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Transplantation of stem cells derived from donors with CCR5Δ32 homozygous genotype is a potential strategy to achieve both the control of malignant hematological disease as well as sustained remission of the HIV infection, and researchers in different countries are looking for CCR5Δ32 homozygous donors to replicate such a 'double-target' strategy. We determined the frequency of the CCR5Δ32 variant in a sample of 1,398 bone marrow donors from Rio Grande do Sul State, Brazil. This study also evaluated whether HLA-A, HLA-B and HLA-DRB1 genotypes are homogeneously distributed between CCR5Δ32 carriers and non-carriers in a population characterized by a significant genetic admixture. The CCR5Δ32 allele frequency was 7.4% (CI0.95 6.4-8.4%), and the frequency of the Δ32/Δ32 homozygous genotype was 0.72% (CI0.95 0.34-1.31%). In general, HLA genotypes are homogeneously distributed between CCR5Δ32 carriers and non-carriers. Considering the large number of bone marrow donors in Brazil and the high CCR5Δ32 allele frequency observed in our study, our results clearly indicate the existence of a considerable amount of potential CCR5Δ32 homozygous bone marrow donors in southern Brazil, suggesting that an active search for these donors is not only feasible but an attractive and promising strategy towards effective HIV infection control and treatment.

Breast carcinoma metastasis to the uterine cervix is a rare occurrence with diagnostic intricacies. We present a case of a 38-year-old woman diagnosed with bilateral stages IIIA and IIIB invasive ductal carcinoma of the breast who developed heavy vaginal bleeding post-treatment, revealing metastatic involvement of the cervix, confirmed by CT imaging and pathological examination, as the presenting sign of widely metastatic disease. This case underscores the importance of a thorough review of systems and physical exams as well as considering uncommon metastatic sites in breast cancer patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Boudagh et al.)

Less than 15% of patients with esophageal squamous cell carcinoma (ESCC) survive 5 years after diagnosis. A better understanding of the biology of these tumors and the development of clinical biomarkers is needed. Autophagy is a physiological mechanism involved in the turnover of cellular components that plays a key role in cancer. This study evaluated the differential levels of three key regulators of autophagy (SQSTM1, MAP1LC3B, and BECN1) in patients with ESCC, associating autophagy with histopathologic features, including the grade of differentiation, mitotic rate, inflammation score, and the intensity of tumor-infiltrating lymphocytes. Nuclear morphometry of the tumor parenchyma was also assessed, associating it with autophagy and histopathology. All three markers significantly increased in patients with ESCC compared to the control group. Based on the mean expression of each protein in the control group, 57% of patients with ESCC had high levels of all three markers compared to control patients (14%). The most frequent profiles found in ESCC were BECN high /MAP1LC3 high and BECN high /SQSTM1 high . According to the TCGA database, we found that the main autophagy genes were upregulated in ESCC. Moreover, high levels of autophagy markers were associated with a poor prognosis. Considering nuclear morphometry, ESCC samples showed a significant reduction in nuclear area, which was strongly negatively correlated with autophagy. Finally, the percentage of normal nuclei was associated with tumor differentiation, while poorly differentiated tumors showed lower SQSTM1 levels. ESCC progression may involve increased autophagy and changes in nuclear structure, associated with clinically relevant histopathological features. KEY MESSAGES: Autophagy markers are co-increased in primary ESCC. Autophagy negatively correlates with nuclear morphometry in ESCC parenchyma. Autophagy and nuclear morphometry are associated with histopathological features. Autophagy is increased in ESCC-TCGA database and associated with poor prognosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Reduced mastication could force the stomach to do extra work on crushing food and contribute to dyspeptic symptoms. This study aimed to assess the relationship between mastication and dyspepsia., Methods: This cross-sectional study involved 209 consecutive patients referred for elective upper endoscopy. Before endoscopy, an expert dentist performed an oral examination and scored chewing function in three levels (normal, regular, and reduced), and applied questionnaires for assessment of dyspepsia (Rome IV), xerostomia, and mastication (normal, regular, and reduced). A reduced masticatory function was defined when an oral examination or mastication questionnaire rated the chewing as poor. Associations between mastication, confounders, and dyspepsia were estimated by prevalence ratio [PR (95% Confidence Interval)] using Poisson regression., Results: Thirty-four patients showed relevant organic conditions in the upper gastrointestinal tract (moderate to severe reflux oesophagitis, peptic ulcer, neoplasia, and surgical modification) and were excluded. Among 175 patients with non-organic diseases (aging 51.3 ± 15.7 years; 61.7% women), 50 (28.6%) had reduced mastication, and 125 (71.4%) had normal/regular mastication. After adjusting for age and xerostomia, reduced mastication was associated with postprandial distress syndrome [PR = 1.93 (95%CI 1.27 - 2.91)] but not with epigastric pain syndrome [PR = 1.09 (95%CI 0.75 - 1.60)]., Conclusions: In patients referred for upper digestive endoscopy, reduced mastication was associated with postprandial distress syndrome but not with epigastric pain syndrome. An interdisciplinary approach with dentists and physicians might benefit dyspeptic patients with postprandial distress syndrome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

This is the third year of the SARS-CoV-2 pandemic, and yet most children remain unvaccinated. COVID-19 in children manifests as mostly mild or asymptomatic, however high viral titers and strong cellular and humoral responses are observed upon acute infection. It is still unclear how long these responses persist, and if they can protect from re-infection and/or disease severity. Here, we analyzed immune memory responses in a cohort of children and adults with COVID-19. Important differences between children and adults are evident in kinetics and profile of memory responses. Children develop early N-specific cytotoxic T cell responses, that rapidly expand and dominate their immune memory to the virus. Children's anti-N, but not anti-S, antibody titers increase over time. Neutralization titers correlate with N-specific antibodies and CD8 + T cells. However, antibodies generated by infection do not efficiently cross-neutralize variants Gamma or Delta. Our results indicate that mechanisms that protect from disease severity are possibly different from those that protect from reinfection, bringing novel insights for pediatric vaccine design. They also underline the importance of vaccination in children, who remain at risk for COVID-19 despite having been previously infected., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lima, Fontoura, de Souza, Fazolo, Hilario, Zorzetto, Rodrigues Junior, Coimbra, Borin, Bispo-dos-Santos, Granja, Marques, Zavaglia, Fernandes, Varela, Polese-Bonatto, Tonini, Ikeda do Carmo, de Almeida, Borges, Nakaya, Proenca-Modena, Callegari-Jacques, Scotta, Stein and Bonorino.)

Bacterial resistance is a public and one health problem. Free-living birds can be reservoirs of multidrug-resistant bacteria and resistance genes. This study aimed to characterize the antimicrobial resistance of Escherichia coli isolated from free-living urban pigeons (Columba livia) in South Brazil. Ninety-two animals were sampled, and one isolate was obtained from each one. The isolates were characterized, and the antimicrobial resistance profile and beta-lactam and colistin resistance genes were investigated. The isolates were classified as phylogroups B1 (35%), B2 (33%), A (16%) and D (16%), and 14% of the strains had the eae virulence gene. All isolates were resistant to at least one antimicrobial, and 63% of them were multidrug-resistant. Geographical location where the pigeons were captured and presence of the eae gene were associated with multidrug resistance. bla VIM and mcr-1 genes were detected in one and two isolates, respectively. This is the first report of these genes in E. coli of pigeons. The bla VIM -positive isolate was classified as Shiga toxin-producing E. coli, and the isolates with mcr-1 were classified as Enterohaemorrhagic E. coli and Enteropathogenic E. coli, which raise additional concerns related to public health since these are zoonotic pathotypes. The results reveal that pigeons carry multidrug-resistant pathogenic E. coli, which may interest public health. Nonetheless, further studies on whether these animals are sources of contamination for humans must be performed to understand their role in spreading antimicrobial resistance., (© 2022 Wiley-VCH GmbH.)

A randomised clinical trial was conducted on 20 healthy, low-habitual fibre consumers to assess the short-term effects of water intake (2 l/day) on fibre supplementation with wheat bran, pectin, and green banana flour. During the 14-days trial, fibre intake doubled in both fibre ( n  = 10) and fibre/water ( n  = 10) interventions ( p  < 0.001), whereas daily water intake increased from 538 to 1990 ml in the fibre/water group ( p  < 0.001). Weekly bowel movements increased similarly in both interventions (fibre: 6.8-8.8; fibre/water: 8.6-10; p  < 0.01), while faecal weight (71-126 g; p  = 0.009) increased in the fibre/water group. This group showed higher counts of faecal Bacteroides and Prevotella , Faecalibacterium prausnitzii , and Bifidobacterium , whereas both interventions decreased the count of Desulfovibrio . Transient abdominal symptoms occurred less frequently in the fibre/water than in the fibre group (3 vs. 9 participants; p  = 0.020). In healthy, low-habitual fibre consumers, short-term water intake helps the intestinal adaptation to fibre supplementation. CLINICAL TRIAL REGISTRATION NUMBER: NCT02838849.

Background: The cause of meconium passage in utero is controversial, traditionally being considered evidence of fetal stress and hypoxia, and also associated with intra-amniotic inflammation/infection. It is now recognized to also occur in the absence of fetal stress. Autopsy studies have shown that many term stillborns (SB) have hypoxic/ischemic brain injury and other evidence of stress preceding the time period immediately before demise, including acute thymic involution (ATI); however, these findings, along with placental findings, have not been previously correlated with meconium-stained amniotic fluid (MSAF)., Methods: 35 structurally normal singleton term SB (21 early term, 14 full/late term) with complete autopsies, including brain and placental examination, were identified. MSAF was visually identified at delivery and confirmed on the placental examination. Autopsy evaluation included brain injury and ATI. Placental evaluation included maternal and fetal vascular malperfusion and acute and chronic inflammatory lesions. Demographic and clinical features were compared., Results: 18 (51%) SB had MSAF, and 17 (49%) had clear amniotic fluid (CAF). The was no significant difference in brain injury in the MSAF vs CAF group, including older gray matter injury (karyorrhexis) (67% vs 47%), recent gray matter injury (red neurons, but no karyorrhexis) (28% vs 35%), white matter injury (50% vs 29%), and hemorrhage (22% vs 24%). Severe ATI was more frequent in the MSAF vs CAF group (61% vs 24%, p  = .04). There was no significant difference in placental lesions between groups, including acute maternal inflammation (39% vs 18%), acute fetal inflammation (6% vs 6%), fetal vascular malperfusion (11% vs 18%), maternal vascular malperfusion (39% vs 35%), and chronic inflammatory lesions (39% vs 29%). The MSAF group was more likely to be full/late term than early term (72% vs 28%), in contrast to the CAF group (6% vs 94%) ( p  = .0001). There was no difference in other clinical factors evaluated., Conclusions: 51% of term SB had MSAF, and, in contrast to the CAF group, these were significantly more likely to be full/late term. Brain injury was frequent in both MSAF and CAF groups, supporting hypoxia as the mechanism of demise in most of these SB. No placental lesions correlated with MSAF, including inflammation. This suggests that hypoxia is the cause of the MSAF in these SB, but that some additional biologic factor present in the full/late term SB, but not present in the early term SB, including possibly gastrointestinal maturation, is necessary for the meconium passage.

Background: The role of mastication on gastroesophageal reflux disease (GERD) is unknown., Aims: To assess whether reduced masticatory function predicts GERD and esophageal dysphagia in patients investigated with upper endoscopy., Methods: In this cross-sectional study, 179 adult patients referred for elective upper gastrointestinal endoscopy agreed to participate. Before endoscopy, an expert dentist performed an oral examination and scored chewing function in three levels (normal, regular, and reduced). Patients replied questionnaires for assessment of GERD (heartburn, regurgitation, and dysphagia), xerostomia, and mastication (normal, regular, and reduced). Poor chewing was defined when either oral examination or mastication questionnaire rated the chewing function as reduced. Associations of mastication with GERD and dysphagia were estimated using Poisson regression., Results: Eleven patients were excluded. Among 168 analyzed (aging 49.8 ± 15.5 years; 58.9% women), 46 had reduced masticatory function (27.4%), and 122 had regular/normal mastication (72.6%). Reduced mastication was associated with GERD [PR = 1.38 (95%CI 1.12 - 1.70)], adjusting for age, and with esophageal dysphagia [PR = 2.03 (95%CI 1.02 - 4.04)], adjusting for age and xerostomia., Conclusions: In outpatients referred for upper gastrointestinal endoscopy, reduced masticatory function defined by an expert dentist may be a risk factor for GERD and esophageal dysphagia., (Copyright © 2021. Published by Elsevier Ltd.)

Erythema nodosum leprosum (ENL) is an inflammatory complication caused by a dysregulated immune response to Mycobacterium leprae . Some Toll-like receptors (TLRs) have been identified as capable of recognizing antigens from M. leprae , triggering a wide antimicrobial and inflammatory response. Genetic polymorphisms in these receptors could influence in the appearance of ENL as well as in its treatment. Thus, the objective of this work was to evaluate the association of genetic variants of TLRs genes with the response to treatment of ENL with thalidomide and prednisone. A total of 162 ENL patients were recruited from different regions of Brazil and clinical information was collected from their medical records. Genomic DNA was isolated from blood and saliva samples and genetic variants in TLR1 (rs4833095), TLR2 (rs3804099), TLR4 (rs1927914), and TLR6 (rs5743810) genes were genotyped by TaqMan real-time PCR system. In order to evaluate the variants' association with the dose of the medications used during the treatment, we applied the Generalized Estimating Equations (GEE) analysis. In the present sample, 123 (75.9%) patients were men and 86 (53.1%) were in treatment for leprosy during the ENL episode. We found an association between polymorphisms in TLR1 /rs4833095, TLR2 /rs3804099, TLR4 /rs1927914, and TLR6 /rs5783810 with the dose variation of thalidomide in a time-dependent manner, i.e., the association with the genetic variant and the dose of the drug was different depending on the moment of the treatment evaluated. In addition, we identified that the association of polymorphisms in TLR1 /rs4833095, TLR2 /rs3804099, and TLR6 /rs5783810 with the dose variation of prednisone also were time-dependent. Despite these associations, in all the interactions found, the influence of genetic variants on dose variation was not clinically relevant for therapeutic changes. The results obtained in this study show that TLRs polymorphism might play a role in the response to ENL treatment, however, in this context, they could not be considered as useful biomarkers in the clinical setting due small differences in medication doses. A larger sample size with patients with a more genetic profile is fundamental in order to estimate the association of genetic variants with the treatment of ENL and their clinical significance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maciel-Fiuza, Costa, Kowalski, Schuler-Faccini, Bonamigo, Vetoratto, Eidt, de Moraes, Silveira, Camargo, Callegari-Jacques, Castro and Vianna.)

Beckwith-Wiedemann syndrome (BWS) is an epigenetic disorder of imprinting on the chromosome 11p15 region that presents with clinical features, such as macroglossia, abdominal wall defects, neonatal hypoglycemia, hemihypertrophy, and embryonal tumors. Phyllodes tumors (PTs) are rare fibroepithelial tumors that account for 0.3% to 1% of breast tumors and present in women aged 35 to 55 years. Here we describe a rare case of metastatic malignant phyllodes tumor in a 27-year-old woman with BWS and uniparental disomy (UPD) of chromosome 11p15.5. To our knowledge, this is the first case report in literature to describe metastatic malignant phyllodes tumor in a woman with BWS.

Case Presentation: A 22-year-old woman who was 36 weeks pregnant presented with a 4-day history of cough, hemoptysis, and exertional dyspnea. She had no fever, night sweats, or weight loss. The review of system was otherwise negative. Her medical history was notable for a spontaneous first-trimester abortion a year ago. At that time, she had a transvaginal ultrasound scan that showed a gestational sac with no fetal movement. A post-abortion ultrasound scan revealed no residual fetal parts., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

COVID-19 manifests as a milder disease in children than adults, but the underlying mechanisms are not fully characterized. Here we assess the difference in cellular or humoral immune responses of pediatric and adult COVID-19 patients to see if these factors contribute to the severity dichotomy. Children's non-specific immune profile is dominated by naive lymphocytes and HLA-DR high CX3CR1 low dendritic cells; meanwhile, children show strong specific antibody and T cell responses for viral structural proteins, with their T cell responses differing from adults by having weaker CD8 + TNF + T cells responses to S peptide pool but stronger responses to N and M peptide pools. Finally, viral mRNA is more abundant in pediatric patients. Our data thus support a scenario in which SARS-CoV-2 infected children contribute to transmission yet are less susceptible to COVID-19 symptoms due to strong and differential responses to the virus., (© 2021. The Author(s).)

Objective: Correlation of BPD with placental pathology is important for clarification of the multifactorial pathogenesis of BPD; however, previous reports have yielded varying results. We report placental findings in no/mild BPD compared to moderate/severe BPD, and with and without pulmonary hypertension (PH)., Methods: Eligible infants were 23 0/7 -27 6/7 weeks gestational age. BPD was defined by the need for oxygen at ≥28 days with severity based on need for respiratory support at ≥36 weeks. Acute and chronic inflammatory placental lesions and lesions of maternal and fetal vascular malperfusion were examined., Results: Of 246 eligible infants, 146 (59%) developed moderate/severe BPD. Thirty-four (23%) infants developed PH, all but 1 being in the moderate/severe BPD group. Chronic deciduitis (32% vs 16%, P  = .003), chronic chorioamnionitis (23% vs 12%, P  = .014), and ≥ 2 chronic inflammatory lesions (13% vs 3%, P  = .007) were more frequent in the moderate/severe BPD group. Development of PH was associated with placental villous lesions of maternal vascular malperfusion (30% vs 15%, P  = .047)., Conclusions: The association of chronic inflammatory placental lesions with BPD severity has not been previously reported. This supports the injury responsible for BPD as beginning before birth in some neonates, possibly related to cytokines associated with these chronic inflammatory lesions.

Objective: To evaluate the effect of the probiotic Lactobacillus brevis CD2 on the prevention of early traumatic oral lesions induced by a fixed orthodontic appliance., Settings and Sample Population: Twenty orthodontic patients (14-57 yo) were recruited from a private clinic., Subjects and Methods: In a phase 2, double-blind clinical trial, all patients were randomly allocated (1:1 ratio) to a 21-day course of soluble tablets containing L brevis CD2 (4 billion colony-forming units after breakfast, lunch and dinner) or placebo, starting at the day of orthodontic appliance placement. The primary outcomes were days with oral lesions and lesion-related pain [ranging between 0 (no pain) and 10 (maximum pain)]. Oral health-related quality of life was measured using OHIP-14 before and after treatments., Results: All patients completed the study. Ten were treated with L brevis (28.1 ± 13.3 yo, 70% women), and 10 received placebo (27.5 ± 9.1 yo, 60% women). The oral lesions lasted significantly less time (P = .018) in patients treated with L brevis (2.5 ± 1.0 days) than with placebo (4.9 ± 3.0 days). Pain score was significantly lower (P = .039) when L brevis was used [median (min-max): 0 (0-4) vs. 3 (0-5)]. OHIP-14 scores were not significantly different between treatments., Conclusions: Lactobacillus brevis CD2 reduced almost 50% the persistence of traumatic oral lesions in patients with fixed orthodontics. Yet, there was no improvement in quality of life compared to placebo, suggesting that such differences in persistency and pain related to oral lesions may be considered clinically irrelevant., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The study presents comparisons between blood group frequencies beyond ABO and Rh blood systems in Native American populations and previously published data from Brazilian blood donors. The frequencies of Diego (c.2561C>T, rs2285644), Kell (c.578C>T, rs8176058), Duffy (c.125A>G, rs12075, c.1-67T>C, rs2814778) and Kidd (c.838A>G, rs1058396) variants in Kaingang (n=72) and Guarani (n=234) populations from Brazil (1990-2000) were obtained and compared with data from these populations sampled during the 1960s and with individuals of different Brazilian regions. Data showed high frequencies of DI*01 and FY*01 alleles: 11.8% and 57.6% in Kaingang and 6.8% and 75.7% in Guarani groups, respectively. The main results indicated: (1) reduction in genetic distance over time of Kaingang and Guarani in relation to other Brazilian populations is suggestive of ongoing admixture; (2) significant differences in some frequencies of blood group markers (especially Diego, Kidd and Duffy) in relation to Native Americans and individuals from different geographical regions of Brazil. Our study shows that the frequency of red blood cell polymorphisms in two Native American groups is very different from that of blood donors, when we evaluated blood groups different from ABO and Rh systems, suggesting that a better ethnic characterization of blood unit receptors is necessary.

Several phenotypes that impact the capacity of cancer cells to survive and proliferate are dynamic. Here we used the number of cells in colonies as an assessment of fitness and devised a novel method called Dynamic Fitness Analysis (DynaFit) to measure the dynamics in fitness over the course of colony formation. DynaFit is based on the variance in growth rate of a population of founder cells compared with the variance in growth rate of colonies with different sizes. DynaFit revealed that cell fitness in cancer cell lines, primary cancer cells, and fibroblasts under unhindered growth conditions is dynamic. Key cellular mechanisms such as ERK signaling and cell-cycle synchronization differed significantly among cells in colonies after 2 to 4 generations and became indistinguishable from randomly sampled cells regarding these features. In the presence of cytotoxic agents, colonies reduced their variance in growth rate when compared with their founder cell, indicating a dynamic nature in the capacity to survive and proliferate in the presence of a drug. This finding was supported by measurable differences in DNA damage and induction of senescence among cells of colonies. The presence of epigenetic modulators during the formation of colonies stabilized their fitness for at least four generations. Collectively, these results support the understanding that cancer cell fitness is dynamic and its modulation is a fundamental aspect to be considered in comprehending cancer cell biology and its response to therapeutic interventions. SIGNIFICANCE: Cancer cell fitness is dynamic over the course of the formation of colonies. This dynamic behavior is mediated by asymmetric mitosis, ERK activity, cell-cycle duration, and DNA repair capacity in the absence or presence of a drug., (©2020 American Association for Cancer Research.)

Objectives: Spontaneous preterm labor is an obstetrical syndrome accounting for approximately 65-70% of preterm births, the latter being the most frequent cause of neonatal death and the second most frequent cause of death in children less than five years of age worldwide. The purpose of this study was to determine and compare to uncomplicated pregnancies (1) the frequency of placental disorders of villous maturation in spontaneous preterm labor; (2) the frequency of other placental morphologic characteristics associated with the preterm labor syndrome; and (3) the distribution of these lesions according to gestational age at delivery and their severity., Methods: A case-control study of singleton pregnant women was conducted that included (1) uncomplicated pregnancies (controls, n=944) and (2) pregnancies with spontaneous preterm labor (cases, n=438). All placentas underwent histopathologic examination. Patients with chronic maternal diseases (e.g., chronic hypertension, diabetes mellitus, renal disease, thyroid disease, asthma, autoimmune disease, and coagulopathies), fetal malformations, chromosomal abnormalities, multifetal gestation, preeclampsia, eclampsia, preterm prelabor rupture of the fetal membranes, gestational hypertension, gestational diabetes mellitus, and HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome were excluded from the study., Results: Compared to the controls, the most prevalent placental lesions among the cases were the disorders of villous maturation (31.8% [106/333] including delayed villous maturation 18.6% [62/333] vs. 1.4% [6/442], q<0.0001, prevalence ratio 13.7; and accelerated villous maturation 13.2% [44/333] vs. 0% [0/442], q<0.001). Other lesions in decreasing order of prevalence included hypercapillarized villi (15.6% [68/435] vs. 3.5% [33/938], q<0.001, prevalence ratio 4.4); nucleated red blood cells (1.1% [5/437] vs. 0% [0/938], q<0.01); chronic inflammatory lesions (47.9% [210/438] vs. 29.9% [282/944], q<0.0001, prevalence ratio 1.6); fetal inflammatory response (30.1% [132/438] vs. 23.2% [219/944], q<0.05, prevalence ratio 1.3); maternal inflammatory response (45.5% [195/438] vs. 36.1% [341/944], q<0.01, prevalence ratio 1.2); and maternal vascular malperfusion (44.5% [195/438] vs. 35.7% [337/944], q<0.01, prevalence ratio 1.2). Accelerated villous maturation did not show gestational age-dependent association with any other placental lesion while delayed villous maturation showed a gestational age-dependent association with acute placental inflammation (q-value=0.005)., Conclusions: Disorders of villous maturation are present in nearly one-third of the cases of spontaneous preterm labor., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Objective  In this currently evolving coronavirus disease 2019 (COVID-19) pandemic, the evidence is scarce about the impact of COVID-19 infection on women in labor and neonates in an inner city African-Americans (AA) population. The objective of this study was to evaluate the clinical outcomes and placental pathology in mother-infant dyads in COVID-19 cases. Study Design  Retrospective chart review was conducted on 34 COVID-19 positive mother-infant dyads to study their baseline characteristics and outcomes. Placental pathology was reviewed by two perinatal pathologists. Results  COVID-19 was noted in 3% of pregnant women who delivered in our institution. The majority (82%) of them were asymptomatic. Out of the four mothers who were symptomatic, only three (9%) required supplemental oxygen. None of them required invasive ventilation. All the neonates tested negative for COVID-19 at 24 hours of age. There were no gross or microscopic pathological abnormalities detected that could be definitely associated with any COVID-19 related complications during pregnancy in any of the 34 placentas. Conclusion  COVID-19 does not appear to increase morbidity and mortality among pregnant women and their neonates in a predominantly AA population. Our study did not find any evidence of vertical transmission of COVID-19 infection nor any specific findings on placental pathology. Key Points Majority of women infected by coronavirus disease 2019 (COVID-19) during labor were asymptomatic.None of the newborns tested positive for COVID-19 at 24 hours of age.Placental pathology findings were nonspecific in COVID-19 mothers., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the pathogenesis of the disease or the needs of the clinical care team. A consensus panel was convened to recommend terminology and reporting elements unified across the spectrum of PAS specimens (i.e., delivered placenta, total or partial hysterectomy with or without extrauterine tissues, curetting for retained products of conception). The proposed nomenclature under the umbrella diagnosis of placenta accreta spectrum (PAS) replaces the traditional categorical terminology (placenta accreta, increta, percreta) with a descriptive grading system that parallels the guidelines endorsed by the International Federation of Gynaecology and Obstetrics (FIGO). In addition, the nomenclature for hysterectomy specimens is separated from that for delivered placentas. The goal for each element in the system of nomenclature was to provide diagnostic criteria and guidelines for expected use in clinical practice.

Background: The effect of abdominal palpation on bowel sounds is controversial. The authors developed an auscultation apparatus to count bowel sounds and determined whether abdominal palpation modifies the number of bowel sounds in healthy volunteers and gastrointestinal outpatients., Methods: Four medical students developed an auscultation apparatus by attaching a Littmann stethoscope to an electret condenser microphone. The students examined 20 healthy volunteers and 20 gastrointestinal outpatients between March and June 2018. Abdominal auscultation lasting 4 minutes (1-minute each quadrant) was performed before and after abdominal palpation with registration of sound tracings. The software Audacity was used to count the bowel sounds. The effect of palpation on bowel sounds was analyzed using Generalized Estimating Equations., Results: The volunteers were predominantly young (mean ± SD, 21 ± 2 years) and men (70%), whereas the outpatients were older (60 ± 11 years) and women (80%). The apparatus was able to generate sound tracings with good quality from all participants. In the comparison before/after palpation, the number of bowel sounds did not differ either in volunteers (mean ± SD, 12.6 ± 4.7 and 11.6 ± 3.5; P = 0.482) or in patients (15.6 ± 7.5 and 15.8 ± 7.9; P = 0.714). In the analysis of all participants, the difference before-after palpation was not statistically significant (mean ± SD, 14.1 ± 6.3 and 13.7 ± 6.4, respectively; P = 0.550; mean difference = 0.4; 95% CI -1.2 to 2.0) and did not depend on the group studied., Conclusions: Using an apparatus devised by medical students, the authors found that abdominal palpation did not modify the number of bowel sounds in healthy volunteers and gastrointestinal outpatients., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Poor sleep associates with mental and cardiometabolic pathological outcomes. The participation of sleep timing features in the pathways by which this relationship occurs is not clear. This study aims to evaluate the interrelationship between sleep quality and self-reported psychiatric/cardiometabolic symptoms, considering mediation and moderation effects of sleep timing patterns, and urban versus rural work environment, respectively; and to verify the association between sleep quality and polymorphisms of AANAT, RORA and TIMELESS genes. An epidemiological survey was performed in a rural area in southern Brazil. Eight-hundred and twenty-nine subjects were evaluated for sleep quality using the Pittsburgh Sleep Quality Index, and sleep timing patterns using the Munich Chronotype Questionnaire. Work characteristics and psychiatric/cardiometabolic symptoms were assessed using a structured self-report questionnaire. Three polymorphisms of AANAT, RORA and TIMELESS (rs3760138, rs782931 and rs774045, respectively) were genotyped in blood samples. We found statistically significant associations of poor sleep quality with self-reported psychiatric symptoms (B = 0.382; 95% CI 0.289-0.476; adjusted p-value <.001), and with self-reported cardiometabolic symptoms (B = 0.079; 95% CI 0.013-0.151; adjusted p-value = .048). The genetic analysis showed that RORA GA/AA genotype was associated to poor sleep quality (B = 0.146, 95% CI 0.054-0.239; adjusted p-value = .004). No moderated mediation effects were observed in the conditional analysis. TIMELESS polymorphism was not included in the analysis due to the low frequency of risk genotypes. These results yield new insights regarding the interrelationship between sleep characteristics and psychiatric/cardiometabolic self-reported symptoms, taking into account genes related to the biological clocks and melatonin pathways., (© 2020 European Sleep Research Society.)

The most studied medical condition related with dental erosions is gastroesophageal reflux disease (GERD). The aim of this study was to assess other predictors of dental erosions besides GERD in outpatients referred for upper digestive endoscopy. In a cross-sectional study, we prospectively evaluated 235 patients who underwent upper digestive endoscopy. Patients were interviewed and examined by a trained dentist before the endoscopies, addressing dental health as well as clinical information and food intake. Dental erosion was classified using Basic Erosive Wear Examination score. Potential predictors for dental erosions were: gender, age, chronic use of antidepressants and proton pump inhibitors (PPI), diabetes mellitus, body mass index, heartburn and acid regurgitation scores, chocolate intake, reflux esophagitis and hiatal hernia. Overall prevalence of dental erosions was 23.4%. The most parsimonious Poisson regression model for dental erosions considered age, chocolate intake and acid regurgitation as predictors. Dental erosions were associated with acid regurgitation in patients younger than 50 years [adjusted prevalence ratio (PR) = 1.8 (95% CI 1.1-2.9)] and with chocolate intake in patients older than 50 years [PR = 2.1 (95% CI 1.2-3.9]. The surfaces most eroded were palatine/lingual (n = 25) and occlusal (n = 25), followed by vestibular (n = 5). In outpatients evaluated with upper digestive endoscopy, the variables associated with dental erosions were age younger than 50 years, acid regurgitation and chocolate intake. Referral for dental evaluation should be considered for young patients with GERD and frequent acid regurgitation.

Background: The combination of probiotics and prebiotics might be useful to treat oral halitosis. The aim of this study was to assess the effect of Lactobacillus salivarius G60 (LS) and inulin on oral halitosis and tongue coating., Methods: In this double-masked, randomized, phase II clinical trial, 45 patients (aged 35 ± 15 years, 66% female) with oral halitosis and tongue coating were allocated to three treatment groups (n = 15) using gums of oral dissolution (one gum every 12 hours) for 10 days. Each gum contained LS (1 billion colony forming units [CFUs]) + inulin (1 g), LS (1 billion CFU) or placebo. Primary outcomes were organoleptic test, Halimeter, and tongue coating, whereas secondary outcomes were quality of life (QOL) and treatment safety. Generalized linear models were used, adjusting for age and sex. In vitro tests were performed to verify whether LS interacts with inulin and whether LS inhibits the growth of Porphyromonas gingivalis and Prevotella intermedia., Results: Forty-four patients (97%) completed the study. Patients treated with LS + inulin showed greater reduction in halitosis measured by Halimeter compared with placebo (adjusted post-intervention average: 96.7 versus 142.5 ppb; P = 0.003), whereas LS and placebo did not differ (115.7 versus 142.5 ppb; P = 0.097). Organoleptic measurements and coating index showed a similar decrease for all groups. QOL improved in patients treated with LS + inulin compared with placebo (P = 0.029). Side effects were mild and transient in all groups. LS did not metabolize inulin but inhibited the growth of P. gingivalis and P. intermedia after 72 hours., Conclusions: Treatment with L. salivarius G60 combined or not with inulin showed significant decrease in the outcomes organoleptic test, Halimeter, and coating index, improving oral halitosis. However, no significant difference was obtained between the groups., (© 2019 American Academy of Periodontology.)

Objective The aims of this study were to ascertain the frequency of disorders of villous maturation in fetal death and to also delineate other placental histopathologic lesions in fetal death. Methods This was a retrospective observational cohort study of fetal deaths occurring among women between January 2004 and January 2016 at Hutzel Women's Hospital, Detroit, MI, USA. Cases comprised fetuses with death beyond 20 weeks' gestation. Fetal deaths with congenital anomalies and multiple gestations were excluded. Controls included pregnant women without medical/obstetrical complications and delivered singleton, term (37-42 weeks) neonate with 5-min Apgar score ≥7 and birthweight between the 10th and 90th percentiles. Results Ninety-two percent (132/143) of placentas with fetal death showed placental histologic lesions. Fetal deaths were associated with (1) higher frequency of disorders of villous maturation [44.0% (64/143) vs. 1.0% (4/405), P < 0.0001, prevalence ratio, 44.6; delayed villous maturation, 22% (31/143); accelerated villous maturation, 20% (28/143); and maturation arrest, 4% (5/143)]; (2) higher frequency of maternal vascular malperfusion lesions [75.5% (108/143) vs. 35.7% (337/944), P < 0.0001, prevalence ratio, 2.1] and fetal vascular malperfusion lesions [88.1% (126/143) vs. 19.7% (186/944), P < 0.0001, prevalence ratio, 4.5]; (3) higher frequency of placental histologic patterns suggestive of hypoxia [59.0% (85/143) vs. 9.3% (82/942), P < 0.0001, prevalence ratio, 6.8]; and (4) higher frequency of chronic inflammatory lesions [53.1% (76/143) vs. 29.9% (282/944), P < 0.001, prevalence ratio 1.8]. Conclusion This study demonstrates that placentas of women with fetal death were 44 times more likely to present disorders of villous maturation compared to placentas of those with normal pregnancy. This suggests that the burden of placental disorders of villous maturation lesions is substantial.

A study was conducted to investigate the serum virome of sows with and without stillbirths after farrowing. Sera from sows with at least one stillbirth or with normal litters were collected immediately after farrowing. Viral DNA was extracted from serum pools and submitted to high throughput sequencing. No differences in the proportion of virus-related reads were found in both groups (p > 0.05). A variety of viral DNA genomes were identified, mostly representative of three viral families: Anelloviridae, Circoviridae and Smacoviridae. Besides, a number of novel unclassified circular Rep-encoding single stranded DNA (CRESS DNA) viruses were also identified. These findings suggest that the presence of such viral genomes in sows' sera bears no correlation with stillbirths' occurrence; it seems likely that these constitute part of the normal serum microbiome of sows at farrowing., Competing Interests: The authors have declared that no competing interests exist.

It is a generally held concept that finding increased aspirated amniotic fluid squames at autopsy supports a diagnosis of acute fetal asphyxia, the massive aspiration of squames being an indicator of terminal gasping. To evaluate this concept, we identified autopsies on 15 third-trimester stillborns with clinical acute placental abruption (acute asphyxia); 13 also had thymic petechiae and none had severe acute thymic involution, findings also supporting acute asphyxia. Thirty third-trimester stillborns with findings supporting a subacute or chronic mode of death, including severe thymic involution and absence of thymic petechiae, comprised the comparison group. Intra-alveolar squames were scored as 0, no squames; 1+, scattered squames singly or in small groups; and 2+, squames in many alveoli, at least focally in compacted clusters. In all cases, the squames were patchily distributed, and none received a score of 0. In the abruption group, the intra-alveolar squames were scored as 1+ in 12 (80%) and as 2+ in 3 (20%) cases, while in the comparison group, the squames were scored as 1+ in 20 (67%) and 2+ in 10 (33%) cases ( P  = NS). There was also no difference in the quantification of intra-alveolar squames in term compared to preterm stillborns. In conclusion, quantification of intra-alveolar squames did not aid in separating an acute mode of death (acute asphyxia) from subacute or chronic modes of death.

Alterations in nuclear size and shape are commonly observed in cancers, and its objective evaluation may provide valuable clinical information about the outcome of the disease. Here, we applied the nuclear morphometric analysis in tissues in hematoxylin and eosin-digitized slides of nevi and melanoma, to objectively contribute to the prognostic evaluation of these tumors. To this, we analyzed the nuclear morphometry of 34 melanomas classified according to the TNM stage. Eight cases of melanocytic nevi were used as non-neoplastic tissues to set the non-neoplastic parameters of nuclear morphology. Our samples were set as G1 (control, nevi), G2 (T1T2N0M0), G3 (T3T4N0M0), G4 (T1T2N1M1), and G5 (T3T4N1M1). Image-Pro Plus 6.0 software was used to acquire measurements related to nuclear size (variable: Area) and shape (variables: Aspect, AreaBox, Roundness, and RadiusRatio, which were used to generate the Nuclear Irregularity Index). From these primary variables, a set of secondary variables were generated. All the seven primary and secondary variables related to the nuclear area were different among groups (Pillai's trace P<0.001), whereas Nuclear Irregularity Index, which is the variable related to nuclear shape, did not differ among groups. The secondary variable 'Average Area of Large Nuclei' was able to differ all pairwise comparisons, including thin nonmetastatic from thin metastatic tumors. In conclusion, the objective quantification of nuclear area in hematoxylin and eosin slides may provide objective information about the risk stratification of these tumors and has the potential to be used as an additional method in clinical decision making.

Transposable elements (TEs) are mobile DNA sequences on genomes. Some elements are able to transpose in somatic cells, a process known as somatic transposition (ST), which has been associated with detrimental biological effects. The mariner-Mos1 element of Drosophila promotes transposition in somatic and germline cells and is an excellent model for studies related to the biological consequence of somatic excision (SE). In this work, we used temperature stress to induce increasing transposition of mariner-Mos1 during different stages of the development of D. simulans, aiming to quantify SE during lifespan. Furthermore, strains of D. melanogaster exhibiting differential expression of mariner-Mos1 were employed for estimating some biological consequences of mariner mobilization. It is shown that SE of mariner-Mos1 was not constant during development; the larval phase had the highest rates while the pupal stage exhibited lower rates, and in the embryonic stage, no difference was detected. SE can be detrimental, as suggested by correlation in SE level and reduction in behavioral activities and embryonic viability. This study showed that mariner-Mos1 SE accumulates during the Drosophila life cycle, and can be involved in detrimental effects., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To determine frequency, stage and grade of placental histologic acute maternal inflammatory response (MIR) and fetal inflammatory response (FIR) in meconium-stained amniotic fluid (MSAF) in our predominantly African-American population., Methods: Term placentas with MSAF (n = 310) were evaluated for MIR/FIR, including stage/grade, and compared with placentas with clear amniotic fluid (AF) (n = 250). MIR/FIR were also evaluated in thick compared to thin MSAF subgroups. Selected demographic and clinical features were compared., Results: MIR and FIR were present in 57.7 and 40.3% of the MSAF compared to 44.0 and 29.2% of the clear AF group, respectively (p = .001 and .008). MIR with FIR was present in 35.8% of the MSAF compared to 25.2% of the clear AF group (p = .008); however, there was no significant difference in frequency of MIR without FIR between groups. There was no significant difference in frequency of MIR/FIR in thick compared to thin MSAF; however, thick MSAF was associated with higher FIR stage compared to thin MSAF (29.2 versus 5.4%, p = .004). This association was not seen with MIR stage or MIR/FIR grade., Conclusions: Histologic MIR and FIR are frequent findings in MSAF. Thick MSAF is associated with higher FIR stage when compared to thin MSAF.

Objetive: The aim of this study was to characterize the acoustic signal of silent tracheal aspiration in children with oropharyngeal dysphagia (OPD)., Method: Thirty-two children with OPD were examined with combined digital cervical auscultation (DCA) and videofluoroscopic swallow study (VFSS). Power spectral density (PSD, in 1/√Hz) of the acoustic signal from a sequential series of five liquid swallows was used for comparisons between children who silently aspirated and children who did not aspirate on VFSS. Fourteen children were excluded due to either DCA/VFSS artifact or non-silent aspiration (cough, choking)., Results: The remaining 18 participants (median age 6 years, range 2-12.8) were classified based on VFSS as aspirators (n = 8) and non-aspirators (n = 10). The PSD curve of aspirators presented an ascending pattern (1st vs. 5th deglutition: 695.2 vs. 4421.9 1/√Hz), while the curve of non-aspirators was flat (1st vs. 5th deglutition: 509 vs. 463.4 1/√Hz), with marked differences being observed from the 3rd measure onwards (p < .001). In this study, DCA was able to identify silent tracheal aspiration in children with OPD., Conclusion: This non-invasive technique identified aspiration by an increase in the PSD curve in aspiration sounds.

Objective To determine the frequency and type of histopathologic lesions in placentas delivered by women with a normal pregnancy outcome. Methods This retrospective cohort study included placental samples from 944 women with a singleton gestation who delivered at term without obstetrical complications. Placental lesions were classified into the following four categories as defined by the Society for Pediatric Pathology and by our unit: (1) acute placental inflammation, (2) chronic placental inflammation, (3) maternal vascular malperfusion and (4) fetal vascular malperfusion. Results (1) Seventy-eight percent of the placentas had lesions consistent with inflammatory or vascular lesions; (2) acute inflammatory lesions were the most prevalent, observed in 42.3% of the placentas, but only 1.0% of the lesions were severe; (3) acute inflammatory lesions were more common in the placentas of women with labor than in those without labor; (4) chronic inflammatory lesions of the placenta were present in 29.9%; and (5) maternal and fetal vascular lesions of malperfusion were detected in 35.7% and 19.7%, respectively. Two or more lesions with maternal or fetal vascular features consistent with malperfusion (high-burden lesions) were present in 7.4% and 0.7%, respectively. Conclusion Most placentas had lesions consistent with inflammatory or vascular lesions, but severe and/or high-burden lesions were infrequent. Mild placental lesions may be interpreted either as acute changes associated with parturition or as representative of a subclinical pathological process (intra-amniotic infection or sterile intra-amniotic inflammation) that did not affect the clinical course of pregnancy.

Twin births are an important public health issue due to health complications for both mother and children. While it is known that contemporary factors have drastically changed the epidemiology of twins in certain developed countries, in Brazil, relevant data are still scarce. Thus, we carried out a population-based study of live births in spatial and temporal dimensions using data from Brazil's Live Birth Information System, which covers the entire country. Over 41 million births registered between 2001 and 2014 were classified as singleton, twin or multiple. Twinning rates (TR) averaged 9.41 per 1,000 for the study period and a first-order autoregressive model of time-series analysis revealed a global upward trend over time; however, there were important regional differences. In fact, a Cluster and Outlier Analysis (Anselin Local Moran's I) was performed and identified clusters of high TR in an area stretching from the south of Brazil's Northeast Region to the South Region (Global Moran Index = 0.062, P < 0.001). Spearman's correlation coefficient and a Wilcoxon matched pairs test revealed a positive association between Human Development Index (HDI) and TRs in different scenarios, suggesting that the HDI might be an important indicator of childbearing age and assisted reproduction techniques in Brazil. Furthermore, there was a sharp increase of 26.42% in TR in women aged 45 and over during study period. The upward temporal trend in TRs is in line with recent observations from other countries, while the spatial analysis has revealed two very different realities within the same country. Our approach to TR using HDI as a proxy for underlying socioeconomic changes can be applied to other developing countries with regional inequalities resembling those found in Brazil., Competing Interests: The authors have declared that no competing interests exist.

Objective: Examine the association between placental inflammation and neonatal infections, and 25OH vitamin D (25OH D) levels at birth among very low birth weight infants (VLBWI)., Study Design: Serum 25OH D levels were measured in 89 VLBWI (≤1250 g) and 47 mothers on day one, and in 78 infants on day 21. Placentas were examined for maternal and fetal inflammation. Infants were divided into deficient (≤10 ng/ml) and adequate (>10 ng/ml) groups based on 25OH D levels on day 1., Results: Mean ± SD maternal levels of 25OH D (21 ± 9 ng/ml) correlated with infants' levels (15 ± 8 ng/ml), (p < .001). 25OH D levels were lower in deficient (32/89) than in adequate group (8 ± 2 versus 20 ± 7 ng/ml, p = .011). Infants' 25OH D levels rose significantly by day 21 (p < .001). Univariate analyses showed no differences between infant groups in maternal or fetal inflammation, or neonatal infections (p > .05). Logistic regression analyses revealed no association between deficient 25OH D levels and the odds of maternal or fetal inflammation or other infections. Levels of 25OH D did not correlate with severity of placental inflammation., Conclusions: Deficient levels of 25OH D at birth are not associated with the occurrence of placental inflammation or neonatal infections among VLBWI.

Background/aims: Evaluation of esophageal clearance by orange juice swallowing could be useful to identify different categories of gastroesophageal reflux disease. We determined whether a juice test at the beginning of esophageal pH monitoring can identify nonerosive reflux disease (NERD) among heartburn patients., Methods: Multiple swallows of orange juice (pH 3) were performed at the beginning of esophageal pH monitoring in 71 heartburn patients off acid-suppressive therapy. The area between pH drop below 5 and recovery to 5 was calculated from pH tracings and named Delta5 (mmol∙L⁻¹∙sec). Fifteen healthy subjects served to determine Delta5 cutoff (95th percentile). Patients were classified as NERD, non-NERD (a mix of reflux hypersensitivity, functional heartburn, and undetermined), and erosive disease depending on acid exposure, reflux symptom analysis, and upper endoscopy., Results: Delta5 cutoff in healthy subjects was 251 mmol·L⁻¹∙sec. Among 71 patients, 23 had NERD, 26 had non-NERD, and 22 had erosive disease. Compared to non-NERD, Delta5 was higher in both NERD (median [interquartile range]: 316 [213-472] vs 165 [105-225]; P ＜ 0.01) and erosive disease (310 [169-625] vs 165 [105-225]; P ＜ 0.01). An elevated Delta5 (＞ 251 mmol∙L⁻¹∙sec) showed sensitivity of 74% and specificity of 81% for identification of NERD. Positive and negative likelihood ratios were 3.84 and 0.32 respectively, whereas test accuracy was 78%., Conclusions: A juice test with calculation of Delta5 helps in the identification of true NERD among heartburn patients with endoscopy-negative reflux disease. In these patients, an elevated Delta5 could make prolonged reflux testing unnecessary.

Sisyrinchium is the largest genus of Iridaceae in the Americas and has the greatest amount of cytological data available. This study aimed at investigating how genomes evolved in this genus. Chromosome number, genome size and altitude from species of sect. Viperella were analyzed in a phylogenetic context. Meiotic and pollen analyses were performed to assess reproductive success of natural populations, especially from those polyploid taxa. Character optimizations revealed that the common ancestor of sect. Viperella was probably diploid (2n = 2x =18) with two subsequent polyplodization events. Total DNA content (2C) varied considerably across the phylogeny with larger genomes detected mainly in polyploid species. Altitude also varied across the phylogeny, however no significant relationship was found between DNA content changes and altitude in our data set. All taxa presented regular meiosis and pollen viability (> 87%), except for S. sp. nov. aff. alatum (22.70%), suggesting a recent hybrid origin. Chromosome number is mostly constant within this section and polyploidy is the only source of modification. Although 2C varied considerably among the 20 taxa investigated, the diversity observed cannot be attributed only to polyploidy events because large variations of DNA content were also observed among diploids.

Levodopa is the most used drug to treat motor symptoms in Parkinson's disease (PD). However, dopaminergic side effects such as nausea and vomiting may occur. Several evidences indicate a major role for dopamine receptors D2 (DRD2) and D3 (DRD3) in emetic activity. The aim of this study was to investigate the relationship of DRD2 rs1799732 and DRD3 rs6280 gene polymorphisms with gastrointestinal (GI) symptoms induced by levodopa in PD patients. Two hundred and seventeen PD patients on levodopa therapy were investigated. DRD2 rs1799732 and DRD3 rs6280 polymorphisms were genotyped by PCR-based methods. Multiple Poisson regression method with robust variance estimators was performed to assess the association between polymorphisms and gastrointestinal symptoms. The analyses showed that DRD2 Ins/Ins (prevalence ratio (PR)=2.374, 95% confidence interval (CI): 1.105-5.100; P=0.027) and DRD3 Ser/Ser genotypes (PR=1.677, 95% CI 1.077-2.611; P=0.022) were independent and predictors of gastrointestinal symptoms associated with levodopa therapy. Despite all the efforts to alleviate GI symptoms, this adverse effect still occurs in PD patients. Pharmacogenetic studies of GI symptoms induced by levodopa therapy have the potential to display new ways to better understand the molecular mechanisms involved in these side effects.

Background: Neutrophils are the most abundant white blood cells found in the amniotic cavity of women with intraamniotic infection and/or inflammation. The current belief is that these neutrophils are of fetal origin. However, abundant neutrophils have been found in the amniotic fluid of women with a severe acute maternal inflammatory response but without a severe fetal inflammatory response in the placenta, suggesting that these innate immune cells can also be of maternal origin or a mixture of both fetal and maternal neutrophils., Objective: We sought to investigate the origin of amniotic fluid neutrophils from women with intraamniotic infection and/or inflammation and to correlate these findings with acute histologic maternal and fetal inflammatory responses in the placenta., Study Design: Amniotic fluid was collected from 15 women with suspected intraamniotic infection and/or inflammation (positive microbiological cultures and/or interleukin-6 concentrations ≥2.6 ng/mL). Amniotic fluid neutrophils were purified by fluorescence-activated cell sorting, DNA was extracted, and DNA fingerprinting was performed. DNA fingerprinting was also performed in the umbilical cord and maternal blood DNA. Fluorescence in situ hybridization was assayed in women with male neonates. Blinded placental histopathological evaluations were conducted., Results: First, DNA fingerprinting revealed that 43% (6/14) of women who underwent a single amniocentesis had mostly fetal neutrophils in the amniotic fluid. Second, DNA fingerprinting showed that 36% (5/14) of the women who underwent a single amniocentesis had predominantly maternal neutrophils in the amniotic fluid. Third, DNA fingerprinting indicated that 21% (3/14) of the women who underwent a single amniocentesis had an evident mixture of fetal and maternal neutrophils in the amniotic fluid. Fourth, DNA fingerprinting revealed that a woman who underwent 2 amniocenteses (patient 15) had fetal neutrophils first, and as infection progressed, abundant maternal neutrophils invaded the amniotic cavity. Fifth, fluorescence in situ hybridization confirmed DNA fingerprinting results by showing that both fetal and maternal neutrophils were present in the amniotic fluid. Sixth, most of the women who had predominantly amniotic fluid neutrophils of fetal origin at the time of collection delivered extremely preterm neonates (71% [5/7]). Seventh, all of the women who had predominantly amniotic fluid neutrophils of maternal origin at the time of collection delivered term or late preterm neonates (100% [6/6]). Eighth, 2 of the women who had an evident mixture of fetal and maternal neutrophils in the amniotic fluid at the time of collection delivered extremely preterm neonates (67% [2/3]), and the third woman delivered a term neonate (33% [1/3]). Finally, most of the women included in this study presented acute maternal and fetal inflammatory responses in the placenta (87% [13/15])., Conclusion: Amniotic fluid neutrophils can be either predominantly of fetal or maternal origin, or a mixture of both fetal and maternal origin, in women with intraamniotic infection and/or inflammation. The findings herein provide evidence that both fetal and maternal neutrophils can invade the amniotic cavity, suggesting that both the fetus and the mother participate in the host defense mechanisms against intraamniotic infection., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Neutrophil extracellular traps (NETs) control microbial infections through their antimicrobial activities attributed to DNA, histones, granules, and cytoplasmic proteins (eg, elastase). Intra-amniotic infection is characterized by the influx of neutrophils into the amniotic cavity; therefore, the aim of this study was to determine whether amniotic fluid neutrophils form NETs in this inflammatory process., Methods: Amniotic fluid samples from women with intra-amniotic infection (n = 15) were stained for bacteria detection using fluorescent dyes. Amniotic fluid neutrophils were purified by filtration. As controls, neutrophils from maternal blood samples (n = 3) were isolated by density gradients. Isolated neutrophils were plated onto glass cover slips for culture with and without 100 nM of phorbol-12-myristate-13-acetate (PMA). NET formation was assessed by 4',6-diamidino-2-phenylindole (DAPI) staining and scanning electron microscopy. Different stages of NET formation were visualized using antibodies against elastase and histone H3, in combination with DAPI staining, by confocal microscopy. Finally, maternal or neonatal neutrophils were added to amniotic fluid samples from women without intra-amniotic infection (n = 4), and NET formation was evaluated by DAPI staining., Results: (1) NETs were present in the amniotic fluid of women with intra-amniotic infection; (2) all of the amniotic fluid samples had detectable live and dead bacteria associated with the presence of NETs; (3) in contrast to neutrophils from the maternal circulation, amniotic fluid neutrophils did not require PMA stimulation to form NETs; (4) different stages of NET formation were observed by co-localizing elastase, histone H3, and DNA in amniotic fluid neutrophils; and (5) neither maternal nor neonatal neutrophils form NETs in the amniotic fluid of women without intra-amniotic infection., Conclusion: NETs are detectable in the amniotic fluid of women with intra-amniotic infection.

Problem: To determine whether amniotic fluid (AF) CXCL10 concentration is associated with histologic chronic chorioamnionitis in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PROM)., Method of Study: This study included 168 women who had an episode of PTL or preterm PROM. AF interleukin (IL)-6 and CXCL10 concentrations were determined by immunoassay., Results: (i) Increased AF CXCL10 concentration was associated with chronic (OR: 4.8; 95% CI: 1.7-14), but not acute chorioamnionitis; (ii) increased AF IL-6 concentration was associated with acute (OR: 4.2; 95% CI: 1.3-13.7) but not chronic chorioamnionitis; and (iii) an increase in AF CXCL10 concentration was associated with placental lesions consistent with maternal anti-fetal rejection (OR: 3.7; 95% CI: 1.3-10.4). (iv) All patients with elevated AF CXCL10 and IL-6 delivered preterm., Conclusion: Increased AF CXCL10 concentration is associated with chronic chorioamnionitis or maternal anti-fetal rejection, whereas increased AF IL-6 concentration is associated with acute histologic chorioamnionitis., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Background: Skeletal ciliopathies comprise a spectrum of ciliary malfunction disorders that have a profound effect on the skeleton. Most common among these disorders is short rib polydactyly syndrome (SRPS), a recessively inherited perinatal lethal condition characterized by a long narrow chest, markedly shortened long bones, polydactyly and, often, multi-organ system involvement. SRPS shows extensive locus heterogeneity with mutations in genes encoding proteins that participate in cilia formation and/or function., Results: Herein we describe mutations in IFT43 , a satellite member of the retrograde IFT-A complex, that produce a form of SRPS with unusual bending of the ribs and appendicular bones. These newly described IFT43 mutations disrupted cilia formation, produced abnormalities in cartilage growth plate architecture thus contributing to altered endochondral ossification. We further show that the IFT43 SRPS phenotype is similar to SRPS resulting from mutations in the gene encoding IFT121 (WDR35), a direct interactor with IFT43., Conclusions: This study defines a new IFT43 -associated phenotype, identifying an additional locus for SRPS. The data demonstrate that IFT43 is essential for ciliogenesis and that the mutations disrupted the orderly proliferation and differentiation of growth plate chondrocytes, resulting in a severe effect on endochondral ossification and mineralization. Phenotypic similarities with SRPS cases resulting from mutations in the gene encoding the IFT43 direct interacting protein IFT121 suggests that similar mechanisms may be disrupted by defects in these two IFT-A satellite interactors.

Adrenal histologic changes, including compact cell change (CCC), cystic change (CYC), and adrenal hemorrhage (AH), and their clinical correlations have only infrequently been investigated in stillbirth. We evaluated 75 third trimester singleton stillborns with complete autopsies (30 term and 45 preterm). A total of 58 had unexplained stillbirth and 17 had clinical placental abruption. The mothers were predominantly African-American (89%). CCC and CYC were diagnosed as cytoplasmic eosinophilia and cystic cavities in the definitive cortex, respectively. Adrenal changes were correlated with acute thymic involution (ATI), thymic petechiae, and clinical features, including abruption. CCC, CYC, and AH were present in 58 (77%), 51 (68%), and 15 (20%) of the 75 stillborns, respectively. CCC and CYC were frequently seen together ( P < .001). CCC and CYC were associated with higher ATI grade ( P < .001 and P = .010, respectively). The presence of CCC, but not CYC, was associated with absence of thymic petechiae ( P = .013) and was more frequent with unexplained stillbirth compared to abruption ( P = .017). AH was associated with lower ATI grade ( P = .002), with thymic petechiae ( P < .001), and with abruption ( P = .004). CYC was associated with diabetes ( P = .015). Overall, CCC and CYC were frequent findings and correlated with higher ATI grade, suggesting similar causes and time frames. CCC, but not CYC, correlated with unexplained stillbirth compared to abruption, but its high frequency in both groups limits its usefulness in their separation. AH was more frequent in the abruption group and correlated with lower ATI grade and thymic petechiae, supporting an association with sudden asphyxial death.