The nuclear receptor Nurr1 is preferentially expressed in human pro-inflammatory macrophages and limits their inflammatory profile.

Nurr1 is a member of the orphan nuclear receptor family NR4A (nuclear receptor subfamily 4 group A) that modulates inflammation in several cell lineages, both positively and negatively. Macrophages are key regulators of inflammatory responses, yet information about the role of Nurr1 in human macrophages is scarce. Here we examined Nurr1 expression and activity in steady state and activated human macrophages. Pro- and anti-inflammatory macrophages were generated in vitro by culture of blood monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Nurr1 expression was predominant in macrophages with the pro-inflammatory phenotype. Nurr1 activation with the agonists 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane (C-DIM12) or isoxazolo-pyridinone 7e (IP7e) did not globally modify the polarization status of pro-inflammatory macrophages, but they decreased their production of TNF, IL-1ß, IL-6, IL-8, IL-12 p40, CCL2, IFN-ß, and reactive oxygen species, with variable potencies. Conversely, Nurr1 deficient macrophages increased the expression of transcripts encoding inflammatory mediators, particularly that of IL6, IFNB1, and CCL2. Mechanistically, endogenous Nurr1 interacted with NF-κB p65 in basal conditions and upon lipopolysaccharide (LPS)-mediated activation. C-DIM12 stabilized those complexes in cells exposed to LPS and concurrently decreased NF-κB transcriptional activity and p65 nuclear translocation. Expression of high levels of Nurr1 was associated with a subset of dermal macrophages that display enhanced levels of TNF and lower expression of the anti-inflammatory marker CD163L1 in skin lesions from patients with bullous pemphigoid (BP), a chronic inflammatory autoimmune blistering disorder. These results suggest that Nurr1 expression is linked with the pro-inflammatory phenotype of human macrophages, both in vivo and in vitro, where it may constitute a brake to attenuate the synthesis of inflammatory mediators.

Synovial Sarcoma of the Temporomandibular Joint and Infratemporal Fossa: A Case Report.

Temporomandibular joint (TMJ) and infratemporal fossa (ITF) tumors, even though rare, present diagnostic complexities due to their nonspecific symptoms. Synovial sarcoma comprises 5-10% of adult soft-tissue sarcomas and is uncommon in the head and neck and exceptionally rare in the TMJ/ITF region. We presented a case of monophasic synovial sarcoma affecting the left TMJ/ITF in a 24-year-old man with severe preauricular pain who was misdiagnosed with temporomandibular disorder for 3 years. When in-depth evaluations uncovered a 40 mm tumor adjacent to the TMJ, extensive resection and immediate reconstruction were conducted, followed by postoperative radiotherapy and adjuvant chemotherapy. Magnetic resonance imaging photos of the early stage and after 3 years of tumor progression, initial signs and symptoms, and intraoperative images allowed tumor evolution assessment.

Postsurgical Volumetric Airway Changes in Class III Patients Receiving Bimaxillary Orthognathic Surgery.

The purpose of the present study was to investigate the pharyngeal airway space (PAS) changes in class III patients receiving bimaxillary orthognathic surgery and correlate the PAS volume and minimum axial section changes with the magnitude of the surgical movement. This research involved a retrospective sample composed of 38 patients with class III skeletal occlusions. Three-dimensional measurements of the PAS volume and minimum axial section were conducted. Cephalometric points were used to verify the extent of jaw-hyoid bone movement. No significant differences were found between pre and postoperative total PAS volume (P = 0.280), nasopharyngeal volume (P = 0.545), oropharyngeal volume (P = 0.297), and minimum axial section (P = 0.568). Anterior movement of point A and posterior nasal spine were significantly associated with an increase in total PAS volume, oropharyngeal volume, and minimum axial section (P < 0.05). However, the posterior movement of menton was significantly associated with a decrease in total PAS volume, oropharyngeal volume, and minimum axial section (P < 0.05). The results of the present study indicated that PAS is not negatively affected by bimaxillary surgery in class III patients. However, the planning of class III patients who are prone to the development of airway problems should be done carefully.

Complications related to diabetic foot ulcer and associated social vulnerability factors at a referral centre in Brazil.

OBJECTIVE: To analyse the prevalence and associated social vulnerability factors of complications related to diabetic foot ulcer (DFU) among individuals followed up in a public care centre in Brazil. METHOD: This is a cross-sectional study carried out with individuals followed up at the diabetic foot service of the State Referral Center for Diabetes and Endocrinology Assistance (CEDEBA) between December 2019 and October 2020, during the COVID-19 pandemic. Descriptive analysis and comparison of the prevalence of complications related to DFU were carried out. The factors associated with the outcome variables were verified by hierarchical logistic regression analysis. RESULTS: Among the 253 participants in this study, 30.4% had an active ulcer, 57.1% had a previous ulcer and 45.1% had an amputation. Lower limb ulcers were positively associated with male sex (prevalence ratio (PR): 1.22 (1.04-1.43)) and negatively associated with age >60 years (PR: 0.71 (0.61-0.83)), screening for diabetic foot (PR: 0.79 (0.67-0.92)) and the use of public transport to access CEDEBA (PR: 0.82 (0.71-0.96)). On the other hand, amputations were positively associated with male sex (PR: 1.61 (1.23-2.11)) and not working (PR: 3.83 (1.48-9.95)) and negatively associated with age >60 years (PR: 0.57 (0.45-0.74)) and the use of public transport to access CEDEBA (PR: 0.63 (0.49-0.81)). CONCLUSION: The prevalence of complications was higher than in previous studies, and associated with sociodemographic and clinical characteristics. Further research should be encouraged to investigate the role that determinants of health play in the course of the disease, contributing to the construction of strategies that incorporate formulations developed in the social and economic spheres to broaden the impact of health actions on the prevention of major diabetic foot complications.

Lpx1p links glucose-induced calcium signaling and plasma membrane H+-ATPase activation in Saccharomyces cerevisiae cells.

In yeast, as in other eukaryotes, calcium plays an essential role in signaling transduction to regulate different processes. Many pieces of evidence suggest that glucose-induced activation of plasma membrane H+-ATPase, essential for yeast physiology, is related to calcium signaling. Until now, no protein that could be regulated by calcium in this context has been identified. Lpx1p, a serine-protease that is also involved in the glucose-induced activation of the plasma membrane H+-ATPase, could be a candidate to respond to intracellular calcium signaling involved in this process. In this work, by using different approaches, we obtained many pieces of evidence suggesting that the requirement of calcium signaling for activation of the plasma membrane H+-ATPase is due to its requirement for activation of Lpx1p. According to the current model, activation of Lpx1p would cause hydrolysis of an acetylated tubulin that maintains the plasma membrane H+-ATPase in an inactive state. Therefore, after its activation, Lpx1p would hydrolyze the acetylated tubulin making the plasma membrane H+-ATPase accessible for phosphorylation by at least one protein kinase.

Fetal modified left myocardial performance index monitoring during open surgery for myelomeningocele repair.

OBJECTIVE: Fetal hemodynamic changes have already been described during open myelomeningocele repair. This study aimed to access fetal myocardial performance index (MPI) during this high-complexity surgery. METHODS: Open myelomeningocele repair was performed in 37 fetuses between the 24th and 27th week of gestation. MPI was calculated at specific periods: pre-anesthesia, postanesthesia, neurosurgery (early skin manipulation, spinal cord releasing, and sintesis), and end of surgery. Mean ± standard deviation (SD) of MPI and its related times-isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and ejection time (ET)-was determined for each period. Analysis of variance (ANOVA) with repeated measures was used to assess differences among these periods. Tukey multiple comparison times test compared global surgery stages. RESULTS: The mean of MPI in the specific time points was 0.32, 0.32, 0.34, 0.48, 0.36, and 0.32, respectively (P < .001). In the two-tailed comparison times, neurosurgery stage presents MPI highest levels, especially on stage 3b (early skin manipulation and spinal cord releasing) related to ICT and IRT rising and ET decreased levels. CONCLUSION: Fetal global cardiac function is altered during the open myelomeningocele repair. The neurosurgery stage represents the critical phase of the procedure.

Prenatally diagnosed fetal tumors of the head and neck: a systematic review with antenatal and postnatal outcomes over the past 20 years.

AIM: The aim of this study was to review prenatally diagnosed tumors of the head and neck in the fetus and to report antenatal and postnatal outcomes. METHODS: PubMed/Medline, EMBASE/SCOPUS, Cochrane database and Google Scholar were reviewed over the last 20 years. No language or article type restriction was used. RESULTS: A total of 1940 record were retrieved. Of the 713 records screened, 566 full-text articles were assessed for eligibility. After 445 articles were excluded for specified reasons, 111 studies met the research criteria and were included for qualitative analysis. Overall, 306 cases of fetal tumors of the head and neck were reviewed. Maternal age was an independent factor. The mean maternal age was 28.2 years and gestational age at prenatal diagnosis was 27.1 weeks. Conventional 2D ultrasound was the standard diagnostic procedure in 27.9% of cases and was implemented in 27.3% of cases by 3D ultrasound and fetal magnetic resonance imaging (MRI). Diagnostic evaluation of intracranial spreading and high-airway obstructions was greatly enhanced by fetal MRI. The more common type of fetal tumor was hemangioma/lymphangioms (42.1%), followed by teratomas (29.7%), tumors of the gingiva (10.1%) and lymphatic venous malformations (9.1%), respectively. Fetal karyotyping was performed only in 9.8% of cases; within fetuses undergoing karyotype, chromosomal abnormalities accounted for 20% of cases. The most common pregnancy complication was polyhydramnios (26.3%). Ex utero intrapartum treatment (EXIT) procedure was performed in 30.1% of cases while surgical excision was used in 22.9% during postnatal life. The survival rate was 35.35%. CONCLUSION: Fetal tumors of the head and neck are rare congenital malformations. Two-dimensional ultrasound is diagnostic in almost all cases; however, MRI may be an important diagnostic adjunct in targeted cases and help patient selection for immediate intubation at the time of delivery. EXIT procedure and surgical removal of the tumor was associated with good prognosis.

Simple approach based on maternal characteristics and mean arterial pressure for the prediction of preeclampsia in the first trimester of pregnancy.

AIM: To propose a simple model for predicting preeclampsia (PE) in the 1st trimester of pregnancy on the basis of maternal characteristics (MC) and mean arterial pressure (MAP). METHODS: A prospective cohort was performed to predict PE between 11 and 13+6 weeks of gestation. The MC evaluated were maternal age, skin color, parity, previous PE, smoking, family history of PE, hypertension, diabetes mellitus and body mass index (BMI). Mean arterial blood pressure (MAP) was measured at the time of the 1st trimester ultrasound. The outcome measures were the incidences of total PE, preterm PE (delivery <37 weeks) and term PE (delivery ≥37 weeks). We performed logistic regression analysis to determine which factors made significant contributions for the prediction of the three outcomes. RESULTS: We analyzed 733 pregnant women; 55 developed PE, 21 of those developed preterm PE and 34 term PE. For total PE, the best model was MC+MAP, which had an area under the receiver operating characteristic curve (AUC ROC) of 0.79 [95% confidence interval (CI)=0.76-0.82]. For preterm PE, the best model was MC+MAP, with an AUC ROC of 0.84 (95% CI=0.81-0.87). For term PE, the best model was MC, with an AUC ROC of 0.75 (0.72-0.79). The MC+MAP model demonstrated a detection rate of 67% cases of preterm PE, with a false-positive rate of 10%, positive predictive value of 17% and negative predictive value of 99%. CONCLUSION: The MC+MAP model showed good accuracy in predicting preterm PE in the 1st trimester of gestation.

Fetal Heart Rate Monitoring during Intrauterine Open Surgery for Myelomeningocele Repair.

OBJECTIVE: The aim of this study was to assess fetal hemodynamics during intrauterine open surgery for myelomeningocele (MMC) repair by describing fetal heart rate (FHR) monitoring in detail related to each part of the procedure. METHODS: A study was performed with 57 fetuses submitted to intrauterine MMC repair between the 24th and 27th week of gestation. Evaluations of FHR were made in specific periods: before anesthesia, after anesthesia, at the beginning of laparotomy, during uterus abdominal withdrawal, hysterotomy, neurosurgery (before incision, during early skin manipulation, spinal cord releasing, and at the end of neurosurgery), abdominal cavity reintroduction, and abdominal closure, and at the end of surgery. Means ± standard deviations of FHR were established for each period, and analysis of variance with repeated measures was used to assess differences between these periods. The mean differences were assessed with 95% confidence intervals and were analyzed by Tukey's multiple comparison test. RESULTS: The mean FHR during the specific periods mentioned above was 140.2, 140, 139.2, 138.8, 135.1, 133.9, 123.1, 134.0, 134.5, 137.9, and 139.9 bpm, respectively (p < 0.0001). Comparing the different periods, the highest frequencies were observed in the initial and final moments. The neurosurgery stage presents lower frequencies, especially during the release of the spinal cord. CONCLUSION: FHR monitoring revealed interesting findings in terms of physiological fetal changes during MMC repair, especially during neurosurgery, which was the most critical period.

Assessment of ultrasound and Doppler parameters in the third trimester of pregnancy as predictors of adverse perinatal outcome in unselected pregnancies.

OBJECTIVES: The aim of the study was to investigate ultrasound and Doppler parameters in the third trimester of pregnancy as possible predictors of adverse perinatal outcome in unselected pregnancies. MATERIAL AND METHODS: We performed a retrospective cross-sectional study including unselected pregnant women be-tween 27 and 36 + 6 weeks of gestation. The following ultrasound and Doppler parameters were assessed: estimated fetal weight (EFW) [g], EFW percentile, placental maturity grade (Grannum classification), single vertical deepest pocket (SVDP) of amniotic fluid [cm], amniotic fluid index (AFI) [cm], mean uterine artery (UtA) pulsatility index (PI), umbilical artery (UA) PI, middle cerebral artery (MCA) PI, MCA peak systolic velocity (PSV) [cm/s], and cerebroplacental ratio (CPR). Adverse perinatal outcome was defined as Apgar score of < 7 at 1 min, birth weight of < 2500 g at delivery, and gestational age of < 37 weeks at delivery. The unpaired t test was used to compare the groups. RESULTS: AFI (p = 0.01), mean UtA PI (p = 0.04) and mean UA PI (p = 0.03) were significantly different with regard to the Apgar score at 1 min. EFW, EFW percentile, SVDP of amniotic fluid, AFI, mean UtA PI, UA PI, and MCA PI were significantly different (p < 0.001) in terms of birth weight. Placental maturity grade (p = 0.02), SVDP of the amniotic fluid (p < 0.001), AFI (p < 0.001), mean UtA PI (p < 0.001), UA PI (p = 0.001), and MCA PI (p < 0.001) were significantly different as far as gestational age at delivery is concerned. CONCLUSION: Ultrasound and Doppler parameters may predict adverse perinatal outcomes in unselected pregnancies in the third trimester of pregnancy.

Reference charts of fetal biometric parameters in 31,476 Brazilian singleton pregnancies.

OBJECTIVES: The purpose of this study was to establish reference charts of fetal biometric parameters measured by 2-dimensional sonography in a large Brazilian population. METHODS: A cross-sectional retrospective study was conducted including 31,476 low-risk singleton pregnancies between 18 and 38 weeks' gestation. The following fetal parameters were measured: biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight. To assess the correlation between the fetal biometric parameters and gestational age, polynomial regression models were created, with adjustments made by the determination coefficient (R(2)). RESULTS: The means ± SDs of the biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight measurements at 18 and 38 weeks were 4.2 ± 2.34 and 9.1 ± 4.0 cm, 15.3 ± 7.56 and 32.3 ± 11.75 cm, 13.3 ± 10.42 and 33.4 ± 20.06 cm, 2.8 ± 2.17 and 7.2 ± 3.58 cm, and 256.34 ± 34.03 and 3169.55 ± 416.93 g, respectively. Strong correlations were observed between all fetal biometric parameters and gestational age, best represented by second-degree equations, with R(2) values of 0.95, 0.96, 0.95, 0.95, and 0.95 for biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight. CONCLUSIONS: Fetal biometric parameters were determined for a large Brazilian population, and they may serve as reference values in cases with a high risk of intrauterine growth disorders.

Effect of low-level laser therapy on metalloproteinase MMP-2 and MMP-9 production and percentage of collagen types I and III in a papain cartilage injury model.

Osteoarthritis (OA) resulting from injury or disease is associated with increased levels of several matrix metalloproteinases (MMPs), which degrade all components of the complex extracellular matrix in the cartilage. The objective of this study is to investigate the effect of low-level laser therapy (LLLT) on papain-induced joint damage in rats by histopathology and analysis of metalloproteinase 2 and 9 production. Sixty male Wistar rats were randomly distributed into four groups of 15 animals: (1) non-injury negative control, (2) injury positive control, (3) treated with LLLT at 50 mW, and (4) treated with LLLT at 100 mW. OA was induced in animals using papain (4 % solution) followed by treatment with LLLT. After 7, 14, and 21 days, the animals were euthanized. The articular lavage was collected and centrifuged; then, the supernatant was stored prior to protein analysis by western blot. The material was stained with hematoxylin and eosin for histopathological analysis, and Picrosirius Red was used to estimate the percentage of collagen fibers. To determine normal distribution, ANOVA and Tukey's post hoc test were used for comparison between and within each group at each time period. All data are expressed as mean and standard deviation values, with the null hypothesis considered as p < 0.05. Both laser groups (50 and 100 mW) were effective in tissue repair, decreasing collagen type III expression and increasing type I expression in all experimental periods; however, LLLT at 50 mW reduced metalloproteinase 9 more than at 100 mW in 21 days. LLLT at 50 mW was more efficient in the modulation of matrix MMPs and tissue repair.

Non-RhD alloimmunization in pregnancy: an updated review.

RhD alloimmunization in pregnancy is still the main cause of hemolytic disease of the fetus and neonate (HDFN). Nevertheless, there are other antigens that may be associated with the occurrence of this phenomenon and that have been growing in proportion, given that current prevention strategies focus only on anti-RhD antibodies. Although not widespread, the screening and diagnostic management of the disease caused by these antibodies has recommendations in the literature. For this reason, the following review was carried out with the objective of listing the main red blood cell antigen groups described - such as Rh, ABO, Kell, MNS, Duffy, Kidd, among others - addressing the clinical importance of each one, prevalence in different countries, and recommended management when detecting such antibodies during pregnancy.

Navigating obstetric bad news: Insights from tertiary care medical teams.

OBJECTIVES: To analyze the self-reported perception of obstetric medical teams regarding the practice of delivering bad news in public and private hospitals. METHODS: Cross-sectional study considering physicians delivering obstetric care at the Municipal Hospital Vila Santa Catarina, Municipal Hospital Dr. Moysés Deutsch, and Albert Einstein Israelite Hospital, in São Paulo, Brazil. The applied questionnaire reflected the steps of the SPIKES protocol for delivering difficult news, with the questions adapted to obstetric and fetal medicine practice context. RESULTS: Specialists self-reported higher levels of knowledge, better emotional management, and superior strategy planning and summarization skills than residents. Participants with more than five years of experience reported higher knowledge levels, better emotional management, and superior strategy development skills. When comparing professionals from private and public hospitals, no significant differences emerged in self-reported communication aspects. CONCLUSIONS: Experience duration significantly influences professionals' impressions in their ability to provide information, manage emotions, and plan post-diagnosis. Specialists and those with more years of experience self-report enhanced readiness in executing communication steps effectively. PRACTICE IMPLICATIONS: Our findings underscore the importance of tailored training and experience in navigating sensitive medical conversations in the field of Obstetrics.

Neurological morbidity in monochorionic twins with selective fetal growth restriction.

The increased risks of various obstetric, maternal and fetal comorbidities of monochorionic twin pregnancies are widely known. However, despite its high prevalence and significance, the assessment of neurological morbidity as more commonly in selective fetal growth restriction (sFGR) is concerned with more health care. This literature review aims to provide more information about such an assessment. To this end, retrospective cases of sFGR were studied in monochorionic twins, already diagnosed, classified and who had the recommended management, published between 2001 and 2018 in 17 scientific articles. In the assessment of fetal mortality, the highest risk of death of the restricted fetus was found in type 3 of sFGR, while type 2 sFGR was responsible for the highest death rates of both fetuses and also the lowest mean gestational age at delivery, 30.9 weeks. Regarding neurological morbidity, however, studies have shown a higher risk of brain damage in the habitually growing twin compared to the restricted one in the case of sFGR. This may be due to prematurity or intermittent diastolic flow on Doppler in type 2 and 3 of sFGR, however, statements about its pathophysiology still lack further studies.

Tuberous Sclerosis Complex: Prenatal Diagnosis Using Ultrasound and Magnetic Resonance Imaging-A Report of Two Cases.

Tuberous sclerosis complex (TSC) is a multiple system neurocutaneous syndrome with a genetic disorder caused by different mutations in TSC1 or TSC2. Usually, TSC causes tumors in the heart, brain, kidneys, eyes, and lungs. However, tumors can also develop in any other organs. The prenatal diagnosis of TCS is based on the identification of fetal cardiac tumors by ultrasound and brain subependymal nodules, usually identified by fetal magnetic resonance imaging (MRI). We present two case reports of the prenatal diagnosis of TCS using both ultrasound and MRI, which were confirmed by clinical and radiological methods in the postnatal period accordingly.

Estimated atmospheric emissions from biodiesel and characterization of pollutants in the metropolitan area of Porto Alegre-RS.

The purpose of the present study was to estimate emissions of some pollutants (CO, NO(X), HC, SO(X), and PM) in diesel fleet due to the addition of biodiesel in different blends, as well as to assess atmospheric pollutant concentrations in the metropolitan area of Porto Alegre (MAPA). The methodology was based on inventories from mobile sources based on US EPA's technical report. Regarding air quality the following parameters were determined: PM(10), PM(2.5), CO, NO(X), O(3), SO(2), HC and PAHs. The results showed a decrease for emissions PM, CO, and HC, and a slight increase for NO(X). The characterization of atmospheric pollutants in the metropolitan area of Porto Alegre showed that they are influenced by mobile sources, particularly diesel vehicles. The diagnosis of ratios analysis that was applied to facilitate the identification of sources of PAHs, indicated an influence of diesel oil.

The role of fetal surveillance in monochorionic twins: review of the current findings.

Maternal age has increased significantly over the years and assisted reproduction techniques are becoming more available in less developed countries, contributing to the rising number of multiple gestations. Multiple pregnancy is associated with greater risk for both the mother and the fetus than a singleton pregnancy and needs well-trained professionals to assist and surveil its progression. This review aimed to describe the available evidence and summarize the current recommendations for fetal surveillance and delivery timing for monochorionic gestations. The information contained in this review aimed to improve prenatal care and management of monochorionic twin pregnancies, reducing complications and adverse perinatal outcomes.

Placental and Umbilical Cord Anomalies Diagnosed by Two- and Three-Dimensional Ultrasound.

The aim of this review is to present a wide spectrum of placental and umbilical cord pathologies affecting the pregnancy. Placental and umbilical cord anomalies are highly associated with high-risk pregnancies and may jeopardize fetal well-being in utero as well as causing a predisposition towards poor perinatal outcome with increased fetal and neonatal mortality and morbidity. The permanent, computerized perinatology databases of different international centers have been searched and investigated to fulfil the aim of this manuscript. An extended gallery of prenatal imaging with autopsy correlation in specific cases will help to provide readers with a useful iconographic tool and will assist with the understanding and definition of this critical obstetrical and perinatological issue.