Cardiac Overexpression of PDE4B Blunts ß-Adrenergic Response and Maladaptive Remodeling in Heart Failure.

BACKGROUND: The cyclic AMP (adenosine monophosphate; cAMP)-hydrolyzing protein PDE4B (phosphodiesterase 4B) is a key negative regulator of cardiac ß-adrenergic receptor stimulation. PDE4B deficiency leads to abnormal Ca2+ handling and PDE4B is decreased in pressure overload hypertrophy, suggesting that increasing PDE4B in the heart is beneficial in heart failure. METHODS: We measured PDE4B expression in human cardiac tissues and developed 2 transgenic mouse lines with cardiomyocyte-specific overexpression of PDE4B and an adeno-associated virus serotype 9 encoding PDE4B. Myocardial structure and function were evaluated by echocardiography, ECG, and in Langendorff-perfused hearts. Also, cAMP and PKA (cAMP dependent protein kinase) activity were monitored by Förster resonance energy transfer, L-type Ca2+ current by whole-cell patch-clamp, and cardiomyocyte shortening and Ca2+ transients with an Ionoptix system. Heart failure was induced by 2 weeks infusion of isoproterenol or transverse aortic constriction. Cardiac remodeling was evaluated by serial echocardiography, morphometric analysis, and histology. RESULTS: PDE4B protein was decreased in human failing hearts. The first PDE4B-transgenic mouse line (TG15) had a ≈15-fold increase in cardiac cAMP-PDE activity and a ≈30% decrease in cAMP content and fractional shortening associated with a mild cardiac hypertrophy that resorbed with age. Basal ex vivo myocardial function was unchanged, but ß-adrenergic receptor stimulation of cardiac inotropy, cAMP, PKA, L-type Ca2+ current, Ca2+ transients, and cell contraction were blunted. Endurance capacity and life expectancy were normal. Moreover, these mice were protected from systolic dysfunction, hypertrophy, lung congestion, and fibrosis induced by chronic isoproterenol treatment. In the second PDE4B-transgenic mouse line (TG50), markedly higher PDE4B overexpression, resulting in a ≈50-fold increase in cardiac cAMP-PDE activity caused a ≈50% decrease in fractional shortening, hypertrophy, dilatation, and premature death. In contrast, mice injected with adeno-associated virus serotype 9 encoding PDE4B (1012 viral particles/mouse) had a ≈50% increase in cardiac cAMP-PDE activity, which did not modify basal cardiac function but efficiently prevented systolic dysfunction, apoptosis, and fibrosis, while attenuating hypertrophy induced by chronic isoproterenol infusion. Similarly, adeno-associated virus serotype 9 encoding PDE4B slowed contractile deterioration, attenuated hypertrophy and lung congestion, and prevented apoptosis and fibrotic remodeling in transverse aortic constriction. CONCLUSIONS: Our results indicate that a moderate increase in PDE4B is cardioprotective and suggest that cardiac gene therapy with PDE4B might constitute a new promising approach to treat heart failure.

Phosphodiesterase 2 Protects Against Catecholamine-Induced Arrhythmia and Preserves Contractile Function After Myocardial Infarction.

RATIONALE: Phosphodiesterase 2 is a dual substrate esterase, which has the unique property to be stimulated by cGMP, but primarily hydrolyzes cAMP. Myocardial phosphodiesterase 2 is upregulated in human heart failure, but its role in the heart is unknown. OBJECTIVE: To explore the role of phosphodiesterase 2 in cardiac function, propensity to arrhythmia, and myocardial infarction. METHODS AND RESULTS: Pharmacological inhibition of phosphodiesterase 2 (BAY 60-7550, BAY) led to a significant positive chronotropic effect on top of maximal ß-adrenoceptor activation in healthy mice. Under pathological conditions induced by chronic catecholamine infusions, BAY reversed both the attenuated ß-adrenoceptor-mediated inotropy and chronotropy. Conversely, ECG telemetry in heart-specific phosphodiesterase 2-transgenic (TG) mice showed a marked reduction in resting and in maximal heart rate, whereas cardiac output was completely preserved because of greater cardiac contraction. This well-tolerated phenotype persisted in elderly TG with no indications of cardiac pathology or premature death. During arrhythmia provocation induced by catecholamine injections, TG animals were resistant to triggered ventricular arrhythmias. Accordingly, Ca2+-spark analysis in isolated TG cardiomyocytes revealed remarkably reduced Ca2+ leakage and lower basal phosphorylation levels of Ca2+-cycling proteins including ryanodine receptor type 2. Moreover, TG demonstrated improved cardiac function after myocardial infarction. CONCLUSIONS: Endogenous phosphodiesterase 2 contributes to heart rate regulation. Greater phosphodiesterase 2 abundance protects against arrhythmias and improves contraction force after severe ischemic insult. Activating myocardial phosphodiesterase 2 may, thus, represent a novel intracellular antiadrenergic therapeutic strategy protecting the heart from arrhythmia and contractile dysfunction.

Efficacy of Internal Limiting Membrane Flap Techniques with Vitrectomy for Macular Detachment Associated with an Optic Disc Pit.

PURPOSE: To compare the anatomical and functional outcome of adjuvant pars plana vitrectomy (PPV) procedures using the techniques of translocation of an internal limiting membrane (ILM) flap and transplantation of an inverted ILM flap for the treatment of chronic and/or refractory optic disc pit (ODP) maculopathy. METHODS: In this prospective interventional case series study, 9 patients (9 eyes) with chronic and/or refractory ODP maculopathy underwent PPV with either translocation of an ILM flap or transplantation of an inverted ILM flap as adjuvant techniques along with gas tamponade. The anatomical success, rates of macular reattachment, and visual improvement were assessed. RESULTS: The mean preoperative central retinal thickness (CRT) was 723.4 µm (range: 366-1,151). The mean postoperative CRT was 398.1 ± 212.2 µm (range: 210-758). An increased preoperative CRT was associated with a lower chance of postoperative reattachment of the macula (p = 0.047). The overall reattachment rate at the end of the follow-up period was 56% (n = 5). The mean preoperative visual acuity (logMAR unit [Snellen acuity]) was 0.48 (20/60) (range: 1.30 [20/400] to 0.10 [20/25]). The mean change in best corrected visual acuity (BCVA) was 0.48 ± 0.233 logMAR units (approx. 3 lines of visual improvement). CONCLUSIONS: ILM flap techniques are logical and straightforward approaches as adjuvants to PPV treatment of ODP maculopathy. They could be viable adjuvant treatments for improvement in BCVA and CRT in patients with ODP maculopathy.

Persistent gender disparity in leading dental publications across 4 decades: an observational study.

OBJECTIVES: This observational study assessed the differences in the gender of the first and last authors in the most-cited dental articles over the last 4 decades. STUDY DESIGN AND SETTING: Articles were obtained through an electronic search of the most-cited articles in dentistry by decade (total n = 400 articles). The 100 most-cited studies in each decade (1980-1989, 1990-1999, 2000-2009, and 2010-2019), with any study design, with results in dentistry were eligible. The gender of the first and last authors was determined using the Genderize database. Comparative evaluation of gender distribution in general and across the 4 decades was performed with the Chi-square test, and the contribution of variables on the citation rate of articles was performed using linear regression. RESULTS: There were statistical differences between the gender distributions, with a predominance of men in the first (83.8%) and the last (86.8%) positions (P < .001). Over the decades, there was a tendency for an increase in the proportion of women as the last author (P = .002; Chi-square trend Test), with an increase of women from 6% to 22% across the last 4 decades. However, no statistically significant differences were observed between the genders for the first author in the last 4 decades (P = .163; Chi-square trend Test). CONCLUSION: The findings indicate that men lead a large percentage of the most-cited articles in dentistry and that this trend has not shown substantial modifications over the last years. Nonetheless, for the position of last authorship, an increase in women's representativity was observed over the last decades.

Differential effect of social mobility on tooth loss by race in adulthood: 1982 Pelotas Birth Cohort Study.

OBJECTIVES: To examine the association between social mobility and tooth loss in adults from the 1982 Pelotas Birth Cohort Study and whether race modifies this association. METHODS: The Oral Health Study used data from 541 individuals who were followed up to 31 years of age. Social mobility, composed of the participants' socioeconomic position (SEP) at birth and at age 30, was categorized as never poor, upwardly mobile, downwardly mobile and always poor. The outcome was the prevalence of at least one tooth lost due to dental caries when the participants were examined at 31 years of age. The effect modifier was race (Black/Brown versus white people). Log-binomial regression models were used to estimate crude and sex-adjusted prevalence ratios (PR) and to determine whether the association varied with race. Statistical interactions were tested using an additive scale. RESULTS: The prevalence of any tooth loss was 50.8% (n = 274). In social mobility groups, the prevalence of at least one tooth lost in the never-poor group was about 31% points higher for Black/Brown (68.2%) than for white people (37.4%). Antagonistic findings were found for the interaction between race and social mobility (Sinergy Index = 0.48; 95% CI 0.24, 0.99; and relative excess of risk due to the interaction = -1.38; 95% CI -2.34, -0.42), suggesting that the observed joint effect of race and social mobility on tooth loss was lower than the expected sum of these factors. The estimates for Black/Brown people were smaller for those who were always poor during their lives, relative to their white counterparts. CONCLUSIONS: The findings suggest a higher prevalence of at least one tooth lost among people in the downward mobile SEP group and Black/Brown people. Greater racial inequity was found among Black/Brown people who had never experienced episodes of poverty, with Black/Brown people having a greater prevalence of at least one tooth lost than their white counterparts.

Carbon dynamics in the future forest: the importance of long-term successional legacy and climate-fire interactions.

Understanding how climate change may influence forest carbon (C) budgets requires knowledge of forest growth relationships with regional climate, long-term forest succession, and past and future disturbances, such as wildfires and timber harvesting events. We used a landscape-scale model of forest succession, wildfire, and C dynamics (LANDIS-II) to evaluate the effects of a changing climate (A2 and B1 IPCC emissions; Geophysical Fluid Dynamics Laboratory General Circulation Models) on total forest C, tree species composition, and wildfire dynamics in the Lake Tahoe Basin, California, and Nevada. The independent effects of temperature and precipitation were assessed within and among climate models. Results highlight the importance of modeling forest succession and stand development processes at the landscape scale for understanding the C cycle. Due primarily to landscape legacy effects of historic logging of the Comstock Era in the late 1880s, C sequestration may continue throughout the current century, and the forest will remain a C sink (Net Ecosystem Carbon Balance > 0), regardless of climate regime. Climate change caused increases in temperatures limited simulated C sequestration potential because of augmented fire activity and reduced establishment ability of subalpine and upper montane trees. Higher temperatures influenced forest response more than reduced precipitation. As the forest reached its potential steady state, the forest could become C neutral or a C source, and climate change could accelerate this transition. The future of forest ecosystem C cycling in many forested systems worldwide may depend more on major disturbances and landscape legacies related to land use than on projected climate change alone.

Use of dental services among adults from a birth cohort in the South region of Brazil.

OBJECTIVE: Measure the prevalence of use of dental services in the previous year and associated factors among 31-year-old adults from a birth cohort of 1982. METHODS: This is a cross-sectional study that analyzed a birth cohort of 1982 from the city of Pelotas. In 1997, a systematic sample of 27% of the city's census sectors was defined and all households in these sectors were visited, where 1,076 15-year-old adolescents were interviewed. For the oral health studies, 900 of these individuals were randomly selected and followed up at 24 and 31 years of age. The study used data collected from 523 individuals in 2013 (at 31 years old). The outcome was visit to the dentist (use of dental services) in the previous year. Demographic factors (sex), socioeconomic factors (income, education), and oral health factors (reason and type of service, self-perception of oral health, dental pain and caries experience - DMFT) were used as independent variables. Prevalence ratios were estimated using Poisson regression. RESULTS: The prevalence of use of dental services in the previous year was 55.3% (95%CI: 51.0-59.5%). In the adjusted analysis, the reason and type of service, self-perception of oral health, and DMFT were associated with the outcome. A stronger association was found with use of dental services in individuals who visited for prevention and used the private service, who were satisfied with their oral health, and who had more caries experiences. CONCLUSION: 55.3% of the cohort sample used dental services in the previous year. Individuals who visited the dentist of private service for preventive reasons, who were very satisfied with their oral health, used these services in a higher proportion. In addition, a higher DMFT index also led to higher use of services.

Pediatric dentistry procedures performed within the Brazilian National Health System in the state of Rio Grande do Sul before and during the COVID-19 pandemic: difference between the years 2018 and 2021.

OBJECTIVE: to analyze the difference in the number of primary teeth dental procedures performed within the Brazilian National Health System (SUS) in the state of Rio Grande do Sul, before and during the COVID-19 pandemic. METHODS: this was a descriptive ecological study, using secondary data from the SUS Outpatient Information System (SIA-SUS), from 2018 to 2021, in the state and in its seven health macro-regions; we calculated the relative and absolute frequencies and the percentage difference of the dental procedures performed. RESULTS: 94,443 and 36,151 dental procedures were recorded before and during the pandemic, respectively, corresponding to a 61.7% reduction; relevant percentage reductions were found in restorative procedures, which reached 20% in the southern region of the state; an increase in the percentage of exodontic and endodontic procedures was found. CONCLUSION: the results suggest that the COVID-19 pandemic had negative repercussions on the performance of primary teeth dental procedures in Ro Grande do Sul.

Discriminatory episodes negatively impact the quality of life of Brazilian dental students: A cross-sectional study.

PURPOSE: This study aimed to evaluate whether discriminatory episodes occurring in the university environment were associated with dental students' self-perceived overall quality of life and assess the cumulative effect of perceived discriminatory experiences on the overall quality of life. METHODS: In this cross-sectional study, all students enrolled in three Brazilian dental schools were invited to participate in a survey between August and October 2019. The outcome was students' self-perceived quality of life, measured through the overall quality of life item of the World Health Organization-Quality of Life Abbreviated Version (WHOQOL-BREF). Descriptive, bivariate, and multivariable logistic regression analyses (95% confidence intervals and α of 5%) were conducted using RStudio software. RESULTS: The sample was composed of 732 students (70.2% response rate). The great part was female (66.9%), white or yellow skin color (67.9%), and were children of highly educated mothers. About 68% of the students reported having experienced at least one of the seven discriminatory experiences presented in the questionnaire and 18.1% reported neutral or negative quality of life. In multivariable analyses, it was estimated that students who experienced at least one episode of discrimination were 2.54 times (95% CI: 1.47-4.34) more likely to report worse quality of life than their counterparts who reported no experience of discrimination. There was also a 25% (95% CI: 1.10-1.42) increase in the odds of reporting poorer quality of life for each additional discriminatory experience reported. CONCLUSION: Reporting at least one discriminatory situation in the academic environment was associated with worse quality of life among dental students, and a cumulative effect was also noted.

Socioeconomic inequalities related to maternal perception of children's oral health at age 4: Results of a birth cohort.

OBJECTIVES: To estimate socioeconomic inequalities in the maternal perception of children's oral health from a birth cohort study in Brazil. METHODS: The data from this study were collected through perinatal interviews and at the 48-month follow-up from the 2015 Pelotas Birth Cohort Study. The main outcome was the maternal perception of children's oral health, dichotomized into positive (good/very good) and negative (fair/bad/very bad). The secondary outcome was untreated dental caries (absence and presence, according to the ICDAS index - International Caries Detection and Assessment System). For the statistical analysis, the absolute inequality index (Slope Index of Inequality - SII) and the relative concentration index (Concentration Index - CIX) were used. Analyses were stratified by maternal educational level, family income and wealth index. RESULTS: The prevalence of outcomes was 19.4% (95% CI 18.2; 20.7) for the negative maternal perception of children's oral health and 15.6% (95% CI 14.4; 16.8) for untreated dental caries. Socioeconomics inequalities were observed in negative maternal perception of children's oral health in both absolute and relative terms. A SII of -16.6 (95% CI -20.8; -12.5) was observed for family income, with higher prevalence in poor families. A higher prevalence of the negative maternal perception of children's oral health was observed in mothers without any educational level or a few years of study (CIX -21.1 [95% CI -24.5; -17.7]). CONCLUSIONS: This study demonstrates socioeconomics disparities in the maternal perception of children's oral health and in the prevalence of untreated caries in children. A higher concentration of negative maternal perception of children's oral health was identified among the most socioeconomically vulnerable individuals. The findings reinforce the presence of socioeconomic inequalities in subjective measures about children's oral health.

Association among oral health and academic performance: a longitudinal study in a university in Southern Brazil.

This longitudinal study aimed to investigate the association between self-perceived oral health, oral-health-related quality-of-life (OHRQoL), toothache, and university students' academic performance or dropout. A cohort of 2,089 students from 64 different courses at a public university in southern Brazil was interviewed in 2016 regarding their self-perceived oral health (Locker instrument; dichotomized into good/poor), OHRQoL (Oral Impacts on Daily Performances instrument, OIDP) and having had any toothache over the last 6 months (yes/no). After three years (2020), the academic records of 1,870 of these students were assessed, their average grade over all courses evaluated, and their dropout status was determined. Multivariable linear or logistic regression adjusting for gender, skin color, age, family income and maternal education was used to associate oral health variables (self-perceived oral health, OIDP, toothache) and academic performance or dropout. In 2016, 28.6% reported negative self-perceived oral health through the Locker instrument and 31.4% had toothache in the last 6 months. Over the next three years, 36.2% had dropped out. In multivariable regression, toothache in the last 6 months had a decrease of 0.32 (ß -0.32, CI95% -0.59; -0.04) points in the final grade and were 35% (OR 1.35 CI95% 1.08; 1.69) more likely to dropout than students without toothache. In conclusion, this study showed that worse oral health conditions may be associated with worse academic performance or dropping out.

Notifications of physical, sexual and emotional violence and neglect against children in Brazil, 2011-2019: an ecological time-series study.

OBJECTIVE: To describe the temporal trend of notifications of physical, sexual and emotional violence and neglect against children in Brazil between 2011 and 2019. METHODS: This was an ecological time-series study based on notifications of violence against children aged 0-9 years held on the Brazilian Notifiable Health Conditions Information System. Age-adjusted notification rates were calculated for Brazil as a whole, by national macro-region and by sex. Trends were assessed using Joinpoint Regression. RESULTS: We analyzed 88,820 notifications of physical violence, 87,141 notifications of sexual violence, 52,359 notifications of emotional violence and 166,664 notifications of neglect. A rising trend was identified for notifications of physical, sexual and emotional violence and neglect for Brazil as a whole and for both sexes. Neglect accounted for the highest rate (95.24 notifications per 100,000 children in 2019). The Northeast and Southeast macro-regions had rising trends for all forms of violence. CONCLUSION: Notifications of physical, sexual and emotional violence and neglect showed rising trends in Brazil in the period studied. IMPLICATIONS FOR SERVICES: Increasing trends in notifications of violence against children highlight the continued need for capacity building in health services, crucial for early detection, effective prevention and coordinated intervention, taking regional variations into account. PERSPECTIVES: Notification of violence against children by health services requires greater commitment by health workers. Future studies could combine multiple national databases and surveys to increase the accuracy of rates and trends.

Association Involving Possible Sleep Bruxism, Stress, and Depressive Symptoms in Brazilian University Students: A Cross-sectional Study.

The aim of the present study was to examine the association regarding sleep bruxism (SB), depression, and stress in Brazilian university students. We conducted a cross-sectional study with a large-sample of university students ( n = 2,089) in the city of Pelotas, Rio Grande do Sul, Southern Brazil. A self-administered questionnaire was sent to classrooms to evaluate socioeconomic and demographic characteristics. Possible SB was detected by self-report according to the International Consensus on The Assessment of Bruxism Criteria (2018). The Patient Health Questionnaire-9 and the Perceived Stress Scale were used to assess depression and stress symptoms respectively. Crude and adjusted Poisson regression analyses were performed. The prevalence of possible SB, high level of stress, and depressive symptoms in the sample were of 20.4%, 16.6%, and 16.6% respectively. Stress in female students was significantly associated with an increased prevalence of possible SB, but not in male students. Regarding depression, the prevalence of SB was 28% higher in students with depressive symptoms. Students with stress or depression had a 35% higher prevalence of SB than those without any symptoms. Conclusion The findings have shown that university students with stress and depressive symptoms were more likely to be detected with possible SB.

Two decades of socioeconomic inequalities in the prevalence of untreated dental caries in early childhood: Results from three birth cohorts in southern Brazil.

OBJECTIVES: To estimate the socioeconomic disparities in untreated dental caries in early childhood according to socioeconomic characteristics in three birth cohorts in Southern Brazil. METHODS: The socioeconomic data to this study were collected at the 48-month follow-up and oral health studies of 1993, 2004 and 2015 Pelotas birth cohort studies. The outcome was untreated dental caries in children aged 6 (1993 cohort), 5 (2004 cohort) and 4 years (2015 cohort), dichotomized into absence/presence. Analyses were stratified by maternal skin colour/race, maternal education and family income. For statistical purposes, the prevalence difference, relative risk and absolute and relative indices of health inequality (Slope Index of Inequality-SII and Concentration Index-CIX) were used. RESULTS: The prevalence of untreated dental caries in primary dentition was 63.4%, 45.5% and 15.6%, in 1993, 2004 and 2015 cohorts, respectively. The prevalence of untreated dental caries was concentrated in the poorest quintile and lower maternal education group in both absolute (SII) and relative (CIX) measures of inequality, being characterized as a pro-poor event. A higher risk of untreated caries was found in the poorest quintile of family income compared with the richest quintile in the 1993 cohort (RR 1.44 [95% CI 1.05; 1.98]). That risk was higher considering the 2004 Cohort (RR 1.78 [95% CI 1.42; 2.23]) and 2015 cohort (RR 4.20 [95% CI 2.97; 5.94]) data. CONCLUSIONS: Over the course of two decades, a higher prevalence of untreated dental caries is concentrated among the most socioeconomically deprived children.

Intestinal parasites of Apodemus mystacinus along altitudinal stratification of Ibrahim River, Mount Lebanon.

This study documents the diversity of intestinal parasites in the eastern broad-toothed field mouse (Apodemus mystacinus) along the altitudinal gradient of Ibrahim River in Mount Lebanon during the spring and autumn of 2017. A total of 190 A. mystacinus were trapped in seventeen sites (6 riparian, 11 non-riparian) and examined for intestinal parasites. Eight intestinal parasites were identified including Heligmosomoides polygyrus, Trichuris muris, Syphacia frederici, Protospirura muris, and Aspiculuris tetraptera (nematodes), Hymenolepis diminuta (cestode), Brachylaima spp. (trematode), and Eimeria alorani (coccidian). Most of the trapped mice (85%) were infected with intestinal parasites and 38.84% showed concurrent infection with at least two parasitic species. The season had a significant effect on mice infection with Syphacia frederici, and mice are most likely to have infection with this nematode in spring season. The vegetation zone had a significant overall impact on mice infection with the nematodes Heligmosomoides polygyrus and Trichuris muris while gender did not influence significantly mouse infection with intestinal parasites. This is the first study that has been carried out to identify the intestinal parasite community in A. mystacinus of Ibrahim River region. The findings pave the way for future studies on intestinal parasites in rodents and the environmental variations affecting their dynamics.

Social and racial inequity in self-rated oral health in adults in Southern Brazil.

This study aimed to estimate social and racial inequalities in self-rated oral health in adults from the Brazilian birth cohort study. This study belongs to 1982 Pelotas (Brazil) birth cohort study. Data from this study was collected for oral health conditions 31 years old (Oral Health Study). The outcome was self-rated oral health, dichotomized into positive (good/very good) and negative (regular/bad/very bad). Analyses were stratified by gender, racial/skin color groups, schooling level and income. For statistical analysis, the slope index of inequality (SII) and the concentration index (CIX) were used. The prevalence of negative self-rated oral health was 36.1%. Social inequalities were observed in self-rated oral health in both absolute and relative terms. A SII of -30.0 (95%CI: -43.6; -16.4) was observed for income, and -27.7 (95%CI: -41.9; -13.4) for schooling level. Both the individuals' income and the schooling level had negative CIX (CIXincome -14.6 [95%CI: -21.2; -8.0] and CIXschooling level -14.1 [95%CI: -20.7; -7.5]). Furthermore, the prevalence of negative self-rated oral health in black/brown/indigenous individuals from the highest income/schooling level was comparable to prevalence of the outcome in the white individuals belonging to the lowest income/schooling levels. This study results demonstrate racial disparities in oral health regardless of income and schooling levels. Furthermore, a higher concentration of negative self-rated oral health was identified among the most socioeconomically vulnerable individuals. Our findings reinforce the presence of racial and socioeconomic inequalities in oral health.

Oral health and academic performance or absenteeism: Findings from a University in Southern Brazil.

OBJECTIVES: To evaluate the association between oral health conditions and academic performance and absenteeism in university students. METHODS: This cross-sectional study was carried out on a comprehensive sample of 1865 freshman students from the Federal University of Pelotas/Southern Brazil in 2017. A self-administered questionnaire was applied in the classroom, inquiring about socioeconomic, demographic, psychological, academic characteristics and oral conditions (tooth loss, self-reported oral health and toothache). For the dependent variables, academic performance was evaluated by the question: 'How would you describe your academic performance?' while absenteeism was assessed with the question 'In the last six months, have you missed some class for dental reasons?'. Multivariable analyses used hierarchical Poisson regression with backward selection. RESULTS: The prevalence of low academic performance was 38.6% and absenteeism due to dental reasons 6.2%. The prevalence of toothache and poor self-perceived oral health was 28% and 20%, respectively. Multivariable analysis found low academic performance to be more prevalent in students with poor self-perceived oral health (PR 1.46; 95% CI 1.22-1.77), and absenteeism to be almost six times more prevalent (PR 5.85; 95% CI 3.84-8.90) in students reporting toothache. CONCLUSIONS: Poor oral health is associated with both poor academic performance and absenteeism in university students.

Association between dental pain, use of dental services and school absenteeism: 2015 National School Health Survey, Brazil. / Associação entre dor dentária, uso de serviços odontológicos e absenteísmo escolar: Pesquisa Nacional de Saúde do Escolar 2015.

OBJECTIVE: To analyze association between dental pain, use of dental services and school absenteeism in Brazilian adolescents. METHODS: This was a cross-sectional study with data from the National School Health Survey (PeNSE 2015). The study's dependent variable was school absenteeism due to health reasons in the last 12 months. Socioeconomic characteristics, dental pain and use of dental services were the independent variables evaluated. Logistic regression was used to estimate odds ratios (OR) and respective 95% confidence intervals (95%CI). RESULTS: Data on 102,072 schoolchildren were included. Absenteeism prevalence due to health reasons was 53.7% (95%CI 53.2;54.3). In the adjusted analysis, there was association between dental pain and school absenteeism (OR=1.35 - 95%CI 1.26;1.45), and an increase in absenteeism occurrence the greater the number of dental visits. CONCLUSION: The results suggest that dental pain and frequency of dental visits may be related to school absenteeism.

Prototypical oncogene family Myc defines unappreciated distinct lineage states of small cell lung cancer.

Comprehensive genomic analyses of small cell lung cancer (SCLC) have revealed frequent mutually exclusive genomic amplification of MYC family members. Hence, it has been long suggested that they are functionally equivalent; however, more recently, their expression has been associated with specific neuroendocrine markers and distinct histopathology. Here, we explored a previously undescribed role of L-Myc and c-Myc as lineage-determining factors contributing to SCLC molecular subtypes and histology. Integrated transcriptomic and epigenomic analyses showed that L-Myc and c-Myc impart neuronal and non-neuroendocrine-associated transcriptional programs, respectively, both associated with distinct SCLC lineage. Genetic replacement of c-Myc with L-Myc in c-Myc-SCLC induced a neuronal state but was insufficient to induce ASCL1-SCLC. In contrast, c-Myc induced transition from ASCL1-SCLC to NEUROD1-SCLC characterized by distinct large-cell neuroendocrine carcinoma-like histopathology. Collectively, we characterize a role of historically defined general oncogenes, c-Myc and L-Myc, for regulating lineage plasticity across molecular and histological subtypes.

Gag proteins of the two Drosophila telomeric retrotransposons are targeted to chromosome ends.

Drosophila telomeres are formed by two non-LTR retrotransposons, HeT-A and TART, which transpose only to chromosome ends. Successive transpositions of these telomeric elements yield arrays that are functionally equivalent to the arrays generated by telomerase in other organisms. In contrast, other Drosophila non-LTR retrotransposons transpose widely through gene-rich regions, but not to ends. The two telomeric elements encode very similar Gag proteins, suggesting that Gag may be involved in their unique targeting to chromosome ends. To test the intrinsic potential of these Gag proteins for targeting, we tagged the coding sequences with sequence of GFP and expressed the constructs in transiently transfected Drosophila-cultured cells. Gag proteins from both elements are efficiently transported into the nucleus where the protein from one element, HeT-A, forms structures associated with chromosome ends in interphase nuclei. Gag from the second element, TART, moves into telomere-associated structures only when coexpressed with HeT-A Gag. The results suggest that these Gag proteins are capable of delivering the retrotransposons to telomeres, although TART requires assistance from HeT-A. They also imply a symbiotic relationship between the two elements, with HeT-A Gag directing the telomere-specific targeting of the elements, whereas TART provides reverse transcriptase for transposition.