Adiponectin deficiency induces hepatic steatosis during pregnancy and gestational diabetes in mice.

AIMS/HYPOTHESIS: Obesity and hepatic steatosis are risk factors for gestational diabetes mellitus (GDM), a common complication of pregnancy. Adiponectin is a fat-derived hormone that improves hepatic steatosis and insulin sensitivity. Low levels of circulating adiponectin are associated with GDM development. We hypothesised that adiponectin deficiency causes fatty liver during pregnancy, contributing to the development of GDM. METHODS: To determine the role of adiponectin in fatty liver development during pregnancy, we compared pregnant (third week of pregnancy) adiponectin knockout (KO) mice (strain B6;129-Adipoqtm1Chan/J) with wild-type mice and assessed several variables of hepatic lipid metabolism and glucose homeostasis. The impact of adiponectin supplementation was measured by administering adenovirus-mediated full-length adiponectin at the end of the second week of pregnancy and comparing with green fluorescent protein control. RESULTS: In the third week of pregnancy, fasted pregnant adiponectin KO mice were hyperglycaemic on a low-fat diet (9.2 mmol/l vs 7.7 mmol/l in controls, p<0.05) and were glucose and pyruvate intolerant relative to wild-type mice. Pregnant adiponectin KO mice developed hepatic steatosis and a threefold elevation in hepatic triacylglycerols (p<0.05) relative to wild-type mice. Gestational weight gain and food consumption were similar in KO and wild-type mice. Adenoviral-mediated adiponectin supplementation to pregnant adiponectin KO mice improved glucose tolerance, prevented fasting hyperglycaemia and attenuated fatty liver development. CONCLUSIONS/INTERPRETATION: Adiponectin deficiency increased hepatic lipid accumulation during the period of pregnancy associated with increased fat utilisation. Consequently, adiponectin deficiency contributed to glucose intolerance, dysregulated gluconeogenesis and hyperglycaemia, all of which are characteristic of GDM. Increasing adiponectin in the last week of pregnancy alleviated hepatic steatosis and restored normal glucose homeostasis during pregnancy.

Maternal diabetes promotes offspring lung dysfunction and inflammation in a sex-dependent manner.

Exposure to maternal diabetes is increasingly recognized as a risk factor for chronic respiratory disease in children. It is currently unclear; however, whether maternal diabetes affects the lung health of male and female offspring equally. This study characterizes the sex-specific impact of a murine model of diet-induced gestational diabetes (GDM) on offspring lung function and airway inflammation. Female adult mice are fed a high-fat (45% kcal) diet for 6 wk prior to mating. Control offspring are from mothers fed a low-fat (10% kcal) diet. Offspring were weaned and fed a chow diet until 10 wk of age, at which point lung function was measured and lung lavage was collected. Male, but not female, offspring exposed to GDM had increased lung compliance and reduced lung resistance at baseline. Female offspring exposed to GDM displayed increased methacholine reactivity and elevated levels of proinflammatory cytokines [e.g., interleukin (IL)-1ß, IL-5, and CXCL1] in lung lavage. Female GDM offspring also displayed elevated abundance of matrix metalloproteinases (MMP) within their airways, namely, MMP-3 and MMP-8. These results indicate disparate effects of maternal diabetes on lung health and airway inflammation of male and female offspring exposed to GDM. Female mice may be at greater risk of inflammatory lung conditions, such as asthma, whereas male offspring display changes that more closely align with models of chronic obstructive pulmonary disease. In conclusion, there are important sex-based differences in the impact of maternal diabetes on offspring lung health that could signal differences in future disease risk.

Maternal resveratrol administration protects against gestational diabetes-induced glucose intolerance and islet dysfunction in the rat offspring.

KEY POINTS: Maternal resveratrol (RESV) administration in gestational diabetes (GDM) restored normoglycaemia and insulin secretion. GDM-induced obesity was prevented in male GDM+RESV offspring but not in females. GDM+RESV offspring exhibited improved glucose tolerance and insulin sensitivity. GDM+RESV restored hepatic glucose homeostasis in offspring. Glucose-stimulated insulin secretion was enhanced in GDM+RESV offspring. ABSTRACT: Gestational diabetes (GDM), the most common complication of pregnancy, is associated with adverse metabolic health outcomes in offspring. Using a rat model of diet-induced GDM, we investigated whether maternal resveratrol (RESV) supplementation (147 mg kg-1  day-1 ) in the third week of pregnancy could improve maternal glycaemia and protect the offspring from developing metabolic dysfunction. Female Sprague-Dawley rats consumed a high-fat and sucrose (HFS) diet to induce GDM. Lean controls consumed a low-fat (LF) diet. In the third trimester, when maternal hyperglycaemia was observed, the HFS diet was supplemented with RESV. At weaning, offspring were randomly assigned a LF or HFS diet until 15 weeks of age. In pregnant dams, RESV restored glucose tolerance, normoglycaemia and improved insulin secretion. At 15 weeks of age, GDM+RESV-HFS male offspring were less obese than the GDM-HFS offspring. By contrast, the female GDM+RESV-HFS offspring were similarly as obese as the GDM-HFS group. Hepatic steatosis, insulin resistance, glucose intolerance and dysregulated gluconeogenesis were observed in the male GDM offspring and were attenuated in the offspring of GDM+RESV dams. The dysregulation of several metabolic genes (e.g. ppara, lpl, pepck and g6p) in the livers of GDM offspring was attenuated in the GDM+RESV offspring group. Glucose stimulated insulin secretion was also improved in the islets from offspring of GDM+RESV dams. Thus, maternal RESV supplementation during the third trimester of pregnancy and lactation induced several beneficial metabolic health outcomes for both mothers and offspring. Therefore, RESV could be an alternative to current GDM treatments.

Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome.

Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring.

DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes.

OBJECTIVE: Youth-onset type 2 diabetes (T2D) is physiologically distinct from adult-onset, but it is not clear how the two diseases differ at a molecular level. In utero exposure to maternal type 2 diabetes (T2D) is known to be a specific risk factor for youth-onset T2D. DNA methylation (DNAm) changes associated with T2D but which differ between youth- and adult-onset might delineate the impacts of T2D development at different ages and could also determine the contribution of exposure to in utero diabetes. METHODS: We performed an epigenome-wide analysis of DNAm on whole blood from 218 youth with T2D and 77 normoglycemic controls from the iCARE (improving renal Complications in Adolescents with type 2 diabetes through REsearch) cohort. Associations were tested using multiple linear regression models while adjusting for maternal diabetes, sex, age, BMI, smoking status, second-hand smoking exposure, cell-type proportions and genetic ancestry. RESULTS: We identified 3830 differentially methylated sites associated with youth T2D onset, of which 3794 were moderately (adjusted p-value < 0.05 and effect size estimate > 0.01) associated and 36 were strongly (adjusted p-value < 0.05 and effect size estimate > 0.05) associated. A total of 3725 of these sites were not previously reported in the EWAS Atlas as associated with T2D, adult obesity or youth obesity. Moreover, three CpGs associated with youth-onset T2D in the PFKFB3 gene were also associated with maternal T2D exposure (FDR < 0.05 and effect size > 0.01). This is the first study to link PFKFB3 and T2D in youth. CONCLUSION: Our findings support that T2D in youth has different impacts on DNAm than adult-onset, and suggests that changes in DNAm could provide an important link between in utero exposure to maternal diabetes and the onset of T2D.

Exploiting Polyelectrolyte Complexation for the Development of Adhesive and Bioactive Membranes Envisaging Guided Tissue Regeneration.

Mussels secrete protein-based byssal threads to tether to rocks, ships, and other organisms underwater. The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. Inspired by such mussel bioadhesion, we demonstrate that catechol-modified polysaccharides can be used to obtain adhesive membranes using the compaction of polyelectrolyte complexes (CoPEC) method. It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. The CoPEC technique also allowed the entrapment of ternary bioactive glass nanoparticles to stimulate mineralization. Moreover, combinations of these polymers modified with catechol groups were made to enhance the adhesive properties of the assembled membranes. Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. Considering the promising properties exhibited by the obtained membranes, new adhesives suitable for the regeneration of hard tissues can be envisaged.

Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: A cross-sectional study.

Objective: Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D. Methods: We performed a cross sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells with serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal Complications in Adolescents with type 2 diabetes through Research (iCARE) cohort study, to explore the molecular changes in adolescents with T2D. Results: Our analysis showed that 43 serum metabolites and 36 differentially methylated regions (DMR) were associated with T2D. Several DMRs were located near the transcriptional start site of genes with established roles in metabolic disease and associated with altered serum metabolites (e.g. glucose, leucine, and gamma-glutamylisoleucine). These included the free fatty acid receptor-1 (FFAR1), upstream transcription factor-2 (USF2), and tumor necrosis factor-related protein-9 (C1QTNF9), among others. Conclusions: We identified DMRs and metabolites that merit further investigation to determine their significance in controlling gene expression and metabolism which could define T2D risk in adolescents.

Tafazzin Deficiency Reduces Basal Insulin Secretion and Mitochondrial Function in Pancreatic Islets From Male Mice.

Tafazzin (TAZ) is a cardiolipin (CL) biosynthetic enzyme important for maintaining mitochondrial function. TAZ affects both the species and content of CL in the inner mitochondrial membrane, which are essential for normal cellular respiration. In pancreatic ß cells, mitochondrial function is closely associated with insulin secretion. However, the role of TAZ and CL in the secretion of insulin from pancreatic islets remains unknown. Male 4-month-old doxycycline-inducible TAZ knock-down (KD) mice and wild-type littermate controls were used. Immunohistochemistry was used to assess ß-cell morphology in whole pancreas sections, whereas ex vivo insulin secretion, CL content, RNA-sequencing analysis, and mitochondrial oxygen consumption were measured from isolated islet preparations. Ex vivo insulin secretion under nonstimulatory low-glucose concentrations was reduced ~52% from islets isolated from TAZ KD mice. Mitochondrial oxygen consumption under low-glucose conditions was also reduced ~58% in islets from TAZ KD animals. TAZ deficiency in pancreatic islets was associated with significant alteration in CL molecular species and elevated polyunsaturated fatty acid CL content. In addition, RNA-sequencing of isolated islets showed that TAZ KD increased expression of extracellular matrix genes, which are linked to pancreatic fibrosis, activated stellate cells, and impaired ß-cell function. These data indicate a novel role for TAZ in regulating pancreatic islet function, particularly under low-glucose conditions.

Applied science facilitates the large-scale expansion of protected areas in an Amazonian hot spot.

Meeting international commitments to protect 17% of terrestrial ecosystems worldwide will require >3 million square kilometers of new protected areas and strategies to create those areas in a way that respects local communities and land use. In 2000-2016, biological and social scientists worked to increase the protected proportion of Peru's largest department via 14 interdisciplinary inventories covering >9 million hectares of this megadiverse corner of the Amazon basin. In each landscape, the strategy was the same: convene diverse partners, identify biological and sociocultural assets, document residents' use of natural resources, and tailor the findings to the needs of decision-makers. Nine of the 14 landscapes have since been protected (5.7 million hectares of new protected areas), contributing to a quadrupling of conservation coverage in Loreto (from 6 to 23%). We outline the methods and enabling conditions most crucial for successfully applying similar campaigns elsewhere on Earth.

Dlx2 homeobox gene transcriptional regulation of Trkb neurotrophin receptor expression during mouse retinal development.

Dlx homeobox genes are first expressed in embryonic retina at E11.5. The Dlx1/Dlx2 null retina has a reduced ganglion cell layer (GCL), with loss of late-born differentiated retinal ganglion cells (RGCs) due to increased apoptosis. TrkB signaling is proposed to regulate the dynamics of RGC apoptosis throughout development. DLX2 expression markedly precedes the onset of TrkB expression in the GCL; TrkB co-expression with Dlx2 and RGC markers is well-established by E13.5. In the Dlx1/Dlx2 null retina, TrkB expression is significantly reduced by E16.5. We demonstrated that DLX2 binds to a specific region of the TrkB promoter in retinal neuroepithelium during embryogenesis. In vitro confirmation and the functional consequences of DLX2 binding to this TrkB regulatory region support TrkB as a Dlx2 transcriptional target. Furthermore, ectopic Dlx2 expression in retinal explants activates TrkB expression and Dlx2 knockdown in primary retinal cultures results in reduced TrkB expression. RGC differentiation and survival require the coordinated expression of transcription factors. This study establishes a direct transcriptional relationship between a homeodomain protein involved in RGC differentiation and a neurotrophin receptor implicated in RGC survival. Signaling mediated by TrkB may contribute to survival of late-born RGCs whose terminal differentiation is regulated by Dlx gene function.

Gestational Diabetes Adversely Affects Pancreatic Islet Architecture and Function in the Male Rat Offspring.

Fetal exposure to gestational diabetes mellitus (GDM) and poor postnatal diet are strong risk factors for type 2 diabetes development later in life, but the mechanisms connecting GDM exposure to offspring metabolic health remains unclear. In this study, we aimed to determine how GDM interacts with the postnatal diet to affect islet function in the offspring as well as characterize the gene expression changes in the islets. GDM was induced in female rats using a high-fat, high-sucrose (HFS) diet, and litters from lean or GDM dams were weaned onto a low-fat (LF) or HFS diet. Compared with the lean control offspring, GDM exposure reduced glucose-stimulated insulin secretion in islets isolated from 15-week-old offspring, which was additively worsened when GDM exposure was combined with postnatal HFS diet consumption. In the HFS diet-fed offspring of lean dams, islet size and number increased, an adaptation that was not observed in the HFS diet-fed offspring of GDM dams. Islet gene expression in the offspring of GDM dams was altered in such categories as inflammation (e.g., Il1b, Ccl2), mitochondrial function/oxidative stress resistance (e.g., Atp5f1, Sod2), and ribosomal proteins (e.g., Rps6, Rps14). These results demonstrate that GDM exposure induced marked changes in gene expression in the male young adult rat offspring that cumulatively interact to worsen islet function, whole-body glucose homeostasis, and adaptations to HFS diets.

Identification of a direct Dlx homeodomain target in the developing mouse forebrain and retina by optimization of chromatin immunoprecipitation.

Understanding homeobox gene specificity and function has been hampered by the lack of proven direct transcriptional targets during development. Dlx genes are expressed in the developing forebrain, retina, craniofacial structures and limbs. Dlx1/Dlx2 double knockout mice die at birth with multiple defects including abnormal forebrain development and decreased Dlx5 and Dlx6 expression. We have successfully applied chromatin immunoprecipitation (ChIP) to identify a direct transcriptional target of DLX homeoproteins from embryonic tissues in vivo. We optimized cross-linking conditions to enrich for protein-DNA complexes, then using specific high affinity DLX antibodies captured immunoenriched DLX genomic DNA transcriptional targets. DLX homeobox proteins bind differentially to the Dlx5/Dlx6 intergenic enhancer in newborn retina (DLX2) and embryonic striatum (DLX1, DLX2) in situ. Reporter gene assays demonstrated the functional significance of the binding of DLX proteins to this regulatory element, confirmed in vitro by electrophoretic mobility shift assays, using tissue extracts or recombinant DLX proteins. ChIP provides the best approach to identify direct Dlx homeoprotein targets from developing tissues in situ. The use of this technology will advance our understanding of Dlx gene function in the vertebrate in vivo and can be applied to examine targets of other homeobox genes and other classes of transcription factors.

Dlx homeobox genes promote cortical interneuron migration from the basal forebrain by direct repression of the semaphorin receptor neuropilin-2.

Dlx homeobox genes play an important role in vertebrate forebrain development. Dlx1/Dlx2 null mice die at birth with an abnormal cortical phenotype, including impaired differentiation and migration of GABAergic interneurons to the neocortex. However, the molecular basis for these defects downstream of loss of Dlx1/Dlx2 function is unknown. Neuropilin-2 (NRP-2) is a receptor for Class III semaphorins, which inhibit neuronal migration. Herein, we show that Neuropilin-2 is a specific DLX1 and DLX2 transcriptional target by applying chromatin immunoprecipitation to embryonic forebrain tissues. Both homeobox proteins repress Nrp-2 expression in vitro, confirming the functional significance of DLX binding. Furthermore, the homeodomain of DLX1 and DLX2 is necessary for DNA binding and this binding is essential for Dlx repression of Nrp-2 expression. Of importance, there is up-regulated and aberrant expression of NRP-2 in the forebrains of Dlx1/Dlx2 null mice. This is the first report that DLX1 or DLX2 can function as transcriptional repressors. Our data show that DLX proteins specifically mediate the repression of Neuropilin-2 in the developing forebrain. As well, our results support the hypothesis that down-regulation of Neuropilin-2 expression may facilitate tangential interneuron migration from the basal forebrain.

Influência da Dieta e da Higiene Oral na Prevalência da Cárie Dentária de Crianças Com Paralisia Cerebral / Influence of Diet and Oral Hygiene on Dental Caries Prevalence of Children with Cerebral Palsy

Objetivo: Comparar a prevalência de cárie dentária na dentadura decídua e dentição mista, o índice de higiene oral e a dieta de crianças institucionalizadas e não institucionalizadas com paralisia cerebral; verificar a influência da dieta e da higiene oral na incidência da cárie e descrever os fatores econômicos das crianças não institucionalizadas.Métodos: Foi realizado estudo transversal com trinta e três crianças institucionalizadas e trinta e sete não institucionalizadas que definiram os grupos de estudo I e II respectivamente. Os grupos foram subdivididos por idade para avaliação do CPOD e ceod. Foram obtidos dados relativos à higiene bucal diária, o diário dietético recordatório de 3 dias, os fatores socioeconômicos e à disfunção alimentar. Após exame clínico e análise dos questionários, os dados foram tabulados e analisados estatisticamente. Para a comparação entre os grupos em relação à idade, utilizou-se o teste t de Student para amostras independentes. Para a diferença entre os grupos, quanto à higiene oral e à disfunção alimentar aplicou-se o teste Qui-quadrado ou o teste exato de Fisher (nos casos em que ocorreram valores esperados >5). A comparação entre os grupos, bem como a avaliação da influência da freqüência da escovação, uso do fio dental, pasta fluoretada, o fato de receber ajuda para higienização bucal e alimentação, foi realizada utilizando-se o teste de Mann-Whitney. Para a avaliação da influência do grau de disfunção alimentar nos índices CPOD, biofilme dentário, cálculo e IHOS foi realizado o teste de Kruskal-Wallis. Todos os resultados foram considerados significativos para a probabilidade de significância inferior a 5% (p<0,05). A concordância intra-examinador foi avaliada através do índice de Kappa (89,1% e 94,6%).

Resultados: Os resultados mostraram valores menores para o grupo I no CPOD e ceod e no IHO-S quando comparados com o grupo II. Somente os valores do CPOD (3-6 anos de idade=0) foram iguais para ambos os grupos. O índice do consumo de sacarose foi 22 para o grupo I e 8.6 para o grupo II. A disfunção alimentar avaliada demonstrou presença de disfunção no grupo I (GI=54%) e no grupo II (GII=81.9%). O grupo II consistiu em 51.45% na classe econômica C e 35.1% de classe D. O índice de higiene oral e de consumo de sacarose não demonstraram relação com os índices de cárie dentária nos dois grupos. Quanto a dieta, as alterações alimentares encontradas em conjunto com as alterações motoras inerentes à doença influenciaram o IHO-S em toda amostra estudada.Conclusão: A alteração da dieta e a educação dos pais e responsáveis quanto à saúde oral devem ser objetivo de todos aqueles que trabalham com pacientes com paralisia cerebral

Objective: To compare the prevalence of dental caries in deciduous and mixed dentition, the oral hygiene index and the diet of institutionalized and non-institutionalized children with cerebral palsy; to verify the influence of the diet and of the oral hygiene in the caries incidence and to describe the economic factor of the non-institutionalized children.Methods: A cross-sectional study involving thirty-three institutionalized and thirty-seven non-institutionalized children defined the groups of study I and II respectively. The groups have been subdivided by age, for evaluation of the DMFT and dmft. Information related to the daily oral hygiene, the 3-day food record, the social and economic factors and the feeding dysfunction has been obtained. After the exam in a clinic environment, the analysis of the questionnaires and of the daily diet, the data have been analyzed statistically. For comparison between groups regarding age, we used the Student t test for independent samples. The difference between groups in respect to oral hygiene and eating disorders has applied the chi-square or Fisher exact test (where expected values were >5). The comparison between groups, as well as assessing the influence of frequency of brushing, flossing, fluoride toothpaste, the fact of receiving aid for oral hygiene and diet, was performed using the Mann-Whitney test. The evaluation of the degree of eating disorders in DMFT, dental plaque, calculus and OHI-S was performed using the Kruskal-Wallis. All results were considered significant for the probability of significance at 5% (p<0.05). The intraexaminer was assessed using the kappa index (89.1% and 94,6%).

Results: The results showed lower values for group I of DMFT and dmft and OHI-S than the group II. Only the values to the DMFT (3-6 years old =0) was equal for both groups. The sugar intake index was 22 for group I e 8.6 for group II. The evaluated feeding dysfunction has demonstrated dysfunction in group-I (GI=54%) and the group II (GII=81.9%). Group-II was consisted of 51.45% of class C and 35.1% of class D. The rate of oral hygiene and of sugar consumption has not demonstrated any relation to the rates of dental caries in both groups. Regarding the diet, the feeding alterations found together with the motor alterations inherent to the disease have influenced the OHI-S score in the entire studied sample.Conclusion: The alteration of the diet and the education of the parents and the responsible ones regarding the oral health should be the objective of all of those who work with patients with cerebral palsy

Dlx1 and Dlx2 function is necessary for terminal differentiation and survival of late-born retinal ganglion cells in the developing mouse retina.

Dlx homeobox genes, the vertebrate homologs of Distal-less, play important roles in the development of the vertebrate forebrain, craniofacial structures and limbs. Members of the Dlx gene family are also expressed in retinal ganglion cells (RGC), amacrine and horizontal cells of the developing and postnatal retina. Expression begins at embryonic day 12.5 and is maintained until late embryogenesis for Dlx1, while Dlx2 expression extends to adulthood. We have assessed the retinal phenotype of the Dlx1/Dlx2 double knockout mouse, which dies at birth. The Dlx1/2 null retina displays a reduced ganglion cell layer (GCL), with loss of differentiated RGCs due to increased apoptosis, and corresponding thinning of the optic nerve. Ectopic expression of Crx, the cone and rod photoreceptor homeobox gene, in the GCL and neuroblastic layers of the mutants may signify altered cell fate of uncommitted RGC progenitors. However, amacrine and horizontal cell differentiation is relatively unaffected in the Dlx1/2 null retina. Herein, we propose a model whereby early-born RGCs are Dlx1 and Dlx2 independent, but Dlx function is necessary for terminal differentiation of late-born RGC progenitors.

Indicação profissional e disponibilidade dos principais instrumentos para o controle mecânico do biofilme dentário / Professional indication and availability of lhe main instruments for mechanic plaque control

Introdução - Os instrumentos para o controle mecânico do biofilme dentário usualmente recomendados são as escovas dentárias, fio/fitas dentários e dentifrícios. Material e Método - Foi realizado o estudo com 120 cirurgiões-dentistas de três cidades do Estado de Minas Gerais, em 30 supermercados e farmácia dessas cidades, com o objetivo de conhecer como os profissionais indicam os principais instrumentos para o controle mecânico do biofilme dentário a seus pacientes, qual é a disponibilidade destes produtos no mercado e a frequência em que cada um deles é encontrado. Resultados - Não houve diferença significativa de indicação dos produtos para procedimentos de higiene bucal pelos profissionais. Conclusão - Nos estabelecimentos comerciais pesquisados foi encontrado pelo menos um tipo de cada instrumento recomendado.

lntroduction - A literature review on the main instruments for lhe promotion of health in pediatric dentistry was undertaken: toothbrushes, fluoridated dentifrice, and dental floss. Material and Method - A research was undertaken in Minas Gerais State with 120 dentists and in 30 supermarkets and drugstores with the purpose of finding out exactlv how those professional are indicating the materials of plaque mechanic cleanliness for their patients, how those products are available in the market, and the frequencv that each of them is offered. Results . No significant difference in lhe prescription of products for procedure of hygiene mouth was observed. Concerning the products are frequently more purchased than others. Conclusion - There was always at least one brand of toothpaste, dentifrice, and dental floss available in the drugstore or supermarkets.

Novos paradigmas em saúde

O curso de especialização saúde da família, no módulo novos paradigmas em saúde, aula 5 , aborda o paradigma biopsicossocial ou paradigma da integralidade e suas principais características. Bem como, as principais diferenças em relação ao paradigma biomédico/biotecnológico.

Clínica da Atenção Primária à Saúde II [caso dona Antônia]

O curso de especialização saúde da família, no módulo clínica da atenção primária à saúde II, apresenta o material sobre o caso dona Antônia. Espera-se que os profissionais sejam capazes de otimizar o processo de trabalho em equipe, de forma que se realize um planejamento de ações que resulte num incremento da qualidade de vida e da assistência à saúde da população sob sua responsabilidade sanitária.