Prevalence of somatic and germline mutations of Fumarate hydratase in uterine leiomyomas from young patients.

AIMS: Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is caused by germline mutations in the Fumarate hydratase (FH) gene. In young women, the syndrome often presents with symptomatic uterine leiomyomas, leading to myomectomy or hysterectomy. In this study, we aimed to investigate the incidence and mutational profiles of FH-negative leiomyomas from young patients, thus allowing for early identification and triage of syndromic patients for surveillance. METHODS AND RESULTS: We evaluated 153 cases of uterine leiomyomas from women aged up to 30 years for loss of FH expression by tissue microarray (TMA)-based immunohistochemical staining. Mutational analysis of tumours with loss of FH was carried out by polymerase chain reaction (PCR) amplification of 10 exons within the FH gene and subsequent Sanger sequencing. The status of promoter methylation was assessed by bisulphite sequencing. Loss of FH protein expression was detected in seven (4.6%) of 153 tested uterine leiomyomas from young patients. All FH-negative leiomyomas displayed staghorn vasculature and fibrillary/neurophil-like cytoplasm. We found that six (86%) of seven FH-negative tumours detected by immunohistochemistry harboured FH mutations, 50% of which contained germline mutations. In particular, the germline mutational rate in FH gene was 2.0% (three of 153 cases). Bisulphite sequencing analysis failed to detect promoter methylation in any of the seven tumours. CONCLUSION: Our study showed a relatively high rate of FH germline mutation in FH-negative uterine leiomyomas from patients aged up to 30 years. While genetic mutations confer protein expression loss, epigenetic regulation of the FH gene appears to be unrelated to this phenotype.

Development of in vitro fertilization in the United States: a conversation between Zev Rosenwaks and Jairo E. Garcia.

In commemoration of 40 years of in vitro fertilization (IVF), herein we describe the early evolution of the first IVF program at the Eastern Virginia Medical School in Norfolk, Virginia. The birth of the first American IVF baby was the result of the work of many investigators, both in experimental animal models and in humans, heavily relying on the experience of Robert Edwards and Patrick Steptoe in Great Britain. Although their first IVF baby was the result of the retrieval of a single oocyte in the natural cycle, duplicating their methods was not successful in Norfolk. It turns out that the achievement of the first pregnancy in the United States was associated with introducing ovarian stimulation with gonadotropins, establishing the appropriate timing for egg retrieval after hCG administration, retrieving multiple mature oocytes, determining the ideal time for in vitro insemination, and optimizing embryo culture media.

[Analysis of the performance of the assessment battery related to psychosocial factors in Colombia]. / Análisis del desempeño de la batería de evaluación de factores psicosociales en Colombia.

OBJECTIVE: The goal of this study is to analyze the performance of the three questionnaires and the file of general information that comprise the Set of Instruments for the Assessment of Psychosocial Factors in six companies from different economic sectors in Colombia, with regard to: (a) content of the instruments, (b) application methodology, and (c) the response from workers and employers. METHODOLOGY: This research was performed through the study of multiple instances. It was based on the processing of: (1) the observation logs with regard to the application of the questionnaires, (2) workers' annotations about their questionnaires and (3) minutes of meetings with representatives of the workers. A reclassification into more specific subcategories was done taking into consideration some particular and common elements found between companies. RESULTS: Regarding the "Content" category, there are significant limitations in the questionnaires about both outside and inside-of-work factors. This is because some items cannot be applied under specific working conditions such as outsourcing or field work. In "Methodology" it was observed that some practices could decrease the reliability of the assessments, such as not having adequate schedules or locations. In the "Reception" category, it was found that even though this assessment is deemed desirable by most workers and employers, there are, however, some actions taken by companies that could affect this perception. CONCLUSIONS: It is positive to implement the assessment of psychosocial working conditions in companies of this country, even though this assessment, with a universal assessment tool, has difficulties in a changing and increasingly complex working world. It is advisable to complement these assessments with qualitative methods.

Barreras de acceso a la cobertura de riesgos laborales en contratos de prestación de servicios en el sector público de salud en Bogotá / Access barriers to occupational risk coverage in service provision contracts in the public health sector in Bogotá

Objetivo Identificar barreras de acceso al Sistema General de Riesgos Laborales (SGRL) de Colombia en un grupo de profesionales independientes (contratados por prestación de servicios) del sector público de salud en Bogotá. Metodología Investigación cualitativa (narrativa) mediante entrevistas a 4 profesionales independientes de la Secretaria Distrital de Salud, 4 profesionales independientes del Hospital de Tunjuelito y 3 expertos en riesgos profesionales. Para el manejo de la información se utilizó el análisis de contenido. Resultados Enlas dos instituciones consultadas del sector público de salud en Bogotá se han adelantado estrategias que facilitan el acceso a la seguridad social en riesgos laborales de los trabajadores independientes. Sin embargo, los trabajadores y los expertos entrevistados identifican una serie de barreras de acceso que se presentan para la afiliación de los trabajadores independientes al Sistema General de Riesgos Laborales, entre estas barreras de acceso están la falta de cultura de la prevención ante los riesgos laborales, el desconocimiento sobre la normatividad y utilidad del sistema y la no concepción del mismo como parte fundamental del sistema de seguridad social del país. Conclusiones Es necesario que el Sistema General de Riesgos Laborales sea entendido como parte integral y fundamental de la seguridad social del país, lo cual depende de una construcción cultural sobre la importancia de un sistema de riesgos laborales en las organizaciones estatales, los empleadores y los empleados.(AU)

Objective To identify access barriers to the General System for Occupational Risks (SGRL in Spanish) in a group of independent professionals (contracted with service provision contraction) in the public health sector in Bogotá. Methodology Qualitative research (narrative) through interviews of four independent professionals of the Secretaría Distrital de Salud (District Health Secretariat), 4 independent professionals of Tunjuelito Hospital and 3 experts in the field of occupational risks. The content analysis paradigm was used for information analysis. Results The two institutions of the public health sector in Bogotá consulted have implemented strategies that facilitate the access to the SGRL for independent professionals. However, the interviewed workers and experts identified some access barriers membership for independent workers in this occupational risk system; among these barriers are the lack of a culture of occupation risk prevention, lack of knowledge about laws and the utility of the system as well as the non-conception of the SGRL as a fundamental part of the social security system of the country. Conclusion It is necessary for the SGRL to be recognized as an integral and fundamental part of the country's social security. This depends on a cultural construction of the importance of an occupational risk system among the state organizations, employers and employees.(AU)

Análisis del desempeño de la batería de evaluación de factores psicosociales en Colombia / Analysis of the performance of the assessment battery related to psychosocial factors in Colombia

Objetivo Analizar el desempeño de los tres cuestionarios y la ficha de datos generales que conforman la Batería de Instrumentos para la Evaluación de Factores de Riesgo Psicosocial en seis empresas de distintos sectores económicos en Colombia, en lo relacionado con: a. Contenido de los instrumentos; b. Metodología de aplicación, y; c. Recepción por parte de trabajadores y empleadores. Metodología Estudio de casos múltiples a partir del procesamiento de: 1. Los registros de observación de la aplicación de los cuestionarios; 2. Las anotaciones de los trabajadores sobre los cuestionarios resueltos, y; 3. Las actas de reunión con los representantes de los empleadores. Se observó qué elementos comunes y particulares tenían las empresas para hacer una reclasificación en subcategorías. Resultados En relación con la categoría "Contenido", hay limitaciones en los cuestionarios de factores intralaborales y extralaborales, debido a que algunos ítems no aplican para condiciones de trabajo específicas como tercerización o trabajo en campo. En "Metodología", se observaron prácticas que podrían restar confiabilidad a las evaluaciones, como no disponer de espacios o tiempos adecuados. En la categoría "Recepción" se encontró que, aunque dicha evaluación se considera conveniente para la mayoría de trabajadores y empleadores, algunas acciones de las empresas pueden afectar esta percepción. Conclusiones Resulta positiva la implementación de la evaluación de las condiciones de trabajo psicosociales en las empresas del país, si bien dicha evaluación, con un instrumento universal, presenta dificultades en un mundo del trabajo cambiante y complejo. Se recomienda complementar estas evaluaciones con métodos cualitativos.

Objective The goal of this study is to analyze the performance of the three questionnaires and the file of general information that comprise the Set of Instruments for the Assessment of Psychosocial Factors in six companies from different economic sectors in Colombia, with regard to: (a) content of the instruments, (b) application methodology, and (c) the response from workers and employers. Methodology This research was performed through the study of multiple instances. It was based on the processing of: (1) the observation logs with regard to the application of the questionnaires, (2) workers' annotations about their questionnaires and (3) minutes of meetings with representatives of the workers. A reclassification into more specific subcategories was done taking into consideration some particular and common elements found between companies. Results Regarding the "Content" category, there are significant limitations in the questionnaires about both outside and inside-of-work factors. This is because some items cannot be applied under specific working conditions such as outsourcing or field work. In "Methodology" it was observed that some practices could decrease the reliability of the assessments, such as not having adequate schedules or locations. In the "Reception" category, it was found that even though this assessment is deemed desirable by most workers and employers, there are, however, some actions taken by companies that could affect this perception. Conclusions It is positive to implement the assessment of psychosocial working conditions in companies of this country, even though this assessment, with a universal assessment tool, has difficulties in a changing and increasingly complex working world. It is advisable to complement these assessments with qualitative methods.

[Access barriers to occupational risk coverage in service provision contracts in the public health sector in Bogotá]. / Barreras de acceso a la cobertura de riesgos laborales en contratos de prestación de servicios en el sector público de salud en Bogotá.

Objective To identify access barriers to the General System for Occupational Risks (SGRL in Spanish) in a group of independent professionals (contracted with service provision contraction) in the public health sector in Bogotá. Methodology Qualitative research (narrative) through interviews of four independent professionals of the Secretaría Distrital de Salud (District Health Secretariat), 4 independent professionals of Tunjuelito Hospital and 3 experts in the field of occupational risks. The content analysis paradigm was used for information analysis. Results The two institutions of the public health sector in Bogotá consulted have implemented strategies that facilitate the access to the SGRL for independent professionals. However, the interviewed workers and experts identified some access barriers membership for independent workers in this occupational risk system; among these barriers are the lack of a culture of occupation risk prevention, lack of knowledge about laws and the utility of the system as well as the non-conception of the SGRL as a fundamental part of the social security system of the country. Conclusion It is necessary for the SGRL to be recognized as an integral and fundamental part of the country's social security. This depends on a cultural construction of the importance of an occupational risk system among the state organizations, employers and employees.

Marco legal de los riesgos profesionales y la salud ocupacional en Colombia, Siglo XX / The 20th century legal framework regarding risk at work and occupational health in Colombia

Objetivo Analizar la normativa emitida en Colombia desde la perspectiva del derecho del trabajo, la seguridad social y la salud pública en el siglo XX, para identificar las concepciones en torno a la salud ocupacional y los riesgos profesionales, estableciendo las convergencias y diferencias que existen entre cada una de estas líneas y si responden o no a una visión complementaria. Método Investigación documental, mediante un análisis categorial temático de las reglamentaciones y estatutos promulgados en el siglo XX en Colombia, considerando el elemento o materia principal que se encarguen de regular relacionado con los riesgos profesionales o la salud ocupacional. Resultados Se construyó una periodización del desarrollo normativo en salud laboral en el país en el siglo XX, permitiendo evidenciar el predominio histórico de la visión del derecho social, que se concentra en la protección de los riesgos profesionales de los trabajadores dependientes, como una tendencia que se extiende hasta el Sistema General de Riesgos Laborales. Conclusiones Las etapas propuestas como eje ordenador de la normativa en riesgos profesionales y salud ocupacional posibilitan reconocer elementos trascendentales del contexto social, legal e institucional en el que emergieron tales reglamentaciones preocupadas por la salud de los trabajadores, advirtiéndose una tensión histórica entre las preceptivas dirigidas a la reparación y compensación de las contingencias relacionadas con el trabajo y aquellas directrices con una orientación preventiva.(AU)

Objective Analyzing the 20th century Colombian legal framework from the point of view of labor law, social security and public health for identifying concepts regarding occupational health and professional risk and trying to establish convergence and differences between such foci and whether they fulfilled a complementary view. Method This work involved documentary research by means of thematic categorical analysis of the laws and statutes promulgated in 20th century Colombia, considering the main element or entity which should have regulated that related to professional risk or occupational health. Results The development of the 20th century Colombian legal framework regarding health at work was periodized, revealing the predominance of a view of social law focused on protecting dependent workers' work-related risks, as part of a tendency extending to the Colombian Sistema General de Riesgos Laborales. Conclusions The proposed stages used for organizing the legal framework concerning social security regarding professional risk and occupational health facilitated some important elements being recognized concerning the social, legal and institutional context from which workers' health laws emerged. Tension was noted concerning statutes orientated towards redress and compensation regarding accidents at work and legislation emphasizing prevention.(AU)

[The 20th century legal framework regarding risk at work and occupational health in Colombia]. / Marco legal de los riesgos profesionales y la salud ocupacional en Colombia, Siglo XX.

OBJECTIVE: Analyzing the 20th century Colombian legal framework from the point of view of labor law, social security and public health for identifying concepts regarding occupational health and professional risk and trying to establish convergence and differences between such foci and whether they fulfilled a complementary view. METHOD: This work involved documentary research by means of thematic categorical analysis of the laws and statutes promulgated in 20th century Colombia, considering the main element or entity which should have regulated that related to professional risk or occupational health. RESULTS: The development of the 20th century Colombian legal framework regarding health at work was periodized, revealing the predominance of a view of social law focused on protecting dependent workers' work-related risks, as part of a tendency extending to the Colombian Sistema General de Riesgos Laborales. CONCLUSIONS: The proposed stages used for organizing the legal framework concerning social security regarding professional risk and occupational health facilitated some important elements being recognized concerning the social, legal and institutional context from which workers' health laws emerged. Tension was noted concerning statutes orientated towards redress and compensation regarding accidents at work and legislation emphasizing prevention.

The impact of luteal phase support on endometrial estrogen and progesterone receptor expression: a randomized control trial.

BACKGROUND: To assess the impact of luteal phase support on the expression of estrogen receptor (ER) alpha and progesterone receptors B (PR-B) on the endometrium of oocyte donors undergoing controlled ovarian hyperstimulation (COH). METHODS: A prospective, randomized study was conducted in women undergoing controlled ovarian hyperstimulation for oocyte donation. Participants were randomized to receive no luteal support, vaginal progesterone alone, or vaginal progesterone plus orally administered 17 Beta estradiol. Endometrial biopsies were obtained at 4 time points in the luteal phase and evaluated by tissue microarray for expression of ER alpha and PR-B. RESULTS: One-hundred and eight endometrial tissue samples were obtained from 12 patients. No differences were found in expression of ER alpha and PR-B among all the specimens with the exception of one sample value. CONCLUSIONS: The administration of progesterone during the luteal phase of COH for oocyte donor cycles, either with or without estrogen, does not significantly affect the endometrial expression of ER alpha and PR.

[The workers health and the Tropical Oil Company. Barrancabermeja, 1916-1940]. / La salud de los trabajadores y la Tropical Oil Company. Barrancabermeja, 1916-1940.

This article analyses the health of workers engaged in oil exploration and exploitation in Colombia during the time of the so-called De Mares concession from 1916 to 1940. Periodisation was constructed which sought to account for yellow fever and tropical diseases within the sanitary situation related to oil exploration and exploitation during this period and region and how it became displaced from its central position by accidentally. The initial period was characterised by the lack of protection to which the workers were subjected at the start of oil-producing activities between 1916 and 1920. The second period was defined by implementing means of protection within the framework of a labour dispute accompanied by the sanitary problem's great burden between 1921 and 1928. The third period (1929 to 1940) dealt with entrepreneurial initiative becoming consolidated so as to make health become a control device, even though this was accompanied by the persistence of important labour disputes in which accidentality had a notable presence. Aspects are identified which should be gone into in greater depth for characterising oil-workers' health at the time of the De Mares concession.

La salud de los trabajadores y la Tropical Oil Company: Barrancabermeja, 1916-1940 / The workers health and the Tropical Oil Company Barrancabermeja, 1916-1940

El artículo presenta un análisis sobre la salud de los trabajadores en los procesos de exploración y explotación petrolera adelantados en el país en la denominada Concesión de Mares, entre 1916 y 1940. Se construyó una periodización que busca dar cuenta del lugar de la problemática de la Fiebre Amarilla y las enfermedades tropicales en la situación sanitaria de la actividad petrolera en este periodo y región, pasando de ocupar un lugar central a ser desplazadas por la accidentalidad. El periodo inicial se caracteriza por la desprotección a que se ven sometidos los trabajadores al comienzo de las actividades productivas petroleras, entre 1916 y 1920; el segundo periodo se define por la implementación de medidas de protección, en el marco de un conflicto laboral con un gran peso de la problemática sanitaria, entre 1921 y 1928; y en el tercer periodo se consolida la iniciativa empresarial para hacer de la salud un dispositivo de control, pero que se acompaña de la persistencia de conflictos laborales importantes en que la accidentalidad tiene una presencia notoria, entre 1929 y 1940. Finalmente se identifican aspectos a profundizar para una caracterización de la configuración de la salud de los trabajadores petroleros en la Concesión de Mares.

This article analyses the health of workers engaged in oil exploration and exploitation in Colombia during the time of the so-called De Mares concession from 1916 to 1940. Periodisation was constructed which sought to account for yellow fever and tropical diseases within the sanitary situation related to oil exploration and exploitation during this period and region and how it became displaced from its central position by accidentally. The initial period was characterised by the lack of protection to which the workers were subjected at the start of oil-producing activities between 1916 and 1920. The second period was defined by implementing means of protection within the framework of a labour dispute accompanied by the sanitary problem's great burden between 1921 and 1928. The third period (1929 to 1940) dealt with entrepreneurial initiative becoming consolidated so as to make health become a control device, even though this was accompanied by the persistence of important labour disputes in which accidentality had a notable presence. Aspects are identified which should be gone into in greater depth for characterising oil-workers' health at the time of the De Mares concession.

Fewer medications for in vitro fertilization can be better: thinking outside the box.

Minimal stimulation or mild stimulation protocols for in vitro fertilization offer many advantages for all patients, but especially for low and high responders. In the current practice of reducing the number of embryos transferred to a maximum of two for a significant number of patients, using aggressive and high-dose gonadotropins to obtain a large, and sometimes excessive, number of oocytes should be questioned.

Nitric oxide metabolite production in the human preimplantation embryo and successful blastocyst formation.

Eleven patients underwent controlled ovarian hyperstimulation yielding 72 embryos for evaluation. Mean nitric oxide metabolite levels in the insemination media were 2.6 times higher in embryos that progressed to blastocysts by culture day 5 than in those that did not. A comparison of the receiver operating characteristic curves between morphological predictors and nitric oxide metabolite levels revealed a trend toward a stronger association of insemination media nitric oxide metabolite with blastocyst formation.

Endometrial biopsy: a test whose time has come.

The endometrial biopsy is still a precise screening tool for the evaluation of the infertile couple.

Fine tuning cycle day 3 hormonal assessment of ovarian reserve improves in vitro fertilization outcome in gonadotropin-releasing hormone antagonist cycles.

OBJECTIVE: To identify the cut-off values of the baseline (cycle day 3) levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E(2)) for improving the outcome prediction of GnRH antagonist in vitro fertilization (IVF) cycles and to determine whether the predictive accuracy of these values is affected by the patient's clinical prognosis. DESIGN: Retrospective analysis. SETTING: An IVF clinic in a tertiary medical center. Women undergoing 230 consecutive IVF cycles using a GnRH antagonist protocol. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Outcome of IVF, measured by ovarian response and pregnancy rates. RESULT(S): Lower baseline levels of FSH and E(2), but not LH, correlated with improved ovarian response and pregnancy rates in IVF cycles using a GnRH antagonist. Compared with our currently used criteria, the cut-off values of FSH <10 IU/L and E(2) <56 pg/mL would have significantly improved the IVF outcome in a population of patients with normal prognosis. However, a stricter baseline FSH cut-off value of 8 IU/L would have been required to improve the IVF outcome in a population of patients with a poor prognosis. CONCLUSION(S): The outcome of IVF may be improved by modifying the hormonal starting criteria to take into account individual patient characteristics such as clinical prognosis.

Clinical outcome of using ganirelix acetate versus a 4-day follicular phase leuprolide acetate protocol in unselected women undergoing in vitro fertilization.

OBJECTIVE: To compare the clinical outcome of controlled ovarian hyperstimulation (COH) in unselected patients undergoing IVF using multidose ganirelix acetate versus 4 days of administration of leuprolide acetate. DESIGN: Retrospective cohort study. SETTING: A fertility and IVF center. PATIENT(S): Two hundred forty-seven women who underwent COH-IVF between April 1, 1999, and January 30, 2001. INTERVENTION(S): Pituitary suppression according to a 4-day follicular phase leuprolide acetate protocol (236 women) or a multidose ganirelix acetate regimen (133 women). MAIN OUTCOME MEASURE(S): Amount of gonadotropin used, days of stimulation, cancellation rate, number of oocytes retrieved, implantation rate, and clinical pregnancy rate. RESULT(S): Compared with leuprolide acetate recipients, ganirelix recipients required significantly less gonadotropin and the mean day of hCG administration was 4 days earlier. Among women younger than 35 years of age, the implantation rate (15% vs. 6%) and the clinical pregnancy rate per initiated and transferred cycle (27% vs. 12% and 32% vs. 15%, respectively) were significantly higher in the ganirelix group than the leuprolide acetate group. CONCLUSION(S): Compared with a 4-day leuprolide acetate protocol, COH-IVF using a multidose ganirelix acetate protocol reduces treatment duration and amount of gonadotropin used. In younger women, the latter protocol is associated with significantly better pregnancy and implantation rates.