"Y no quedó nada, nada de la casa, todo salió volando" (And there was nothing left, nothing of the house, everything flew away): a critical medical ecological perspective on the lived experience of hurricane María in Puerto Rico.

BACKGROUND: Ecological disasters create dramatic changes as man-made and natural ecosystems adapt to their effects. In 2017, Hurricanes Irma and María devastated Puerto Rico. Public focus after such traumatic ecological events often neglects pre-existing community dynamics, heterogeneity of lived experience, and complexity of decision-making in the disaster context. We intended to better understand the lived experience of this ecological trauma in communities across ecosystems in Puerto Rico and among those displaced to Florida. METHOD: We used the Critical Medical Ecological (CME) framework to assess the relative contribution of ecological dimensions on lived experience across community levels and time. We used qualitative methods with emic coding and etic mapping of salient constructs to the ecological model. In total, 96 people participated in 23 discussion encounters. Two people coded interviews in Spanish using Dedoose. We identified common themes in sequential order mapped to elements of the CME to approximate the participants' temporal experience. RESULTS: Codes applied to the period of the hurricane's landfall, traverse, and exit were markedly distinct from the other two periods (before and after) examined in this study: the experience of the hurricane's strike was highly personal and, at this level, reflected a mix of sociocultural, biological, and abiotic factors. After the hurricanes, social and community factors re-emerged while new risks and conditions arose that were biological (e.g., leptospirosis, no food or water) or abiotic (e.g., unusable roads/bridges, structures destroyed), but created ongoing stressors and social needs for communities. As we found, the dynamics of the social and household landscape sometimes involved the decision to leave Puerto Rico altogether, or forced people to continually face and adapt to the ongoing collapse in basic services that were only slowly and differentially restored. CONCLUSION: Lived experience across each stage of the hurricanes differed substantially from one another. Communities disrupted by ecological disaster are also frequently entangled within global economic and political histories and dependencies that could preclude recovery. Island nations are especially vulnerable to both climate-induced ecological change and political-economic exploitation. The ongoing health effect of the hurricane remains palpable in many communities of Puerto Rico and among the diaspora in Florida.

Conducting an immersive community-based assessment of post-hurricane experience among Puerto Ricans: lived experience of medical ecology in an environmental disaster and migration.

BACKGROUND: Two devastating sequential hurricanes impacted Puerto Rico during September of 2017. The hurricanes were traumatic and created social and ecological upheaval throughout Puerto Rico, and subsequently in communities of Central Florida where affected Puerto Ricans migrated. The 2017 hurricane season exposed and exacerbated previous long-standing socio-political, economic, environmental, and health crises, generating a humanitarian emergency in the country. The consequences of these human-ecological disasters destroyed much of Puerto Rico's residential and environmental infrastructure, displacing thousands of people and resulting in an unprecedented migration to the United States. We report on the lived experience of the investigator team and partnership in conducting community-based formative research subsequent to this disaster, research that aimed to identify salient issues relating to the impact of Hurricanes Irma and María on Puerto Rican communities both in Puerto Rico and in Central Florida. DISCUSSION: The challenges faced during the conduct of this research include but are not limited to (1) emotional distress of participants and team members, (2) access to affected populations, and (3) precarious environmental factors, such as unstable infrastructure. To address these challenges, the researchers applied a Critical Medical Ecological paradigm along with qualitative methods to assist constructing explanatory models while obtaining internally-valid (from the community perspective), cathartic narrative accounts of the lived experience of hurricane survivors. The experience of the research team may help inform other investigators conducting applied research during a humanitarian crisis. CONCLUSION: Lessons learned in this research included: (1) usefulness of applying the Critical Medical Ecological model in the development of the project, (2) incorporating participation and methods that prioritize authenticity, (3) understanding the trauma experience and using study methods sensitive to it, and (4) innovating with best approaches to conduct the study given the challenges in post-hurricane Puerto Rico. These lessons could provide new insights on how to conduct in-depth participatory health research with community members who have been traumatized and - often - displaced. This research also demonstrates the value of pre-existing partnerships, critical consciousness in the field team, and medical ecological modeling as experiential for organizing complex, inter-related, multi-level variables that explain community and individual impact of environmental disasters.

The external genitalia in juvenile Caiman latirostris differ in hormone sex determinate-female from temperature sex determinate-female.

The broad-snouted caiman (Caiman latirostris) is a crocodilian species that inhabits South American wetlands. As in all other crocodilians, the egg incubation temperature during a critical thermo-sensitive window (TSW) determines the sex of the hatchlings, a phenomenon known as temperature-dependent sex determination (TSD). In C. latirostris, we have shown that administration of 17-ß-estradiol (E2) during the TSW overrides the effect of the male-producing temperature, producing phenotypic females (E2SD-females). Moreover, the administration of E2 during TSW has been proposed as an alternative way to improve the recovery of endangered reptile species, by skewing the population sex ratio to one that favors females. However, the ovaries of E2SD-female caimans differ from those of TSD-females. In crocodilians, the external genitalia (i.e. clitero-penis structure or phallus) are sexually dimorphic and hormone-sensitive. Despite some morphological descriptions aimed to facilitate sexing, we found no available data on the C. latirostris phallus histoarchitecture or hormone dependence. Thus, the aims of this study were: (1) to establish the temporal growth pattern of the phallus in male and female caimans; (2) to evaluate histo-morphological features and the expression of estrogen receptor alpha (ERα) and androgen receptor (AR) in the phallus of male and female pre-pubertal juvenile caimans; and (3) to determine whether the phallus of TSD-females differs from the phallus of E2SD-females. Our results demonstrated sexually dimorphic differences in the size and growth dynamics of the caiman external genitalia, similarities in the shape and spatial distribution of general histo-morphological compartments, and sexually dimorphic differences in innervation, smooth muscle fiber distribution, collagen organization, and ERα and AR expressions. The external genitalia of E2SD-females differed from that of TSD-females in many histological features and in the expression of ERα and AR, resembling patterns described in males. Our results alert on the effects of estrogen agonist exposure during TSW and suggest that caution must be taken regarding the use of E2SD as a procedure for wildlife population management.

Dermoscopy of naevi in patients with oculocutaneous albinism.

Oculocutaneous albinism (OCA) increases predisposition to skin malignancies. Nevertheless, the differential diagnosis between melanoma and naevi in patients with OCA is still challenging, because pigmentary lesions have rarely been described in this population. We aimed to describe the dermoscopic patterns of naevi in patients with OCA. We prospectively evaluated 83 naevi from 37 patients with OCA in a single centre in Brazil. Lesions were analysed by eye and by dermoscopy and were grouped by dermoscopic pattern. Eight main patterns were identified: homogeneous structureless pattern (n = 28; 33.7%), globular pattern (n = 27; 32.5%), reticular pattern (n = 8; 9.6%), peripheral reticular pattern with central hypopigmentation (n = 8; 9.6%), peripheral globules (n = 8; 9.6%), irregular brown globules with pink background (n = 2; 2.4%), reticular globular disorganized pattern (n = 1; 1.2%) and peripheral reticular globular with central hypopigmentation (n = 1; 1.2%). We found previously undescribed dermoscopic patterns in patients with OCA, in addition to confirming previously described patterns. These descriptions may help the understanding of pigmented naevi in patients with OCA.

Production of monoclonal antibodies and development of a quantitative immuno-polymerase chain reaction assay to detect and quantify recombinant Glutathione S-transferase.

GST-tagged proteins are important tools for the production of recombinant proteins. Removal of GST tag from its fusion protein, frequently by harsh chemical treatments or proteolytic methods, is often required. Thus, the monitoring of the proteins in tag-free form requires a significant effort to determine the remnants of GST during purification process. In the present study, we developed both a conventional enzyme-linked immunosorbent assay (ELISA) and an immuno-polymerase chain reaction (IPCR) assay, both specific for detection of recombinant GST (rGST). rGST was expressed in Escherichia coli JM109, using a pGEX4T-3 vector, and several anti-rGST monoclonal antibodies were generated using hybridoma technology. Two of these were rationally selected as capture and detection antibodies, allowing the development of a sandwich ELISA with a limit of detection (LOD) of 0.01 µg/ml. To develop the rGST-IPCR assay, we selected "Universal-IPCR" format, comprising the biotin-avidin binding as the coupling system. In addition, the rGST-IPCR was developed in standard PCR tubes, and the surface adsorption of antibodies on PCR tubes, the optimal neutravidin concentrations, the generation of a reporter DNA and the concentration effect were studied and determined. Under optimized assay conditions, the rGST-IPCR assay provided a 100-fold increase in the LOD as well as an expanded working range, in comparison with rGST-ELISA. The proposed method exhibited great potentiality for application in several fields in which measurement of very low levels of GST is necessary, and might provide a model for other IPCR assays.

Thermodynamic uncertainty relations in mesoscopic devices.

We investigate the thermodynamic uncertainty relations (TURs) in mesoscopic devices for all universal symmetry classes of Wigner-Dyson and Dirac (chiral). The observables of interest include the TUR (MS), which is defined in terms of the ratio between the mean noise and mean conductance, as well as a new TUR (R) proposed in this article, which is based on the ensemble mean of the noise-to-conductance ratio. A detailed study is made on the quantum interference corrections associated with the TURs. We also analyze the influence of orbital and sublattice/chiral degrees of freedom for the validity of the observables in these chaotic mesoscopic billiards. Our investigation is based on the concatenation between the Landauer-Büttiker theory, the Mahaux-Wendeinmüller theory, and the TURs. We simulate the universal mesoscopic chaotic quantum dots using the random-matrix theory and compare our numerical results with the pertinent experimental data. The results were obtained for a different number of channels and tunneling rates that vary from the opaque to the ideal regime and, in all cases, demonstrate a clear phenomenological distinction between the TURs. In particular, the opaque regime engenders remarkable differences between the observables, even in the semiclassical regime, which characterizes a clear violation of the central limit theorem. Furthermore, we show that the phenomenology of the quantum interference corrections is strikingly robust, surprisingly exhibiting an order of magnitude greater than the supposedly leading semiclassical term for the TUR (R).

Evaluation of a heart failure knowledge questionnaire and its use in guiding the educational intervention.

INTRODUCTION AND OBJECTIVE: Patient education by nurses is a cornerstone of any heart failure (HF) program, but the models are widely heterogeneous and few specific instruments exist. Our objective is to evaluate our own questionnaire and its utility as a guide for educational intervention. METHODS: This work is a prospective cohort study of patients followed-up on in a specialized unit after diagnosis of HF. The intervention group received educational sessions guided according to their knowledge using the questionnaire and was compared to a group which received standard education. The validity and reliability of the questionnaire was evaluated. The utility of the educational model was determined by the primary composite endpoint of death and/or hospital admission or emergency care for HF. RESULTS: A total of 152 patients were included, 88 which received guided education and 64 which received standard education, with a mean follow-up time of 16±4 months. In the guided education group, the evaluation questionnaire score (qs) rose from 59% to 78.5% (p=0.018), which was associated with greater self-care (28.5-0.6*qs, p=0.04), a tendency toward better quality of life (51.1-1.1*qs, p=0.09), and adherence (5.02+0.04*qs, p=0.06), with acceptable reliability (Cronbach's alpha 0.75). The primary composite endpoint was met in 12 patients (13.6%) in the intervention group compared to 19 (29.7%) in the control group (hazard ratio: 0.46; 95% confidence interval: 0.24-0.88; p=0.019). Only educational level, age, NT-proBNP, and atrial fibrillation were predictors in the multivariate analysis. CONCLUSION: The HF knowledge questionnaire proposed is a valid, reliable tool and allows for quantifying learning. Its utility in guiding education requires a certain degree of skill from the patient that determines a group with better prognosis.

Conductance peaks in open quantum dots.

We present a simple measure of the conductance fluctuations in open ballistic chaotic quantum dots, extending the number of maxima method originally proposed for the statistical analysis of compound nuclear reactions. The average number of extreme points (maxima and minima) in the dimensionless conductance T as a function of an arbitrary external parameter Z is directly related to the autocorrelation function of T(Z). The parameter Z can be associated with an applied gate voltage causing shape deformation in quantum dot, an external magnetic field, the Fermi energy, etc. The average density of maxima is found to be <ρ(Z)>=α(Z)/Z(c), where α(Z) is a universal constant and Z(c) is the conductance autocorrelation length, which is system specific. The analysis of <ρ(Z)> does not require large statistic samples, providing a quite amenable way to access information about parametric correlations, such as Z(c).

The epidemiology of Medical Emergency Team calls for orthopedic patients in a teaching hospital: A retrospective cohort study.

BACKGROUND: Patients undergoing orthopedic surgery are at risk of post-operative complications and needing Medical Emergency Team (MET) review. We assessed the frequency of, and associations with MET calls in orthopedic patients, and whether this was associated with increased in-hospital morbidity and mortality. METHODS: Retrospective cohort study of patients admitted over four years to a University teaching hospital using hospital administrative and MET call databases. RESULTS: Amongst 6344 orthopedic patients, 55.8% were female, the median (IQR) age and Charlson comorbidity index were 66 years (47-79) and 3 (1-5), respectively. Overall, 54.5% of admissions were emergency admissions, 1130 (17.8%) were non-operative, and 605 (9.5%) patients received a MET call. The strongest independent associations with receiving a MET call was the operative procedure, especially hip and knee arthroplasty. Common MET triggers were hypotension (37.5%), tachycardia (25.0%) and tachypnoea (9.1%). Patients receiving a MET call were at increased risk of anemia, delirium, pressure injury, renal failure and wound infection. The mortality of patients who received a MET call was 9.8% compared with 0.8% for those who did not. After adjusting for pre-defined co-variates, requirement for a MET call was associated with an adjusted odd-ratio of 9.57 (95%CI 3.1-29.7) for risk of in-hospital death. CONCLUSIONS: Approximately 10% of orthopedic patients received a MET call, which was most strongly associated with major hip and knee arthroplasty. Such patients are at increased risk of morbidity and in-hospital mortality. Further strategies are needed to more pro-actively manage at-risk orthopedic patients.

Epigenetic Dysregulation of Dopaminergic System by Maternal Cafeteria Diet During Early Postnatal Development.

Dopamine is a neurotransmitter crucial for motor, motivational, and reward-related functions. Our aim was to determine the effect of a palatable maternal diet on the transcriptional regulation of dopaminergic-related genes during perinatal development of rat offspring. For that, female offspring from dams fed with a control (CON) or a cafeteria (CAF) diet were sacrificed on embryonic day 21 (E21) and postnatal day 10 (PND10). Using micropunch techniques, ventral tegmental area (VTA) and nucleus accumbens (NAc) were isolated from brain's offspring. Bioinformatic analysis of the promoter regions, mRNA quantification and methylation studies were done. The increase in tyroxine hidroxylase (TH), dopamine receptor (DRD) 1 and ghrelin receptor (GHSR) expression in VTA and NAc from E21 to PND10 was correlated with changes in DNA methylation of their promoter regions. Maternal diet did not affect the expressionpatternsin E21. At PND10, maternal CAF diet decreased the transcription of TH, GHSR, DRD2 and dopamine transporter (DAT) in VTA. Interestingly, the changes in TH, DRD2 and DAT expression were related to the methylation status of their promoters. In NAc, maternal CAF diet reduced DRD1, DRD2 and DAT expression in the offspring at PND10, although alternations in the methylation patterns were only detected in DAT promoter. These results show the importance of maternal nutrition and provide novel insights into the mechanisms through which maternal junk-food feeding can affect reward system during development and early postnatal life. Particularly important is the expression decline of DRD2 given its physiological implication in obesity and addiction.

Regional changes in the spatio-temporal pattern of progesterone receptor (PR) expression in the guinea-pig genital tract as parturition approaches.

Normal parturition in guinea-pig involves changes in responsiveness of the genital tract to estrogen and progesterone. To better characterize endocrine control of guinea-pig parturition, protein and mRNA expression of estrogen receptor-alpha (ERalpha) and progesterone receptor (PR) were quantitatively evaluated in lower (LUS) and upper (UUS) uterine segments, cervix (C) and pubic symphyseal ligament (PSL) at three stages of pregnancy (established based on interpubic distance, 0mm: non-relaxed group, 4-6mm: 5 days before parturition, 11-14 mm: 1-2 days prepartum) and immediately after parturition. Towards parturition, no changes in PR mRNA levels were recorded in the UUS, whereas the LUS displayed a gradual increase. PR transcripts exhibited decreased levels during parturition in C and PSL. Levels of PR mRNA were increased in the LUS compared with that of the UUS only at parturition. Regarding protein expression during parturition, PR levels decreased in the UUS whereas in the LUS increased. In C and PSL, PR protein expression decreased 1-2 days prepartum and remained low during parturition. None of the regions studied showed changes in mRNA or protein expression of ERalpha. Therefore, functional regionalization of the guinea-pig genital tract is associated with changes in the spatio-temporal pattern of PR expression as parturition approaches.

Apex predator and the cyclic competition in a rock-paper-scissors game of three species.

This work deals with the effects of an apex predator on the cyclic competition among three distinct species that follow the rules of the rock-paper-scissors game. The investigation develops standard stochastic simulations but is motivated by a procedure which is explained in the work. We add the apex predator as the fourth species in a system that contains three species that evolve following the standard rules of migration, reproduction, and predation, and study how the system evolves in this new environment, in comparison with the case in the absence of the apex predator. The results show that the apex predator engenders the tendency to spread uniformly in the lattice, contributing to destroy the spiral patterns, keeping biodiversity but diminishing the average size of the clusters of the species that compete cyclically.

A novel procedure for the identification of chaos in complex biological systems.

We demonstrate the presence of chaos in stochastic simulations that are widely used to study biodiversity in nature. The investigation deals with a set of three distinct species that evolve according to the standard rules of mobility, reproduction and predation, with predation following the cyclic rules of the popular rock, paper and scissors game. The study uncovers the possibility to distinguish between time evolutions that start from slightly different initial states, guided by the Hamming distance which heuristically unveils the chaotic behavior. The finding opens up a quantitative approach that relates the correlation length to the average density of maxima of a typical species, and an ensemble of stochastic simulations is implemented to support the procedure. The main result of the work shows how a single and simple experimental realization that counts the density of maxima associated with the chaotic evolution of the species serves to infer its correlation length. We use the result to investigate others distinct complex systems, one dealing with a set of differential equations that can be used to model a diversity of natural and artificial chaotic systems, and another one, focusing on the ocean water level.

3D power Doppler ultrasound in early diagnosis of preeclampsia.

INTRODUCTION: Preeclampsia is a known cause of maternal, fetal and neonatal morbidity and mortality. Thus, evaluation of the predicting value of comparing 3D power Doppler indices (3DPD) of uteroplacental circulation (UPC) in the first and second trimester in patients who developed preeclampsia (PE) and those who did not and testing the hypothesis that the parameters of vascularization and placenta flow intensity, as determined by three-dimensional ultrasound (3D), are different in normal pregnancies compared with preeclampsia, could be a suitable screening method. METHODS: A prospective observational study using 3D power Doppler were performed to evaluate the placental perfusion in 96 pregnant women who came to do the ultrasound routine between 11 and 14 weeks. The placental vascular index (VI), flow index (FI), blood vessels and blood flow index (VFI) by three-dimensional Doppler histogram were calculated. All patients repeated the exam between 16 and 20 weeks. The outcome was scored as normal or preeclamptic. RESULTS: Placental vascular indices including VI, FI and VFI were significantly lower in preeclamptic placentas compared with controls in the study performed in the second trimester (p<0.001). There was not any statistical difference in the patients examined in the first trimester. DISCUSSION: Our findings suggest that 3D-power Doppler assessment of placental vascular indices in the second trimester has the potential to detect women at risk for subsequent development of PE.

Hypertensive disorders during pregnancy and health outcomes in the offspring: a systematic review.

UNLABELLED: The hypertensive disorders of pregnancy complicate up to 10% of pregnancies worldwide and are a leading cause of maternal, foetal, and neonatal morbidity and mortality. The aim of this study was to present an overview of recent studies addressing offspring's medium and long-term health outcomes after intrauterine exposure to maternal hypertension. A search on PubMed/MEDLINE and Bireme databases was conducted to identify observational studies that reported any offspring outcome measured after the 6th month of life. The search was limited to studies published after May 2008. Forty-five articles were included and categorized into four groups of outcomes: cardiovascular, immune, metabolic and behavioural/neurological effects. According to our findings, hypertensive disorders of pregnancy had an overall negative impact on offspring's cardiovascular, immune and neurological health, although not all parameters analysed in each group had consistent results among studies. The most prominent and reliable associations were verified between gestational hypertension and higher offspring's blood pressure and between preeclampsia and offspring's lower cognitive functioning. In the metabolic outcomes, body composition had conflicting results among papers, while all studies that examined blood biomarkers showed no evidence that preeclampsia or gestational hypertension could be associated with an alteration of this metabolic outcomes. Most included studies were highly heterogeneous regarding the measure of outcomes and covariables used for adjustments. Future studies should consider using the same protocols and cut-off points already published so that results can be better compared and summarized. This review was registered in PROSPERO. REGISTRATION NUMBER: CRD42015020838.

Correlation functions and correlation widths in quantum-chaotic scattering for mesoscopic systems and nuclei.

We derive analytical expressions for the correlation functions of the electronic conductance fluctuations of an open quantum dot under several conditions. Both the variation of energy and that of an external parameter, such as an applied perpendicular or parallel magnetic fields, are considered in the general case of partial openness. These expressions are then used to obtain the ensemble-averaged density of maxima, a measure recently suggested to contain invaluable information concerning the correlation widths of chaotic systems. The correlation width is then calculated for the case of energy variation, and a significant deviation from the Weisskopf estimate is found in the case of two terminals. The results are extended to more than two terminals. All of our results are analytical. The use of these results in other fields, such as nuclei, where the system can only be studied through a variation of the energy, is then discussed.

Extended pelvic lymphadenectomy in patients with clinically localised prostate cancer: A prospective observational study. / Linfadenectomía pélvica extendida en pacientes con cáncer de próstata clínicamente localizado: estudio observacional prospectivo.

OBJECTIVE: To determine the frequency of lymph node involvement in patients with clinically localised prostate adenocarcinoma who had radical prostatectomy and extended pelvic lymphadenectomy. MATERIAL AND METHODS: A prospective observational study was conducted on 137 patients with clinically localised prostate cancer of low, intermediate or high risk according to the D'Amico classification. All participants underwent radical prostatectomy plus extended pelvic lymphadenectomy in 3 reference centres in Bogota, Colombia, between 2013 and 2014. The following variables were assessed: age, prostate specific antigen levels, Gleason score of the biopsy, probability of lymph node involvement calculated with Partin tables and the histopathology result of the surgical specimen, with the definitive Gleason pattern and the total number of resected and involved lymph nodes per tumour, according to the territory of the dissection. RESULTS: A total of 2,876 lymph nodes were extracted (an average of 20.99 lymph nodes per patient). There was lymph node involvement in 14 (10.22%) patients. The high-risk and intermediate-risk group presented lymph node metastases in 28.57% and 5.25%, respectively. There was no lymph node involvement in the low-risk group. Of the patients at risk of lymph node involvement (≥2% according to the Partin tables), 19.40% had lymph node metastases. CONCLUSION: Lymph node involvement in our population is similar to that reported in the worldwide literature. Extended pelvic lymphadenectomy increased the probability of detecting lymph node metastases in our community.

The estrogen receptor alpha sigma3 mRNA splicing variant is differentially regulated by estrogen and progesterone in the rat uterus.

The gene for estrogen receptor alpha (ER alpha) has been shown to be under complex hormonal control and its activity can be regulated by mRNA alternative splicing. Here we examined the regulation of ER alpha transcription and translation in the rat uterus by ovarian steroid hormones. We examined whether expression of ER alpha mRNA splice isoforms is hormonally regulated in ovariectomized (OVX) and cycling rats. Adult OVX female rats were treated daily with 17-beta estradiol (E2) (0.05 microg/rat or 5 microg/rat), progesterone (P4) (1 mg/rat) or a combination of both hormones for 4 days. Animals were killed 24 h after the last injection and uterine horns were removed. In order to determine whether ER alpha mRNA isoforms are differentially expressed under various physiological conditions, animals were evaluated at proestrus, estrus and diestrus. The ER alpha protein and mRNA were detected by immunohistochemistry and comparative RT-PCR analysis respectively. The presence of ER alpha mRNA isoforms was evaluated using a nested RT-PCR assay. In OVX control rats, ER alpha mRNA and protein levels were high, demonstrating a constitutive expression of the ER alpha gene in the uterus. When animals received P4 or the high dose of E2, a significant decrease in both ER alpha mRNA and protein was observed in the uterus. However, when rats were protein was treated with the low dose of E2, only the ER alpha down-regulated; no changes were observed in ER alpha mRNA expression. In addition to the full-length ER alpha mRNA, OVX control rat uteri expressed three shorter transcripts: sigma3, sigma4 and sigma3,4 (lacking exon 3, exon 4, or both 3 and 4 respectively). Surprisingly, when OVX animals were treated with P4, the low dose of E2 or a combination of both steroids, expression of the sigma3 isoform was completely abolished. During the estrous cycle, all ER alpha mRNA splicing variants were detected at proestrus and estrus. However, in diestrus, significant low levels of the sigma3 isoform were observed. In summary, our results suggest a dose-dependent relationship between E2 concentrations and the level of control in the ER alpha transcription-translation cascade. Moreover, the alternative splicing of the ER alpha primary transcript is influenced by the hormonal milieu, suggesting that these events could affect the estrogen responsiveness of the rat uterus during the estrous cycle.

Estrogen and progesterone modulation of eosinophilic infiltration of the rat uterine cervix.

Ripening of the rat cervix involves widespread collagenolysis that follows an eosinophilic leukocyte infiltration. The hormonal control of these events is not well understood. The aims of this study were to investigate the mechanism through which progesterone (P) and 17beta-estradiol (E(2)) modulate eosinophilic invasion and to determine if this event is protein synthesis mediated. Cervical eosinophilic invasion was measured in intact rats during the second half of pregnancy and compared with values from ovariectomized (O) pseudopregnant (PSP) rats treated with P and E(2) in doses that mimicked the levels of pregnancy. Other O-PSP rats were treated with an E(2) antagonist (tamoxifen) and the antiprogestin RU-486. To study the role of protein synthesis in eosinophilic invasion of the cervix, rats were treated with actinomycin-D (an inhibitor of mRNA synthesis), and animals were sacrificed on D21 or D22 to evaluate eosinophilic invasion. Rats treated with E(2) showed high levels of infiltration and tamoxifen blocked this E(2) effect. On the other hand, P antagonized the stimulatory effects of E(2) on eosinophilic invasion, however when the P and E(2) treated rats were injected with RU-486 the inhibitory effect of P was reversed. In intact pregnant rats a sharp rise in eosinophilic infiltration was detected on D23, 20 h after the fall of serum P. Finally, E(2) treated rats injected with actinomycin-D had no invasion of eosinophils. In conclusion, the estrogen-triggered eosinophil invasion is affected by the classic estrogen receptor antagonist tamoxifen and by the mRNA synthesis blocker actinomycin-D suggesting a genomic action of E(2). Furthermore, the estrogen effect is blocked by P and this inhibition is reversed by RU-486.

Urinary protein/creatinine ratio in hypertensive pregnant women.

OBJECTIVES: To determine the correlation between the protein/creatinine ratio and 24-h proteinuria; to estimate the sensitivity and specificity of this ratio for the diagnosis of significant proteinuria; to establish its cutoff point with the best predictive value for the diagnosis of significant proteinuria in patients with systemic arterial hypertension. STUDY DESIGN: A cross-sectional study of 47 hypertensive patients who had been pregnant for 20 weeks or more seen at the Maternity of the University Hospital of Porto Alegre. The studied factor was the protein/creatinine ratio measured in a single random urine sample and the outcome was protein determination in 24-h urine. The level of significance was set at 0.05. RESULTS: The correlation coefficient between the protein/creatinine ratio and 24-h proteinuria was 0.94 when urine was properly collected. A receiver-operator characteristic curve was constructed to determine the sensitivity and specificity of the ratio for the diagnosis of significant proteinuria (> or = 300 mg in 24 h). Specificity and predictive positive value were 100% for a ratio > or = 0.8. The best values for sensitivity, specificity, positive predictive value, and negative predictive value in the diagnosis of proteinuria > or = 300 mg in 24 h were obtained when the protein/creatinine ratio was 0.5 (0.96, 0.96, 0.96, and 0.96, respectively). CONCLUSION: The protein/creatinine ratio measured in a single urine sample taken at random from hypertensive pregnant women showed good sensitivity and specificity for the diagnosis of 24-h proteinuria > or = 300 mg and was strongly correlated with 24-h proteinuria. A ratio of 0.5 mg/mg is predictive of significant proteinuria and can be used for the diagnosis and follow-up of hypertensive pregnant women.