A Prospective Cohort Study Investigating Adverse Perinatal Outcomes in Mosul, Iraq, among Women with Grand Multiparity

@#Introduction: This prospective case-control study aimed to compare the incidence of fetomaternal complications between grand multiparous women under the age of 35 and pregnant women with low parity in the same age group. Methods: The study was conducted at Al-khansaa and Al-Batool Teaching Hospitals from October 1, 2020, to June 1, 2021. One hundred pregnant women with singleton pregnancies in all three trimesters, aged between 18 and 34 years, were selected from the outpatient clinic and the ward. The participants were divided into two groups: Group A consisted of 50 grand multiparous women (with five or more deliveries), and Group B comprised 50 pregnant women with low parity (2-4 pregnancies) in the same age group. Results: The study found that gestational diabetes, anemia, meconium-stained amniotic fluid, cesarean section rate, postpartum hemorrhage, and neonatal intensive care unit admissions were significantly higher in the grand multiparity group compared to the low parity group. The mean Apgar scores at 1 and 5 minutes were significantly lower in Group A compared to Group B. Conclusion: The findings suggest that grand multiparity among younger mothers poses additional risks to pregnancy outcomes, including increased rates of gestational diabetes, anemia, postpartum hemorrhage, cesarean section, and neonatal intensive care unit admissions, especially in cases with inadequate antenatal care. The findings of this study underscore the need for further research in this area. Understanding the underlying mechanisms and risk factors associated with grand multiparity among younger mothers can lead to more targeted interventions and improved outcomes.

COVID-19 impact on newly initiated and restarted antiretroviral treatment patients in the Eastern Cape, South Africa

Background: Initiating newly diagnosed people living with human immunodeficiency virus (HIV) onto antiretroviral treatment (ART) and retaining patients on treatment are vital to South Africa's ART programme. In 2020, coronavirus disease 2019 (COVID-19) and its accompanying containment (lockdown) measures presented unprecedented challenges to achieving these objectives. Aim: This study describes the impact of COVID-19 and related restrictions on district-level numbers of newly diagnosed people living with HIV and defaulting ART patients. Setting: Buffalo City Metropolitan Municipality (BCMM) in the Eastern Cape of South Africa. Methods: Mixed-methods approach: Monthly aggregated electronic patient data (newly initiated and restarted on ART) from 113 public healthcare (PHC) facilities were analysed (December 2019 to November 2020) across varying levels of COVID-19 lockdown regulation periods; telephonic in-depth interviews at 10 rural BCMM PHC facilities were conducted with facility staff, community health workers (CHWs) and intervention personnel. Results: The number of newly initiated ART patients decreased dramatically compared with pre-COVID-19 levels. The overall number of restarted ART patients increased in response to fears of co-infection with COVID-19. Facility-level communications and community outreach promoting HIV testing and treatment were disrupted. Novel approaches to providing services to ART patients were developed. Conclusion: Programmes for identifying undiagnosed people living with HIV and services aimed at retaining ART patients in care were profoundly impacted by COVID-19. The value of CHWs was highlighted, as were communication innovations. Contribution: This study describes the impact of COVID-19 and related regulations on HIV testing, ART initiation and adherence to treatment in a District of the Eastern Cape of South Africa.

Alteração na representação de subpopulações de neurônios no epitélio olfatório de camundongos Ric8b cKO / Altered representation of neuronal sub-populations in the olfactory epithelium of Ric8b conditional knock-out mice

O objetivo desse trabalho foi identificar as consequências moleculares e funcionais da falta da proteína Ric8b no epitélio olfatório de camundongos. Para esse fim, comparamos o transcriptoma de epitélio olfatório de camundongos knock-out tecido específico para a proteína RIC8B (Ric8b cKO) com o dos seus irmãos tipo selvagem (WT). Identificamos muitos genes que apresentaram expressão reduzida no epitélio olfatório do camundongo Ric8b cKO, mas também vários genes que apresentaram a sua expressão aumentada. A maioria dos genes com expressão reduzida corresponde a genes normalmente expressos em neurônios olfatórios maduros, como por exemplo os genes de receptores olfatórios, o que é compatível com o fato já conhecido de que os camundongos Ric8b cKO apresentam um menor número desses neurônios. Inesperadamente, apesar de a maioria dos genes de receptores olfatórios ter a sua expressão diminuída no camundongo Ric8b cKO, observamos que um grupo destes genes de receptores teve a sua expressão aumentada. Os camundongos Ric8b cKO apresentaram também genes marcadores de outros tipos celulares que não neurônios canônicos com expressão aumentada no seu epitélio olfatório. Dentre eles, os mais significativamente alterados foram os genes marcadores de neurônios Trpc2+ tipo B (que expressam a guanilato ciclase solúvel Gucy1b2). Sabe-se que este tipo de neurônio é responsável pela sensibilidade a diferentes gases, e concordantemente, observamos que os camundongos Ric8b cKO apresentaram um aumento da sensibilidade a gás carbônico. Como o olfato apresenta um papel importante na regulação de ingestão alimentar, analisamos como os camundongos Ric8b cKO se comportam frente a diferentes dietas. Interessantemente, observamos que esses animais não apresentam preferência por alimento rico em gorduras quando comparado aos seus irmãos tipo selvagem. Nossos resultados sugerem, portanto, que a ausência da proteína RIC8B resulta na alteração de representatividade de neurônios canônicos e não canônicos no epitélio olfatório de camundongos, o que por sua vez leva a alterações funcionais e comportamentais

The objective of this work was to identify the molecular and functional consequences of the lack of the RIC8B protein in the main olfactory epithelium of mice. To this end, we compared the olfactory epithelium transcriptome of Ric8b tissue-specific knock-out mice (Ric8b cKO) with that of their wild-type littermates (WT). We identified many genes with differential expression, many of which were downregulated and also some which were upregulated in the olfactory epithelium of the Ric8b cKO mice. Most of the downregulated genes correspond to genes normally expressed in mature olfactory sensory neurons, such as olfactory receptor genes. This is compatible with the already known fact that the Ric8b cKO mice have less of this kind of neuron. Unexpectedly, even though most of the olfactory receptor genes were downregulated, we observed a subset of these genes that had their expression upregulated in the Ric8b cKO mice. The Ric8b cKO mice also showed upregulation for genes that are markers for cell types other than canonic neurons in their olfactory epithelium. Among these, the most significantly altered were the markers for neurons Trpc2+ type B (that express the soluble guanylate cyclase Gucy1b2). It is known that this kind of neuron is responsible for sensitivity to different gases. Accordingly, we observed that the Ric8b cKO mice presented a higher sensitivity to carbon dioxide. Since olfaction has an important role in food intake, we analyzed how the Ric8b cKO mice behaved with different diets. Interestingly, we observed that the Ric8b cKO mice lack preference for high fat diet when compared to their wild-type littermates. Our results indicate, therefore, that the lack of the RIC8B protein results in altered representativity of canonic and non-canonic neurons in the olfactory epithelium of mice, which then leads to altered function and behavior

Exploring factors affecting anther culture in rice (Oryza sativa L.)

Anther culture is an important in vitro culture technique for the production of double haploids. It is largely speciesand genotype specific. Asian-cultivated rice (Oryza sativa, ssp. indica) is recalcitrant to anther culture which limits itspractical application in rice breeding. Several researchers tried to optimize the medium recipes and culture techniquesfor callus induction and plantlet regeneration. Negligible response to callus induction and recovery of a higherfrequency of albino plants are the major hindrance for the use of the technique in crop improvement. Shortening theculture period and sexual hybridization of rice subgroups (japonica/indica) may be adopted to improve green plantregeneration from anther-derived callus in indica rice. However, genetic transformation technology using individualgenes related to different aspects of anther culture could be a more direct approach. Besides, the role of genotypes,physiological status of donor plant, developmental stage of pollen, pre-treatment, culture media, phytohormones, andculture conditions for successful anther culture have been discussed.

RIC-8B, uma GEF de sistema olfatório, é essencial para o desenvolvimento do sistema nervoso / RIC-8B, an olfactory GEF, is essential for the development of the nervous system

RIC-8B é um fator trocador de nucleotídeo de guanina (GEF) predominantemente expresso em neurônios olfatórios maduros de camundongos adultos. Trabalhos desenvolvidos em nosso laboratório mostraram que RIC-8B interage com Gαolf e Gγ13, duas subunidades de proteína G que estão enriquecidas nos cílios dos neurônios olfatórios, onde participam da transdução do sinal de odorantes. In vitro, RIC-8B é capaz de amplificar a sinalização de receptores olfatórios através de Gαolf, no entanto, seu papel fisiológico ainda é desconhecido. Para determinar a função desempenhada por essa proteína in vivo, nós utilizamos a tecnologia de Gene Trap com o objetivo de produzir um camundongo knockout para Ric-8B. Apesar de a expressão de Ric-8B ser restrita a poucos tecidos no camundongo adulto, descobrimos que homozigotos para a mutação em Ric-8B são inviáveis e morrem por volta do dia embrionário E10,5. Além disso, são menores e apresentam evidente falha no fechamento do tubo neural na região cranial (exencefalia). Utilizamos o gene repórter ß-galactosidase expresso pelo alelo mutado para determinar o padrão de expressão de Ric-8B em embriões durante o desenvolvimento. Observamos que, no estágio E8,5, Ric-8B é expresso nas pregas neurais da região cefálica e na notocorda. De E9,5 a E12,5, a expressão de Ric-8B é detectada predominante no assoalho da placa. Esse padrão de expressão se assemelha ao de outro gene importante para a embriogênese, Sonic hedgehog (Shh). SHH é um morfógeno diretamente responsável pela padronização dorsoventral do sistema nervoso central e sua sinalização depende de cílio primário. Cílio primário é uma organela baseada em microtúbulos que se projeta da superfície da maioria das células de mamíferos e funciona como um centro de sinalização intracelular. Nossos dados mostram que fibroblastos embrionários Ric-8B-/- formam cílios primários, assim como alguns tecidos do embrião. Além disso, não encontramos alterações na sinalização de Shh em embriões homozigotos mutantes. No entanto, observamos que esses embriões apresentam apoptose aumentada em células migratórias da crista neural cranial. Shh é importante para a sobrevivência de células da crista neural migratória, sugerindo um possível papel para Ric-8B a downstream da sinalização de SHH

Ric-8B is a guanine nucleotide exchange factor (GEF) which is predominantly expressed in mature olfactory sensory neurons in adult mice. We have previously shown that RIC-8B interacts with both Gαolf and Gγ13, two G protein subunits, which are enriched in olfactory cilia and are required for odorant signal transduction. In vitro, RIC-8B is able to amplify odorant receptor signaling through Gαolf, however, its physiological role remains unknown. To determine the role played by RIC-8B in vivo we used the Gene trap technology to generate a Ric-8B knockout mouse. We found that, despite the limited distribution of Ric-8B gene expression in adult mice, Ric-8B homozygous mutants are not viable and die around the E10,5 stage. Mutant embryos are also smaller and fail to close the neural tube at the cranial region (exencephaly). We used the activity of the ß-galactosidase reporter gene to determine the pattern of expression of the Ric-8B gene in heterozygous embryos. At E8,5 the Ric-8B gene is expressed in the notochord and neural folds of the cephalic regions. From E9,5 to E12,5 Ric-8B is predominantly expressed in the floor plate, in a pattern that strongly resembles the one shown by Sonic hedgehog (Shh). SHH is a morphogen directly responsible for the dorsoventral patterning of the central nervous system and its signaling depends on primary cilia. Primary cilia are microtubule-based organelles that protrude from the surface of mammalian cells and act as a signaling center. We show that Ric-8B-/- embryonic fibroblasts and some embryonic tissues grow primary cilia normally. In addition, we did not find alterations in the SHH signaling of homozygous mutants. Instead, we found an increased apopotosis in migratory cells of the cranial neural crest in these embryos. Shh is an important factor to survival of neural crest cells, suggesting a role for RIC-8B downstream of the SHH signaling

RIC-8B, um fator trocador de nucleotídeo guanina (GEF), é essencial para a embriogênese / RIC-8B, a guanine nucleotide exchange factor (GEF), is essential for embryogenesisPalavras-chave em inglês Cilia

RIC-8B é uma proteína que apresenta, in vitro, atividade de fator de troca de nucleotídeos guanina (GEF). No entanto, seu papel in vivo não é conhecido. Dados anteriores do nosso laboratório demonstraram que essa proteína interage especificamente com Gαolf, que é uma proteína G exclusiva do sistema olfatório, presente nos cílios dos neurônios olfatórios, onde ocorre a transdução de sinal ativada pelos odorantes. No camundongo adulto verificou-se, por meio de ensaios de hibridização in situ, que RIC-8B está presente somente em regiões de expressão de Gαolf: no epitélio olfatório maduro e no núcleo estriado do sistema nervoso central. Para avaliar a função fisiológica de RIC-8B in vivo, resolvemos gerar uma linhagem de camundongo knockout para Ric-8B. Verificamos que a linhagem é inviável devido à letalidade dos embriões já em fases precoces do desenvolvimento (por volta de E8,5 e E9,0). A coloração de embriões com X-gal mostra que RIC-8B é especificamente expressa em regiões que darão origem ao sistema nervoso, como na região ventral do tubo neural, e em regiões cefálicas. Interessantemente, mostramos que RIC-8B é expressa na placa do assoalho do tubo neural, de uma maneira muito semelhante ao padrão de expressão de Sonic Hedgehog (SHH), que apresenta um papel fundamental para a organização do sistema nervoso, entre outras funções. Nossos resultados indicam, portanto, que RIC-8B desempenha um papel crucial durante a embriogênese, e que este papel pode estar relacionado com o papel exercido por SHH. Além disso, como a via de sinalização de SHH ocorre em cílios primários nas células alvo, nossos dados levantam a interessante possibilidade de que RIC-8B apresenta funções relacionadas a cílios, tanto no camundongo adulto (neste caso nos cílios dos neurônios olfatórios) como no embrião (neste caso nos cílios primários)

RIC-8B is a protein that, in vitro, acts as a guanine nucleotide exchange factor (GEF). However, its role in vivo remains unknown. Previous data from our laboratory demonstrated that this protein is able to interact specifically with Gαolf, a G protein found only in the olfactory system. This G protein is located in the cilia from olfactory neurons, where odorant signaling occurs. In situ hybridization experiments showed that RIC-8B, in adult mice, is expressed only in regions where Gαolf is expressed, such as the olfactory epithelium and the nucleus striatum in the central nervous system. In order to determine the function of RIC-8B in vivo, we decided to generate a knockout mouse strain for Ric-8B. We found that this strain is not viable due to the lethality of embryos in the early stages of development (around days E8.5 and E9.0). X-gal staining of embryos shows that RIC-8B is specifically expressed in regions that originate the nervous system, such as the ventral neural tube and also cephalic regions. Interestingly, we show that RIC-8B is restrictedly expressed in the floor plate of the neural tube, in a pattern that is very similar to the one shown by Sonic Hedgehog (SHH). The SHH protein plays a fundamental role in the organization of the nervous system, among other functions. Therefore, our results indicate that RIC-8B plays an essential role during the embryogenesis, and that this role can be related to the role played by SHH. Furthermore, because the SHH signaling pathway occurs in primary cilia in the target cells, our data raise the interesting possibility that the role played by RIC-8B is related to ciliary functions, both in adult mice (in this case, in olfactory cilia), and in the embryo (in this case, in primary cilia)

The Odorant Signaling Pathway

Through the sense of smell mammals can obtain information about food, danger, sexual partners and predators. Two main different types of signals can be recognized by the olfactory system: volatile odorants, which are detected by the olfactory sensory neurons of the nose; and pheromones, which are detected by the vomeronasal neurons of the accessory olfactory system, or vomeronasal organ. These sensory neurons express respectively hundreds of odorant and pheromone receptors, which belong to the superfamily of G protein-coupled receptors. We review the general organization of the main and accessory olfactory systems, the structures of the receptor families in each of these organs and their signaling pathways.

The action of Shuganwan on experimental gastric ulcer / 西安交通大学学报(医学版)

Objective To study the action of Shuganwan(SHGW) on experimental gastric ulcer in mice. Methods The anti-ga stric ulcer action of SHGW was observed on the gastric ulcer induced by water im mersion stress, reserpine and absolute ethyl alcohol. The effect on gastric secr etion in rats was studied by pyloric ligation. The effect on gastrointestinal mo tility was observed by gastric emptying in mice. The analgesic effect was tested by the hot-plate test and writhing method. Results SHGW m arkedly inhibited gastric ulcer induced by water immersion stress, reserpine and absolute ethyl alcohol. SHGW significantly inhibited the secretion of gastric a cid and pepsin and promoted the secretion of gastric mucus. SHGW markedly delaye d gastric emptying in normal mice and when gastric emptying was stimulated by ne ostigmine. SHGW mildly strengthend the effect of atropine on gastric emptying. S HGW enhanced hot pain threshold and decreased the number of twisting body in mic e. Conclusion Shuganwan may have anti-gastric ulcer ac tion. The mechanism of the action might be associated with its inhibition of the secretion of gastric juice, promotion of the secretion of gastric mucus,inhibit ion of activity of gastric smooth muscle and analgetic effect.