Trabajadoras comunitarias de salud: experiencias en el abordaje de la salud mental en zonas rurales de Chiapas.

OBJETIVO: Analizar, desde la perspectiva de las trabajadoras comunitarias de salud (TCS), los conocimientos y experiencias en la atención de la salud mental (SM) en comunidades rurales de Chiapas. Material y métodos. Se utilizó el enfoque fenomenológico descriptivo. Se realizaron 18 entrevistas semiestructuradas a TCS, las cuales fueron audiograbadas, transcritas, codificadas y analizadas utilizando como técnica, el análisis cualitativo de contenido con ayuda del software Atlas ti. RESULTADOS: Las TCS mental tienen una amplia comprensión de la cultura, el lenguaje y los problemas de sus comunidades, permitiéndoles fungir como enlace entre los servicios de salud y la población. Identifican que hay buena SM cuando "una persona tiene ánimo de realizar su trabajo diario" y enfermedad cuando "las personas sufren o tienen pensamientos chuecos". Sus experiencias de trabajo están ligadas con el acompañamiento individual (psico-educación) y el apoyo de actividades realizadas por profesionales de Compañeros En Salud (CES). Conclusión. Las TCS mental que trabajan con CES desarrollan un papel importante en la promoción de la SM, de riesgos y acompañamiento de pacientes con trastornos mentales. Estos hallazgos consolidan la evidencia e importancia del desarrollo de las intervenciones comunitarias en SM a través de este personal, en contextos de escasa disponibilidad de servicios de salud.

Integration of mouse ovary morphogenesis with developmental dynamics of the oviduct, ovarian ligaments, and rete ovarii.

Morphogenetic events during the development of the fetal ovary are crucial to the establishment of female fertility. However, the effects of structural rearrangements of the ovary and surrounding reproductive tissues on ovary morphogenesis remain largely uncharacterized. Using tissue clearing and lightsheet microscopy, we found that ovary folding correlated with regionalization into cortex and medulla. Relocation of the oviduct to the ventral aspect of the ovary led to ovary encapsulation, and mutual attachment of the ovary and oviduct to the cranial suspensory ligament likely triggered ovary folding. During this process, the rete ovarii (RO) elaborated into a convoluted tubular structure extending from the ovary into the ovarian capsule. Using genetic mouse models in which the oviduct and RO are perturbed, we found the oviduct is required for ovary encapsulation. This study reveals novel relationships among the ovary and surrounding tissues and paves the way for functional investigation of the relationship between architecture and differentiation of the mammalian ovary.

In humans and other mammals, the female reproductive organs, or ovaries, develop early in life, while the young are still in their mother's womb. Ovaries contain several different compartments, including the ovarian follicles. These are small groups of cells that produce reproductive hormones, and each follicle also has the potential to produce one egg for fertilisation. The ovaries are further surrounded by different tissues that develop alongside them. These include the oviducts, which carry fertilised eggs from the ovaries into the womb, and ligaments, which anchor the ovaries to the wall of the body cavity. During the development of ovaries, ovarian follicles are sorted into two distinct groups. The first, called medullary follicles, are lost before puberty. The second group, or cortical follicles, remain in a state of 'suspended animation' until puberty. After that, they act as a 'reserve' of eggs for the rest of the reproductive lifespan. Once each cortical follicle has produced an egg, it is not replenished. This means that proper follicle sorting is crucial for establishing female fertility, and therefore the ability to conceive. The mechanisms behind follicle sorting, however, are still poorly understood. McKey et al. set out to determine how the ovary's structure changed during its development. In the experiments, high-resolution microscopy techniques were used to reconstruct ovaries of mice in 3D across different stages of development. This revealed that the ends of each ovary started folding towards each other just before birth, and that the folding also happened at the same time as follicle sorting. Simultaneous changes in the shape and orientation of the ligaments suggested that these tissues might direct the folding, for example by pushing or pulling on the rest of the ovary. These results suggest that the changes in ovary structure in early life are critically linked to the establishment of the ovary's egg reserves. McKey et al. hope that this study will pave the way to a better understanding of infertility and, ultimately, better treatments.

Mammalian uterine morphogenesis and variations.

In eutherian and marsupial mammals, the site of embryo implantation and gestation is the uterus. Uterine morphologies vary between mammalian species. For example, laboratory mice have a bipartite uterus with two uterine horns and a single cervix, whereas humans have a simplex uterus with a single chamber and single cervix. The precursor tissue of the uterus, oviducts, and upper vagina is the Müllerian duct epithelium and its adjacent mesenchyme. Morphological variation between species is established during embryogenesis by species-specific differences in Müllerian duct fusion at the midline, growth, and differentiation. In humans, alterations in Müllerian duct development can lead to variations in uterine morphology that correlate with increased risks of miscarriage and infertility. Here we review the developmental genetic factors that regulate Müllerian duct development, uterine morphogenesis, and human uterine variation.

AMH and AMHR2 mutations: A spectrum of reproductive phenotypes across vertebrate species.

Anti-Müllerian hormone (AMH) is a member of the Transforming Growth Factor-ß family of secreted signaling proteins. AMH is expressed in Sertoli cells of the fetal and adult testes and granulosa cells of the postnatal ovary. AMH is required for the regression of the Müllerian ducts in mammalian fetuses during male differentiation. AMH signals through its Type II receptor, AMHR2. AMHR2 is expressed in mesenchyme adjacent to the Müllerian ducts, and in Sertoli, Leydig, and granulosa cells. Although AMH and AMHR2 genes have been identified in numerous vertebrate species, spontaneous or engineered mutations or variants have been found or created in only a few mammals and teleost fishes. AMH or AMHR2 mutations in mammals lead to the development of Persistent Müllerian Duct Syndrome (PMDS), a recessive condition in which affected males are fully virilized but retain Müllerian duct-derived tissues, including a uterus and oviducts, and in human and dog, undescended testes. Amh mutant female mice had accelerated ovarian primordial follicle recruitment, suggesting a role for AMH in regulating germ cells. amh and amhr2 mutations have also been experimentally generated in various teleost fishes. Depending on the fish species, loss of AMH signaling results in infertility, germ cell tumors, or male-to-female sex reversal. Here we compare the spectrum of phenotypes caused by AMH and AMHR2 mutations in a variety of vertebrate species. There are both common and unique phenotypes between species, highlighting the range of biological processes regulated by AMH signaling.

The impact of time of delivery on gestations complicated by preterm premature rupture of membranes: daytime versus nighttime.

Background: Perinatal death, in particular intrapartum stillbirth and short-term neonatal death, as well as neonatal short-term and long-term morbidity have been associated with the time of day that the birth occurs. Indeed, evening and nighttime deliveries were associated with an increased risk of an adverse perinatal outcome when compared to similar daytime deliveries. Impact of shift change, as well as time of day delivery have been extensively studied in the context of maternal and neonatal complications of cesarean delivery, however, no studies were previously performed on timing of delivery and its effect on the outcome of pregnancies complicated by preterm premature rupture of membranes. Objective: Our objective was to compare obstetric, neonatal as well as long-term outcomes between women delivered in the daytime versus nighttime, in singleton gestations whose pregnancies were complicated by preterm premature rupture of membranes. Study design: This was a secondary analysis of a trial of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network "A Randomized Clinical Trial of the Beneficial Effects of Antenatal Magnesium Sulfate for the Prevention of Cerebral Palsy." For this analysis, the time of delivery was divided into the daytime, from 07:01 to 19:00, and the nighttime, from 19:01 to 07:00. Epidemiological, obstetric characteristics as well as neonatal and long-term outcomes were compared between deliveries occurring during the daytime versus the nighttime periods. Inclusion criteria consisted of singleton gestations diagnosed with preterm premature rupture of membranes (PPROM). Multifetal gestations and pregnancies with preterm labor without preterm premature rupture of membranes were excluded. Results: A total of 1752 patients met inclusion criteria, 881 delivering during the daytime, while 871 during the nighttime. There were no differences in demographic maternal variables. There were no differences in the number of patients receiving steroids and the doses of steroids. Antibiotic prophylaxis was also equal in both groups. Postpartum endometritis, chorioamnionitis, and the latency to delivery were also equivalent between both the groups. Cesarean delivery for distress was the only different outcome, more prevalent in daytime deliveries (157 (44.7%) versus 108 (35.9%) of the nighttime ones p = .02). Neonatal adverse outcomes as well as long-term outcomes were similar between the two groups. Conclusions: In the setting of delivery at a tertiary care center, and in the era of universal use of steroids, and latency antibiotics for the management of preterm premature of membranes, there is no marked difference in pregnancy, neonatal as well as long-term outcomes for infants delivered in the daytime versus nighttime.

The Relationship of Assisted Reproductive Technology on Perinatal Outcomes in Triplet Gestations.

OBJECTIVE: To assess whether assisted reproductive technology (ART) is associated with increased risk of adverse perinatal outcomes in triplet gestations compared with spontaneous conception. STUDY DESIGN: Secondary analysis of a multicenter randomized trial for the prevention of preterm birth in multiple gestations. Triplets delivered at ≥ 24 weeks were studied. The primary outcome was the rate of composite neonatal morbidity (CNM) that included one or more of the following: bronchopulmonary dysplasia, respiratory distress syndrome, necrotizing enterocolitis, culture proven sepsis, pneumonia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, or perinatal death. RESULTS: There were 381 triplets (127 women) of which 89 patients conceived via ART and 38 patients spontaneously. Women with ART were more likely to be older, Caucasian, married, nulliparous, have higher level of education, and develop pre-eclampsia. Spontaneously conceived triplets were more likely to delivery at an earlier gestation (31.2 ± 3.5 vs 32.8 ± 2.7 weeks) (p = 0.009) with a lower birth weight (p < 0.001). After adjusting for confounders, no differences were noted in culture proven sepsis, perinatal death, CNM, respiratory distress syndrome, or Apgar score < 7 at 5 minutes. All remaining perinatal outcomes were similar. CONCLUSION: Triplets conceived by ART had similar perinatal outcomes compared with spontaneously conceived triplets.

Uterus-targeted liposomes for preterm labor management: studies in pregnant mice.

Preterm labor caused by uterine contractions is a major contributor to neonatal morbidity and mortality. Treatment intended to reduce uterine contractions include tocolytic agents, such as indomethacin. Unfortunately, clinically used tocolytics are frequently inefficient and cross the placenta causing fetal side effects. Here we show for the first time in obstetrics the use of a targeted nanoparticle directed to the pregnant uterus and loaded with a tocolytic for reducing its placental passage and sustaining its efficacy. Nanoliposomes encapsulating indomethacin and decorated with clinically used oxytocin receptor antagonist were designed and evaluated in-vitro, ex-vivo and in-vivo. The proposed approach resulted in targeting uterine cells in-vitro, inhibiting uterine contractions ex-vivo, while doubling uterine drug concentration, decreasing fetal levels, and maintaining the preterm birth rate in vivo in a pregnant mouse model. This promising approach opens new horizons for drug development in obstetrics that could greatly impact preterm birth, which currently has no successful treatments.

The effect of combined inositol supplementation on maternal metabolic profile in pregnancies complicated by metabolic syndrome and obesity.

BACKGROUND: Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype. OBJECTIVE: The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model. STUDY DESIGN: Female heterozygous endothelial nitric oxide synthase(-/+) mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic-like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high-fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome-myoinositol/D-chiroinositol-treated vs metabolic-like syndrome-nontreated mice and obese-myoinositol/D-chiroinositol-treated vs obese nontreated mice. RESULTS: Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo (P = .04), whereas there was no difference in systolic blood pressure between treated and placebo-treated obese pregnant mice. Pregnant metabolic-like syndrome mice treated with myoinositol/D-chiroinositol showed lower glucose values during the glucose tolerance test and in the area under the curve (myoinositol/D-chiroinositol: 17512.5 ± 3984.4 vs placebo: 29687.14 ± 8258.7; P = .003), but no differences were seen in the obese pregnant mice. Leptin serum levels were lower in the metabolic-like syndrome-myoinositol/D-chiroinositol-treated mice compared with the placebo group (myoinositol/D-chiroinositol: 16985 ± 976.4 pg/dL vs placebo: 24181.9 ± 3128.2 pg/dL, P = .045). No other differences were seen in any of the remaining serum metabolic biomarkers studied in metabolic-like syndrome and in obese pregnant mice. Maternal weight gain was not different in the pregnant metabolic-like syndrome dams, whereas it was lower in the obese myoinositol/D-chiroinositol-treated dams compared with the placebo group (myoinositol/D-chiroinositol: 10.9 ± 0.5 g vs 12.6 ± 0.6 g, P = .04). Fetal and placental weights did not differ between myoinositol/D-chiroinositol-treated and nontreated pregnant dams with metabolic-like syndrome and obesity. CONCLUSION: Combined inositol treatment during pregnancy improves blood pressure, glucose levels at the glucose tolerance test, and leptin levels in pregnant dams with metabolic-like syndrome phenotype but not in obese pregnant dams. In addition, inositol treatment was associated with lower gestational weight gain in the obese but not in the metabolic-like syndrome pregnant dams.

Sildenafil treatment in a nonsevere hypertensive murine model lowers blood pressure without reducing fetal growth.

BACKGROUND: Treatment of nonsevere hypertension during pregnancy is controversial. Sildenafil is a phosphodiesterase inhibitor that potentiates nitric oxide by promoting vasodilation. Nitric oxide plays a vital role in mediating the vascular adaptations during pregnancy. OBJECTIVE: The objective of the study was to determine whether treatment with sildenafil during pregnancy would lower maternal systolic blood pressure without adversely affecting fetal growth. STUDY DESIGN: Females with nonsevere hypertension (endothelial nitric oxide synthase(+/-)) were cross-bred with normotensive wild-type males. At gestational day 1, pregnant dams were randomized to either sildenafil (0.4 mg/mL per day, comparable dose used in human pregnancy) or water for 3 weeks. Four groups were then generated: wild type (n = 7), wild type-sildenafil (n = 11), endothelial nitric oxide synthase(+/-) (n = 8), and endothelial nitric oxide synthase(+/-)sildenafil (n = 7). On gestational day 18, systolic blood pressure was measured. Dams were killed, fetal and placental weights were obtained, and carotid arteries were dissected to measure in vitro vascular reactivity with a wire-myography system. Responses to phenylephrine, L-NG-nitroarginine methyl ester, acetylcholine, and sodium nitroprusside were studied. RESULTS: Mean systolic blood pressure was elevated in the endothelial nitric oxide synthase(+/-) dams compared with wild-type controls (P = .03). Treatment with sildenafil decreased systolic blood pressure in the endothelial nitric oxide synthase(+/-)-treated dams compared with nontreated endothelial nitric oxide synthase(+/-) dams (P = .03). No differences were seen in the wild-type dams with or without sildenafil (P = .47). Fetuses from endothelial nitric oxide synthase(+/-) dams were smaller compared with wild-type controls (P < .001); however, when these endothelial nitric oxide synthase(+/-) dams were treated with sildenafil, fetal weight increased compared with the nontreated endothelial nitric oxide synthase(+/-) group (P < .001). No difference were seen in wild-type groups treated or not treated with sildenafil (P = .41). Placental weights were not significantly different among groups (endothelial nitric oxide synthase(+/-)sildenafil vs endothelial nitric oxide synthase(+/-) [P = .48]; wild-type-sildenafil vs wild type [P = .52]). Maximal vascular contraction induced by phenylephrine was blunted in endothelial nitric oxide synthase(+/-) dams treated with sildenafil compared with nontreated endothelial nitric oxide synthase(+/-) dams (P < .01). No change in contractile response was seen in wild-type groups treated or not treated (P = .53). When vessels were preincubated with L-NG-nitroarginine methyl ester, the contractile responses were similar among all groups (P = .54). In addition, maximal vascular relaxation induced by acetylcholine was improved in the endothelial nitric oxide synthase(+/-) dams treated with sildenafil compared with endothelial nitric oxide synthase(+/-) nontreated dams (P < .01). No change in relaxation response was seen in wild-type groups treated or not treated (P = .62). Sodium nitroprusside did not change the contractile response in any of the groups (P = .31). CONCLUSION: Pregnant dams deficient in endothelial nitric oxide synthase, a nonsevere hypertensive murine model, treated with sildenafil had lower maternal systolic blood pressure, increased fetal growth, and improvement in vascular reactivity. Treatment with sildenafil may be beneficial in pregnancies complicated by nonsevere hypertension.

Safety of anticonvulsant agents in pregnancy.

INTRODUCTION: Seizures in pregnancy are particularly challenging, as their management requires careful consideration of not only the etiology of the seizure, but also the physiologic changes of pregnancy as well as potential adverse effects on the developing embryo or fetus. Newer antiepileptic drugs (AEDs) have increasingly shown promising results of lower rate of teratogenesis, as well as better seizure control during pregnancy. AREAS COVERED: We performed a review of the scientific literature of seizures in pregnancy including status epilepticus as well as eclampsia, with a focus on safety of currently used AEDs. This covers the different generations of antiepileptic medications, their interactions and seizure recurrence preventative measures. In addition, we summarized our personal approach to the care for these women. EXPERT OPINION: In summary, morbidity associated with seizure in pregnancy is decreasing as treatments and supportive therapies have improved. The understanding of teratogenesis as well as novel targeted therapeutics will allow women on AEDs during their pregnancy, to receive the safest drug for their developing fetus as well as themselves.

Development of chagas cardiac manifestations among Texas blood donors.

Chagas disease, infection with the parasite Trypanosoma cruzi, has recently been identified as an important emerging parasitic disease in the United States. To describe the cardiac abnormalities in T. cruzi-positive blood donors in southeastern Texas, a pilot study of donors who had screened positive from 2007 to 2012 was performed. This one-time assessment included (1) a questionnaire to evaluate the source of infection, cardiac symptoms, and health co-morbidities; (2) electrocardiography; (3) echocardiography if electrocardiographic findings were abnormal; and (4) measurement of a high-sensitivity troponin T biomarker. Of those with confirmed infection, 41% (7 of 17) had electrocardiographic abnormalities consistent with Chagas cardiomyopathy. In addition, 36% (6 of 17) were suspected to be locally acquired cases. High-sensitivity troponin T serum levels increased with cardiac severity. In conclusion, cardiologists should consider Chagas disease in their differential diagnoses for patients who may have clinically compatible electrocardiographic changes or nonischemic cardiomyopathy, even if the patients have no histories of residing in Chagas-endemic countries.