PlexinA4 is necessary as a downstream target of Islet2 to mediate Slit signaling for promotion of sensory axon branching

Slit is a secreted protein known to repulse the growth cones of commissural neurons. By contrast, Slit also promotes elongation and branching of axons of sensory neurons. The reason why different neurons respond to Slit in different ways is largely unknown. Islet2 is a LIM/homeodomaintype transcription factor that specifically regulates elongation and branching of the peripheral axons of the primary sensory neurons in zebrafish embryos. We found that PlexinA4, a transmembrane protein known to be a coreceptor for class III semaphorins, acts downstream of Islet2 to promote branching of the peripheral axons of the primary sensory neurons. Intriguingly, repression of PlexinA4 function by injection of the antisense morpholino oligonucleotide specific to PlexinA4 or by overexpression of the dominant-negative variant of PlexinA4 counteracted the effects of overexpression of Slit2 to induce branching of the peripheral axons of the primary sensory neurons in zebrafish embryos, suggesting involvement of PlexinA4 in the Slit signaling cascades for promotion of axonal branching of the sensory neurons. Colocalized expression of Robo, a receptor for Slit2, and PlexinA4 is observed not only in the primary sensory neurons of zebrafish embryos but also in the dendrites of the pyramidal neurons of the cortex of the mammals, and may be important for promoting the branching of either axons or dendrites in response to Slit, as opposed to the growth cone collapse.

Berberine - a novel approach to cholesterol lowering

Although low-density lipoprotein (LDL)-cholesterol lowering with the statins reduces the mortality and morbidity associated with coronary artery disease, considerable mortality and morbidity remains. Berberine upregulates the LDL receptor (LDLR) by a mechanism distinct from that of the statins, which involves stabilising the LDLR mRNA. In hamsters fed a high-fat and high-cholesterol diet for 2 weeks, the oral administration of berberine 100 mg/kg for 10 days reduced total serum cholesterol from ∼ 4.8 to 2.7 mmol/l, and LDL-cholesterol from ∼ 2.5 to 1.4 mmol/l. In subjects with hypercholesterolaemia, berberine hydrochloride (0.5 g b.i.d. for 3 months) reduced LDL-cholesterol (from 3.2 to 2.4 mmol/l) without any effect on high-density lipoprotein-cholesterol. Berberine also caused a reduction in triglyceride levels from 2.3 to 1.5 mmol/l. As berberine and statins both upregulate LDLR, their lipid-lowering profiles are similar. Thus, this mechanism is unlikely to make berberine an attractive alternative to statins for lipid lowering in most circumstances. However, the other effects of berberine (anti hypertensive, inotropic and class III antiarrhythmic properties) may make it a useful agent in the treatment of cardiovascular disease.

DNA Motifs Suppressing TLR9 Responses

Immune cells respond to bacterial DNA containing unmethylated CpG motifs via Toll-like receptor 9 (TLR9). Given the apparent role of TLR9 in development of systemic lupus erythernatosus (SLE), there is interest in the development of TLR9 inhibitors. TLR9-mediated responses are reported to be inhibited by a confusing variety of different DNA sequences and structures. To aid characterization, we have provisionally categorized TLR9-inhibitory oligodeoxynucleoti des (ODN) into 4 classes, on the basis of sequence and probable mode of action. Class I are short G-rich ODN, which show sequence-specific inhibition of all TLR9 responses, and may be direct competitive inhibitors for DNA binding to TLR9. Class II are telomeric repeat motifs that inhibit STAT signaling, and thus are not specific to TLR9 responses. Because Class II ODN are generally made as 24-base phosphorothioate-modified ODN (PS-ODN), they also fall into Class IV, defined as long PS-ODN, which inhibit TLR9 responses in a sequence-nonspecific manner. Class III includes oligo (dG) that forms a 4-stranded structure and inhibits DNA uptake. The Class I G-rich motifs show the most promise as selective and potent TLR9 inhibitors for therapeutic applications.

Evaluation of resynchronization of contractile function following biventricular pacing using colour tissue Doppler imaging

Biventdcular (BV) pacing is evaluated as an alternative treatment for patients with dilated cardiomyppathy (both ischemic and non-ischemic) and end-stage heart failure. Colour tissue Doppler imaging using echocardiography allows noninvasive, quantitative assessment of radial motion in the long-axis with measurement of peak systolic velocity timing. The aim of the present study was to evaluate quantitatively, the systolic performance of the left ventricle and the resynchrenization of contraction (before vs after implantation). Patients and methods: 25 patients with dilated cardiomyopathy (11 ischemic), NYHA class III or IV, QRS duration >120 ms received a biventricular pacemaker. Routine 2D echo and colour tissue Doppler imaging were performed before and within 1 week following implantation. LVEF was assessed using the biplane Sampson's method.Peak systolic velocity (PSV) and time to PSV (TPV) were assessed in 4 regions (basal anterior, inferior, lateral and septal). By averaging the TPV from all 4 regions, a synchronization index was dedved from these measurements. Reaults: LVEF improved by 9±9% following pacing; 17 patients improved LVEF 5% or more. The change in PSV in the septal and lateral regions related significantly to the change in LVEF (r=0.74, r=0.62).The change in synchronization index before vs after pacing (as a measurement of REsynchronization) was related to the change in LVEF (y=120x+5.6, r=0.79, P

EFEITOS ESQUELÉTICOS DA TRAÇÃO REVERSA DA MAXILA UTILIZANDO TOMOGRAFIA COMPUTADORIZADA

Este estudo avaliou os efeitos esqueléticos da tração reversa da maxila utilizando imagens 2D (telerradiografia lateral) geradas a partir da tomografia de feixe cônico (imagens 3D). A amostra foi composta por 20 crianças (15 do gênero feminino, e 5 do masculino), com idade variando de 5,6 a 10,7 anos que apresentavam má-oclusão de Classe III de Angle. A tomografia foi realizada antes do tratamento (T1) e logo após o tratamento (T2). O tratamento foi realizado por meio da tração reversa da maxila utilizando-se o aparelho expansor Hyrax associado à máscara facial individualizada, com força de 600 a 800g de cada lado, durante 14 horas por dia. A correção da relação de caninos em Classe I ou com sua sobrecorreção em Classe II foi obtida após 4 a 8 meses de tratamento. Para verificar o erro sistemático e casual foi utilizado o teste t pareado e a fórmula de Dahlberg, respectivamente. O teste t pareado (p<0,05) mostrou diferença significante entre as medidas cefalométricas obtidas em T1 e T2. Na maxila houve aumento do SNA 2,2°, A-Nperp 1,47mm e em Co-A 2,58mm. Na mandíbula, SNB diminuiu -0,54° e P-Nperp, -1,45mm, enquanto Co-Gn aumentou 1,04mm. Houve melhora na relação maxilo-mandibular ANB 2,74° e Wits 4,23mm. As variáveis GoGn.SN, Gn.SN, FH.Md, Mx.Md, e AFAI aumentaram demonstrando que houve uma rotação da mandíbula no sentido horário. O plano palatino rotacionou no sentido anti-horário. Pode se concluir que o tratamento de tração reversa da maxila na idade precoce promoveu uma melhora na relação maxilo-mandibular devido a um avanço da maxila e um deslocamento da mandíbula para baixo e para trás.

ESTUDO DAS DIMENSÕES TRANSVERSAIS DOS ARCOS DENTAIS MANDIBULARES EM INDIVÍDUOS COM DIFERENTES PADRÕES FACIAIS

O presente estudo avaliou as dimensões transversais dos arcos dentais mandibulares em indivíduos com diferentes padrões faciais. A amostra foi constituída por telerradiografias em norma lateral direita e modelos em gesso de 33 indivíduos, leucodermas, em ambos os sexos, com idade entre 13 e 25 anos, na fase de dentição permanente. O Padrão Facial foi obtido pela análise facial subjetiva em fotografias frontal e de perfil de 1500 documentações ortodonticas, foi utilizada análise cefalométrica por meio do ângulo ANB para confirmar o padrão esquelético, o qual deveria coincidir com a classificação de maloclusão de Angle. A amostra foi dividida em três grupos: Grupo I Padrão I, Classe I de Angle e ANB 2,0 o ±0,5o; Grupo II Padrão II, Classe II divisão 1 de Angle e ANB ≥ 4,0, e Grupo III Padrão III, Classe III de Angle e ANB ≥ - 4,5o. As dimensões transversais do arco foram mensuradas após a digitalização dos modelos em gesso pelo Scanner Dental Wings (3D), a partir dos quais foram estabelecidas as distâncias transversais intercanino, inter 1º PM, inter 2º PM, inter 1º M (cúspide mesial e distal), inter 2º M (cúspide mesial e distal), com o auxílio do software Geomagic Studio® 12. As médias e desvio padrão das dimensões transversais foram obtidas, e, para comparação entre os três grupos foi utilizado a Análise de Variância e teste de Tukey. Em todos os testes estatísticos foi adotado nível de significância de 5% (p<0,05). Houve diferença estatística em duas dimensões transversais das 14 avaliadas no arco maxilar na região mesial do segundo molar (p=0,024) e no mandibular na região distal do primeiro molar (p=0,047). Os arcos dentais mandibulares foram semelhantes nos três grupos estudados.

PÊNDULO ANCORADO EM MINI-IMPLANTES: AVALIAÇÃO DENTÁRIA E ESQUELÉTICA

O aparelho Pêndulo é eficaz na correção das más oclusões de Classe II, com comprometimento dentoalveolar superior. No entanto, a perda de ancoragem caracterizada pela mesialização dos pré-molares superiores, e pela vestibularização e protrusão dos incisivos superiores, constitui um grave efeito colateral deste dispositivo. O objetivo deste estudo foi avaliar as possíveis alterações dentárias e esquelética, sagitais e verticais, decorrentes do uso do Pêndulo modificado, ancorado em mini-implantes. Dez indivíduos foram tratados neste estudo, sendo que telerradiografias em norma lateral foram realizadas no início do tratamento, e imediatamente após a remoção do Pêndulo. Em cada indivíduo foram instalados dois mini-implantes no palato, que receberam carga imediata por meio da ativação do Pêndulo modificado, apoiado nestes dispositivos de ancoragem temporária. Nenhum dos dentes avaliados apresentou alterações verticais estatisticamente significantes; o mesmo ocorreu para as alterações esqueléticas verticais e sagitais, e para o trespasse vertical e horizontal. Com relação às alterações estatisticamente significantes, o primeiro molar superior moveu-se para distal aproximadamente 5,6mm em 6,2 meses, e com inclinação distal média de 7,100. Os segundos pré-molares superiores distalizaram em média 2,7mm e inclinaram 5,550; já os segundos molares superiores moveram-se em média 4,6mm para distal com uma inclinação de 13,700; valores estes também considerados estatisticamente significantes. O sistema de distalização de molares superiores, composto pelo Pêndulo modificado ancorado em mini-implantes, mostrou-se eficaz na correção da má oclusão de Classe II, sem produzir os efeitos de perda de ancoragem. (AU)

Rotação e processos de acreção e coalescência em sistemas planetários e sistemas binários

The discovery of giant stars in the spectral regions G and K, showing moderate to rapid rotation and single behavior, namely with constant radial velocity, represents one important topic of study in Stellar Astrophysics. Indeed, such anomalous rotation clearly violates the theoretical predictions on the evolution of stellar rotation, since in evolved evolutionary stages is expected that the single stars essentially have low rotation due to the evolutionary expansion. This property is well-established from the observational point of view, with different studies showing that for single giant stars of spectral types G and K values of the rotation are typically smaller than 5kms−1 . This Thesis seeks an effective contribution to solving the paradigm described above, aiming to search for single stars of spectral types G and K with anomalous rotation, tipically rotation of moderate to rapid, in other luminosity classes. In this context, we analyzed a large stellar sample consisting of 2010 apparently single stars of luminosity classes IV, III, II and Ib with spectral types G and K, with rotational velocity v sin i and radial velocity measurements obtained from observations made by CORAVEL spectrometers. As a first result of impact we discovered the presence of anomalous rotators also among subgiants, bright giants and supergiants stars, namelly stars of luminosity classes IV, II and Ib, in contrast to previous studies, that reported anomalous rotators only in the luminosity class III classic giants. Such a finding of great significance because it allows us to analyze the presence of anomalous rotation at different intervals of mass, since the luminosity classes considered here cover a mass range between 0.80 and 20MJ, approximately. In the present survey we discovered 1 subgiant, 9 giants, 2 bright giants and 5 Ib supergiants, in spectral regions G and K, with values of v sin i ≥ 10kms−1 and single behavior. This amount of 17 stars corresponds to a frequency of 0.8% of G and K single evolved stars with anomalous rotation in the mentioned classes of luminosities, listed at the Bright Star Catalog, which is complete to visual magnitude 6.3. Given these new findings, based on a stellar sample complete in visual magnitude, as that of the Bright Star Catalog, we conducted a comparative statistical analysis using the Kolmogorov- Smirnov test, from where we conclude that the distributions of rotational velocity, v sin i, for single evolved stars with anomalous rotation in luminosity classes III and II, are similar to the distributions of v sin i for spectroscopic binary systems with evolved components with the same spectral type and luminosity class. This vii result indicates that the process of coalescence between stars of a binary system might be a possible mechanism to explain the observed abnormal rotation in the referred abnormal rotators, at least among the giants and bright giants, where the rotation in excess would be associated with the transfer of angular momentum for the star resulting from the merger. Another important result of this Thesis concerns the behavior of the infrared emission in most of the stars with anomalous rotation here studied, where 14 stars of the sample tend to have an excess in IR compared with single stars with low rotation, within of their luminosity class. This property represents an additional link in the search for the physical mechanisms responsible for the abnormal observed rotation, since recent theoretical studies show that the accretion of objects of sub-stellar mass, such as brown dwarfs and giant planets, by the hosting star, can significantly raise its rotation, producing also a circumstellar dust disk. This last result seems to point in that direction, since it is not expected that dust disks occurring during the stage of star formation can survive until the stages of subgiants, giants and supergiants Ib. In summary, in this Thesis, besides the discovery of single G and K evolved stars of luminosity classes IV, II and Ib with anomalously high rotation compared to what is predicted by stellar evolution theory, we also present the frequency of these abnormal rotators in a stellar sample complete to visual magnitude 6.3. We also present solid evidence that coalescence processes in stellar binary systems and processes of accretion of brown dwarfs star or giant planets, by the hosting stars, can act as mechanisms responsible for the puzzling phenomenon of anomalous rotation in single evolved stars.

Ethics in the provision of removable partial dentures

Aim: To investigate the construction of cobalt-chromium removable partial dentures by commercial private dental laboratories. Methods: Ninety master casts for fabrication of cobalt-chromium removable partial dentures were obtained from three commercial laboratories randomly selected. Casts were assessed for dental arch treated, Kennedy classification, cast surveying, denture design information provided by the dentist, and mouth preparation (rest seat, guiding plane and retentive area). Dental technicians answered a questionnaire regarding qualification of assisted dentists, monthly number of framework castings, and use of dental surveyor. Mouth preparation was compared among laboratories using Kruskal-Wallis test (α=0.05). Results: The percentage of Kennedy class I was 16%, class II 19%, class III 56%, and class IV 9%. The majority of master cats (51%) examined was sent to dental laboratories without any design information and did not comply with ethical guidelines in the provision of RPD. Approximately half of the casts were considered “inappropriate” for guiding planes and retentive areas. One of the laboratories presented all casts “inappropriate” for rest seat distribution (p<0.001). Conclusions: Mouth preparation frequently failed for guiding planes, retentive areas and distribution of rest seats. It is necessary to provide students with adequate clinical experience at the dental school environment, which will actually be carried into the practice of dentistry.

Ethics in the provision of removable partial dentures

Aim: To investigate the construction of cobalt-chromium removable partial dentures by commercial private dental laboratories. Methods: Ninety master casts for fabrication of cobalt-chromium removable partial dentures were obtained from three commercial laboratories randomly selected. Casts were assessed for dental arch treated, Kennedy classification, cast surveying, denture design information provided by the dentist, and mouth preparation (rest seat, guiding plane and retentive area). Dental technicians answered a questionnaire regarding qualification of assisted dentists, monthly number of framework castings, and use of dental surveyor. Mouth preparation was compared among laboratories using Kruskal-Wallis test (α=0.05). Results: The percentage of Kennedy class I was 16%, class II 19%, class III 56%, and class IV 9%. The majority of master cats (51%) examined was sent to dental laboratories without any design information and did not comply with ethical guidelines in the provision of RPD. Approximately half of the casts were considered “inappropriate” for guiding planes and retentive areas. One of the laboratories presented all casts “inappropriate” for rest seat distribution (p<0.001). Conclusions: Mouth preparation frequently failed for guiding planes, retentive areas and distribution of rest seats. It is necessary to provide students with adequate clinical experience at the dental school environment, which will actually be carried into the practice of dentistry.

Busca por excesso no infravermelho médio em estrelas evoluídas com fotometria WISE e 2MASS

Debris discs are commonly detected orbiting main-sequence stars, but little is known regarding their fate as stars evolve along subgiant and giant stages. Jones (2008) has found strong evidence on the presence of mid-IR excess in G and K stars of luminosity class III, using photometric data from the Two-Micron All-Sky Survey (2MASS) and GLIMPSE catalogues. While the origin of these excesses remains uncertain, it is plausible that they arise from debris discs around these stars. The present study brings an unprecedent survey in the search for mid-IR excess among single and binary F, G and K-type evolved stars of luminosity classes IV, III, II and Ib. For this study, we use WISE and 2MASS photometric data for a sample of 3000 evolved stars, complete up to visual magnitude of 6.5. As major results, we found that the frequency of evolved stars showing mid-IR WISE excess increases from the luminosity classes IV and III to luminosity classes II and Ib. In addition, there is no clear difference between the presence of IR excess in binary and single stars for all the analyzed luminosity classes.

Busca por excesso no infravermelho médio em estrelas evoluídas com fotometria WISE e 2MASS

Debris discs are commonly detected orbiting main-sequence stars, but little is known regarding their fate as stars evolve along subgiant and giant stages. Jones (2008) has found strong evidence on the presence of mid-IR excess in G and K stars of luminosity class III, using photometric data from the Two-Micron All-Sky Survey (2MASS) and GLIMPSE catalogues. While the origin of these excesses remains uncertain, it is plausible that they arise from debris discs around these stars. The present study brings an unprecedent survey in the search for mid-IR excess among single and binary F, G and K-type evolved stars of luminosity classes IV, III, II and Ib. For this study, we use WISE and 2MASS photometric data for a sample of 3000 evolved stars, complete up to visual magnitude of 6.5. As major results, we found that the frequency of evolved stars showing mid-IR WISE excess increases from the luminosity classes IV and III to luminosity classes II and Ib. In addition, there is no clear difference between the presence of IR excess in binary and single stars for all the analyzed luminosity classes.

Clinical Outcomes in 3343 Children and Adults with Rheumatic Heart Disease from 14 Low and Middle Income Countries: 2-Year Follow-up of the Global Rheumatic Heart Disease Registry (the REMEDY study)

BACKGROUND: -There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease (RHD) or information on their predictors. We report the two year follow-up of individuals with RHD from 14 low and middle income countries in Africa and Asia.

METHODS: -Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for two years to assess mortality, congestive heart failure (CHF), stroke or transient ischemic attack (TIA), recurrent acute rheumatic fever (ARF), and infective endocarditis (IE).

RESULTS: -Vital status at 24 months was known for 2960 (88.5%) patients. Two thirds were female. Although patients were young (median age 28 years, interquartile range 18 to 40), the two year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.80-3.11), CHF (HR 2.16, 95% CI 1.70-2.72), New York Heart Association functional class III/IV (HR 1.67, 95% CI 1.32-2.10), atrial fibrillation (AF) (HR 1.40, 95% CI 1.10-1.78) and older age (HR 1.02, 95% CI 1.01-1.02 per year increase) at enrolment. Post-primary education (HR 0.67, 95% CI 0.54-0.85) and female sex (HR 0.65, 95%CI 0.52-0.80) were associated with lower risk of death. 204 (6.9%) had new CHF (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or TIA (8.45/1000 patient-years), 19 (0.6%) had ARF (3.49/1000 patient-years), and 20 (0.7%) had IE (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/TIA or systemic embolism. Patients from low and lower-middle income countries had significantly higher age- and sex-adjusted mortality compared to patients from upper-middle income countries. Valve surgery was significantly more common in upper-middle income than in lower-middle- or low-income countries.

CONCLUSIONS: -Patients with clinical RHD have high mortality and morbidity despite being young; those from low and lower-middle income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and treatment of clinical RHD are required to improve outcomes.

Development of Medical Devices

The medical devices sector helps save lives by providing innovative health care solutions regarding diagnosis, prevention, monitoring, treatment, and alleviation. Medical devices are classified into 1 of 3 categories in the order of increasing risk: Class I, Class II, and Class III.1 Medical devices are distinguished from drugs for regulatory purposes based on mechanism of action. Unlike drugs, medical devices operate via physical or mechanical means and are not dependent on metabolism to accomplish their primary intended effect.

Caraterização físico-química e polínica de méis da Beira Alta

A apicultura é uma atividade em crescimento em Portugal, e por isso é cada vez mais importante caracterizar os produtos que dela derivam, e em particular o mel que é, em geral, o mais conhecido pelos consumidores. A designação DOP (Denominação de Origem Protegida) pode representar uma valorização em termos comerciais, podendo ser uma forma de diferenciação do mel português em contexto nacional e internacional. Deste modo é importante o conhecimento das suas características físico-químicas e polínicas, como fonte de demonstração dessa mesma diferenciação. O presente trabalho faz parte de um projeto de caraterização físico-química e polínica de méis, como contributo para a certificação do mel da Beira Alta como produto DOP. Recolheram-se amostras de méis produzidos pelos associados da Associação dos Apicultores da Beira Alta (AABA), no ano de 2014, afetos a 10 concelhos da área de intervenção da AABA. Os respetivos apiários localizam-se nos concelhos de Viseu, Tondela, Carregal do Sal, Nelas, Penalva do Castelo, Satão, Aguiar da Beira, Mangualde, Sernancelhe e Fornos de Algodres. Foram estudadas 27 amostras de méis representativas da região da Beira Alta de acordo com o número de unidades epidemiológicas dentro de cada concelho. Os resultados para cada parâmetro analisado foram obtidos em triplicado. O pH variou entre 3,4 e 4,3; o teor de água entre 17,5 e 19,7%; o teor de sólidos solúveis totais entre 80,3 e 82,5%; a condutividade elétrica entre 0,29 e 0,82 mS/cm; cinzas totais entre 0,2 e 0,6%; e ácidos livres entre 15 e 57 meq/kg. Para a determinação da cor, recorreu-se à análise colorimétrica, tendo-se efetuado 20 determinações por amostra, obtendo-se um intervalo de variação para L entre 23,08 e 75,51, a entre -0,30 e 16,76 e b entre -1,31 e 58,36. Para a caraterização polínica dos méis construiu-se uma palinoteca de referência da flora da região, sendo as preparações de pólen elaboradas de acordo com o método acetolítico. A análise polínica quantitativa revelou que 4 amostras de méis enquadraram-se na Classe I (<20 000 grãos de pólen por 10g de mel) e as restantes 23 na Classe III (100 000 a 500 000 grãos de pólen por 10g de mel). Na análise polínica qualitativa verificou-se que 11 dos méis analisados eram multiflorais (41%), 15 monoflorais de tília (56%) e 1 monofloral de urze (4%). O pólen de Eucalyptus sp. e de Castanea sativa esteve presente em 100% das amostras.Com estes primeiros resultados pretende-se contribuir para uma caracterização mais vasta da apicultura da Beira Alta e dos méis produzidos nesta região.