Autophagy and nuclear morphometry are associated with histopathologic features in esophageal squamous cell carcinoma.

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 BECNhigh/MAP1LC3high and BECNhigh/SQSTM1high. 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.

SARS-CoV-2 infected children form early immune memory responses dominated by nucleocapsid-specific CD8+ T cells and antibodies.

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.

Reduced mastication is a risk factor for Rome IV postprandial distress syndrome in patients investigated with upper endoscopy.

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.

Short-term intestinal effects of water intake in fibre supplementation in healthy, low-habitual fibre consumers: a phase 2 clinical trial.

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.

Multidrug-resistant Escherichia coli from free-living pigeons (Columba livia): Insights into antibiotic environmental contamination and detection of resistance genes.

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. blaVIM 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 blaVIM -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.

Reduced masticatory function predicts gastroesophageal reflux disease and esophageal dysphagia in patients referred for upper endoscopy: A cross-sectional study.

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.

Pediatric COVID-19 patients in South Brazil show abundant viral mRNA and strong specific anti-viral responses.

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-DRhighCX3CR1low 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.

Blood groups in Native Americans: a look beyond ABO and Rh.

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.

Evaluation of Polymorphisms in Toll-Like Receptor Genes as Biomarkers of the Response to Treatment of Erythema Nodosum Leprosum.

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.

Lactobacillus brevis CD2 attenuates traumatic oral lesions induced by fixed orthodontic appliance: A randomized phase 2 trial.

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.

Cancer Cell Fitness Is Dynamic.

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.

Abdominal Palpation Does Not Modify the Number of Bowel Sounds in Healthy Volunteers and Gastrointestinal Outpatients.

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.

Predictors of dental erosions in patients evaluated with upper digestive endoscopy: a cross-sectional study.

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.

Viral DNA genomes in sera of farrowing sows with or without stillbirths.

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.

Poor sleep quality associates with self-reported psychiatric and cardiometabolic symptoms independently of sleep timing patterns in a large sample of rural and urban workers.

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.

Are Lactobacillus salivarius G60 and inulin more efficacious to treat patients with oral halitosis and tongue coating than the probiotic alone and placebo? A randomized clinical trial.

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.

Nuclear morphometric analysis in tissue as an objective tool with potential use to improve melanoma staging.

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.

The somatic mobilization of transposable element mariner-Mos1 during the Drosophila lifespan and its biological consequences.

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.

Acoustic signal of silent tracheal aspiration in children with oropharyngeal dysphagia.

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.