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INTRODUCTION: The aim of this study was to compare the effectiveness of a combined misoprostol-Foley catheter induction of labor protocol against the current guidelines of our department. MATERIAL AND METHODS: A randomized trial was conducted comparing two cervical ripening study groups: combined misoprostol-cervical Foley and the current department practice (misoprostol alone or dinoprostone alone). Women were stratified randomly according to parity for the two intervention groups. The primary outcome was defined as time to delivery (in hours). Secondary outcomes were cesarean delivery rate, time to active labor (defined as dilatation 6 cm or greater), delivery within 12 h, delivery within 24 h, maternal length of stay and indication for cesarean delivery. A composite of maternal morbidity and neonatal morbidity were also analyzed. RESULTS: 142 women were randomized into one of the two groups (74 for treatment group and 68 for control group). Demographic and clinical characteristics were similar among the two groups. The primary outcome, the average time to delivery, was faster in the treatment group (22.7 h vs 27.2 h, p = 0.03) and this difference was higher in the nulliparous subgroup (24.2 h vs 29.2 h, p = 0.03). Active phase of labor was achieved faster in the treatment group (17.9 h vs 22.7 h, p = 0.008). The risk for cesarean section was similar in both groups (OR 0.801 (0.527-1.217) vs OR 1.203 (0.871-1.662), p = 0.278). CONCLUSIONS: Our study suggests that the combined method of cervical Foley with vaginal misoprostol for women presenting to induction of labor with unfavorable Bishop scores reduces time to delivery safely. The risk for cesarean section was similar in both groups.
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Misoprostol , Oxitócicos , Recién Nacido , Embarazo , Femenino , Humanos , Cesárea , Trabajo de Parto Inducido/métodos , DinoprostonaRESUMEN
OBJECTIVE: The aim of the study was to evaluate risk factors for positive margins on surgical specimens of patients submitted to transformation zone excision (TZE). MATERIALS AND METHODS: We conducted a retrospective study evaluating women submitted to TZE in our center, between 2012 and 2020. Our study population included only women with the diagnosis of high-grade intraepithelial lesion (HSIL) in the pathologic examination of the TZE surgical specimen. Positive margins were defined as the presence of HSIL in the endocervical and/or ectocervical margin of the specimen. Factors evaluated included demographic characteristics, pretreatment Pap smear and human papillomavirus test, colposcopic findings, TZE indication, and pathologic features of the surgical specimen. We performed univariate analysis and logistic regression modeling including variables associated with the outcome of positive margins in the univariate analysis. RESULTS: Our sample included 264 women, with a 15.2% positive margins rate (40 patients). In the univariate analysis, patients with immunocompromised status, HSIL Pap smear, and higher number of quadrants involved in colposcopic examination were more likely to have positive margins. After multivariate analysis, only immunocompromised status was found to be an independent risk factor (odds ratio = 4.94; 95% CI = 1.43-17.15; p < .05). CONCLUSIONS: Immunocompromised status was the sole significant predictor for positive margins in TZE surgical specimens. To our knowledge, this is the first report of immunodepression as a risk factor for positive margins in cervical excisional procedures.
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Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Electrocirugia/métodos , Femenino , Humanos , Márgenes de Escisión , Estudios Retrospectivos , Factores de Riesgo , Neoplasias del Cuello Uterino/diagnóstico , Displasia del Cuello del Útero/patologíaRESUMEN
OBJECTIVE: The aim of the study was to assess the risk of vulvar cancer and precursors in a cohort of women with vulvar lichen planus (LP) and the clinical and therapeutic features of these patients. MATERIALS AND METHODS: A retrospective cohort study, including all the women with the diagnosis of vulvar LP, followed in one institution during a period of 11 years, was performed. Demographic and clinical data, as well as treatment, follow-up, and histology results, were evaluated. RESULTS: A total of 127 women were diagnosed with vulvar LP. The mean follow-up time was 3.9 ± 0.5 years (range = 1-11 years). Ultrapotent topical corticosteroids were first-line treatment in 91.8% (n = 112), with 32 cases (25.2%) needing an alternative treatment. Overall, 30 biopsies were performed in 19 women (15%). Vulvar high-grade squamous intraepithelial lesion was diagnosed in 3 women (2.4%), 2 (1.6%) of whom were later diagnosed with vulvar squamous cell carcinoma. No cases of differentiated vulvar intraepithelial neoplasia were observed. CONCLUSIONS: Premalignant/malignant transformation in women with vulvar LP under surveillance and compliant with treatment is low. A close follow-up seems to be crucial to prevent future malignancy. Biopsies should be performed whenever a suspicious lesion seems during follow-up.
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Transformación Celular Neoplásica/patología , Liquen Plano/patología , Vulva/patología , Neoplasias de la Vulva/patología , Corticoesteroides/uso terapéutico , Anciano , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Liquen Plano/tratamiento farmacológico , Liquen Plano/epidemiología , Persona de Mediana Edad , Portugal , Estudios Retrospectivos , Factores de RiesgoRESUMEN
We report the first cesarean delivery in a woman with COVID-19 in a level III hospital in Portugal. It refers to a healthy woman with a term pregnancy that tested positive for COVID-19 on the day of labor induction. Given a Bishop score < 4 and the prior history of a cesarean section, the team decided to perform a surgical delivery. Appropriate personal protective equipment and safety circuits were employed, as described in more detail in the case report. Both the mother and the newborn are well. With this report we aimed to share our concerns, clinical management, maternal and neonatal outcomes, and to present our current circuits and adjustments regarding the COVID-19 pandemic in our maternity hospital.
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Cesárea , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Complicaciones Infecciosas del Embarazo , Adulto , COVID-19 , Infecciones por Coronavirus/terapia , Femenino , Humanos , Recién Nacido , Neumonía Viral/terapia , Portugal , Embarazo , Complicaciones Infecciosas del Embarazo/terapia , Resultado del EmbarazoRESUMEN
Objective: The aim of this study was to describe the effect of obesity on the duration of labor, specifically latent and active phases of labor, and on mode of delivery, among nulliparous women with epidural analgesia.Study design: We conducted a retrospective cohort study, comparing a sample of nulliparous obese women (body mass index ≥30 kg/m2, n = 121) with a random sample of normal weight nulliparous (18.5 kg/m2 ≤body mass index ≤25 kg/m2, n = 161). Analysis included all obese women delivered at the Department of Obstetrics and Gynecology of Centro Hospitalar, São João, Porto, Portugal between 1 January and 31 December, 2016. Only women submitted to epidural analgesia were included. Information on maternal age, obstetric history, current pregnancy and labor characteristics (gestational age, birthweight, mode of delivery, total duration of labor, latent and active phases duration) was retrieved from electronic obstetrical databases and labor charts.Results: In our department, the prevalence of maternal obesity was 12.0%. Obese women had a significantly higher rate of cesarean delivery (47.1 versus 27.3%), fewer normal vaginal deliveries (28.9 versus 32.9%) and fewer instrumental vaginal deliveries (24.0 versus 39.8%). Labor induction was significantly more frequent among obese women (51.2 versus 29.2%; p = 0.001). The median (interquartile range) for length of latent phase when labor was induced with prostaglandins in the obese group was 23.3 hours (20.9). This was significantly longer than in normal weight women -15.6 hours (13.15) (p = 0.001). However, there was no significant difference in latent phase duration when labor was induced with oxytocin (12.4 versus 9.4 hours; p = 0.150). The medians (interquartile range) for length of latent phase in spontaneous delivery -6.5 hours (6.8) versus 6.6 hours (6.5) did not differ (p = 0.992). The duration of active phase was not significantly different between obese and normal weight (5.1 versus 5.1 hours; p = 0.784). For spontaneous labor, there was no difference between the two groups in the total duration of labor (11.9 versus 11.3 hours; p = 0.573). But for induced labor, the total duration was significantly higher among obese women (31.1 versus 21.4 hours; p = 0.001).Conclusion: Latent phase was longer in obese than normal weight women undergoing labor induction with prostaglandins. Obesity had no effect on duration of active phase. Obese women undergoing labor induction had a longer total duration of labor, compared to normal weight women mainly due to prolonged latent phase.
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Primer Periodo del Trabajo de Parto , Obesidad Materna/epidemiología , Adulto , Analgesia Epidural/efectos adversos , Analgesia Epidural/estadística & datos numéricos , Estudios de Casos y Controles , Cesárea/estadística & datos numéricos , Bases de Datos Factuales , Femenino , Humanos , Trabajo de Parto Inducido/métodos , Obesidad Materna/complicaciones , Embarazo , Estudios Retrospectivos , Factores de TiempoRESUMEN
Damage-associated molecular patterns (DAMPs) are molecules exposed or released by dead cells that trigger or modulate immunity and tissue repair. In vertebrates, the cytoskeletal component F-actin is a DAMP specifically recognised by DNGR-1, an innate immune receptor. Previously we suggested that actin is also a DAMP in Drosophila melanogaster by inducing STAT-dependent genes (
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Actinina/farmacología , Actinas/farmacología , Proteínas de Drosophila/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Factores de Transcripción STAT/metabolismo , Actinina/administración & dosificación , Actinina/genética , Actinas/administración & dosificación , Actinas/genética , Animales , Animales Modificados Genéticamente , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genéticaRESUMEN
Animals live together with diverse bacteria that can impact their biology. In Drosophila melanogaster, gut-associated bacterial communities are relatively simple in composition but also have a strong impact on host development and physiology. It is generally assumed that gut bacteria in D. melanogaster are transient and their constant ingestion with food is required to maintain their presence in the gut. Here, we identify bacterial species from wild-caught D. melanogaster that stably associate with the host independently of continuous inoculation. Moreover, we show that specific Acetobacter wild isolates can proliferate in the gut. We further demonstrate that the interaction between D. melanogaster and the wild isolated Acetobacter thailandicus is mutually beneficial and that the stability of the gut association is key to this mutualism. The stable population in the gut of D. melanogaster allows continuous bacterial spreading into the environment, which is advantageous to the bacterium itself. The bacterial dissemination is in turn advantageous to the host because the next generation of flies develops in the presence of this particularly beneficial bacterium. A. thailandicus leads to a faster host development and higher fertility of emerging adults when compared to other bacteria isolated from wild-caught flies. Furthermore, A. thailandicus is sufficient and advantageous when D. melanogaster develops in axenic or freshly collected figs, respectively. This isolate of A. thailandicus colonizes several genotypes of D. melanogaster but not the closely related D. simulans, indicating that the stable association is host specific. This work establishes a new conceptual model to understand D. melanogaster-gut microbiota interactions in an ecological context; stable interactions can be mutualistic through microbial farming, a common strategy in insects. Moreover, these results develop the use of D. melanogaster as a model to study gut microbiota proliferation and colonization.
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Bacterias/metabolismo , Drosophila melanogaster/microbiología , Microbioma Gastrointestinal , Simbiosis/fisiología , Animales , Bacterias/crecimiento & desarrollo , Biodiversidad , Femenino , Tracto Gastrointestinal/microbiología , Modelos Biológicos , Especificidad de la EspecieRESUMEN
Bacterial communities can sense their neighbors, regulating group behaviors in response to cell density and environmental changes. The diversity of signaling networks in a single species has been postulated to allow custom responses to different stimuli; however, little is known about how multiple signals are integrated and the implications of this integration in different ecological contexts. In the plant pathogen Pectobacterium wasabiae (formerly Erwinia carotovora), two signaling networks-the N-acyl homoserine lactone (AHL) quorum-sensing system and the Gac/Rsm signal transduction pathway-control the expression of secreted plant cell wall-degrading enzymes, its major virulence determinants. We show that the AHL system controls the Gac/Rsm system by affecting the expression of the regulatory RNA RsmB. This regulation is mediated by ExpR2, the quorum-sensing receptor that responds to the P. wasabiae cognate AHL but also to AHLs produced by other bacterial species. As a consequence, this level of regulation allows P. wasabiae to bypass the Gac-dependent regulation of RsmB in the presence of exogenous AHLs or AHL-producing bacteria. We provide in vivo evidence that this pivotal role of RsmB in signal transduction is important for the ability of P. wasabiae to induce virulence in response to other AHL-producing bacteria in multispecies plant lesions. Our results suggest that the signaling architecture in P. wasabiae was coopted to prime the bacteria to eavesdrop on other bacteria and quickly join the efforts of other species, which are already exploiting host resources.IMPORTANCE Quorum-sensing mechanisms enable bacteria to communicate through small signal molecules and coordinate group behaviors. Often, bacteria have various quorum-sensing receptors and integrate information with other signal transduction pathways, presumably allowing them to respond to different ecological contexts. The plant pathogen Pectobacterium wasabiae has two N-acyl homoserine lactone receptors with apparently the same regulatory functions. Our work revealed that the receptor with the broadest signal specificity is also responsible for establishing the link between the main signaling pathways regulating virulence in P. wasabiae This link is essential to provide P. wasabiae with the ability to induce virulence earlier in response to higher densities of other bacterial species. We further present in vivo evidence that this novel regulatory link enables P. wasabiae to join related bacteria in the effort to degrade host tissue in multispecies plant lesions. Our work provides support for the hypothesis that interspecies interactions are among the major factors influencing the network architectures observed in bacterial quorum-sensing pathways.
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Regulación Bacteriana de la Expresión Génica , Pectobacterium carotovorum/fisiología , Percepción de Quorum , Factores de Virulencia/metabolismo , Acil-Butirolactonas/metabolismo , Proteínas Bacterianas/metabolismo , Pectobacterium carotovorum/efectos de los fármacos , Pectobacterium carotovorum/genética , Pectobacterium carotovorum/patogenicidad , Factores de Transcripción/metabolismo , VirulenciaRESUMEN
Damage-associated molecular patterns (DAMPs) are molecules released by dead cells that trigger sterile inflammation and, in vertebrates, adaptive immunity. Actin is a DAMP detected in mammals by the receptor, DNGR-1, expressed by dendritic cells (DCs). DNGR-1 is phosphorylated by Src-family kinases and recruits the tyrosine kinase Syk to promote DC cross-presentation of dead cell-associated antigens. Here we report that actin is also a DAMP in invertebrates that lack DCs and adaptive immunity. Administration of actin to Drosophila melanogaster triggers a response characterised by selective induction of STAT target genes in the fat body through the cytokine Upd3 and its JAK/STAT-coupled receptor, Domeless. Notably, this response requires signalling via Shark, the Drosophila orthologue of Syk, and Src42A, a Drosophila Src-family kinase, and is dependent on Nox activity. Thus, extracellular actin detection via a Src-family kinase-dependent cascade is an ancient means of detecting cell injury that precedes the evolution of adaptive immunity.
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Actinas/metabolismo , Alarminas/metabolismo , Drosophila melanogaster/fisiología , Estrés Fisiológico , Animales , Transducción de SeñalRESUMEN
UNLABELLED: Pectobacterium wasabiae (previously known as Erwinia carotovora) is an important plant pathogen that regulates the production of plant cell wall-degrading enzymes through an N-acyl homoserine lactone-based quorum sensing system and through the GacS/GacA two-component system (also known as ExpS/ExpA). At high cell density, activation of GacS/GacA induces the expression of RsmB, a noncoding RNA that is essential for the activation of virulence in this bacterium. A genetic screen to identify regulators of RsmB revealed that mutants defective in components of a putative Trk potassium transporter (trkH and trkA) had decreased rsmB expression. Further analysis of these mutants showed that changes in potassium concentration influenced rsmB expression and consequent tissue damage in potato tubers and that this regulation required an intact Trk system. Regulation of rsmB expression by potassium via the Trk system occurred even in the absence of the GacS/GacA system, demonstrating that these systems act independently and are both required for full activation of RsmB and for the downstream induction of virulence in potato infection assays. Overall, our results identified potassium as an essential environmental factor regulating the Rsm system, and the consequent induction of virulence, in the plant pathogen P. wasabiae. IMPORTANCE: Crop losses from bacterial diseases caused by pectolytic bacteria are a major problem in agriculture. By studying the regulatory pathways involved in controlling the expression of plant cell wall-degrading enzymes in Pectobacterium wasabiae, we showed that the Trk potassium transport system plays an important role in the regulation of these pathways. The data presented further identify potassium as an important environmental factor in the regulation of virulence in this plant pathogen. We showed that a reduction in virulence can be achieved by increasing the extracellular concentration of potassium. Therefore, this work highlights how elucidation of the mechanisms involved in regulating virulence can lead to the identification of environmental factors that can influence the outcome of infection.
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Proteínas Bacterianas/metabolismo , Proteínas Portadoras/metabolismo , Pectobacterium/patogenicidad , Potasio/metabolismo , Factores de Transcripción/metabolismo , Proteínas Bacterianas/genética , Proteínas Portadoras/genética , Regulación Bacteriana de la Expresión Génica/fisiología , Mutación , Pectobacterium/metabolismo , Factores de Transcripción/genéticaRESUMEN
In a rat model of artificial ureteral calculosis, the aim of the study was to characterize the behavioural manifestations of direct visceral pain and to evaluate the relationship between number, duration and complexity of the visceral episodes and the extent of referred lumbar muscular hyperalgesia. As evidenced by non-stop video-tape recordings over 4-14 days, almost 98% of stone-implanted rats showed episodes similar to the writhing behaviour characteristic of noxious visceral stimulation in animals. From one rat to another, these episodes varied from very few (1-3) to a very high number (+/- 60), lasted a few minutes to over 45 min and were of variable complexity, as evaluated via an arbitrary scale on the basis of the combination of movements. Their number and duration decreased significantly, in a linear fashion, as time passed after the operation, so that they were mostly concentrated during the first 3 days. Number, duration and complexity of episodes were reduced by chronic treatment with morphine in a dose-dependent fashion. Stone-implanted rats displaying visceral episodes also showed hyperalgesia of the ipsilateral oblique musculature, as evidenced by a decrease in the vocalization threshold to electrical muscle stimulation, which was maximum on the first 3-4 days after implantation but lasted up to 10 days. The visceral episodes and the muscle hyperalgesia showed a strict relationship of interdependence: a significant, direct linear correlation was found between number and duration of episodes and tendency to also develop a contralateral muscle hyperalgesia. By applying the results of the study to the interpretation of human pathology, referred lumbar muscle hyperalgesia from ureteral calculosis would appear to be a strict function of the colic pain experienced.