Triple Jeopardy in Oral Health: Additive Effects of Immigrant Status, Education, and Neighborhood.

PURPOSE: To estimate the additive effects of parent's nativity status/language spoken at country of birth, education, and area-level socioeconomic status (SES) on untreated dental caries among children aged 5 to 9 y in Australia. METHODS: Cross-sectional population-based data were obtained from the 2014 National Child Oral Health Study (N = 12,140). Indicators of social position used to explore additive effects on dental caries included nativity status, language, university degree, and neighborhood socioeconomic level. Multiple-way interactions were examined, and departure from additivity resulting from 2- and 3-way interactions were estimated as relative excess risk due to interaction (RERI). RESULTS: Children marginalized across multiple layers of disadvantage had substantially higher frequencies of dental caries compared with children in the most advantaged category. RERI for the 3-way interaction between immigrant status, education, and neighborhood SES was negative (RERI3: -0.14; 95% confidence interval [CI]: -1.68, 1.40). When operationalizing language, education, and neighborhood SES, the joint effect of the 3 marginalized positions was additive (RERI3: 0.43; 95% CI: -2.08, 2.95). CONCLUSION: Children marginalized across multiple intersecting axes of disadvantage bear the greatest burden of dental caries, with frequencies surpassing the cumulative effect of each social position alone. Findings emphasize the need to account for intersecting inequities and their oral health effects among children with immigrant backgrounds. KNOWLEDGE TRANSFER STATEMENT: Our analysis underscores the necessity for policies and public health strategies targeting dental caries-related inequities to comprehensively account for various indicators of social disadvantage, particularly encompassing language proficiency, educational attainment, and neighborhood socioeconomic status. Within the intricate interplay of these factors, we identify a vulnerable subgroup comprising children with the highest prevalence of dental decay. Therefore, prioritizing this specific demographic should be the focal point of policies and public health initiatives aimed at fostering equitable oral health outcomes.

The mind-skin connection: A narrative review exploring the link between inflammatory skin diseases and psychological stress.

Inflammatory skin diseases are known to negatively impact patient psychology, with individuals experiencing higher rates of stress and subsequent diminished quality of life, as well as mental health issues including anxiety and depression. Moreover, increased psychological stress has been found to exacerbate existing inflammatory skin diseases. The association between inflammatory skin diseases and psychological stress is a timely topic, and a framework to better understand the relationship between the two that integrates available literature is needed. In this narrative review article, we discuss potential neurobiological mechanisms behind psychological stress due to inflammatory skin diseases, focusing mainly on proinflammatory cytokines in the circulating system (the brain-gut-skin communications) and the default mode network in the brain. We also discuss potential descending pathways from the brain that lead to aggravation of inflammatory skin diseases due to psychological stress, including the central and peripheral hypothalamic-pituitary-adrenal axes, peripheral nerves and the skin barrier function.

Role of collagen and immunostaining for TGF-ß in the clinical and microscopic findings of pyogenic granuloma and peripheral ossifying fibroma.

BACKGROUND: Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of collagen and immunostaining for Transforming Growth Factor beta (TGF-ß) in the clinical and microscopic findings of PG and POF. MATERIAL AND METHODS: PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-ß) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0). RESULTS: The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-ß+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-ß suffered from modifications by the time of evolution and the size of the lesion. CONCLUSIONS: Although PG and POF are reactive gingival lesions, the expression of TGF-ß and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components.

Associations and discrepancies between global self-ratings of oral health and general health: a Bayesian approach.

OBJECTIVE: To estimate the discrepancies between global ratings of oral health and general health and investigate the factors associated with self-rated oral health (SROH) and self-rated general health (SRGH). METHODS: Data were collected from 502 participants aged 18 to 81 years. A structured questionnaire was used to obtain data regarding sociodemographic characteristics and self-reported conditions. Global self-ratings of oral health and general health were the main outcomes. Discrepancies between self-ratings of oral health and general health were stratified by independent variables. Bayesian ordinal logistic regression models were fitted to estimate the posterior distributions of parameters and 95% credible intervals (95% CrI). RESULTS: The proportion of participants who rated their oral health worse than general health was 28.6% (95% CrI: 24.7-32.3). Negative discrepancies between SROH and SRGH were associated with being men, reporting gingivitis, and lower income. Sex (95% CrI: 1.12-2.25) impacted only on SRGH. Income (SROH - 95% CrI: 1.52-6.40; SRGH - 95% CrI: 1.08-4.56), tertiary education (SROH - 95% CrI: 1.13-2.53; SRGH - 95% CrI: 1.01-2.32), self-reported missing teeth (SROH - 95% CrI: 1.57-3.46; SRGH - 95% CrI: 2.21-4.92), self-reported gingivitis (SROH - 95% CrI: 1.10-2.40; SRGH - 95% CrI: 1.71-3.82), and self-reported chronic health problem (SROH - 95% CrI: 1.38-3.08; SRGH - 95% CrI: 1.61-3.59) impacted on both outcomes. CONCLUSIONS: Substantial discrepancies between self-rated oral health and self-rated general health were found and were associated with being male, reporting gingivitis, and having lower income.

Oral health profile of Australian children from different immigrant backgrounds.

OBJECTIVES: To profile the oral health of Australian children from different immigrant backgrounds. METHOD: Cross-sectional data for Australian children were obtained from the 2012-14 National Child Oral Health Study (NCOHS). Three categories of immigrant status were created based on parents' country of birth and language (non-immigrant, non-visible immigrant, and visible immigrant). Descriptive analyses reported weighted estimates for experience of dental caries, self-rated oral health, and dental services utilisation separately for children aged 5-9 years and 10-14 years. RESULTS: The sample comprised 10,610 children aged 5-9 years (3,605 from immigrant backgrounds), and 8,741 children aged 10-14 years (3,074 from immigrant backgrounds). Children from non-visible immigrant backgrounds presented worse dental service utilisation and poorer self-rated oral health than children from non-immigrant and visible immigrant families. Greater inequalities in dental caries experience were observed in the 5-9-year-olds. Untreated caries was substantially higher among visible immigrant children aged 5-9 years (38.8%, 95% CI: 35.5-42.3) than non-immigrant (24.9%, 95% CI: 23.4-26.6) and non-visible immigrant children (21.0%, 95% CI: 17.7-24.7). CONCLUSIONS: Australian children from immigrant families constitute a highly heterogeneous group with substantial discrepancies in oral health outcomes.

Morphology and molecular phylogeny of Chauhanellus Bychowsky & Nagibina, 1969 (Monogenoidea) parasitizing marine catfish (Ariidae) from the Atlantic coast of South America: a new species, supplementary taxonomic information and new insights.

In this study, a new dactylogyrid species is described from the gills of two ariid fish species of the Brazilian coast, Genidens barbus and Genidens genidens, by combining morphological characters with partial 18S rDNA sequences. The new species can be distinguished from its congeners by the following morphological characteristics: a male copulatory organ (MCO), a coiled tubular shaft of around one counterclockwise ring, base with a sclerotized cap; MCO with tapered distal region; a T-shaped accessory piece; a vagina, a cup-shaped vaginal vestibule, slightly sclerotized; and a pharynx comprising a muscular, glandular bulb. Supplementary taxonomic data for Chauhanellus velum from Sciades couma (type-host) are also presented and new 18S rDNA sequences of Chauhanellus spp. from other ariid fish from South America are provided. Phylogenetic analyses based on partial 18S rDNA gene sequences placed Chauhanellus riograndinensis n. sp. and Chauhanellus velum as two early divergent lineages within Chauhanellus from South America. Finally, a way to test the monophyly of Chauhanellus and Hamatopeduncularia is also discussed, which may be useful for future studies.

Immigrants experience oral health care inequity: findings from Australia's National Study of Adult Oral Health.

BACKGROUND: Oral health service utilization contributes to positive oral health and indicates realised access to services. The study aimed to describe patterns of oral health service use among overseas-born and Australian-born populations and assess equity in access to services. METHODS: The study used data from Australia's National Study of Adult Oral Health 2017-2018 and was guided by the Aday and Andersen framework of access to health and Australia's National Oral Health Plan. Descriptive analyses of service use by perceived need, enabling and predisposing factors were compared between four groups: Australian-born and overseas-born who mainly speak English and Australian-born and overseas-born who mainly speak a language other than English. RESULTS: Overseas-born who mainly speak a language other than English experienced greater oral health care inequity, largely driven by financial difficulty (avoided care due to cost: 42% vs 27%-28%; avoided/delayed visiting due to cost: 48% vs. 37%-38%; cost prevented treatment: 32% vs. 18%-24%). The most favourable visiting patterns were among the Australian-born population who speak a language other than English. CONCLUSIONS: The study shows clear inequity experienced among immigrants in accessibility as measured through indicators of oral health care utilization and factors related to inequity, such as the ability to pay for services.

A Psychometric Network Analysis of OHIP-14 across Australian and Brazilian Populations.

OBJECTIVES: The aim of this study was to assess the structural validity of the Oral Health Impact Profile-14 (OHIP-14) instrument in Indigenous and non-Indigenous populations from Australia and Brazil using a network analysis approach. METHODS: Cross-sectional data collected using OHIP-14 were obtained for Indigenous and non-Indigenous populations from Australia and Brazil. Networks were estimated using the Gaussian graphical model. Items of the OHIP-14 instrument are represented as nodes and the partial correlations between items as edges. Dimensionality was assessed using exploratory graph analysis. Structural consistency and item stability were computed using a bootstrap sampling method. Standardized node strength across each dimension was also calculated. RESULTS: Four dimensions were identified across all samples, although the item arrangement of most dimensions presented variation. Similarities with the theoretical domains of the instrument were found. Items from the conceptually derived OHIP-14 domains formed separated clusters or blended with other items in a single dimension. Most dimensions across all samples showed an acceptable structural consistency. Item stability revealed some discrepancies among items of dimensions of both Indigenous networks. CONCLUSION: The psychometric network perspective adopted in this study provides validation of the OHIP-14 structure in Indigenous and non-Indigenous populations. The structural consistency and item stability analyses showed that both Indigenous networks present a higher number of cross-domain items and less defined boundaries between dimensions. These findings indicate that OHIP-14 does not measure attributes in the same extent among different cultures. KNOWLEDGE TRANSFER STATEMENT: This study demonstrates a new analytical framework from which to conceptualize and interpret the construct oral health-related quality of life using the Oral Health Impact Profile (OHIP-14). Network graphs facilitate knowledge translation of findings to professionals with no expertise in psychometric methods. OHIP-14 is a valuable tool to oral health research and clinical practice. Differences in conceptions of health may influence the extent that the instrument measures oral health impacts. Consequently, dimension scores do not always provide appropriate measures and should be avoided in research reports and assessments of treatment outcomes.

Changes in cardiac biomarkers in goats naturally affected by pregnancy toxemia.

Pregnancy toxemia (PT) is considered one of the most common metabolic diseases with high impact on the production of small ruminants. The objective of this study was investigate possible myocardial damage in goats affected with PT by the determination of serum myocardial biomarkers CK-MB and cTnI. A total of 44 goats affected with PT, and 10 apparently healthy goats (control group or CG) were used in the study. In goats with PT, the serum concentrations of cTnI (0.43 ng/mL) were significantly higher than that in CG goats (0.06 ng/mL). Although CK-MB showed no significant difference, it was approximately three times higher in animals with PT. The serum concentrations of insulin were significantly lower in PT goats (5.03 ppmol/L) compared to CG goats (10.66 pmol/L). The serum concentrations of cortisol in PT goats (155.41 nmol/L) were significantly higher than that in CG goats (36.58 nmol/L). Results of this study indicate that a clinically significant myocardial damage might occur in goats affected with PT leading to significant elevations in values of cTnI and CK-MB. Therefore, these parameters could be used as a potential prognostic indicator in goats affected with this important disease.

Monogenoidean parasites of Acestrorhynchus falcatus (Characiformes: Acestrorhynchidae) from Pará, Brazil: species of Diaphorocleidus and Rhinoxenoides n. gen. (Monogenoidea: Dactylogyridae).

Two new species of Diaphorocleidus and one new species of Rhinoxenoides n. gen. are described from the gills of Acestrorhynchus falcatus (Bloch) from rivers of north-eastern Pará, Brazil. Diaphorocleidus jaymedeloyolai n. sp. is characterized by a male copulatory organ (MCO) possessing three counterclockwise coils; similar anchors with subtriangular superficial roots; a ventral bar with posteromedial projection; and hooks of pairs 1, 4 and 7 approximately three times longer than hook pair 5. Diaphorocleidus sclerocolpus n. sp. differs from its congeners by a dual-branched accessory piece articulated with the MCO and a sclerotized tubular vagina with a bottle-shaped vestibule. Rhinoxenoides n. gen. is proposed and is characterized by possessing: MCO sclerotized with clockwise coils; an accessory piece articulated to the base of MCO; a sinistroventral vaginal aperture; ventral anchor with conspicuous roots; dorsal anchor with superficial root five times longer than deep root; and absence of dorsal bar. The proposal of Rhinoxenoides n. gen. is also supported by its phylogenetic relationship with Protorhinoxenus prochilodi and species of Rhinoxenus, using 16 morphological characters, which resulted in the following hypothesis of sister-group relationships: Rhinoxenoides n. gen. [Protorhinoxenus (Rhinoxenus curimatae (R. nyttus (R. bulbovaginatus (R. guianensis, R. piranhus, R. euryxenus (R. arietinus, R. anaclaudiae)))))].

Prevalence of carotid artery calcifications among 2,500 digital panoramic radiographs of an adult Brazilian population.

BACKGROUND: The aim of the present study was to analyze the epidemiological data of digital panoramic radiographs revealing suggestive images of carotid artery calcifications (CAC) from a Northeast Brazilian population. MATERIAL AND METHODS: A cross-sectional retrospective study was conducted with 2,500 digital panoramic radiographs obtained from a single imaging reference center in Northeast Brazil. Images from individuals of both sexes and older than 18 years were included and those that did not cover the region of cervical vertebrae or presented low radiographic quality were excluded. Data were analyzed regarding prevalence, location (bilateral, right or left), sex, and age using the Chi-square test at the significance level of 5%. RESULTS: An amount of 96 (4%) patients presented suggestive images of CAC. The female sex (p=0.003) and individuals aged up to 70 years (p=0.002) were statically significant. 40.4% were found bilaterally, 37.6% on the right side (p<0.001) and 22% on the left side. CONCLUSIONS: In conclusion, this study showed a low prevalence of suggestive images of CAC in digital panoramic radiographs from a Northeast Brazilian population. It was observed a higher prevalence of CAC associated with female sex, older patients, and right side location.

A New Species of Pararrhopalites Bonet & Tellez (Collembola, Symphypleona, Sminthuridae) from Iron Caves in Brazil.

A second species of the genus Pararrhopalites is described from caves inserted in iron ore lithology. Both species present a particular sensory organ in the interantennal region. The new species, Pararrhopalites ubiquum n.sp., has a wider distribution and it is not restricted to a single cave, as it is the case of Pararrhopalites sideroicus Zeppelini & Brito, in Fla Entomol 97(4):1733-1744, 2014, being found even in the Mesovoid Shallow Substratum. An update to the previously published identification key is presented.

Functionalization of cotton cellulose for improved wound healing.

Wound dressing research has been determined by population aging, persistence of wound infection and the increase in chronic wound cases. Thus, besides mechanical protection, wound dressings must interact with the wound and improve the healing process. To achieve this demanding goal, wound dressing research has been focussing on the development of composite wound dressings that combine the best of two or more polymeric materials. Cellulosic materials are still the most used for wound management. Their importance is reflected in the number of publications on this subject in the textile engineering field. Textile wound dressing can cause maceration to the wound and pain during removal. However, the limitations of cellulosic wound dressings can be overcome by functionalization with hydrogels, which will maintain the moisture environment and improve the drug delivery ability of cotton. Therefore, the present review summarizes the composite materials research on the functionalization of cotton cellulose with hydrogels, to be applied as a wound dressing, and the methods and techniques used to synthesize those composites.

Comprehensive molecular screening strategy of OCLN in band-like calcification with simplified gyration and polymicrogyria.

Occludin (OCLN) is an important component of the tight junction complex, providing apical intercellular connections between adjacent cells in endothelial and epithelial tissue. In 2010 O'Driscoll et al reported mutations in OCLN to cause band-like calcification with simplified gyration and polymicrogyria (BLC-PMG). BLC-PMG is a rare autosomal recessive syndrome, characterized by early onset seizures, progressive microcephaly, severe developmental delay and deep cortical gray matter and basal ganglia calcification with symmetrical, predominantly fronto-parietal, polymicrogyria. Here we report 4 additional cases of BLC-PMG with novel OCLN mutations, and provide a summary of the published mutational spectrum. More generally, we describe a comprehensive molecular screening strategy taking into account the technical challenges associated with the genetic architecture of OCLN, which include the presence of a pseudo-gene and copy number variants.

Avaliação clínica de ovinos após a ingestão de elevada quantidade de manga / Clinical evaluation of sheep after high ingestion of mango fruit

Objetivou-se avaliar clinicamente os efeitos da administração intrarruminal de duas quantidades distintas de manga em ovinos. Foram utilizados sete ovinos machos, hígidos, que não receberam carboidratos não fibrosos por, pelo menos, seis meses previamente ao período experimental, quando se avaliou pH ruminal, total de protozoários no suco de rúmen, pH urinário, pH sanguíneo estimado e parâmetros vitais nos tempos zero, 12, 16, 20 e 24 após a administração da manga. Os sete ovinos foram distribuídos aleatoriamente em dois grupos e receberam 0,625% ou 1,875% da MS de manga/kg/PV (M1 e M2, respectivamente), distribuídos em delineamento cross-over, com uma parcela perdida, e 30 dias de washout. Os ovinos M2 apresentaram valores médios para pH ruminal significativamente inferiores a M1 a partir do tempo T12 (5,1 e 6,9, respectivamente), o que indica ocorrência de acidose ruminal. Os animais tratados com M1 não apresentaram alterações sistêmicas, ao passo que os ovinos tratados com M2 apresentaram acidose metabólica leve, detectada por meio do pH urinário ácido (4,8). A ingestão apenas de manga in natura na quantidade de 1,875% da MS de manga/kg/PV mostrou-se capaz de provocar acidose ruminal em ovinos, levando-os a: ligeira depressão, aumento da frequência cardíaca, diminuição dos movimentos ruminais e diarreia em alguns casos.(AU)

The aim of this study is to clinically evaluate the effects of intra ruminal administration of two different amounts of mango in sheep. The sample was of seven male healthy sheep, which did not receive non-fibrous carbohydrates for at least six months prior to the trial. Rumen fluid pH, total of protozoa in the rumen fluid, urine pH, estimated blood pH, and vital parameters were evaluated at the following times: zero, 12, 16, 20 and 24 hours after administration of the mango. The seven sheep were randomly divided into two groups and received either 0.625% or 1.875% of the dry matter of the pulp and mango peel per kg body weight (M1 and M2, respectively), distributed in cross-over design with a lost portion and 30 days washout. Sheep treated with M2 showed significantly lower average values for ruminal pH than the M1 since T12 (5.1 and 6.9, respectively), indicating the occurrence of ruminal acidosis. The animals treated with M1 showed no systemic changes, while the sheep treated with M2 had mild metabolic acidosis, detected through the lower urinary pH (4.8). The in natura mango ingestion in the amount of 1.875% of the dry matter of mango per kg of body weight proved to provoke rumen acidosis in sheep, leading these animals to: slight depression, rise in heart rate, diminished rumen movement, and diarrhea in some cases.(AU)

Dermatite piogranulomatosa ulcerativa em bovino por Corynebacterium pseudotuberculosis / Ulcerative pyogranulomatous dermatitis in bovine by Corynebacterium pseudotuberculosis

Relata-se um caso de lesão cutânea secundária à infecção por Corynebacterium pseudotuberculosis em bovino. Abscessos e múltiplas lesões cutâneas nodulares, variando de 8x10 para 20x25cm de diâmetro, firmes, sensíveis ao toque e sem mobilidade, algumas com superfície ulcerada, circundada por halo avermelhado e drenando secreção piossanguinolenta, e outras com superfícies alopécicas, foram identificados na região torácica lateral do animal. Exames histopatológicos e o isolamento do agente de fragmentos obtidos após remoção cirúrgica das lesões confirmaram tratar-se da forma cutânea da infecção pelo C. pseudotuberculosis. As lesões microscópicas caracterizaram-se por dermatite nodular piogranulomatosa e ulcerativa. A avaliação da susceptibilidade in vitro do C. pseudotuberculosis a antimicrobianos demonstrou que o agente era resistente à amicacina, kanamicina, neomicina e penicilina G, apresentando sensibilidade à ampicilina adicionada de subactam, amoxicilia com ácido clavulônico, cefalexina, cefalotina, cefotaxima, enrofloxacina, gentamicina e tetraciclina. A retirada cirúrgica das lesões e o tratamento com enrofloxacina resultaram na cura do animal. Lesões de pele observadas em casos de ptiose, carcinoma de células escamosas e na forma atípica da actinobacilose devem ser consideradas no diagnóstico diferencial da forma cutânea da infecção por C. pseudotuberculosis em bovinos. Os dados apresentados demonstram que a infecção pelo C. pseudotuberculosis deve ser considerada no diagnóstico diferencial das lesões de pele em bovinos no Brasil.(AU)

We report a case of secondary skin lesionby infection with Corynebacterium pseudotuberculosis in bovine. Abscesses and multiple nodular lesions, ranging from 8x10 to 20x25 cm in diameter, firm, sensitive to touch, and without mobility, some with ulcerated surface, surrounded by reddish halo and draining piosanguinolenta secretion, and other surfaces with alopecia, were identified in the skin of the animal`s thoracic area. Histopathology and isolation of the agent from fragments obtained after surgical removal of the lesions confirmed the cutaneous infection by C. pseudotuberculosis. Microscopic lesions were characterized by lumpy skin disease and ulcerative pyogranulomatous. Evaluation of in vitro susceptibility to antimicrobial demonstrated that the agent was resistant to amikacin, kanamycin, neomycin and penicillin G, and sensitive to ampicillin + subactam, amoxicilia with clavulonic acid, cephalexin, cephalothin, cefotaxime, enrofloxacin, gentamicin, and tetracycline. The surgical removal of the lesions, and treatment with enrofloxacin resulted in animal cure. Skin lesions observed in case of ptiose, squamous cell carcinoma and atypical form of Actinobacillosis should be considered in the differential diagnosis of cutaneous form of C. pseudotuberculosis infection in cattle. The data presented demonstrate that infection with C. pseudotuberculosis should be considered in the differential diagnosis of skin lesions in cattle in Brazil.(AU)

Perturbations in the apoptotic pathway and mitochondrial network dynamics in peripheral blood mononuclear cells from bipolar disorder patients.

Bipolar disorder (BD) is a severe psychiatric disorder characterized by phasic changes of mood and can be associated with progressive structural brain change and cognitive decline. The numbers and sizes of glia and neurons are reduced in several brain areas, suggesting the involvement of apoptosis in the pathophysiology of BD. Because the changes in mitochondrial dynamics are closely related with the early process of apoptosis and the specific processes of apoptosis and mitochondrial dynamics in BD have not been fully elucidated, we measured the apoptotic pathway and the expression of mitochondrial fission/fusion proteins from BD patients and healthy controls. We recruited 16 patients with BD type I and sixteen well-matched healthy controls and investigated protein levels of several pro-apoptotic and anti-apoptotic factors, as well as the expression of mitochondrial fission/fusion proteins in peripheral blood mononuclear cells (PBMCs). Our results showed that the levels of the anti-apoptotic proteins Bcl-xL, survivin and Bcl-xL/Bak dimer were significantly decreased, while active caspase-3 protein levels were significantly increased in PBMCs from BD patients. Moreover, we observed the downregulation of the mitochondrial fusion-related proteins Mfn2 and Opa1 and the upregulation of the fission protein Fis1 in PBMCs from BD patients, both in terms of gene expression and protein levels. We also showed a significantly decrease in the citrate synthase activity. Finally, we found a positive correlation between Mfn2 and Opa1 with mitochondrial content markers, as well as a negative correlation between mitochondrial fission/fusion proteins and apoptotic markers. Overall, data reported here are consistent with the working hypothesis that apoptosis may contribute to cellular dysfunction, brain volume loss and progressive cognitive in BD. Moreover, we show an important relationship between mitochondrial dynamics and the cell death pathway activation in BD patients, supporting the link between mitochondrial dysfunction and the pathophysiology of BD.

Duodenal-jejunal bypass normalizes pancreatic islet proliferation rate and function but not hepatic steatosis in hypothalamic obese rats.

Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans and rodents. Since these strategies fail to treat hypothalamic obesity, we have assessed the possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism and the morphophysiology of pancreatic islets, in hypothalamic obese (HyO) rats. During the first 5 days of life, male Wistar rats received subcutaneous injections of monosodium glutamate (4 g/kg body weight, HyO group), or saline (CTL). At 90 days of age, HyO rats were randomly subjected to DJB (HyO DJB group) or sham surgery (HyO Sham group). HyO Sham rats were morbidly obese, insulin resistant, hypertriglyceridemic and displayed higher serum concentrations of non-esterified fatty acids (NEFA) and hepatic triglyceride (TG). These effects were associated with higher expressions of the lipogenic genes and fatty acid synthase (FASN) protein content in the liver. Furthermore, hepatic genes involved in ß-oxidation and TG export were down-regulated in HyO rats. In addition, these rats exhibited hyperinsulinemia, ß-cell hypersecretion, a higher percentage of islets and ß-cell area/pancreas section, and enhanced nuclear content of Ki67 protein in islet-cells. At 2 months after DJB surgery, serum concentrations of TG and NEFA, but not hepatic TG accumulation and gene and protein expressions, were normalized in HyO rats. Insulin release and Ki67 positive cells were also normalized in HyO DJB islets. In conclusion, DJB decreased islet-cell proliferation, normalized insulinemia, and ameliorated insulin sensitivity and plasma lipid profile, independently of changes in hepatic metabolism.

Integrated transcriptome and methylome analysis in youth at high risk for bipolar disorder: a preliminary analysis.

First-degree relatives of patients with bipolar disorder (BD), particularly their offspring, have a higher risk of developing BD and other mental illnesses than the general population. However, the biological mechanisms underlying this increased risk are still unknown, particularly because most of the studies so far have been conducted in chronically ill adults and not in unaffected youth at high risk. In this preliminary study we analyzed genome-wide expression and methylation levels in peripheral blood mononuclear cells from children and adolescents from three matched groups: BD patients, unaffected offspring of bipolar parents (high risk) and controls (low risk). By integrating gene expression and DNA methylation and comparing the lists of differentially expressed genes and differentially methylated probes between groups, we were able to identify 43 risk genes that discriminate patients and high-risk youth from controls. Pathway analysis showed an enrichment of the glucocorticoid receptor (GR) pathway with the genes MED1, HSPA1L, GTF2A1 and TAF15, which might underlie the previously reported role of stress response in the risk for BD in vulnerable populations. Cell-based assays indicate a GR hyporesponsiveness in cells from adult BD patients compared to controls and suggest that these GR-related genes can be modulated by DNA methylation, which poses the theoretical possibility of manipulating their expression as a means to counteract the familial risk presented by those subjects. Although preliminary, our results suggest the utility of peripheral measures in the identification of biomarkers of risk in high-risk populations and further emphasize the potential role of stress and DNA methylation in the risk for BD in youth.