The S/S Genotype of the 5-HTTLPR (Serotonin-Transporter-Linked Promoter Region) Variant of the SLC6A4 Gene Decreases the Risk of Pre-Eclampsia.

Pre-eclampsia (PE) is a disorder characterized by hypertension in the second trimester of pregnancy that results from abnormal placentation affecting fetal development and maternal health. Previous studies have shown the role of serotonin (5-HT) that leads to poor placental perfusion, where S/S and S/L polymorphisms promote the solute carrier family 6 member 4 (SLC6A4) gene associated with the risk of developing changes in the microvasculature of the placenta. This study looked at the association between the gene variant 5-HTTLPR (serotonin-transporter-linked promoter region) of the SLC6A4 gene and the occurrence of PE. A total of 200 women were included: 100 cases (pregnant with PE) and 100 controls (pregnant without complications). Genotyping of the 5-HTTLPR variant was performed using polymerase chain reaction (PCR). Associations between the presence of the genetic variant of interest and PE and other clinical features were evaluated statistically. The frequencies of S/S, S/L, and L/L genotypes were 32%, 53%, and 15% for the cases and 55%, 25%, and 20% in the control group. Compared to the controls, the genotype frequencies S/S vs. S/L + L/L (recessive model) in the cases group were different (p = 0.002). The S/S genotype decreased the probability of PE (OR = 0.39, 95% IC: 0.22-0.69, p = 0.002) and PE with severity criteria (OR = 0.39, 95% IC: 0.17-0.91, p = 0.045). The 5-HTTLPR gene variant of the SLC6A4 gene modifies the risk of PE development among the studied population.

Training for the surgical management of postpartum hemorrhage: a multicenter survey of resident physicians.

BACKGROUND: To actively address maternal morbidity and mortality in Mexico, proficiency among obstetrics and gynecology (OBGYN) residents in the surgical management of postpartum hemorrhage (PPH) is a priority. However, the capacity of programs to provide this training is unknown. OBJECTIVE: The self-reported knowledge, education, and proficiency of common surgical techniques for the management of PPH among OBGYN residents in Mexico was evaluated. Educational resources, perceived barriers to acquiring skills, and clinical decision-making were explored. MATERIALS AND METHODS: In July of 2018, an anonymous electronic survey was sent to 86 residents at four hospitals throughout Mexico. Surgical techniques queried included uterine tamponade (UT), uterine compression sutures (UCS), uterine devascularization (UD), hypogastric artery ligation (HAL), and gravid hysterectomy (HT). Participants also answered case-based questions about a patient with PPH. RESULTS: The survey response rate was 59.3% (51/86). Seventy-nine percent of residents reported understanding the rationale and techniques for the surgical intervention of PPH. However, 43.9% reported limited ability to perform these procedures with autonomy. Eighty-six percent of residents reported exposure to these techniques while performing a rescue procedure during PPH and 49% reported learning these procedures while performing prophylactic techniques in patients without PPH. Only 25.5% had been exposed to simulation training. Lack of a training module for these skills in their curriculum was noted by 74.5%. The majority of the participants chose UCS, UD, HAL, and HT as the first, second, third, and fourth rescue procedures to perform for PPH, respectively. CONCLUSION: Most residents reported theoretical knowledge of surgical interventions for PPH, but their self-rated ability to independently perform such skills and a curriculum focused on PPH management was suboptimal.

The implementation of the Plan Esperanza and response to the imPACT Review.

Following the implementation of the National Cancer Prevention and Control Results-based Budget Programme (PpR Cancer-024) in 2011, the Peruvian Government approved the Plan Esperanza-a population-based national cancer control plan-in 2012. Legislation that ensured full government-supported funding for people who were otherwise unable to access or afford care and treatment accompanied the Plan. In 2013, the Ministry of Health requested an integrated mission of the Programme of Action for Cancer Therapy (imPACT) report to strengthen cancer control in Peru. The imPACT Review, which was executed in 2014, assessed Peru's achievements in cancer control, and areas for improvement, including cancer control planning, further development of population-based cancer registration, increased prevention, early diagnosis, treatment and palliative care, and the engagement and participation of civil society in the health-care system. This Series paper gives a brief history of the development of the Plan Esperanza, describes the innovative funding model that supports it, and summarises how funds are disseminated on the basis of disease, geography, and demographics. An overview of the imPACT Review, and the government's response in the context of the Plan Esperanza, is provided. The development and execution of the Plan Esperanza and the execution of and response to the imPACT Review demonstrates the Peruvian Government's commitment to fighting cancer across the country, including in remote and urban areas.

Hypoxia-inducible factor-1 mediates neuronal expression of the receptor for advanced glycation end products following hypoxia/ischemia.

Activation of the receptor for advanced glycation endproducts (RAGE) by its multiple ligands can trigger diverse signaling pathways with injurious or pro-survival consequences. In this study, we show that Rage mRNA and protein levels were stimulated in the mouse brain after experimental stroke and systemic hypoxia. In both cases, RAGE expression was primarily associated with neurons. Activation of RAGE-dependent pathway(s) post-ischemia appears to have a neuroprotective role because mice genetically deficient for RAGE exhibited increased infarct size 24 h after injury. Up-regulation of RAGE expression was also observed in primary neurons subjected to hypoxia or oxygen-glucose deprivation, an in vitro model of ischemia. Treatment of neurons with low concentrations of S100B decreased neuronal death after oxygen-glucose deprivation, and this effect was abolished by a neutralizing antibody against RAGE. Conversely, high concentrations of exogenous S100B had a cytotoxic effect that seems to be RAGE-independent. As an important novel finding, we demonstrate that hypoxic stimulation of RAGE expression is mediated by the transcription factor hypoxia-inducible factor-1. This conclusion is supported by the finding that HIF-1alpha down-regulation by Cre-mediated excision drastically decreased RAGE induction by hypoxia or desferrioxamine. In addition, we showed that the mouse RAGE promoter region contains at least one functional HIF-1 binding site, located upstream of the proposed transcription start site. A luciferase reporter construct containing this RAGE promoter fragment was activated by hypoxia, and mutation at the potential HIF-1 binding site decreased hypoxia-dependent promoter activation. Specific binding of HIF-1 to this putative HRE in hypoxic cells was detected by chromatin immunoprecipitation assay.

Experiencia de la cirugía laparoscópica infantil en el Instituto Especializado de Salud del Niño / Experience of laparoscopic surgery in childrens in Instituto Especializado de Salud del Niño

Se estudió a los pacientes pediátricos que habían sido sometidos a cirugía laparoscópica en el Instituto Especializado de Salud del Niño, desde el inicio de las operaciones en noviembre de 1999 hasta mayo del 2004. El objetivo fue conocer las características derivadas del uso de esta nueva técnica quirúrgica, progresos en su seguridad y sus beneficios. Involucra a 304 pacientes que corresponden al total de casos, a través del uso de una ficha de recolección de datos aplicada a las historias clínicas. Las edades oscilaron entre el mes de vida y 18 años. Las operaciones más frecuentes fueron la laparoscopia exploratoria con biopsia hepática 78 casos (25,7 por ciento), ligadura de varicocele 73 casos (24,1 por ciento), apendicectomía 47 casos (15,5 por ciento), laparoscopia exploratoria 33 casos (10,9 por ciento), colecistectomía 22 casos (7,3 por ciento), gonadectomía 11 (3,6 por ciento), esplenectomía 7 (2,3 por ciento) además: liberación de bridas y adherencias, nefrectomía, histerectomía, fundoplicatura de Nissen. El presente estudio demuestra que la cirugía laparoscópica es una alternativa tan segura y efectiva como la cirugía abierta en pacientes pediátricos, incluyendo situaciones de emergencia.

Absceso hepático debido a apendicitis aguda en niños / Liver abscess due to acute appendicitis in children

Se reporta 2 casos de pacientes de edad pediátrica que presentaron apendicitis aguda perforada y que desarrollaron absceso hepático piógeno. A uno de ellos se realizó apendicectomía laparoscópica y al otro niño se le practicó una apendicectomía convencional. Son dos casos de apendicitis aguda perforada con absceso hepático, que en la actualidad son descritos raramente en la literatura.

Structural and functional adaptation to hypoxia in the rat brain.

Chronic exposure to a hypoxic environment leads to structural and functional adaptations in the rat brain. One significant adaptation is a decrease in intercapillary distances through a near doubling of the capillary density, which begins after about 1 week of hypoxic exposure and is completed by 3 weeks. Hypoxic angiogenesis is controlled by activation of downstream genes by Hypoxia Inducible Factor-1 and Angiopoietin-2. The processes that increase capillary density are reversible upon restoration of the ambient oxygen concentration. Capillary regression, which also occurs over a 3-week period, is accomplished through activation of apoptosis. The implication from these observations is that the brain naturally functions in a low, but controlled, oxygen environment. Acute imbalances in oxygen delivery and metabolic demand are addressed through changes in blood flow; persistent imbalances activate mechanisms that adjust capillary density. The mechanisms that control these processes decline with age.

Role of nitric oxide in the regulation of HIF-1alpha expression during hypoxia.

Hypoxia-inducible factor-1 (HIF-1), a heterodimeric transcription factor consisting of HIF-1alpha and HIF-1beta subunits, controls the expression of a large number of genes involved in the regulation of cellular responses to reduced oxygen availability. The oxygen-regulated subunit, HIF-1alpha, is stabilized in cells exposed to hypoxia. The regulation of hypoxic responses by nitric oxide (NO) is believed to have wide pathophysiological relevance, thus we investigated whether NO affects HIF-1 activation in hypoxic cells. Here we show that NO generated from NO donors prevented HIF-1alpha hypoxic accumulation in Hep 3B and PC-12 cells. Addition of a glutathione analog or peroxynitrite scavengers prevented the NO-induced inhibition of HIF-1alpha accumulation in both cell lines. Exposure to NO was associated with inhibition of mitochondrial electron transport and compensatory glycolysis, which maintained normal cellular ATP content. Succinate, a Krebs cycle intermediate and respiratory chain substrate, restored HIF-1alpha hypoxic induction in the cells, suggesting involvement of mitochondria in regulation of HIF-1alpha accumulation during hypoxia. Regulation of HIF-1alpha by NO is an additional important mechanism by which NO might modulate cellular responses to hypoxia in mammalian cells.