydia prevalences as moving averages across prevalences observed in representative general population surveys. For adult syphilis, Spectrum-STI applied segmented polynomial regression through prevalence data from antenatal care (ANC) surveys, routine ANC-based screening, and general population surveys. CS cases and ABOs were estimated from Spectrum's maternal syphilis estimates and proportions of women screened and treated for syphilis, applying World Health Organization case definitions and risk probabilities. Results The Spectrum model estimated prevalences in 2016 of 0.70% (95% confidence interval (CI): 0.15%-1.9%) in women and 0.60% (0.1%-1.9%) in men for gonorrhea and of 9.2% (4.4%-15.4%) in women and 7.4% (3.5%-14.7%) in men for chlamydia, without evidence for trends over 1995-2016. The prevalence of active syphilis in 2016 was 1.25% (1.22-1.29%) in women and 1.25% (1.1%-1.4%) in men, decreasing from 2.6% (2.1%-3.2%) in women in 1995. Corresponding CS cases in 2016 (including cases without clinical symptoms) totaled 3 851, of which 2 245 were ABOs. Annual CS and ABO estimates decreased over 2008-2016, reflecting decreasing maternal prevalence and increasing cases averted through ANC-based screening and treatment. Conclusions The available surveillance and monitoring data synthesized in Spectrum-STI— and the resulting first-ever national STI estimates for Colombia—highlighted Colombia's persistently high STI burden. Adult syphilis and congenital syphilis are estimated to be falling, reflecting improving screening efforts. Strengthened surveillance, including with periodic screening in low-risk populations and future refined Spectrum estimations, should support planning and implementation of STI prevention and control, including CS elimination.

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RESUMO Objetivos Estimar a incidência e a prevalência na população adulta (com idade de 15-49 anos) de sífilis ativa, gonorreia e clamídia e a incidência de sífilis congênita (SC) e desfechos adversos congênitos na Colômbia no período de 1995 a 2016. Métodos O modelo epidemiológico Spectrum-STI foi o instrumento usado para estimar a prevalência de gonorreia e clamídia como médias móveis nas prevalências observadas em pesquisas representativas da população geral. A sífilis em adultos foi estimada com a regressão polinomial segmentada aplicada ao modelo Spectrum-STI com dados de prevalência obtidos de pesquisas da atenção pré-natal, exames pré-natais de rotina de detecção precoce e pesquisas da população geral. Casos de SC e desfechos adversos congênitos foram estimados a partir das estimativas de sífilis materna do modelo Spectrum e percentuais de mulheres que fizeram testes de detecção e foram tratadas para sífilis, segundo as definições de casos da Organização Mundial da Saúde (OMS) e probabilidades de risco. Resultados O modelo Spectrum estimou, para 2016, uma prevalência de gonorreia de 0,70% (intervalo de confiança de 95% [IC 95%] 0,15%-1,9%) no sexo feminino e 0,60% (0,1%-1,9%) no sexo masculino e uma prevalência de clamídia de 9,2% (4,4%-15,4%) no sexo feminino e 7,4% (3,5%-14.7%) no sexo masculino, sem evidência de tendências no período 1995-2016. A prevalência de sífilis ativa em 2016 foi de 1,25% (1,22-1,29%) no sexo feminino e 1,25% (1,1%-1,4%) no sexo masculino, demonstrando um declínio da prevalência de 2,6% (2,1%-3,2%) observada em 1995 para o sexo feminino. Houve, ao todo, 3.851 casos correspondentes de SC em 2016 (incluindo casos assintomáticos), dos quais 2.245 foram desfechos adversos congênitos. Observou-se uma redução nas estimativas anuais de SC e desfechos adversos congênitos em 2008-2016, refletindo a diminuição da prevalência materna e o número crescente de casos evitados com exames pré-natais de detecção e tratamento. Conclusões Os dados disponíveis de vigilância e monitoramento condensados no modelo Spectrum-STI, e as resultantes estimativas nacionais de infeções sexualmente transmissíveis (IST) obtidas pela primeira vez na Colômbia, evidenciam a alta carga persistente de IST no país. Estima-se que a ocorrência de sífilis do adulto e sífilis congênita esteja diminuindo em decorrência da melhoria nos esforços de detecção precoce. A vigilância reforçada, consistindo também de exames periódicos de detecção precoce nas populações de baixo risco e estimavas futuras aprimoradas do instrumento Spectrum, deve sustentar o planejamento e a implementação de controle e prevenção de IST e a eliminação da SC.

World health organization global health sector strategy on sexually transmitted infections: an evidence-to-action summary for Colombia / Estrategia global de la Organización Mundial de la Salud contra infecciones de transmisión sexual: de la evidencia a la acción. Resumen para Colombia

ABSTRACT Curable and incurable sexually transmitted infections (STI) are acquired by hundreds of millions of people worldwide each year. Undiagnosed and untreated STIs cause a range of negative health outcomes including adverse birth outcomes, infertility and other long term sequelae such as cervical cancer. In 2016, the World Health Organization (WHO) launched the Global STI Strategy (20162021). The WHO Global STI Strategy's public health approach focuses on three causative organisms of STIs that need immediate action and for which cost-effective interventions exist: (a) Neisseria gonorrhoeae as a cause of infertility, a risk factor for coinfection with other STIs and because of increasing bacterial resistance to antibiotic treatment, (b) Treponema pallidum given the contribution of syphilis to adverse birth outcomes including stillbirth and neonatal death and (c) Human papillomavirus due to its link to cervical cancer. The range of actions recommended for countries includes: (a) strengthening surveillance, with program monitoring and progress evaluation, (b) STI prevention, (c) early diagnosis of STIs, (d) patient and partner management, and (e) approaches to reach the most vulnerable populations. This summary describes the WHO Global STI Strategy alongside findings from a STI surveillance workshop held in Colombia in May of 2017. Observations related to the Global STI Strategy and findings from the STI estimation workshop are described here for stakeholders in Colombia to consider as they identify opportunities to improve STI services and surveillance.

RESUMEN En el mundo, cientos de millones de personas adquieren anualmente infecciones de transmisión sexual (ITS), algunas de ellas curables y otras incurables. Las ITS que no se diagnostican y no se tratan producen una serie de desenlaces negativos para la salud, entre los cuales se cuentan malos resultados perinatales, infertilidad y otras secuelas crónicas, además del cáncer de cuello uterino. En 2016, la Organización Mundial de la Salud (OMS) lanzó la Estrategia Mundial contras las ITS (2016-2021). El enfoque de salud pública contemplado en la Estrategia Global de la OMS se centra en tres microorganismos causantes de las ITS que requieren acciones inmediatas y para los cuales existen intervenciones costo-efectivas: (a) Neisseria gonorrhoea como causa de infertilidad y factor de riesgo para coinfección con otras ITS, y por su mayor resistencia al tratamiento con antibióticos; (b) Treponema pallidum por la contribución de la sífilis a resultados adversos al nacimiento, entre ellos muerte fetal y muerte neonatal; y (c) virus del papiloma humano debido a su relación con el cáncer de cuello uterino. Entre las acciones recomendadas para los países están las siguientes: (a) fortalecer la vigilancia, el monitoreo y la evaluación de los programas y los avances logrados; (b) prevención de las ITS; (c) diagnóstico temprano de las ITS; (d) manejo del paciente y la pareja; (e) mecanismos para llegar a las poblaciones más vulnerables. Esta síntesis de la política resume la Estrategia Mundial de la OMS contra las ITS, además de los hallazgos de un taller de vigilancia llevado a cabo en Colombia en mayo de 2017. Aquí se describen las observaciones relacionadas con la Estrategia, y los hallazgos del taller a fin de que los distintos grupos de interés en Colombia, los tomen en consideración a la hora de identificar las oportunidades de mejorar los servicios y la vigilancia en lo que atañe a las ITS.

Síndrome metabólico y sus complicaciones: el pie diabético / Metabolic syndrome and its complications: The diabetic foot

Resumen En la actualidad, México ocupa el primer lugar con obesidad infantil y el segundo con obesidad en el adulto. Este fenómeno ya ha alcanzado niveles de pandemia, por lo que de no evitar que continúe aumentando el número de pacientes obesos, en pocos años la cantidad de discapacitados a causa de alteraciones metabólicas será alarmante. En esta revisión se pretenden establecer las causas del síndrome metabólico, los mecanismos que se alteran para conducirá diabetes mellitus, y se mencionan los mecanismos fisiológicos que se alteran en la condición de hiperglucemia. Y dentro de las consecuencias que resultan de esta enfermedad, analizar una de las que más cuesta al paciente y a la familia como lo es el pie diabético.

Abstract Mexico currently occupies the first place with childhood obesity and the second with adult obesity. This phenomenon has already reached pandemic levels so if the increasing number of obese patients is not prevented, in a fewyears the number of patients with disabilities resulting from metabolic alterations will be alarming. This review aims to establish the causes of the metabolic syndrome, the mechanisms that are altered and lead to diabetes mellitus, also we will mention the physiological mechanisms altered in hyperglycemia and its consequences. We will analyze one of the diseases with the highest costs for the patient and their family: the diabetic foot.

Relationship of inflammatory profile of elderly patients serum and senescence-associated secretory phenotype with human breast cancer cells proliferation: Role of IL6/IL8 ratio.

Aging is considered a systemic, chronic and low-grade inflammatory state, called "inflammaging", which has been contemplated as a risk factor for cancer development and progression in the elderly population. Cellular senescence is a multifactorial phenomenon of growth arrest and distorted function, which has been recognized as a contributor to aging. Senescent cells have an altered secretion pattern called Senescent Associated Secretory Phenotype (SASP), that comprise a complex mix of factors including cytokines, growth factors, chemokines and matrix metalloproteinases among others. The SASP secreted by accumulated senescent cells during old age has been related to local inflammation that leads to cellular transformation and therefore may be supporting the inflammaging process. Here, we evaluated if the pro-inflammatory profile within the serum obtained from elderly patients (EPS) was able to induce cellular proliferation in the breast cancer transformed cell line (MCF-7), in a similar way to the proliferation stimulated by the SASP obtained from WI-38 primary cells prematurely induced to senescence by oxidative stress (SIPS). At the same time, the participation of IL-6/IL-8 ratio was determined. Our results showed that not all the EPS increased MCF-7 proliferation. However, there was an interesting relationship between IL-6 and IL-8 concentrations, when the IL-6 was higher than IL-8. Similar results were found with SASP from SIPS-WI-38 on the MCF-7 proliferation. Although it is known that those cytokines are fundamental factors to induce proliferation; the occurrence of other components in the cellular microenvironment is necessary to carry out this effect.

WORLD HEALTH ORGANIZATION GLOBAL HEALTH SECTOR STRATEGY ON SEXUALLY TRANSMITTED INFECTIONS: AN EVIDENCE-TO-ACTION SUMMARY FOR COLOMBIA.

Curable and incurable sexually transmitted infections (STI) are acquired by hundreds of millions of people worldwide each year. Undiagnosed and untreated STIs cause a range of negative health outcomes including adverse birth outcomes, infertility and other long term sequelae such as cervical cancer. In 2016, the World Health Organization (WHO) launched the Global STI Strategy (2016-2021). The WHO Global STI Strategy's public health approach focuses on three causative organisms of STIs that need immediate action and for which cost-effective interventions exist: (a) Neisseria gonorrhoeae as a cause of infertility, a risk factor for coinfection with other STIs and because of increasing bacterial resistance to antibiotic treatment, (b) Treponema pallidum given the contribution of syphilis to adverse birth outcomes including stillbirth and neonatal death and (c) Human papillomavirus due to its link to cervical cancer. The range of actions recommended for countries includes: (a) strengthening surveillance, with program monitoring and progress evaluation, (b) STI prevention, (c) early diagnosis of STIs, (d) patient and partner management, and (e) approaches to reach the most vulnerable populations. This summary describes the WHO Global STI Strategy alongside findings from a STI surveillance workshop held in Colombia in May of 2017. Observations related to the Global STI Strategy and findings from the STI estimation workshop are described here for stakeholders in Colombia to consider as they identify opportunities to improve STI services and surveillance.

En el mundo, cientos de millones de personas adquieren anualmente infecciones de transmisión sexual (ITS), algunas de ellas curables y otras incurables. Las ITS que no se diagnostican y no se tratan producen una serie de desenlaces negativos para la salud, entre los cuales se cuentan malos resultados perinatales, infertilidad y otras secuelas crónicas, además del cáncer de cuello uterino. En 2016, la Organización Mundial de la Salud (OMS) lanzó la Estrategia Mundial contras las ITS (2016­2021). El enfoque de salud pública contemplado en la Estrategia Global de la OMS se centra en tres microorganismos causantes de las ITS que requieren acciones inmediatas y para los cuales existen intervenciones costo-efectivas: (a) Neisseria gonorrhoea como causa de infertilidad y factor de riesgo para coinfección con otras ITS, y por su mayor resistencia al tratamiento con antibióticos; (b) Treponema pallidum por la contribución de la sífilis a resultados adversos al nacimiento, entre ellos muerte fetal y muerte neonatal; y (c) virus del papiloma humano debido a su relación con el cáncer de cuello uterino. Entre las acciones recomendadas para los países están las siguientes: (a) fortalecer la vigilancia, el monitoreo y la evaluación de los programas y los avances logrados; (b) prevención de las ITS; (c) diagnóstico temprano de las ITS; (d) manejo del paciente y la pareja; (e) mecanismos para llegar a las poblaciones más vulnerables. Esta síntesis de la política resume la Estrategia Mundial de la OMS contra las ITS, además de los hallazgos de un taller de vigilancia llevado a cabo en Colombia en mayo de 2017. Aquí se describen las observaciones relacionadas con la Estrategia, y los hallazgos del taller a fin de que los distintos grupos de interés en Colombia, los tomen en consideración a la hora de identificar las oportunidades de mejorar los servicios y la vigilancia en lo que atañe a las ITS.

Reacción lepromatosa tipo I, a propósito de un caso / Type I lepra reaction: a case report

La lepra es una infección crónica, granulomatosa, producida por Mycobacterium leprae, que afecta piel y nervios periféricos. Se describen dos tipos de reacciones leprosas: tipo I y tipo II, las que corresponden a cuadros agudos que exacerban la enfermedad. Estas leproreacciones pueden ocurrir antes, durante o después del tratamiento. Se presenta el caso de un paciente masculino que acude a consultar con lesiones cutáneas y resultado de biopsia de piel con diagnóstico de lepra. Se inicia tratamiento multidroga OMS-MB1. Posteriormente presenta una leproreacción tipo I, por lo que se le realiza tratamiento con prednisona.

Leprosy is a chronic granulomatous infection of the skin and peripheral nervous system produced by Mycobacterium leprae. Two types of acute leprosy reactions have been described: type I and type II. These reactions can occur before, during or after treatment. We present the case of an adult male patient presenting with skin lesions and skin biopsy diagnostic for leprosy. A multidrug WHO-MB 1 treatment was initiated, after which he presents with type I lepra reaction requiring corticosteroids.

Comparative effectiveness of single and dual rapid diagnostic tests for syphilis and HIV in antenatal care services in Colombia / Comparación de la eficacia de la prueba rápida individual y la prueba rápida dual para el diagnóstico de la sífilis y la infección por el VIH en los servicios de atención prenatal en Colombia

Objective. To assess the effectiveness of a dual rapid test compared to a single rapid test for syphilis and HIV screening. Methods. A cluster-randomized open-label clinical trial was performed in 12 public antenatal care (ANC) centers in the cities of Bogotá and Cali, Colombia. Pregnant women who were over 14 years of age at their first antenatal visit and who had not been previously tested for HIV and syphilis during the current pregnancy were included. Pregnant women were randomized to single HIV and single syphilis rapid diagnostic tests (Arm A) or to dual HIV and syphilis rapid diagnostic tests (Arm B). The four main outcomes measured were: (1) acceptability of the test, (2) uptake in testing, (3) treatment on the same day (that is, timely treatment), and (4) treatment at any time for positive rapid test cases. Bivariate and multivariate analyses were calculated to adjust for the clustering effect and the period. Results. A total of 1 048 patients were analyzed in Arm A, and 1 166 in Arm B. Acceptability of the rapid tests was 99.8% in Arm A and 99.6% in Arm B. The prevalence of positive rapid tests was 2.21% for syphilis and 0.36% for HIV. Timely treatment was provided to 20 of 29 patients (69%) in Arm A and 16 of 20 patients (80%) in Arm B (relative risk (RR), 1.10; 95% confidence interval (CI): (1.00 −1.20). Treatment at any time was given to 24 of 29 patients (83%) in Arm A and to 20 of 20 (100%) in Arm B (RR, 1.11; 95% CI: 1.01−1.22). Conclusions. There were no differences in patient acceptability, testing and timely treatment between dual rapid tests and single rapid tests for HIV and syphilis screening in the ANC centers. Same-day treatment depends also on the interpretation of and confidence in the results by the health providers.

Objetivo. Evaluar la eficacia de la prueba rápida dual en comparación con la prueba rápida individual para la detección sistemática de la sífilis y la infección por el VIH. Métodos. Se realizó un ensayo clínico sin enmascaramiento y aleatorizado por grupos en 12 centros públicos de atención prenatal en las ciudades de Bogotá y Cali (Colombia). Se incluyó a las mujeres embarazadas de 14 o más años de edad que asistían a su primera consulta prenatal y no se habían realizado pruebas en este embarazo. Las embarazadas se dividieron de forma aleatoria para realizarles las pruebas rápidas individuales para el diagnóstico de sífilis y de infección por el VIH (Grupo A) o la prueba rápida dual para el diagnóstico de la sífilis y la infección por el VIH (Grupo B). Se midieron principalmente cuatro resultados: (1) aceptabilidad de la prueba, (2) uso de los servicios de prueba, (3) tratamiento el mismo día (es decir, tratamiento oportuno) y (4) tratamiento en cualquier momento en los casos con resultados positivos en las pruebas rápidas. Se realizaron análisis bifactoriales y multifactoriales para hacer los ajustes pertinentes por el efecto de la división en grupos y el período. Resultados. Se estudió a 1 048 pacientes en el Grupo A y a 1 166 en el Grupo B. La aceptabilidad de las pruebas rápidas fue de 99,8% en el Grupo A y 99,6% en el Grupo B. La prevalencia de resultados positivos en las pruebas rápidas fue de 2,21% para la sífilis y 0,36% para la infección por el VIH. Se administró tratamiento oportuno a 20 de 29 pacientes (69%) del Grupo A y a 16 de 20 pacientes (80%) del Grupo B (riesgo relativo, 1,10; intervalo de confianza de 95% (IC): 1,00-1,20). Se administró tratamiento en cualquier momento a 24 de 29 pacientes (83%) del Grupo A y a 20 de 20 (100%) del Grupo B (riesgo relativo, 1,11; IC de 95%: 1,01-1,22). Conclusiones. No hubo diferencias en cuanto a la aceptabilidad por parte de los pacientes, y el uso de los servicios de cribaje y el tratamiento oportuno entre las pruebas rápidas duales y las pruebas rápidas individuales para la detección sistemática de la sífilis y la infección por el VIH en los centros de atención prenatal. El tratamiento el mismo día depende también de la interpretación y la confianza en los resultados del trabajador de salud.

Comparative effectiveness of single and dual rapid diagnostic tests for syphilis and HIV in antenatal care services in Colombia / Comparación de la eficacia de la prueba rápida individual y la prueba rápida dual para el diagnóstico de la sífilis y la infección por el VIH en los servicios de atención prenatal en Colombia

ABSTRACT Objective To assess the effectiveness of a dual rapid test compared to a single rapid test for syphilis and HIV screening. Methods A cluster-randomized open-label clinical trial was performed in 12 public antenatal care (ANC) centers in the cities of Bogotá and Cali, Colombia. Pregnant women who were over 14 years of age at their first antenatal visit and who had not been previously tested for HIV and syphilis during the current pregnancy were included. Pregnant women were randomized to single HIV and single syphilis rapid diagnostic tests (Arm A) or to dual HIV and syphilis rapid diagnostic tests (Arm B). The four main outcomes measured were: (1) acceptability of the test, (2) uptake in testing, (3) treatment on the same day (that is, timely treatment), and (4) treatment at any time for positive rapid test cases. Bivariate and multivariate analyses were calculated to adjust for the clustering effect and the period. Results A total of 1 048 patients were analyzed in Arm A, and 1 166 in Arm B. Acceptability of the rapid tests was 99.8% in Arm A and 99.6% in Arm B. The prevalence of positive rapid tests was 2.21% for syphilis and 0.36% for HIV. Timely treatment was provided to 20 of 29 patients (69%) in Arm A and 16 of 20 patients (80%) in Arm B (relative risk (RR), 1.10; 95% confidence interval (CI): (1.00 −1.20). Treatment at any time was given to 24 of 29 patients (83%) in Arm A and to 20 of 20 (100%) in Arm B (RR, 1.11; 95% CI: 1.01−1.22). Conclusions There were no differences in patient acceptability, testing and timely treatment between dual rapid tests and single rapid tests for HIV and syphilis screening in the ANC centers. Same-day treatment depends also on the interpretation of and confidence in the results by the health providers.

RESUMEN Objetivo Evaluar la eficacia de la prueba rápida dual en comparación con la prueba rápida individual para la detección sistemática de la sífilis y la infección por el VIH. Métodos Se realizó un ensayo clínico sin enmascaramiento y aleatorizado por grupos en 12 centros públicos de atención prenatal en las ciudades de Bogotá y Cali (Colombia). Se incluyó a las mujeres embarazadas de 14 o más años de edad que asistían a su primera consulta prenatal y no se habían realizado pruebas en este embarazo. Las embarazadas se dividieron de forma aleatoria para realizarles las pruebas rápidas individuales para el diagnóstico de sífilis y de infección por el VIH (Grupo A) o la prueba rápida dual para el diagnóstico de la sífilis y la infección por el VIH (Grupo B). Se midieron principalmente cuatro resultados: (1) aceptabilidad de la prueba, (2) uso de los servicios de prueba, (3) tratamiento el mismo día (es decir, tratamiento oportuno) y (4) tratamiento en cualquier momento en los casos con resultados positivos en las pruebas rápidas. Se realizaron análisis bifactoriales y multifactoriales para hacer los ajustes pertinentes por el efecto de la división en grupos y el período. Resultados Se estudió a 1 048 pacientes en el Grupo A y a 1 166 en el Grupo B. La aceptabilidad de las pruebas rápidas fue de 99,8% en el Grupo A y 99,6% en el Grupo B. La prevalencia de resultados positivos en las pruebas rápidas fue de 2,21% para la sífilis y 0,36% para la infección por el VIH. Se administró tratamiento oportuno a 20 de 29 pacientes (69%) del Grupo A y a 16 de 20 pacientes (80%) del Grupo B (riesgo relativo, 1,10; intervalo de confianza de 95% (IC): 1,00-1,20). Se administró tratamiento en cualquier momento a 24 de 29 pacientes (83%) del Grupo A y a 20 de 20 (100%) del Grupo B (riesgo relativo, 1,11; IC de 95%: 1,01-1,22). Conclusiones No hubo diferencias en cuanto a la aceptabilidad por parte de los pacientes, y el uso de los servicios de cribaje y el tratamiento oportuno entre las pruebas rápidas duales y las pruebas rápidas individuales para la detección sistemática de la sífilis y la infección por el VIH en los centros de atención prenatal. El tratamiento el mismo día depende también de la interpretación y la confianza en los resultados del trabajador de salud.

Comparative effectiveness of single and dual rapid diagnostic tests for syphilis and HIV in antenatal care services in Colombia.

OBJECTIVE: To assess the effectiveness of a dual rapid test compared to a single rapid test for syphilis and HIV screening. METHODS: A cluster-randomized open-label clinical trial was performed in 12 public antenatal care (ANC) centers in the cities of Bogotá and Cali, Colombia. Pregnant women who were over 14 years of age at their first antenatal visit and who had not been previously tested for HIV and syphilis during the current pregnancy were included. Pregnant women were randomized to single HIV and single syphilis rapid diagnostic tests (Arm A) or to dual HIV and syphilis rapid diagnostic tests (Arm B). The four main outcomes measured were: (1) acceptability of the test, (2) uptake in testing, (3) treatment on the same day (that is, timely treatment), and (4) treatment at any time for positive rapid test cases. Bivariate and multivariate analyses were calculated to adjust for the clustering effect and the period. RESULTS: A total of 1 048 patients were analyzed in Arm A, and 1 166 in Arm B. Acceptability of the rapid tests was 99.8% in Arm A and 99.6% in Arm B. The prevalence of positive rapid tests was 2.21% for syphilis and 0.36% for HIV. Timely treatment was provided to 20 of 29 patients (69%) in Arm A and 16 of 20 patients (80%) in Arm B (relative risk (RR), 1.10; 95% confidence interval (CI): (1.00 -1.20). Treatment at any time was given to 24 of 29 patients (83%) in Arm A and to 20 of 20 (100%) in Arm B (RR, 1.11; 95% CI: 1.01-1.22). CONCLUSIONS: There were no differences in patient acceptability, testing and timely treatment between dual rapid tests and single rapid tests for HIV and syphilis screening in the ANC centers. Same-day treatment depends also on the interpretation of and confidence in the results by the health providers.

Progress and challenges in implementing HIV care and treatment policies in Latin America following the treatment 2.0 initiative.

BACKGROUND: The Pan American Health Organization provides technical cooperation to countries in Latin America and the Caribbean for the scale-up of HIV care and treatment based on the Treatment 2.0 initiative. Fourteen Joint Review Missions (JRMs) were conducted between March 2012 and October 2014. Evaluating the degree of implementation of the recommendations of the JRMs and their impact on health policies, would help countries identify their gaps and areas for priority interventions. METHODS: A descriptive analysis of the JRM recommendations was conducted for eight countries. An in-depth cross-sectional retrospective analysis of the degree of implementation of these recommendations in Ecuador, Venezuela, Bolivia, and El Salvador was performed through a standardized self-administered questionnaire applied to key informants. A comparative quantitative analysis on the optimization of antiretroviral regimens 'before/after' JRMs was conducted in three of the latter four countries, using data reported in 2013 and 2014. RESULTS: The priority areas with most recommendations were the optimization of antiretroviral treatment (ART) regimens (n = 57), the rational and efficient use of resources (n = 27) and the provision of point-of-care diagnostics and monitoring tools (n = 26), followed by community mobilization (n = 23), strategic information (n = 17) and the adaptation of delivery services (n = 15). The in-depth analysis in four countries showed that the two priority areas where most progress was observed were the rational and efficient use of resources (62%) and the optimization of ART regimens (60%). Adaptation of delivery services, community mobilization and strategic information were rated at 52% and the provision of point-of-care diagnostics and monitoring tools 38%. The quantitative analysis on optimization evidenced a 36% reduction in the number of first-line and second-line ART regimens, a 5.4% increase in the proportion of patients on WHO-recommended first-line regimens, a 19.4% increase in the use of the WHO preferred first-line regimen, 51% increase in the use of WHO-recommended second-line regimens, and a significant reduction in the use of obsolete drugs in first- and second-line regimens (respectively 1 and 9% of regimens in 2013). CONCLUSIONS: A relatively good level of progress was perceived in the recommendations related to optimization of ART regimens. Challenges remain on the improvement of recommendations related to health system strengthening and the promotion and support aimed at community-based organizations as part of the response to HIV/AIDS in Latin America. The JRMs are a useful mechanism for providing coherent technical support to guide countries in the pursuit of a comprehensive response to HIV/AIDS in the Latin American region.

[Involvement of phenotype secretor of senescent cells in the development of cancer, aging and the diseases associated with age]. / Participación del fenotipo secretor de las células senescentes en el desarrollo del cáncer, el envejecimiento y las enfermedades asociadas a la edad.

Cellular senescence is defined as the physiological program of terminal growth arrest; in mammals it is an important tumor-suppressor mechanism since it stops premalignant cell proliferation. However, senescence also contributes to the decline associated to aging and the development of several diseases. This is explained by the fact that senescent cells secrete diverse molecules, which compromise the cellular microenvironment, and altogether are referred as senescent-associated secretory phenotype (SASP). The SASP is composed by cytokines, chemokines, growth factors, proteases, etc., whose function is to maintain the antiproliferative state and promote senescent cell clearance by the immune system. Nevertheless, over time, and particularly during old age, SASP might stimulate proliferation and premalignant cell transformation. The multifunctional roles of SASP would depend on the cell type and their physiological nature. Therefore, relying on the biological context, SASP could be beneficial and participate in the repair and regeneration processes, or detrimental and induce degenerative pathologies and cancer.

A continuing HIV epidemic and differential patterns of HIV-STI risk among MSM in Quito, Ecuador: an urgent need to scale up HIV testing and prevention.

This study characterized the HIV epidemic among men who have sex with men (MSM) in Quito, Ecuador and contrasted risk patterns with other STI's. 416 MSM ages 15 years and older were recruited using respondent-driven sampling in 2010-2011. Biological testing and a self-interview survey assessed HIV and STI infections and risk behaviors. Analysis incorporated recruiter-level variables and clustering adjustments to control for recruitment patterns. We identify high levels of HIV (11 %), HSV-2 (14 %) and active syphilis (5.5 %) infections, low levels of lifetime HIV testing (57 %), limited knowledge of HIV and STI's (<48 %) and limited consistent condom use independent of partner type (<40 %). Sex work was associated with all infections while associations with residential location, how casual partners are met and other variables, varied. Scale-up of behavioral prevention and HIV testing is urgently needed. Interventions should target male sex workers and exploit differential patterns of HIV-STI risk to stay ahead of the epidemic.

A proteomic approach to the analysis of the components of the phycobilisomes from two cyanobacteria with complementary chromatic adaptation: Fremyella diplosiphon UTEX B590 and Tolypothrix PCC 7601.

Tolypothrix PCC 7601 and Fremyella diplosiphon UTEX B590 can produce two alternative phycobilisome (PBS) rods. PE-PBSs with one phycocyanin (PC) disk and multiple phycoerythrin (PE) disks are found in cells grown under green light (GL). PC-PBSs with only PC disks are obtained from cells grown under red light (RL). In this manuscript, we show the localization of the linker proteins and ferredoxin-NADP(+) oxidoreductase (FNR) in the PC-PBS and of PE-PBS rods using visible spectroscopy and mass spectrometry. PE-PBSs with different [PE]/[PC] ratios and PC-PBSs with different [PC]/[AP] (AP, allophycocyanin) ratios were isolated. CpeC was the primary rod linker protein found in the PBSs with a [PE]/[PC] ratio of 1.1, which indicates that this is the rod linker at the interphase PC-PE. CpeC and CpeD were identified in the PBSs with a [PE]/[PC] ratio of 1.6, which indicates that CpcD is the linker between the first and the second PE hexamers. Finally, CpeC, CpeD, and CpeE were found in the PBSs with a [PE]/[PC] ratio of 2.9, indicating the position of CpeE between the second and third PE moieties. CpcI2 was identified in the two PC-PBSs obtained from cells grown under RL, which indicates that CpcI2 is the linker between the first and second PC hexamers. CpcH2 was identified only in the PC-PBSs from Tolypothrix with a high [PC]/[AP] ratio of 1.92, which indicates that CpcH2 is the linker between the second and third PC hexamers. The PC-PBSs contained the rod cap protein L(R)(10) (CpcD), but this protein was absent in the PE-PBSs. PE-PBSs (lacking L(R)(10)) incorporated exogenous rFNR in a stoichiometry of up to five FNRs per PBS. A maximum of two FNRs per PBS were found in PC-PBSs (with L(R)(10)). These observations support the hypothesis that FNR binds at the distal ends of the PBS rods in the vacant site of CpcD L(R)(10). Finally, the molecular mass of the core membrane linker (L(CM)) was determined to be 102 kDa from a mass spectrometry analysis.

Morphine administration and abrupt cessation alter the behavioral diurnal activity pattern.

In mammals, there is an underlying mechanism that dictates the organism's biological functions and daily activity schedule, known as circadian rhythms, which play a major role in maintaining steady metabolism, homeostasis, and immunity. Limited research has been done investigating the effects of continuous opiate administration on the circadian rhythm activity pattern. A change in circadian activity pattern is suggested as an experimental model to demonstrate long-term effect of the drug. The objective of this study was to investigate the effects of morphine treatment on the long term activity (24 h) of the animal as well as the activity after abrupt removal, since prescribed medication containing morphine is widely used and abused and its long term effects are not known. Male Sprague-Dawley rats were contained in stable conditions with a standard light/dark cycle recordings taken before, during and after morphine pellet implantation. Cosinor analysis was used to fit a 24-hour curve to the activity pattern. Results indicate that morphine pellet administration alters the mesor, amplitude, the day-time and night-time activity levels, and demonstrates a remarkable change in the maximal circadian rhythm timing during the withdrawal period. The question whether morphine changes the circadian rhythm or a change in circadian rhythm results in tolerance and withdrawal is discussed.