An Assessment of Maternal Quality of Life in the Postpartum Period in Southern Brazil: A Comparison of Two Questionnaires

OBJECTIVES: To assess maternal quality of life (QoL) during the postpartum period and to compare the performance of two QoL questionnaires across a sample of 101 women in southern Brazil. To our knowledge, this is the first study that measures maternal quality of life during the postpartum period in Brazil. INTRODUCTION: There is limited information about postpartum maternal quality of life in Brazil. The are no Portuguese versions of instruments specifically designed to measure quality of life during the postpartum period. METHODS: Research participants completed the Portuguese version of the World Health Organization Quality of Life Assessment-Bref (WHOQOL-BREF) and Multicultural Quality of Life Index (MQLI) questionnaires. The correlations between the MQLI and the discrete areas of WHOQOL-BREF were examined using Pearson Product-Moment Correlation Coefficients. RESULTS: We report a significant correlation between the global MQLI and the four domains of the WHOQOL-BREF scores (p < 0.01). An analysis of variance revealed a significant difference in mean scores in the Psychological and Environment domains according to different socio-economic strata: F (3, 97) = 3.81, p = 0.012 and F (3, 97) = 4.03, p = 0.01, respectively. DISCUSSION: The WHOQOL-BREF questionnaire may be more sensitive than the MQLI in detecting the impact of socioeconomic status on the QoL of postpartum women. CONCLUSION: The sample of postpartum women evaluated in this study presented favorable QoL scores according to both the MQLI and WHOQOL-BREF questionnaires. Our results also indicate that the WHOQOL-BREF and the MQLI questionnaires have a significant correlation in terms of their assessments of postpartum mothers

An assessment of maternal quality of life in the postpartum period in southern Brazil: a comparson of two questionnaires

OBJECTIVES: To assess maternal quality of life (QoL) during the postpartum period and to compare the performance of two QoL questionnaires across a sample of 101 women in southern Brazil. To our knowledge, this is the first study that measures maternal quality of life during the postpartum period in Brazil. INTRODUCTION: There is limited information about postpartum maternal quality of life in Brazil. The are no Portuguese versions of instruments specifically designed to measure quality of life during the postpartum period. METHODS: Research participants completed the Portuguese version of the World Health Organization Quality of Life Assessment-Bref (WHOQOL-BREF) and Multicultural Quality of Life Index (MQLI) questionnaires. The correlations between the MQLI and the discrete areas of WHOQOL-BREF were examined using Pearson Product-Moment Correlation Coefficients. RESULTS: We report a significant correlation between the global MQLI and the four domains of the WHOQOL-BREF scores (p < 0.01). An analysis of variance revealed a significant difference in mean scores in the Psychological and Environment domains according to different socio-economic strata: F (3, 97) = 3.81, p = 0.012 and F (3, 97) = 4.03, p = 0.01, respectively. DISCUSSION: The WHOQOL-BREF questionnaire may be more sensitive than the MQLI in detecting the impact of socioeconomic status on the QoL of postpartum women. CONCLUSION: The sample of postpartum women evaluated in this study presented favorable QoL scores according to both the MQLI and WHOQOL-BREF questionnaires. Our results also indicate that the WHOQOL-BREF and the MQLI questionnaires have a significant correlation in terms of their assessments of postpartum mothers

The Human Splice Variant Δ16HER2 Induces Rapid Tumor Onset in a Reporter Transgenic Mouse

Several transgenic mice models solidly support the hypothesis that HER2 (ERBB2) overexpression or mutation promotes tumorigenesis. Recently, a HER2 splice variant lacking exon-16 (Δ16HER2) has been detected in human breast carcinomas. This alternative protein, a normal byproduct of HER2, has an increased transforming potency compared to wild-type (wt) HER2 receptors. To examine the ability of Δ16HER2 to transform mammary epithelium in vivo and to monitor Δ16HER2-driven tumorigenesis in live mice, we generated and characterized a mouse line that transgenically expresses both human Δ16HER2 and firefly luciferase under the transcriptional control of the MMTV promoter. All the transgenic females developed multifocal mammary tumors with a rapid onset and an average latency of 15.11 weeks. Immunohistochemical analysis revealed the concurrent expression of luciferase and the human Δ16HER2 oncogene only in the mammary gland and in strict correlation with tumor development. Transgenic Δ16HER2 expressed on the tumor cell plasma membrane from spontaneous mammary adenocarcinomas formed constitutively active homodimers able to activate the oncogenic signal transduction pathway mediated through Src kinase. These new transgenic animals demonstrate the ability of the human Δ16HER2 isoform to transform “per se” mammary epithelium in vivo. The high tumor incidence as well as the short latency strongly suggests that the Δ16HER2 splice variant represents the transforming form of the HER2 oncoprotein

Infections in pediatric patients submitted to hepatic transplant

OBJETIVO: Identificar infecções bacterianas, virais e fúngicas nos primeiros 20 pacientes pediátricos submetidos a transplante de fígado no HCPA. PACIENTES E MÉTODOS: 21 transplantes foram realizados em 20 crianças e adolescentes, no período de março de 1995 a setembro de 1997, no HCPA. Todos os transplantes foram de doador cadavérico, do mesmo grupo sangüíneo ABO. Nove transplantes foram de fígado inteiro e 11, de fígado reduzido. O diagnóstico de infecção bacteriana foi feito quando havia evidências clínico-laboratoriais e/ou hemocultura e/ou outros culturais positivos. Os vírus pesquisados foram citomegalo e Epstein Barr. Fungos eram pesquisados através de hemoculturas e culturas de secreções, drenos e coleções, cateteres e urina. RESULTADOS: Dos 20 pacientes transplantados, dois morreram nas primeiras 24-48 horas e apenas quatro não apresentaram infecção e/ou culturais positivos, clinicamente significativos. Quatorze pacientes apresentaram infecção bacteriana, sendo que nove pacientes apresentaram mais do que um episódio infeccioso. Os organismos mais freqüentes foram Staphylococus aureus e epidermidis e Xantomonas maltophilia. Cinco receptores positivaram antigenemia para CMV, sendo que apenas um apresentava sorologia negativa no pré-transplante. Infecção fúngica foi diagnosticada em dois pacientes e um terceiro paciente apresentou cultura do dreno biliar positiva. CONCLUSÕES: Dos 20 pacientes transplantados, quatro foram ao óbito por complicações infecciosas. Um controle cuidadoso e medidas profiláticas e terapêuticas adequadas podem diminuir infecções e suas conseqüências após transplante hepático.OBJECTIVE: To identify bacterial, viral, and fungal infections in the first 20 pediatric patients submitted to liver transplant at Hospital de Clínicas de Porto Alegre. PATIENTS AND METHODS: Twenty-one liver transplants were performed in 20 infant and adolescent patients from March 1995 to September 1997, at Hospital de Clínicas de Porto Alegre. All transplanted organs were taken from deceased donors with the same ABO blood type as the organ transplant recipient. Nine patients received a whole liver transplant, and 11 patients received a reduced liver transplant. Bacterial infection was diagnosed by the existence of clinical and laboratory evidence; and/or by hemoculture; and/or by positive cultures. For the diagnosis of viral infections, patients were examined for Epstein Barr virus and for cytomegalovirus. For the diagnosis of fungal infection, hemocultures and secretion cultures were taken, and patients were also submitted to draining and sample collections, such as urine samples using a catheter. RESULTS: Of the 20 organ transplant recipient patients, two died within the first 24- 48 hours, and only four of the patients did not present any infections and/or positive cultures that were clinically significant. Fourteen patients had bacterial infection, and nine patients had more than one case of infection. The most frequently found organisms were Staphylococus aureus and epidermidis, and Xanthomonas maltophilia. Five transplant recipients were positive for cytomegalovirus antigenemia, and only one of these recipients was seronegative before the transplant. Fungal infection was diagnosed in two patients, and a third patient presented a positive culture of the biliary drain. CONCLUSIONS: Of the 20 liver transplant recipients, four died due to infection complications. By exerting a careful control, and establishing appropriate prophylactic and therapeutic measures, infection and its consequences may be reduced

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17–74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS

Maternal outcomes and risk factors for COVID-19 severity among pregnant women.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease

The bHLH transcription factor SPATULA enables cytokinin signaling, and both activate auxin biosynthesis and transport genes at the medial domain of the gynoecium

[EN] Fruits and seeds are the major food source on earth. Both derive from the gynoecium and, therefore, it is crucial to understand the mechanisms that guide the development of this organ of angiosperm species. In Arabidopsis, the gynoecium is composed of two congenitally fused carpels, where two domains: medial and lateral, can be distinguished. The medial domain includes the carpel margin meristem (CMM) that is key for the production of the internal tissues involved in fertilization, such as septum, ovules, and transmitting tract. Interestingly, the medial domain shows a high cytokinin signaling output, in contrast to the lateral domain, where it is hardly detected. While it is known that cytokinin provides meristematic properties, understanding on the mechanisms that underlie the cytokinin signaling pattern in the young gynoecium is lacking. Moreover, in other tissues, the cytokinin pathway is often connected to the auxin pathway, but we also lack knowledge about these connections in the young gynoecium. Our results reveal that cytokinin signaling, that can provide meristematic properties required for CMM activity and growth, is enabled by the transcription factor SPATULA (SPT) in the medial domain. Meanwhile, cytokinin signaling is confined to the medial domain by the cytokinin response repressor ARABIDOPSIS HISTIDINE PHOSPHOTRANSFERASE 6 (AHP6), and perhaps by ARR16 (a type-A ARR) as well, both present in the lateral domains (presumptive valves) of the developing gynoecia. Moreover, SPT and cytokinin, probably together, promote the expression of the auxin biosynthetic gene TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1 (TAA1) and the gene encoding the auxin efflux transporter PIN-FORMED 3 (PIN3), likely creating auxin drainage important for gynoecium growth. This study provides novel insights in the spatiotemporal determination of the cytokinin signaling pattern and its connection to the auxin pathway in the young gynoecium.IRO, VMZM, HHU and PLS were supported by the Mexican National Council of Science and Technology (CONACyT) with a PhD fellowship (210085, 210100, 243380 and 219883, respectively). Work in the SDF laboratory was financed by the CONACyT grants CB-2012-177739, FC-2015-2/1061, and INFR-2015-253504, and NMM by the CONACyT grant CB-2011-165986. SDF, CF and LC acknowledge the support of the European Union FP7-PEOPLE-2009-IRSES project EVOCODE (grant no. 247587) and H2020-MSCARISE-2015 project ExpoSEED (grant no. 691109). SDF also acknowledges the Marine Biological Laboratory (MBL) in Woods Hole for a scholarship for the Gene Regulatory Networks for Development Course 2015 (GERN2015). IE acknowledges the International European Fellowship-METMADS project and the Universita degli Studi di Milano (RTD-A; 2016). Research in the laboratory of MFY was funded by NSF (grant IOS-1121055), NIH (grant 1R01GM112976-01A1) and the Paul D. Saltman Endowed Chair in Science Education (MFY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Reyes Olalde, J.; Zuñiga, V.; Serwatowska, J.; Chávez Montes, R.; Lozano-Sotomayor, P.; Herrera-Ubaldo, H.; Gonzalez Aguilera, K.... (2017). The bHLH transcription factor SPATULA enables cytokinin signaling, and both activate auxin biosynthesis and transport genes at the medial domain of the gynoecium. PLoS Genetics. 13(4):1-31. https://doi.org/10.1371/journal.pgen.1006726S131134Reyes-Olalde, J. I., Zuñiga-Mayo, V. M., Chávez Montes, R. A., Marsch-Martínez, N., & de Folter, S. (2013). Inside the gynoecium: at the carpel margin. Trends in Plant Science, 18(11), 644-655. doi:10.1016/j.tplants.2013.08.002Alvarez-Buylla, E. 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Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes