Antibiotics for pre-term pre-labour rupture of membranes: prevention of neonatal deaths due to complications of pre-term birth and infection

Background In high-income countries, it is standard practice to give antibiotics to women with pre-term, pre-labour rupture of membranes (pPROM) to delay birth and reduce the risk of infection. In low and middle-income settings, where some 2 million neonatal deaths occur annually due to complications of pre-term birth or infection, many women do not receive antibiotic therapy for pPROM

Human Hereditary Cardiomyopathy Shares a Genetic Substrate With Bicuspid Aortic Valve.

The complex genetics underlying human cardiac disease is evidenced by its heterogenous manifestation, multigenic basis, and sporadic occurrence. These features have hampered disease modeling and mechanistic understanding. Here, we show that 2 structural cardiac diseases, left ventricular noncompaction (LVNC) and bicuspid aortic valve, can be caused by a set of inherited heterozygous gene mutations affecting the NOTCH ligand regulator MIB1 (MINDBOMB1) and cosegregating genes. We used CRISPR-Cas9 gene editing to generate mice harboring a nonsense or a missense MIB1 mutation that are both found in LVNC families. We also generated mice separately carrying these MIB1 mutations plus 5 additional cosegregating variants in the ASXL3, APCDD1, TMX3, CEP192, and BCL7A genes identified in these LVNC families by whole exome sequencing. Histological, developmental, and functional analyses of these mouse models were carried out by echocardiography and cardiac magnetic resonance imaging, together with gene expression profiling by RNA sequencing of both selected engineered mouse models and human induced pluripotent stem cell-derived cardiomyocytes. Potential biochemical interactions were assayed in vitro by coimmunoprecipitation and Western blot. Mice homozygous for the MIB1 nonsense mutation did not survive, and the mutation caused LVNC only in heteroallelic combination with a conditional allele inactivated in the myocardium. The heterozygous MIB1 missense allele leads to bicuspid aortic valve in a NOTCH-sensitized genetic background. These data suggest that development of LVNC is influenced by genetic modifiers present in affected families, whereas valve defects are highly sensitive to NOTCH haploinsufficiency. Whole exome sequencing of LVNC families revealed single-nucleotide gene variants of ASXL3, APCDD1, TMX3, CEP192, and BCL7A cosegregating with the MIB1 mutations and LVNC. In experiments with mice harboring the orthologous variants on the corresponding Mib1 backgrounds, triple heterozygous Mib1 Apcdd1 Asxl3 mice showed LVNC, whereas quadruple heterozygous Mib1 Cep192 Tmx3;Bcl7a mice developed bicuspid aortic valve and other valve-associated defects. Biochemical analysis suggested interactions between CEP192, BCL7A, and NOTCH. Gene expression profiling of mutant mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes revealed increased cardiomyocyte proliferation and defective morphological and metabolic maturation. These findings reveal a shared genetic substrate underlying LVNC and bicuspid aortic valve in which MIB1-NOTCH variants plays a crucial role in heterozygous combination with cosegregating genetic modifiers.This study was supported by grants PID2019-104776RB-I00 and PID2020-120326RB-I00, CB16/11/00399 (CIBER CV) financed by MCIN/AEI/10.13039/501100011033, a grant from the Fundación BBVA (Ref. BIO14_298), and a grant from Fundació La Marató de TV3 (Ref. 20153431) to J.L.d.l.P. M.S.-A. was supported by a PhD contract from the Severo Ochoa Predoctor-al Program (SVP-2014-068723) of the MCIN/AEI/10.13039/501100011033. J.R.G.-B. was supported by SEC/FEC-INV-BAS 21/021. A.R. was funded by grants from MCIN (PID2021123925OB-I00), TerCel (RD16/0011/0024), AGAUR (2017-SGR-899), and Fundació La Marató de TV3 (201534-30). J.M.P.-P. was supported by RTI2018-095410-B-I00 (MCIN) and PY2000443 (Junta de Andalucía). B.I. was supported by the European Commission (H2020-HEALTH grant No. 945118) and by MCIN (PID2019-107332RB-I00). DO’R was sup-ported by the Medical Research Council (MC-A658-5QEB0) and KAMcG by the British Heart Foundation (RG/19/6/34387, RE/18/4/34215). The cost of this publication was supported in part with funds from the European Regional Devel-opment Fund. The Centro Nacional de Investigaciones Cardiovasculares is sup-ported by the ISCIII, the MCIN, and the Pro Centro Nacional de Investigaciones Cardiovasculares Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020001041-S) financed by MCIN/AEI/10.13039/501100011033. For the purpose of open access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising.S

Optimization of enzymatic protein hydrolysis conditions of okara with endopeptidase alcalase

The production of soymilk and tofu results in an insoluble residue called okara that present 23% of soybean protein. The objective of this study was to optimize the protein hydrolysis conditions of okara with Alcalase@ endopeptidase. A central composite rotational design was carried out to evaluate the influence of enzymatic reaction temperature (40 - 70°C), enzyme:substrate ratio (1.0 - 10.0%, g enzyme/100 g protein) and pH (7.0 - 9.0) on the degree of hydrolysis (DH). Kinetic of reaction curves (DH versus time) were characterized by high initial reaction rates followed by decreases in the reaction rate up to the stationary phase. By the response surface methodology, the process of hydrolysis was optimized in order to get higher values of DH. The results showed a quadratic dependence of DH in respect to all independent variables. The optimum condition of enzymatic hydrolysis was 55°C, enzyme:substrate ratio of 8.8% and pH 9.0. Under this condition, a experimental DH of 37.3% was obtained and the predicted model was validated. In addition, the pretreatment of okara using ultrasound was evaluated, aiming to increase the DH. There was significant difference (p < 0.1) on DH value (38.8%) obtained at optimum condition, increasing 4%24310671074CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO ARAUCÁRIA DE APOIO AO DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO DO ESTADO DO PARANÁ - FA473117/2013- 4160/201

IQGAP1 regulates ERK1/2 and AKT signalling in the heart and sustains functional remodelling upon pressure overload

The Raf-MEK1/2-ERK1/2 (ERK1/2-extracellular signal-regulated kinases 1/2) signalling cascade is crucial in triggering cardiac responses to different stress stimuli. Scaffold proteins are key elements in coordinating signalling molecules for their appropriate spatiotemporal activation. Here, we investigated the role of IQ motif-containing GTPase-activating protein 1 (IQGAP1), a scaffold for the ERK1/2 cascade, in heart function and remodelling in response to pressure overload. IQGAP1-null mice have unaltered basal heart function. When subjected to pressure overload, IQGAP1-null mice initially develop a compensatory hypertrophy indistinguishable from that of wild-type (WT) mice. However, upon a prolonged stimulus, the hypertrophic response develops towards a thinning of left ventricular walls, chamber dilation, and a decrease in contractility, in an accelerated fashion compared with WT mice. This unfavourable cardiac remodelling is characterized by blunted reactivation of the foetal gene programme, impaired cardiomyocyte hypertrophy, and increased cardiomyocyte apoptosis. Analysis of signalling pathways revealed two temporally distinct waves of both ERK1/2 and AKT phosphorylation peaking, respectively, at 10 min and 4 days after aortic banding in WT hearts. IQGAP1-null mice show strongly impaired phosphorylation of MEK1/2-ERK1/2 and AKT following 4 days of pressure overload, but normal activation of these kinases after 10 min. Pull-down experiments indicated that IQGAP1 is able to bind the three components of the ERK cascade, namely c-Raf, MEK1/2, and ERK1/2, as well as AKT in the heart. These data demonstrate, for the first time, a key role for the scaffold protein IQGAP1 in integrating hypertrophy and survival signals in the heart and regulating long-term left ventricle remodelling upon pressure overload

The mammalian CHORD-containing protein melusin is a stress response protein interacting with Hsp90 and Sgt1.

Melusin is a mammalian muscle specific CHORD containing protein capable of activating signal transduction pathways leading to cardiomyocytes hypertrophy in response to mechanical stress. To define melusin function we searched for molecular partners possibly involved in melusin dependent signal transduction. Here we show that melusin and heat shock proteins are co-regulated. Moreover, melusin directly binds to Hsp90, a ubiquitous chaperone involved in regulating several signaling pathways. In addition, melusin interacts with Sgt1, an Hsp90 binding molecule. Melusin does not behave as an Hsp90 substrate but rather as a chaperone capable to protect citrate synthase from heat induced aggregation. These results describe melusin as a new component of the Hsp90 chaperone machinery

O sentido da sexualidade de mulheres submetidas a histerectomia: uma contribuição da enfermagem para a integralidade da assistência ginecológica

A histerectomia é um procedimento cirúrgico irreversível, realizado por indicação médica, com a finalidade de restabelecer a saúde ou mesmo salvar a vida da mulher. Ser submetida a esta cirurgia acarreta modificações em seu cotidiano porque as recomendações pertinentes ao pós-operatório de histerectomia impõem implicações em seu mundo-vida. Este estudo de natureza qualitativa teve como objetivo analisar o sentido da sexualidade de mulheres após a histerectomia à luz do pensamento de Martin Heidegger. Foram depoentes 25 mulheres submetidas à retirada total do útero; a entrevista fenomenológica ocorreu num tempo variado, de 4 a 19 meses após o procedimento cirúrgico. A interpretação da estrutura de significação "a atividade sexual foi considerada" desvelou que na dinâmica assistencial, médica e de enfermagem, as rotineiras orientações de abstinência sexual determinadas pelo pós-operatório devem ser consideradas a partir da subjetividade da mulher que será/foi submetida à histerectomia.La histerectomia es un procedimiento quirúrgico irreversible realizado por indicación médica con la finalidad de restablecer la salud o mismo salvar la vida de la mujer. Ser sometida a esta cirurgía acarrea modificaciones en su cotidiano porque las recomendaciones para después de una operación de histerectomia imponen implicaciones en su mundo-vida. Este estudio de naturaleza cualitativa tuvo como objetivo analizar el sentido de la sexualidad de mujeres tras la histerectomia a la luz del pensamiento de Martin Heidegger. Fueron oídas 25 mujeres sometidas a la retirada total de útero siendo que la encuesta fenomenológica ocurrió en un tiempo entre cuatro y diecinueve meses tras el procedimiento quirúrgico. La interpretación de la estructura de la significación "la actividad sexual fue considerada" enseñó que en la dinámica asistencial médica y de enfermería, las orientaciones de rutina de abstinencia sexual determinada por el periodo que sigue a la operación deben ser consideradas a partir de la subjetividad de la mujer que será/fue sometida a histerectomiaHisterectomy is a irreversible surgical procedure carried through by medical indication with the purpose to reestablish the health or even to save the woman´s life. To be submitted to this surgery causes modifications at woman´s daily life because the pertinent recommendations to the Histerectomy post operative impose implications in her world-life. This qualitative study had as object to analyze the meaning of women's sexuality after Histerectomy, supported by Martin Heidegger´s thoughts. The informants were 25 women submitted to a total withdrawal of the uterus between nineteen to four months before the data collection. The interpretation of the meaning structure "sexual activity was considered", showed that in the medical and nursing assistential dynamics the routine orientations of sexual abstinence determined by the post operative must be considered from the subjectivity of the woman who will /was submitted to the Histerectomy