Exploring the molecular pathways linking sleep phenotypes and POGZ-associated neurodevelopmental disorder.

Pogo transposable element-derived protein with ZNF domain (POGZ) gene encodes a chromatin regulator and rare variants on this gene have been associated with a broad spectrum of neurodevelopmental disorders, such as White-Sutton syndrome. Patient clinical manifestations frequently include developmental delay, autism spectrum disorder and obesity. Sleep disturbances are also commonly observed in these patients, yet the biological pathways which link sleep traits to the POGZ-associated syndrome remain unclear. We screened for sleep implications among individuals with causative POGZ variants previously described. Sleep disturbances were observed in 52% of patients, and being obese was not observed as a risk factor for sleep problems. Next, we identified genes associated with sleep-associated traits among the POGZ regulatory targets, aiming to uncover the molecular pathways that, when disrupted by POGZ loss of function, contribute to the aetiology of sleep phenotypes in these patients. The intersect between POGZ targets and sleep-related genes was used in a pathway enrichment analysis. Relevant pathways among these overlapping genes are involved in the regulation of circadian rhythm, tau protein binding, ATPase activator activity. This study may represent the beginning for novel functional investigations on shared molecular mechanisms between sleep disturbances and rare developmental syndromes related to POGZ and its regulatory targets.

Lipid metabolism and neuromuscular junction as common pathways underlying the genetic basis of erectile dysfunction and obstructive sleep apnea.

Erectile dysfunction (ED) incidence is higher in patients with obstructive sleep apnea (OSA). Studies have suggested that ED and OSA may activate similar pathways; however, few have investigated the links between their underlying genotypic profiles. Therefore, we conducted an in-silico analysis to test whether ED and OSA share genetic variants of risk and to identify any molecular, cellular and biological interactions between them. Two gene lists were manually curated through a literature review based on a PUBMED search, which resulted in one gene list associated with ED (total of 205 genes) and the other with OSA (total of 2622 genes). Between those gene sets, 35 were common for both lists (Fisher exact test, p-value = 0.027). The Protein-protein interaction (PPI) analysis using the intersect list as input showed that 3 of them had direct interactions (LPL, DGKB and PLCB1). In addition, the biological function of the genes contained in the intersect list suggested that pathways related to lipid metabolism and the neuromuscular junction were commonly found in the genetic basis of ED and OSA. From the shared genes between both conditions, the biological pathways highlighted in this study may serve as preliminary findings for future functional investigations on OSA and ED association.

The relationship between neurodevelopmental transcriptional programs and insomnia: From Rubinstein-Taybi syndrome into energy metabolism.

Neurodevelopmental disorders (NDD) are characterized by cognitive, emotional, and/or motor skills impairment since childhood, and sleep disturbances are a common comorbidity. Rubinstein-Taybi syndrome (RSTS), a rare genetic syndrome associated with NDD, is caused by CREBBP haploinsufficiency. This gene encodes an acetyltransferase with crucial role on the establishment of transcriptional programs during neurodevelopment. Although insomnia has been reported in RSTS patients, the convergent mechanisms between this sleep disturbance and CREBBP loss-of-function are not fully understood. We tested weather the genetic architecture underlying CREBBP regulatory targets and insomnia-associated genes is significantly shared. We then identified the biological pathways enriched among these shared genes. The intersection between CREBBP regulatory targets and genes associated with insomnia included 7 overlapping genes, indicating significantly more overlap than expected by chance. An over-representation analysis on these intersect genes identified pathways related to mitochondrial activity. This finding indicates that the transcriptional programs established by CREBBP might impact insomnia-related biological pathways through the modulation of energy metabolism. The overlapping gene set and biological pathways highlighted by this study may serve as a primer for new functional investigations of shared molecular mechanisms between insomnia and CREBBP regulatory targets.

Endocrine and Epigenetic Regulation as Common Pathways Underlying the Genetic Basis of Sleep Traits and Longevity.

The amount of sleep needed over one's lifespan is age dependent and not sleeping enough or sleeping in excess is associated with increased morbidity and mortality. Yet, the convergent molecular mechanisms that link longevity and sleep are largely unknown. We performed a gene enrichment study that (1) identified genes associated with both longevity and sleep traits and (2) determined molecular pathways enriched among these shared genes. We manually curated two sets of genes, one associated with longevity and aging and the other with sleep traits (e.g., insomnia, narcolepsy, sleep duration, chronotype, among others), with both gene lists heavily driven by hits from recent large-scale Genome-Wide Association Studies. There were 47 overlapping genes between the gene list associated with sleep traits (1064 genes total) and the genes associated with longevity (367 genes total), indicating significantly more overlap than expected by chance. An overrepresentation analysis identified enriched pathways that suggest endocrine and epigenetic regulation as potential shared mechanisms between sleep traits and longevity. Concordantly, functional network analysis retrieved two clusters, being one associated with proteins of nuclear functions and the other, with extracellular proteins. This overlapping gene set, and the highlighted biological pathways may serve as preliminary findings for new functional investigations of sleep and longevity shared genetic mechanisms.

Medo da covid-19 e sofrimento psicológico: o efeito mediador da "infoxicação" durante a pandemia

Durante a pandemia, o medo da covid-19 afetou a vida das pessoas, principalmente associado à infoxicação, que corresponde ao consumo excessivo de conteúdos que comprometem a capacidade de absorção e de filtragem quanto à relevância e à veracidade deles. A presente pesquisa objetivou verificar o papel mediador da infoxicação na relação entre medo da covid-19 e as sintomatologias de ansiedade, estresse e depressão. Contou-se com 424 pessoas da população geral (M = 25.48, variando de 18 até 75 anos; DP = 8.63), em maioria mulheres (56.1%) de diferentes estados brasileiros, que responderam a EPININ, FCV-19S, DASS-21 e questões demográficas. Correlações, seguidas de regressões e modelos de mediação demonstraram a contribuição do medo da covid-19 e da infoxicação nos sintomas de ansiedade, depressão e estresse. Discute-se como níveis elevados de medo, quando mediados pela busca exacerbada por informações, tendem a prejudicar a saúde mental durante a pandemia. Contudo, o acesso excessivo aos meios digitais foi associado ao aumento do sofrimento psicológico. O dado obtido é resultante da infoxicação, pois esta atuou como mediador do adoecimento mental no período pandêmico.

Abstract: During the pandemic, the fear of COVID-19 affected people's lives, mainly associated with infoxication, which corresponds to the excessive consumption of content that compromises absorption and filtering capacity for relevance and veracity. This research aimed to verify the mediating role of infoxication in the relationship between fear of COVID-19 and symptoms of anxiety, stress and depression. It counted with 424 people from the general population (M = 25.48, ranging from 18 up to 75 years; SD = 8.63), mostly women (56.1%) from different Brazilian states, who responded to EPININ, FCV-19S, DASS-21 and demographic questions. Correlations, followed by regressions and mediation models demonstrated the contribution of the fear of COVID-19 and infoxication in the symptoms of anxiety, depression and stress. It is discussed how high levels of fear, when mediated by the exacerbated search for information, tend to harm mental health during the pandemic. However, excessive access to digital media was associated with increased psychological distress. The data obtained is the result of infoxication, as it acted as a mediator of mental illness in the pandemic period.

Distúrbios do olfato, uma revisão narrativa do diagnóstico ao tratamento / Olfactory dysfunction: a narrative review from diagnosis to treatment

Os distúrbios do olfato (DO) impactam de forma significativa na qualidade de vida dos indivíduos, e o conhecimento teórico a respeito do assunto deve ser de domínio dos alergologistas e imunologistas clínicos, possibilitando, assim, o seu diagnóstico e implementação de intervenções. Suas causas podem ser variadas, entre elas estão: rinite alérgica, rinossinusite crônica com ou sem pólipos, infecções de vias aéreas superiores, exposição a substâncias químicas, doenças neurológicas, drogas, traumas e o próprio envelhecimento. O olfato pode ser avaliado e mensurado através de testes com metodologias diferentes, cujo objetivo é avaliar parâmetros como a identificação de odores, limiar e discriminação olfativa. Esses testes são de fundamental importância para caracterizar objetivamente a queixa do paciente, como também avaliar o olfato antes e após determinada aplicação terapêutica. O tratamento das desordens olfativas é baseado em sua etiologia, portanto determinar a sua causa é indispensável para uma melhor eficácia no manejo. Entre as principais opções estão os corticoides tópicos, com impacto significativo nos pacientes com doença sinusal associada, treinamento olfatório e outras intervenções como ômega 3, vitamina A intranasal, e terapias que ainda requerem mais estudos.

Olfactory dysfunction significantly impacts quality of life, and allergists and clinical immunologists must be informed about it for diagnostic and interventional purposes. The causes are varied: allergic rhinitis, chronic rhinosinusitis with or without polyps, upper airway infections, exposure to chemicals, neurological diseases, drugs, trauma, and aging itself. Olfactory function can be evaluated and measured by several tests that use different methodologies to evaluate and identify odors, olfactory threshold, and olfactory discrimination. These tests are fundamental for objectively characterizing patient complaints and evaluating olfactory function before and after therapeutic interventions. Olfactory disorders are treated according to their etiology, so determining their cause is a major factor in treatment efficacy. The main options include topical corticosteroids, which have a significant impact on patients with sinus disease, olfactory training, other therapies (such as omega 3 and intranasal vitamin A), in addition to therapies that require further research.

Characterization of rumen microbiome and metabolome from oro-esophageal tubing and rumen cannula in Holstein dairy cows.

Less invasive rumen sampling methods, such as oro-esophageal tubing, became widely popular for exploring the rumen microbiome and metabolome. However, it remains unclear if such methods represent well the rumen contents from the rumen cannula technique. Herein, we characterized the microbiome and metabolome in the rumen content collected by an oro-esophageal tube and by rumen cannula in ten multiparous lactating Holstein cows. The 16S rRNA gene was amplified and sequenced using the Illumina MiSeq platform. Untargeted metabolome was characterized using gas chromatography of a time-of-flight mass spectrometer. Bacteroidetes, Firmicutes, and Proteobacteria were the top three most abundant phyla representing ~ 90% of all samples. Although the pH of oro-esophageal samples was greater than rumen cannula, we found no difference in alpha and beta-diversity among their microbiomes. The overall metabolome of oro-esophageal samples was slightly different from rumen cannula samples yet more closely related to the rumen cannula content as a whole, including its fluid and particulate fractions. Enrichment pathway analysis revealed a few differences between sampling methods, such as when evaluating unsaturated fatty acid pathways in the rumen. The results of the current study suggest that oro-esophageal sampling can be a proxy to screen the 16S rRNA rumen microbiome compared to the rumen cannula technique. The variation introduced by the 16S rRNA methodology may be mitigated by oro-esophageal sampling and the possibility of increasing experimental units for a more consistent representation of the overall microbial population. Studies should consider an under or over-representation of metabolites and specific metabolic pathways depending on the sampling method.

The C-terminal mutation beyond the catalytic site of brown spider phospholipase D significantly impacts its biological activities.

Loxosceles spider envenomation results in dermonecrosis, principally due to phospholipases D (PLDs) present in the venom. These enzymes have a strongly conserved sequence, 273ATXXDNPW280, in the C-terminal region (SMD-tail) that make contact with ß-sheets of the TIM barrel, in which the amino acids Asp277 and Trp280 establish the energetically strongest contacts. The SMD-tail is conserved in PLDs from different species but absent in the non-toxic PLD ancestral glycerophosphodiester phosphodiesterases (GDPDs). This work aims to understand the role of the C-terminal region in the structural stability and/or function of phospholipases D. Through site-directed mutagenesis of the rLiD1 protein (recombinant Loxosceles intermedia dermonecrotic protein 1), we produced two mutants: rLiD1D277A and rLiD1W280A (both with sphingomyelinase activity), in which Asp277 and Trp280 were replaced by alanine. rLiD1D277A showed similar sphingomyelinase activity but at least 2 times more dermonecrotic activity than rLiD1 (wild-type protein). Conversely, while the rLiD1W280A displayed a slight increase in sphingomyelinase activity, its biological activity was similar or lower compared to rLiD1, potentially due to its decreased thermostability and formation of amyloid aggregates. In conclusion, these new findings provide evidence that SMD-tail mutants impact the structure and function of these proteins and point out that residues outside the active site can even increase the function of these enzymes.

Genetic basis of sleep phenotypes and rare neurodevelopmental syndromes reveal shared molecular pathways.

Sleep-related phenotypes have been frequently reported in early on-set epileptic encephalopathies and in developmental delay syndromes, in particular in syndromes related to autism spectrum disorder. Yet the convergent pathogenetic mechanisms between these comorbidities are largely unknown. We first performed a gene enrichment study that identified shared risk genes among rare epileptic encephalopathies/neurodevelopmental disorders, rare developmental delay genetic syndromes and sleep disturbances. We then determined cellular and molecular pathways enriched among genes shared between sleep phenotypes and those two early onset mental illnesses, aiming to identify genetic disparities and commonalities among these phenotypic groups. The sleep gene set was observed as significantly overlapped with the two gene lists associated to rare genetic syndromes (i.e., epileptic encephalopathies/neurodevelopmental disorders and developmental delay gene sets), suggesting shared genetic contribution. Similarities across significantly enriched pathways between the two intersect lists comprehended mostly synapse-related pathways, such as retrograde endocannabinoid signaling, serotonergic, and GABAergic synapse. Network analysis indicates epileptic encephalopathies/neurodevelopmental disorders versus sleep-specific clusters and developmental delay versus sleep-specific clusters related to synaptic and transcriptional regulation, respectively. Longstanding functional patterns previously described in epileptic encephalopathies and neurodevelopmental disorders genetic architecture were recaptured after dissecting the overlap between the genes associated to those developmental phenotypes and sleep disturbances, suggesting that during neurodevelopment different molecular and functional mechanisms are related to alterations on circadian rhythm. The overlapping gene set and biological pathways highlighted by this study may serve as a primer for new functional investigations of shared molecular mechanisms between sleep disturbances and rare developmental syndromes.

Relevance of sward structure and forage nutrient contents in explaining methane emissions from grazing beef cattle and sheep.

Forage nutrient contents are an important factor explaining the dry matter intake (DMI), average daily gain (ADG), and methane emissions (CH4) of ruminants fed indoors. However, for grazing animals, the forage nutrient contents might be limited in explaining such response variables. We aimed to verify the explanatory power of forage nutrient contents and sward structure on daily intake, performance, and CH4 emissions by sheep and beef cattle grazing different grassland types in southern Brazil. We analyzed data from five grazing trials using sheep and beef cattle grazing on Italian ryegrass (Lolium multiflorum), mixed Italian ryegrass and black oat (Lolium multiflorum + Avena strigosa), pearl millet (Pennisetum americanum), and multispecies native grassland. We used mixed models, including the forage nutrient contents [crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF)], sward structure (sward height and herbage mass) and their interactions, as fixed effects and trial, season, methodologies, animal species, grassland type, and paddock, as random effects. The model for DMI (kg DM/LW0.75) had an adjusted coefficient of determination (R2adj) of 71.6 %, where 11.3, 23.1, and 37.2 % of the R2adj were explained by the forage nutrient contents, sward structure, and their interaction, respectively. The ADG (kg/LW0.75) model presented an R2adj of 74.2 %, with 12.5 % explained by forage nutrient contents, 29.3 % by sward structure, and 32.4 % by their interaction. The daily CH4 emission (g/LW0.75) model had a lower adjusted coefficient of determination (R2adj = 47.6 %), with 16.8 % explained by forage nutrient contents and 30.8 % explained by sward structure, but no effect of the interaction. Our results show that in grazing ecosystems, the forage nutrient contents explain a small fraction, and the greater explanatory power for DMI, ADG, and CH4 emissions models is related to sward structure descriptors, such as sward height and herbage mass. Moreover, the interaction between these variables explains most of the variation. In conclusion, forage nutrient contents and sward structure have different influences on DMI, ADG, and CH4 emissions by grazing ruminants. Because of its relevance to daily CH4 emissions, offering an optimal sward structure to grazing animals is a major climate-smart strategy to improve animal production and mitigate CH4 emissions in pastoral ecosystems.

Cuestionario de Gratitud-20 (G-20): evidências psicométricas e parâmetros de seus itens no Brasil / Gratitude Questionnaire-20 (G-20): psychometric evidences and parameters of their items in Brazil / Cuestionario de Gratitud-20 (G-20): evidencias psicométricas y parámetros de sus ítems en Brasil

Objetivou-se explorar os parâmetros psicométricos do Cuestionario de Gratitud por meio da Teoria de Resposta ao Item (TRI), utilizando o Modelo de Resposta Graduada. Para tanto, participaram 533 respondentes (M idade = 29,9), a maioria mulheres (67,7%). Inicialmente, checou-se a dimensionalidade da escala, que apoiou uma estrutura quadrifatorial (CFI = 0,99; TLI = 0,99). Os parâmetros dos itens foram realizados separadamente para cada fator, e os resultados indicaram que todos os itens discriminam adequadamente os participantes. Os itens do fator Reconhecimento de Dons exigiram uma maior quantidade de theta para serem completamente endossados e o fator Gratidão Interpessoal demandou menor quantidade de theta para ser a opção de reposta, talvez por ser melhor aceito socialmente. Estima-se que os objetivos do estudo foram alcançados, conhecendo evidências psicométricas de uma medida que avalia a gratidão numa perspectiva mais integradora, recomendando-se o seu uso em possibilidades futuras. (AU)

The aim of this study was to explore the psychometric parameters of the Gratitude Questionnaire through the Item Response Theory (IRT), using the Graduated Response Model. Therefore, 533 respondents participated (Mage = 29.9), mostly women (67.7%). At the beginning, we checked the dimensionality of the scale, which supported a quadratic structure (CFI = 0.99; TLI = 0.99). The parameters of the items were performed separately for each factor, and the results indicated that all items adequately discriminate participants. The items of the Gift Recognition factor required a greater amount of theta to be fully endorsed and the Interpersonal Gratitude factor required less amount of theta to be the answer option, perhaps because it is better accepted socially. It is estimated that the objectives of the study were reached, knowing psychometric evidence of a measure that evaluates gratitude in a more inclusive perspective, recommending its use in future possibilities. (AU)

Se objetivó conocer los parámetros psicométricos del Cuestionario de Gratitud por medio de la Teoría de Respuesta al Item (TRI), utilizando el Modelo de Respuesta Graduada. Participaron 533 sujetos (M edad = 29,9), la mayoría mujeres (67,7%). Inicialmente, se verificó las dimensiones de la escala, que apoyó una estructura cuadrifatorial (CFI = 0,99; TLI = 0,99). Los parámetros de los ítems fueron realizados separadamente para cada factor, y los resultados indicaron que los ítems discriminan adecuadamente a los participantes. Los elementos del factor Reconocimiento de Dons requirieron una mayor cantidad de theta para ser completamente endosados y el factor Gratitud Interpersonal demandó menor cantidad de theta para ser la opción de respuesta, tal vez por ser mejor aceptado socialmente. Se estima que los objetivos del estudio se alcanzaron, conociendo evidencias psicométricas de una medida que evalúa la gratitud en una perspectiva más integradora, recomendándose su uso en posibilidades futuras. (AU)

Evaluation of Recombinant Bovine Interleukin-8 (rbIL-8) as a Treatment for Chronic Intramammary Infection in Dairy Cows.

Mastitis is one of the main contributors to antimicrobial resistance in livestock, so alternative therapies are being investigated to address it. The present study assessed the capability of recombinant bovine interleukin-8 (rbIL-8) to improve neutrophil function in the mammary gland and resolve chronic high somatic cell count (SCC) in Holstein cows. Multiparous cows (n = 8) with more than 300,000 SCC per mL were allocated to one of two intramammary infusions: saline (10 mL of saline solution) or rbIL-8 (1.57 mg/mL of recombinant bovine IL-8 diluted in 9 mL of saline). In addition, there was an untreated control group (n = 2, SCC < 300,000 SCC/mL). Milk samples were collected post-treatment at 0, 4, 8, 12, 24, 48, and 144 h to quantify milk SCC, haptoglobin, and IgG concentrations. Neutrophil's phagocytosis in milk and blood was evaluated via flow cytometry at 0, 24, and 48 h. The log of SCC did not differ between the infused groups (p = 0.369). Neutrophils presented a similar log of cells with high fluorescence for propidium-iodide (PI) and dihydrorhodamine (DHR) in milk (p = 0.412) and blood samples (p = 0.766) in both infused groups. Intramammary infusion of 1.57 mg/mL of rbIL-8 did not improve neutrophils response and failed to resolve chronic high SCC.

Intrauterine Blood Plasma Platelet-Therapy Mitigates Persistent Breeding-Induced Endometritis, Reduces Uterine Infections, and Improves Embryo Recovery in Mares.

Microorganisms, including pathogenic or opportunistic bacteria and fungi, may gain access to the uterus during breeding, and infectious endometritis plays a major role in equine subfertility. This study aimed to assess the post-breeding inflammatory response, endometrial culture, and embryo recovery of mares susceptible to persistent breeding-induced endometritis (PBIE) treated with plasma-rich (PRP) or -poor (PPP) plasma. Mares (n = 12) susceptible to PBIE had three cycles randomly assigned to receive intrauterine infusions of lactate ringer solution (LRS, control), or autologous PRP or PPP pre- (-48 and -24 h) and post-breeding (6 and 24 h). Mares were bred with fresh semen from one stallion. Intrauterine fluid accumulation (IUF) and endometrial neutrophils were assessed every 24 h up to 96 h post-breeding. Uterine cytokines (Ilß, IL6, CXCL8, and IL10) were evaluated before (0 h), 6, and 24 h post-breeding, and endometrial culture three and nine days after breed. Embryo flushing was performed 8 days post-ovulation. Data were analyzed with mixed model, Tukey's post-hoc test, and multivariate regression. PRP treatment reduced endometrial neutrophils, post-breeding IUF, and pro-inflammatory cytokines when compared to control-assigned cycles, but not significantly different than PPP. Controls had a significantly higher percentage of positive bacterial cultures (33%) in comparison to PRP-assigned cycles (0%), whereas cycles treated with PPP were not significantly different from the other groups (25%). The PRP-assigned cycles had significantly greater embryo recovery rates (83%) than the control (33%), though not significantly different than PPP (60%). Plasma infusion reduced the duration and intensity of the post-breeding inflammatory response and improved embryo recovery in mares susceptible to PBIE. Platelets incrementally downregulate PBIE and appear to have a dose-dependent antimicrobial property.

Donkey Epididymal Transport for Semen Cooling and Freezing.

The objectives of this study were to assess the cooling and freezing of donkey epididymal semen harvested immediately after castration (Experiment 1, n = 4) or after the shipment (24 or 48 h) of epididymides attached to testicles (Experiment 2, n = 14) or dissected apart (Experiment 3, n = 36). In each experiment, semen was frozen immediately (Non-Centrif) in an egg yolk-based semen extender (EY) or after processing through cushion-centrifugation (Centrif) while extended in a skim milk-based extender (SC). In all three experiments, cooled, pre-freeze, and post-thaw epididymal semen was assessed for total motility (TM), progressive motility (PM), plasma membrane integrity (PMI), and high mitochondrial membrane potential (HMMP). Data were analyzed with R using mixed models and Tukey's test as posthoc. Results showed that the cooling of epididymal semen up to 24 h after harvesting did not affect motility parameters or plasma membrane integrity; furthermore, in Experiment 3, the post-thaw evaluation of both Centrif and Non-Centrif achieved similar TM and PM. Collectively, the post-thaw results revealed low motility parameters across groups; while, the PMI and HMMP did not reflect this trend, and the values remained high, suggesting that there was a lack of epididymal sperm activation with either centrifugation or extenders. In summary, freshly harvested and cooled-shipped and cooled semen had satisfactory semen parameters. Future studies need to address donkey epididymal semen fertility in mares and jennies.

Administration of nerve growth factor-ß to heifers with a pre-ovulatory follicle enhanced luteal formation and function and promoted LH release.

The objective of this study was to determine the effects of bovine nerve growth factor-ß (NGF) on pre-ovulatory follicle vascular area, LH release, ovulation, and luteal function when administered systemically to heifers. Post-pubertal Holstein heifers (n = 12) received an intravaginal progesterone-releasing device (CIDR) and GnRH agonist (100 µg IM). The CIDR was removed 5 d later, and heifers were given dinoprost (25 mg IM) at CIDR removal and 24 h later, followed by a second dose of GnRH agonist 48 h later. Heifers were randomly assigned to treatments using a cross-over design. For example, heifers assigned to NGF (250 µg reconstituted in 12 mL PBS IM) in replicate 1 were assigned to control (12 mL PBS IM) in replicate 2. Transrectal ultrasonography was performed before treatment and repeated every 4 h up to 32 h to determine the pre-ovulatory follicle diameter, vascular area, and ovulation. Serum samples were obtained to assess LH concentrations during the periovulatory period and every 2 d post-ovulation for measuring progesterone concentrations. A subset of heifers had luteal biopsies performed on days 9 (n = 6 per treatment) and 14 (n = 6 per treatment) post-ovulation to count luteal cell numbers and measure relative mRNA abundance for steroidogenic and angiogenic enzymes and LH receptor. Treatment with NGF increased pre-ovulatory follicle diameter (P = 0.02) and serum LH concentrations (P = 0.03) but did not affect time to ovulation (P = 0.42). Heifers treated with NGF had increased serum progesterone concentrations in the subsequent luteal phase (P = 0.03), but no change in vascular area of the follicle (P = 0.16) or CL (P = 0.20). Heifers treated with NGF had a greater number of small luteal cells (P < 0.01) and a tendency for increased LH receptor (LHR) mRNA abundance in the CL (P = 0.10). There was also increased steroidogenic acute regulatory protein (STAR; P = 0.05) and a tendency for increased cytochrome P450 family 11 (CYP11A1; P = 0.10) mRNA abundance in the CL of NGF-treated heifers. There was decreased prostaglandin E2 synthase (PGES; P = 0.03) and its receptor (PGER; P = 0.05) mRNA abundance and a tendency for decreased cytochrome P450 family 17 subfamily A member 1 (CYP17A1; P = 0.08) and hydroxysteroid 17-beta dehydrogenase (HSD17B; P = 0.06) mRNA abundance in the CL of NGF-treated heifers. Administration of NGF improved CL function in heifers potentially as a result of increased LH release.

Oral cancer preventive campaigns: are we reaching the real target? / Campanha de prevenção do câncer de boca: estamos atingindo o verdadeiro público-alvo?

Introduction: Oral cavity malignant neoplasms have a high mortality rate. For this reason, preventive campaigns have been developed, both to educate the population and to diagnose lesions at an early stage. However, there are studies that contest the validity of these endeavors, principally because the target audience of the campaigns may not conform to the group at highest risk for oral malignancy. Objective: To describe the profile of patients who avail themselves of the preventive campaign, identify the presence of oral lesions in that population, and compare that data with the epidemiological profile of patients with oral cancer. Methods: Cross-sectional historical cohort study performed by analysis of epidemiological data of the campaign "Abra a Boca para a Saúde" collected in the years from 2008 to 2013. Results: In the years analyzed, 11,965 people were treated and 859 lesions were diagnosed, all benign. There was a female predominance (52.7%), with mean age of 44 years (±15.4 years); 26% were smokers and 29% reported alcohol consumption. It is known that the group at highest risk to develop oral cancer is 60to 70-year-old men, who are alcoholic smokers. Conclusion: The population that seeks preventive campaigns is not the main risk group for the disease. This fact explains the low number of lesions and the lack of cancer detection. .

Introdução: As neoplasias malignas de cavidade oral possuem alta taxa de mortalidade. Por essa razão, existem diversas campanhas de prevenção do câncer bucal, visando orientar a população e diagnosticar lesões em estágio precoce. Contudo, vários estudos contestam a validade dessas iniciativas, uma vez que o público alvo atingido pode não representar o verdadeiro grupo de risco. Objetivo: Descrever o perfil dos pacientes que procuraram a campanha de prevenção, identificar a presença de lesões orais e comparar os dados com o perfil epidemiológico de pacientes portadores de câncer bucal. Método: Coorte histórica transversal. Foram levantados os dados epidemiológicos da campanha "Abra a boca para a saúde" dos anos de 2008 a 2013. Resultados: Nos anos avaliados, 11965 pessoas foram atendidas e 859 lesões diagnosticadas, todas benignas. A predominância foi do sexo feminino (52,7%), com média de idade de 44 anos (± 15,4 anos), 26% eram tabagistas e 29% relatavam uso de álcool. Sabe-se que o grupo de risco corresponde a homens, entre 60 e 70 anos, tabagistas e etilistas. Conclusão: A população que procura a campanha não é o principal grupo de risco para a doença, fato que explica o baixo número de lesões detectadas e nenhum câncer. .

Oral cancer preventive campaigns: are we reaching the real target?

INTRODUCTION: Oral cavity malignant neoplasms have a high mortality rate. For this reason, preventive campaigns have been developed, both to educate the population and to diagnose lesions at an early stage. However, there are studies that contest the validity of these endeavors, principally because the target audience of the campaigns may not conform to the group at highest risk for oral malignancy. OBJECTIVE: To describe the profile of patients who avail themselves of the preventive campaign, identify the presence of oral lesions in that population, and compare that data with the epidemiological profile of patients with oral cancer. METHODS: Cross-sectional historical cohort study performed by analysis of epidemiological data of the campaign "Abra a Boca para a Saúde" collected in the years from 2008 to 2013. RESULTS: In the years analyzed, 11,965 people were treated and 859 lesions were diagnosed, all benign. There was a female predominance (52.7%), with mean age of 44 years (±15.4 years); 26% were smokers and 29% reported alcohol consumption. It is known that the group at highest risk to develop oral cancer is 60- to 70-year-old men, who are alcoholic smokers. CONCLUSION: The population that seeks preventive campaigns is not the main risk group for the disease. This fact explains the low number of lesions and the lack of cancer detection.

Consequências individuais e socioeconômicas da síndrome da apneia obstrutiva do sono / Individual and socioeconomic consequences of obstructive sleep apnea syndrome

A Síndrome da Apneia Obstrutiva do Sono (SAOS) é definida como a obstrução da passagem de ar pelas vias aéreas superiores durante o sono. Acontecem episódios repetidos de hipoxemia e hipercapnia, e com eles o sono torna-se superficial e fragmentado, resultando em distintas complicações ao indivíduo e à coletividade. O objetivo deste estudo foi revisar a literatura quanto às consequências individuais, econômicas e sociais causadas pela SAOS. Identificaram-se diversas complicações da SAOS relacionadas ao indivíduo: (1) alterações físicas e comportamentais: sono excessivo, fadiga, ansiedade, irritabilidade, depressão, redução da libido, diminuição da qualidade de vida, astenia, consequências metabólicas (ganho de peso, diabetes e dislipidemia) e cardiovasculares (hipertensão arterial sistêmica, aterosclerose e doença coronariana); (2) disfunção neurocognitiva: déficits de atenção, percepção, memória, raciocínio, juízo, pensamento e linguagem. Quanto à relação da SAOS e repercussões socioeconômicas, tem-se: (1) aumento do número, proporção e gravidade de acidentes automobilísticos devido à diminuição da concentração do motorista; (2) prejuízos ocupacionais com queda na produtividade, demissões e acidentes de trabalho; (3) prejuízo social: o individuo com SAOS representa também um perigo potencial para toda a sociedade por aumento de imperícias; (4) aumento de gastos públicos e privados: manutenção de rodovias e estrutura de fiscalização e apoio, gastos previdenciários, custos diagnósticos, terapêuticos e hospitalares. A SAOS deveria ser considerada uma doença de saúde pública, dados seus inequívocos prejuízos individuais, sociais e econômicos. Políticas específicas deveriam ser implementadas visando à redução do impacto dessas consequências.

Obstructive Sleep Apnea Syndrome (OSAS) is defined as obstruction of air passage through the upper airways during sleep. The patient has repeated episodes of hypoxemia and hypercapnia, and because of those events, the sleep becomes superficial and fragmented, resulting in a series of complications for the individual and the community. The aim of the present study was to review the literature about individual, economic and social consequences caused by OSAS. Several complications of OSAS related to the individual were identified: (1) physical and behavioral changes: excessive sleeping, fatigue, anxiety, irritability, depression, decreased libido,decreased quality of life, metabolic (such as weight gain, diabetes and dyslipidemia) and cardiovascular consequences (such as hypertension, atherosclerosis and coronary heart disease); (2) neurocognitive impairment: deficits in attention, perception, memory, reasoning, opinion, thought and language. There are also some socio-economic repercussions related toOSAS, such as: (1) increased number, proportion and gravity of traffic accidents due to the decrease of driver's concentration; (2) occupational injury with a fall in productivity, layoffs and workplace accidents; (3) social loss: the individual with OSAS is also a potential danger to society by increasing malpractice; (4) increased public and private expenditures: maintenance of highways and structure of supervision and support, socialsecurity spending, costs with diagnosis, therapies and hospital. OSAS should be considered a public health disease, given their unequivocal individual, social and economical damages. Specific policies should be implemented to reduce the impact of those consequences.

Panniculitis in a patient with dermatomyositis.

Panniculitis is a rarely reported clinical finding in dermatomyositis. It may precede the other manifestations associated with dermatomyositis by as much as 14 months. In all cases, myositis and panniculitis improve simultaneously during treatment. The present report describes the case of a 30-year-old female patient with clinical and histopathological findings consistent with panniculitis two months after the onset of the muscle and cutaneous symptoms that permitted diagnosis of dermatomyositis. The skin lesions regressed following steroid treatment.

Paniculitis en paciente con dermatomiositis / Panniculitis in a patient with dermatomyositis

La paniculitis es una manifestación cutánea infrecuente de la dermatomiositis. Puede preceder hasta en 14 meses a otras manifestaciones de la dermatomiositis. En todos los casos, la miositis y la paniculitis presentan mejoría simultánea durante el tratamiento. Describimos una paciente de sexo femenino de 30 años que presenta lesiones clínica e histológicamente compatibles con paniculitis luego de 2 meses de que el compromiso muscular y cutáneo permitió el diagnóstico de dermatomiositis. Las lesiones cutáneas remitieron con el tratamiento esteroideo.

Panniculitis is a rarely reported clinical finding in dermatomyositis. It may precede the other manifestations associated with dermatomyositis by as much as 14 months. In all cases, myositis and panniculitis improve simultaneously during treatment. The present report describes the case of a 30-year-old female patient with clinical and histopathological findings consistent with panniculitis two months after the onset of the muscle and cutaneous symptoms that permitted diagnosis of dermatomyositis. The skin lesions regressed following steroid treatment.