Effectiveness of near-infrared spectroscopy as a non-invasive tool to discriminate spectral profiles of in vitro cultured oocytes from goats.

Here, we aimed to discriminate between the spectral profiles of spent culture media after oocyte in vitro maturation (IVM) and culture (IVC) from goats of different ages subjected to repeated hormonal treatments. The profiles were discriminated using near infrared (NIR) spectroscopy combined with multivariate methods. A total of 19 goats (young = 10; old = 9) were subjected to serial hormonal stimulation (HS) with gonadotropins. Cumulus oophorus complexes (COCs) were collected using laparoscopic ovum pick-up (LOPU) and subjected to IVM and parthenogenetic activation. The initial embryos were subjected to IVC. Spent culture media were collected after oocyte IVM and on day 2 of IVC and analyzed using NIR spectroscopy. NIR spectral data were interpreted through chemometric methods, such as principle component analysis (PCA) and partial least square discriminant analysis (PLS-DA). The results of PCA analysis clearly showed a separation in the spectral profiles between the experimental groups (HS sessions; young and old animals) both after IVM and IVC. Overall, the main absorption bands were attributed to the C-H group second overtone, first overtone of O-H and N-H, and C-H combinations and may serve as molecular markers. On the other hand, the spectral data obtained using PLS-DA models provided a better classification of the groups. The results showed the possibility of discriminating young and old groups as well as the three HS sessions with high specificity, sensitivity, and accuracy using NIR spectra. Thus, the culture medium analysis using NIR spectroscopy combined with multivariate methods indicated the dissimilarities between the groups and provided an insight into the in vitro development of goat oocytes. This technique serves as an efficient, objective, rapid, and non-invasive method to discriminate spectral profiles.

Hypoxia increases mutational load of breast cancer cells through frameshift mutations.

Tumor hypoxia-induced downregulation of DNA repair pathways and enhanced replication stress are potential sources of genomic instability. A plethora of genetic changes such as point mutations, large deletions and duplications, microsatellite and chromosomal instability have been discovered in cells under hypoxic stress. However, the influence of hypoxia on the mutational burden of the genome is not fully understood. Here, we attempted to elucidate the DNA damage response and repair patterns under different types of hypoxic stress. In addition, we examined the pattern of mutations exclusively induced under chronic and intermittent hypoxic conditions in two breast cancer cell lines using exome sequencing. Our data indicated that hypoxic stress resulted in transcriptional downregulation of DNA repair genes which can impact the DNA repair induced during anoxic as well as reoxygenated conditions. In addition, our findings demonstrate that hypoxic conditions increased the mutational burden, characterized by an increase in frameshift insertions and deletions. The somatic mutations were random and non-recurring, as huge variations within the technical duplicates were recognized. Hypoxia also resulted in an increase in the formation of potential neoantigens in both cell lines. More importantly, these data indicate that hypoxic stress mitigates DNA damage repair pathways and causes an increase in the mutational burden of tumor cells, thereby interfering with hypoxic cancer cell immunogenicity.

Effect of Continuous Administration of Enalapril Maleate on the Oocyte Quality and In Vitro Production of Parthenote Embryos in Nulliparous and Multiparous Goats Undergoing Serial Laparoscopic Ovum Pick-Up.

The aim of this work was to determine the effect of enalapril maleate administration, during oocyte recovery by serial laparoscopic ovum pick-up (LOPU), on the ovarian response and in vitro embryo production (IVP). Twenty cross-bred goats were allocated equally into two groups: Nulliparous and Multiparous. In each group, five animals were selected to receive daily doses of enalapril maleate during the hormonal protocol. Estrus was synchronized by a PGF2α analog, followed 48 h later by insertion of an intravaginal device with progesterone. Forty-eight hours after, a single dose of FSH/eCG was administered. The FSH/eCG doses were repeated three times, on every four day. Oocytes were recovered by LOPU 24 h after each FSH/eCG dose. Viable oocytes were matured in vitro, to be parthenogenetically activated and cultured for 72 h to the cleavage stage. The drug treatment increased the proportion of total follicles observed at LOPU (p < 0.01) in multiparous goats. In both parity groups, enalapril administration had no effect on the proportion or quality of oocytes recovered. Furthermore, the number of embryos cleaved was similar between the groups. Thus, enalapril maleate affected the ovarian response in multiparous animals only and had no effect on the oocyte quality or IVP.

Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and Plasticity.

Hypoxia, or gradients of hypoxia, occurs in most growing solid tumors and may result in pleotropic effects contributing significantly to tumor aggressiveness and therapy resistance. Indeed, the generated hypoxic stress has a strong impact on tumor cell biology. For example, it may contribute to increasing tumor heterogeneity, help cells gain new functional properties and/or select certain cell subpopulations, facilitating the emergence of therapeutic resistant cancer clones, including cancer stem cells coincident with tumor relapse and progression. It controls tumor immunogenicity, immune plasticity, and promotes the differentiation and expansion of immune-suppressive stromal cells. In this context, manipulation of the hypoxic microenvironment may be considered for preventing or reverting the malignant transformation. Here, we review the current knowledge on how hypoxic stress in tumor microenvironments impacts on tumor heterogeneity, plasticity and resistance, with a special interest in the impact on immune resistance and tumor immunogenicity.

High incidence of cetuximab-related infusion reactions in head and neck patients.

BACKGROUND: Cetuximab is crucial in the management of squamous cell carcinoma of the head and neck of patients. Grade 3-4 cetuximab-induced infusion reactions (CI-IRs) occur in 2% of patients with colorectal cancer. Despite the 2.7% CI-IR rate in the EXTREME trial, higher rates were reported in small series of patients with head and neck squamous cell carcinoma (HNSCC) (6%-18%). There is an urgent need to better appraise the natural history and the predictive factors for CI-IRs in patients with HNSCC exposed to cetuximab. METHODS: The medical records from patients with HNSCC (n=428) treated by cetuximab at Gustave Roussy from January 2013 to December 2015 were reviewed. The impact of potential risk factors was analysed. RESULTS: Out of 428 patients, 24 patients (5.4%) presented CI-IR, including grade 3-4 (95.7%); about 21% (5/24) requiring intensive care unit referral and quasi all occurred within the first cycle (21/24). In a multivariate analysis, the occurrence of grade 3-4 CI-IR was associated with tobacco and alcohol history (p=8.5e-3) and with prior allergy history (p=2.9e-3). CI-IRs tended to be associated with poor overall survival in patients with recurrent and metastatic HNSCC and with a higher number of further lines of chemotherapy. CONCLUSION: In real life, CI-IRs appear far more common in patients with HNSCC (5.4%) than reported in prospective trials. This is the largest series of patients ever focusing on the risk of CI-IR in patients with HNSCC. Prior allergy history and tobacco history are associated with CI-IR and could be used to better allocate treatment. Further prospective data are required to confirm these findings.

Despenalización del aborto en Uruguay: una experiencia de América del Sur / Decriminalization of abortion in Uruguay: a South American experience

La ley de despenalización de la interrupción voluntaria del embarazo del Uruguay, promulgada en el año 2012 fue un hito en la Región. En 2017, y tras una prolongada discusión, Chile por fin entra al mayoritario grupo de países que a nivel mundial han legislado en la materia. Si bien en el caso chileno se trata de una legislación mucho más restrictiva, el proceso de implementación uruguayo, con cinco años de recorrido, nos aporta con la identificación de barreras a través de los ojos de algunas de sus protagonistas.(AU)

[Adolescents' access to contraception: perceptions of health workers in Huechuraba, Chile]. / Acceso a anticoncepción en adolescentes: percepciones de trabajadores de la salud en Huechuraba, Chile.

OBJECTIVE: Identify difficulties in adolescents' access to contraceptive care and information, based on perceptions and experiences of health workers in Huechuraba, in the Metropolitan Region of Chile. METHODS: This qualitative, descriptive study incorporated principles of participatory action research, involving health care teams in the survey and data analysis, and generating proposals for improvement. Seventeen (17) semi-structured individual interviews and one group interview were conducted with professionals and technical personnel involved in adolescent care in the commune's health centers. RESULTS: Health workers perceived that adolescents were having difficulties reaching the centers due to cultural factors, lack of information, lack of health activities in the community, while administrative requirements and procedures hindered access to care. Shortcomings were evident in the management and interpretation of fertility regulation standards and of current legislation, and in the absence of explanatory frameworks recognizing adolescents' gender, sexual, and reproductive rights. CONCLUSIONS: Adolescents and their needs have a low profile and there are conflicts between theory and practice regarding access to contraception and counseling, with a lack of definitions or agreements that take into account social and cultural contexts. It is urgent to provide health workers with training on gender and sexual and reproductive rights, together with opportunities for reflection in order to generate coordinated and effective approaches. Efforts are required to disseminate the program and organize activities in community spaces, together with other community sectors.

Acceso a anticoncepción en adolescentes: percepciones de trabajadores de la salud en Huechuraba, Chile / Adolescents’ access to contraception: perceptions of health workers in Huechuraba, Chile / Acesso aos métodos anticoncepcionais entre adolescentes: percepções dos profissionais de saúde em Huechuraba, Chile

Objetivo. Identificar dificultades para el acceso a atención e información en anticoncepción de adolescentes desde percepciones y experiencias de trabajadores de la salud de Huechuraba, en la Región Metropolitana de Chile. Métodos. Este estudio cualitativo y descriptivo incorporó principios de investigación acción participativa involucrando a equipos de atención en el levantamiento y análisis de información, con generación de propuestas de mejora. Se realizaron 17 entrevistas individuales semiestructuradas y una entrevista grupal, con profesionales y técnicos involucrados en la atención de adolescentes en centros de salud de la comuna. Resultados. Trabajadores de la salud percibían dificultades en la llegada de adolescentes a los centros por razones relacionadas a factores culturales, falta de información y de actividades de salud en la comunidad. Existen requisitos administrativos y tramitaciones que obstaculizan el acceso a la atención. Se evidenciaron falencias en el manejo e interpretación de normas de regulación de la fertilidad y de la legislación vigente y ausencia de marcos explicativos que reconociesen el género y derechos sexuales y reproductivos de los adolescentes. Conclusiones. Existe poca visibilidad de los adolescentes y sus necesidades, y contradicciones entre los discursos y las prácticas, con ausencia de definiciones y acuerdos para el acceso a anticoncepción y consejería que consideren contextos sociales y culturales. Urge la implementación de acciones de capacitación para trabajadores de la salud en género y derechos sexuales y reproductivos, junto con espacios de reflexión para generar abordajes articulados y efectivos. Se requieren esfuerzos de difusión del programa y realización de actividades en espacios comunitarios, junto con otros sectores comunales.

Objetivo. Identificar dificuldades de acesso à atenção e informações relacionadas aos métodos anticoncepcionais entre adolescentes com base em percepções e experiências dos profissionais de saúde de Huechuraba, na região metropolitana de Santiago, Chile. Métodos. Estudo qualitativo descritivo realizado segundo os princípios de pesquisaação participativa envolvendo pessoal da saúde na coleta e análise das informações, com a produção de propostas para melhoria. Foram realizadas 17 entrevistas semiestruturadas individuais e uma entrevista em grupo com profissionais e pessoal técnico que prestam atenção a adolescentes em centros de saúde comunitários. Resultados. Os profissionais de saúde perceberam dificuldade na chegada dos adolescentes aos centros por fatores culturais e pela falta de informação e de atividades de saúde na comunidade. Existem requisitos administrativos e diligências que são obstáculos ao acesso à atenção. Foram evidenciadas falhas na gestão e interpretação das normas de regulação da fertilidade e da legislação vigente e a ausência de enquadramentos explicativos que reconhecessem o gênero e os direitos sexuais e reprodutivos dos adolescentes. Conclusões. Os adolescentes e suas necessidades têm pouca visibilidade e existem contradições entre os discursos e as práticas, com a falta de definições e acordos para o acesso a métodos anticoncepcionais e orientação que levam em consideração os contextos socioculturais. É premente a implementação de ações de capacitação para os profissionais de saúde em gênero e direitos sexuais e reprodutivos, assim como de espaços de reflexão para elaborar enfoques articulados e efetivos. São necessários esforços para divulgar o programa e realizar atividades em espaços comunitários, junto com outros setores da comunidade.

Objective. Identify difficulties in adolescents’ access to contraceptive care and information, based on perceptions and experiences of health workers in Huechuraba, in the Metropolitan Region of Chile. Methods. This qualitative, descriptive study incorporated principles of participatory action research, involving health care teams in the survey and data analysis, and generating proposals for improvement. Seventeen (17) semi-structured individual interviews and one group interview were conducted with professionals and technical personnel involved in adolescent care in the commune’s health centers. Results. Health workers perceived that adolescents were having difficulties reaching the centers due to cultural factors, lack of information, lack of health activities in the community, while administrative requirements and procedures hindered access to care. Shortcomings were evident in the management and interpretation of fertility regulation standards and of current legislation, and in the absence of explanatory frameworks recognizing adolescents’ gender, sexual, and reproductive rights. Conclusions. Adolescents and their needs have a low profile and there are conflicts between theory and practice regarding access to contraception and counseling, with a lack of definitions or agreements that take into account social and cultural contexts. It is urgent to provide health workers with training on gender and sexual and reproductive rights, together with opportunities for reflection in order to generate coordinated and effective approaches. Efforts are required to disseminate the program and organize activities in community spaces, together with other community sectors.

Acceso a anticoncepción en adolescentes: percepciones de trabajadores de la salud en Huechuraba, Chile / Adolescents’ access to contraception: perceptions of health workers in Huechuraba, Chile / Acesso aos métodos anticoncepcionais entre adolescentes: percepções dos profissionais de saúde em Huechuraba, Chile

RESUMEN Objetivo Identificar dificultades para el acceso a atención e información en anticoncepción de adolescentes desde percepciones y experiencias de trabajadores de la salud de Huechuraba, en la Región Metropolitana de Chile. Métodos Este estudio cualitativo y descriptivo incorporó principios de investigación acción participativa involucrando a equipos de atención en el levantamiento y análisis de información, con generación de propuestas de mejora. Se realizaron 17 entrevistas individuales semiestructuradas y una entrevista grupal, con profesionales y técnicos involucrados en la atención de adolescentes en centros de salud de la comuna. Resultados Trabajadores de la salud percibían dificultades en la llegada de adolescentes a los centros por razones relacionadas a factores culturales, falta de información y de actividades de salud en la comunidad. Existen requisitos administrativos y tramitaciones que obstaculizan el acceso a la atención. Se evidenciaron falencias en el manejo e interpretación de normas de regulación de la fertilidad y de la legislación vigente y ausencia de marcos explicativos que reconociesen el género y derechos sexuales y reproductivos de los adolescentes. Conclusiones Existe poca visibilidad de los adolescentes y sus necesidades, y contradicciones entre los discursos y las prácticas, con ausencia de definiciones y acuerdos para el acceso a anticoncepción y consejería que consideren contextos sociales y culturales. Urge la implementación de acciones de capacitación para trabajadores de la salud en género y derechos sexuales y reproductivos, junto con espacios de reflexión para generar abordajes articulados y efectivos. Se requieren esfuerzos de difusión del programa y realización de actividades en espacios comunitarios, junto con otros sectores comunales.

ABSTRACT Objective Identify difficulties in adolescents’ access to contraceptive care and information, based on perceptions and experiences of health workers in Huechuraba, in the Metropolitan Region of Chile. Methods This qualitative, descriptive study incorporated principles of participatory action research, involving health care teams in the survey and data analysis, and generating proposals for improvement. Seventeen (17) semi-structured individual interviews and one group interview were conducted with professionals and technical personnel involved in adolescent care in the commune’s health centers. Results Health workers perceived that adolescents were having difficulties reaching the centers due to cultural factors, lack of information, lack of health activities in the community, while administrative requirements and procedures hindered access to care. Shortcomings were evident in the management and interpretation of fertility regulation standards and of current legislation, and in the absence of explanatory frameworks recognizing adolescents’ gender, sexual, and reproductive rights. Conclusions Adolescents and their needs have a low profile and there are conflicts between theory and practice regarding access to contraception and counseling, with a lack of definitions or agreements that take into account social and cultural contexts. It is urgent to provide health workers with training on gender and sexual and reproductive rights, together with opportunities for reflection in order to generate coordinated and effective approaches. Efforts are required to disseminate the program and organize activities in community spaces, together with other community sectors.

RESUMO Objetivo Identificar dificuldades de acesso à atenção e informações relacionadas aos métodos anticoncepcionais entre adolescentes com base em percepções e experiências dos profissionais de saúde de Huechuraba, na região metropolitana de Santiago, Chile. Métodos Estudo qualitativo descritivo realizado segundo os princípios de pesquisa-ação participativa envolvendo pessoal da saúde na coleta e análise das informações, com a produção de propostas para melhoria. Foram realizadas 17 entrevistas semiestruturadas individuais e uma entrevista em grupo com profissionais e pessoal técnico que prestam atenção a adolescentes em centros de saúde comunitários. Resultados Os profissionais de saúde perceberam dificuldade na chegada dos adolescentes aos centros por fatores culturais e pela falta de informação e de atividades de saúde na comunidade. Existem requisitos administrativos e diligências que são obstáculos ao acesso à atenção. Foram evidenciadas falhas na gestão e interpretação das normas de regulação da fertilidade e da legislação vigente e a ausência de enquadramentos explicativos que reconhecessem o gênero e os direitos sexuais e reprodutivos dos adolescentes. Conclusões Os adolescentes e suas necessidades têm pouca visibilidade e existem contradições entre os discursos e as práticas, com a falta de definições e acordos para o acesso a métodos anticoncepcionais e orientação que levam em consideração os contextos socioculturais. É premente a implementação de ações de capacitação para os profissionais de saúde em gênero e direitos sexuais e reprodutivos, assim como de espaços de reflexão para elaborar enfoques articulados e efetivos. São necessários esforços para divulgar o programa e realizar atividades em espaços comunitários, junto com outros setores da comunidade.

Granulomatosis con poliangeítis de presentación atípica: revisión de la literatura a propósito de un caso de localización ginecológica / Cervicovaginal granuloma as the first manifestation of granulomatosis with polyangiitis

La granulomatosis con poliangeitis (GPA) es una vasculitis sistémica, granulomatosa, con compromiso de pequeños vasos y presencia de anticuerpos c-ANCA. Ocasionalmente es localizada y es rara su manifestación genitourinaria. Se presenta el caso de una mujer de 68 años con sangrado genital causado por una lesión cervicovaginal verrucosa ulcerada, cuya histopatología descartó malignidad, hongos y TBC, con mala respuesta a antibióticos, ácido tricloro acético y crioterapia. Por recidiva al año se practica histerectomía total y colpectomía parcial, pero reincide al mes acompañada de epistaxis, cuyo estudio pornasofibroscopía e imágenes concluye en una lesión de tipo granulomatosa, agregándose anticuerpo anti PR-3 positivo. Se diagnostica GPA y se trata con ciclofosfamida con buena respuesta. La revisión de la literatura permite concluir que la GPA con localización cervicovaginal es muy poco frecuente, especialmente como manifestación inicial, y se debe considerar en el diagnóstico diferencial con cáncer y otras lesiones granulomatosas localizadas.

Granulomatosis with polyangiitis (GPA) is a systemic vasculitis, granulomatous, with commitment of small vessels and the presence of c-ANCA antibodies. Occasionally it is located and its genitourinary manifestation is rare. Presented the case of a 68 year old woman with genital bleeding caused by a lesion cervicovaginal ulcerated verrucosa, whose histopathology ruled out fungal, malignancy and TBC, with poor response to antibiotics, acid trichloro acetic and cryotherapy. By relapse a year is practiced total hysterectomy and partial colpectomia, but repeated a month accompanied by epistaxis, whose study by nasofibroscopia and images concludes in a type granulomatous lesion, adding antibody anti PR-3 positive. GPA is diagnosed and treated with cyclophosphamide with good response. Review of the literature leads to th conclusion that the GPA with cervico-vaginal location is very rare, especially as an initial manifestation, and should be considered in the diagnosis diferenttial with cancer and other localized granulomatous lesions.

Effective vaccine safety systems in all countries: a challenge for more equitable access to immunization.

Serious vaccine-associated adverse events are rare. To further minimize their occurrence and to provide adequate care to those affected, careful monitoring of immunization programs and case management is required. Unfounded vaccine safety concerns have the potential of seriously derailing effective immunization activities. To address these issues, vaccine pharmacovigilance systems have been developed in many industrialized countries. As new vaccine products become available to prevent new diseases in various parts of the world, the demand for effective pharmacovigilance systems in low- and middle-income countries (LMIC) is increasing. To help establish such systems in all countries, WHO developed the Global Vaccine Safety Blueprint in 2011. This strategic plan is based on an in-depth analysis of the vaccine safety landscape that involved many stakeholders. This analysis reviewed existing systems and international vaccine safety activities and assessed the financial resources required to operate them. The Blueprint sets three main strategic goals to optimize the safety of vaccines through effective use of pharmacovigilance principles and methods: to ensure minimal vaccine safety capacity in all countries; to provide enhanced capacity for specific circumstances; and to establish a global support network to assist national authorities with capacity building and crisis management. In early 2012, the Global Vaccine Safety Initiative (GVSI) was launched to bring together and explore synergies among on-going vaccine safety activities. The Global Vaccine Action Plan has identified the Blueprint as its vaccine safety strategy. There is an enormous opportunity to raise awareness for vaccine safety in LMIC and to garner support from a large number of stakeholders for the GVSI between now and 2020. Synergies and resource mobilization opportunities presented by the Decade of Vaccines can enhance monitoring and response to vaccine safety issues, thereby leading to more equitable delivery of vaccines worldwide.