Glutaredoxin-1 Is up-regulated in preeclampsia and increases soluble Flt-1 expression

INTRODUCTION: Preeclampsia is a vascular disorder in pregnancyand is biochemical characterization by high soluble Flt-1 and lowplacenta growth factor as well as an imbalance in redox homeostasis.During conditions of high oxidative stress, cysteine residues on keyproteins are reversibly altered by S-glutathionylation, modifying theirfunction. Glutaredoxin-1 (Glrx) enzymatically catalyzes the removal of S-glutathione adducts, conferring reversible signaling dynamics toproteins with redox-sensitive cysteines. The role of Glrx in preeclampsiais unknown.METHODS: Immunohistochemistry and Western blot analysis for Glrx orglutathione were conducted on human placenta samples collected pre-termfrom early onset preeclamptic patients (n=10) or non-preeclamptic induceddeliveries (n=9). Human endothelial cells were infected with adenovirusencoding Glrx or LacZ prior to the cells being exposed to hypoxia (0.1%O2, 24h) to measure changes in soluble Flt-1 (sFlt-1). Quantitative PCRand ELISA were used to measure sFlt-1 at mRNA and protein level.RESULTS: Immunohistochemical staining for GSH revealed lowerS-glutathionylation adducts in preeclampsia placenta in comparison tocontrols. Glrx expression, which catalyses de-glutathionylation wasenhanced in early onset preeclampsia compared to pre-term controlsamples. In contrast, no change was observed in preeclamptic and IUGRplacentas at full term. In endothelial cells overexpressing Glrx, sFlt-1expression was dramatically enhanced at mRNA (3-fold P<0.05) andprotein level (5 fold P>0.01, n=4) after hypoxia andoverexpressing Glrxin mice enhanced levels of circulating sFlt-1 during in vivo ischemia.CONCLUSIONS: Enhanced Glrx expression in preeclamptic placentain line with an apparent decrease in S-glutathionylation may leavekey proteins susceptible to irreversible oxidation in conditions of highoxidative stress.

Tab. I: Alkenon analyses on sample material of cores Krummland KR-1 und Dagebüll DA-1

Geochemical studies of organic "biomarker" compounds were applied to Eemian sediments cored at Dagebuell (DA-1) on the west coast, and at Krummland (KR-1) in the east of the Baltic Zone of Schleswig-Holstein, Germany. 10 samples from the early stage of the Eemian Transgression to the high Eem at Krummland, and 24 samples from the peak and late phases of the Eemian at Dagebuell provide new insights on the development of the Eemian Sea in the region. C37-C39-ethyl- and methyl-ketones in the Krummland sediments indicated unstable conditions at the onset of the marine trangression, and freshwater influence in keeping with their shallow nearshore environment. In the Dagebuell deposits, patterns typical of marine to brackish conditions were observed, comparable to those found today in the Skagerrak and Belt Sea areas. The sea-surface temperatures estimated from the alkenone unsaturation ratio UK37 at DA-1 corroborate the evidence from "standard" faunal and pollen assemblages, and lithological successions. Here, the temperature maximum attained in pollen assemblage zone PAZ Illc, indicates the early onset of very warm conditions, preceding the highest sea level of the penultimate interglacial by 8,000 years, based on previously published U/Th ages.

Clay-mineral composition and biogenic opal content of Late Neogene to Quaternary sediments of the Antarctic Peninsula region

Clay-mineral composition and biogenic opal content in upper Miocene to Quaternary drift sediments recovered at two Ocean Drilling Program (ODP) sites from the continental rise in the Bellingshausen Sea had been analyzed in order to reconstruct the climatic and glacial history of the Antarctic Peninsula. The clay mineral composition at both sites is dominated by smectite, illite, and chlorite, and alternates between a smectite-enriched and a chlorite-enriched assemblage throughout the last 9.3 my. The spatial distribution of clay minerals in Holocene sediments west of the Antarctic Peninsula facilitates the identification of particular source areas, and thus the reconstruction of transport pathways. The similarity to clay mineral variations reported from upper Quaternary sequences suggests that the short-term clay-mineralogical fluctuations in the ODP cores reflect glacial-interglacial cyclicity. Thus, repeated ice advances and retreats in response to a varying size of the Antarctic Peninsula ice cap are likely to have occurred throughout the late Neogene and Quaternary. The clay minerals in the drift sediments exhibit only slight long-term variations, which are caused by local changes in glacial erosion and in supply of source rocks, rather than by major climatic changes. The opal records at the ODP sites are dominated by long-term variations since the late Miocene. We infer that the opal content in the drift sediments, although it is influenced by dissolution in the water column and the sediment column and by the burial with lithogenic detritus, provides a signal of paleoproductivity. Because the annual sea-ice coverage is regarded as the main factor controlling biological productivity, the opal signal helps to reconstruct paleoceanographic changes in the Bellingshausen Sea. Slightly enhanced opal deposition during the late Miocene indicates slightly warmer climatic conditions in the Antarctic Peninsula area than at present. During the early Pliocene, enhanced opal deposition in the Pacific sector of the Southern Ocean and coinciding high opal concentrations in sedimentary sequences from the Atlantic and Indian sectors document a strong reduction of sea-ice cover and relatively warm climatic conditions. Thereby, the early onset of the Pliocene warmth in the Bellingshausen Sea points to a positive feedback of regional Antarctic climate on the global thermohaline circulation. A decrease of opal deposition between 3.1 and 2.6 Ma likely reflects sea-ice expansion in response to reduced supply of northern-sourced deep-waters to the Southern Ocean, caused by the onset of Northern Hemisphere glaciation. Throughout the Quaternary, a relatively constant level of opal deposition on the Antarctic continental margin indicates relatively stable climatic conditions.

Familial amyloid polyneuropathy: TTR sequencing and "in silico" analysis

Familial amyloid polyneuropathy (FAP) or paramiloidosis is an autosomal dominant neurodegenerative disease with onset on adult age that is characterized by mutated protein deposition in the form of amyloid substance. FAP is due to a point alteration in the transthyretin (TTR) gene and until now more than 100 amyloidogenic mutations have been described in TTR gene. FAP shows a wide variation in age-at-onset (AO) (19-82 years, in Portuguese cases) and the V30M mutation often runs through several generation of asymptomatic carriers, before expressing in a proband, but the protective effect disappear in a single generation, with offspring of late-onset cases having early onset. V30M mutation does not explain alone the symptoms and AO variability of the disease observed in the same family. Our aim in this study was to identify genetic factors associated with AO variability and reduced penetrance which can have important clinical implications. To accomplish this we genotyped 230 individuals, using a directautomated sequencing approach in order to identify possible genetic modifiers within the TTR locus. After genotyping, we assessed a putative association of the SNPs found with AO and an intensive in silico analysis was performed in order to understand a possible regulation of gene expression. Although we did not find any significant association between SNPs and AO, we found very interesting and unreported results in the in silico analysis since we observed some alterations in the mechanism of splicing, transcription factors binding and miRNAs binding. All of these mechanisms when altered can lead to dysregulation of gene expression, which can have an impact in AO and phenotypic variability. These putative mechanisms of regulation of gene expression within the TTR gene could be used in the future as potential therapeutical targets, and could improve genetic counselling and follow-up of mutation carriers.

O paciente com trissomia 21

A Síndrome de Down, também conhecida como Trissomia 21, representa a anomalia cromossómica mais comum da espécie humana. Caracteriza-se por um conjunto clássico de sinais e sintomas que afetam o desenvolvimento neuromotor e cognitivo. O diagnóstico da Síndrome de Down baseia-se numa série de sinais e sintomas, sendo a sua confirmação estabelecida através do estudo cromossómico. Nem toda a população afetada apresenta as mesmas características, sendo necessário uma identificação do cariótipo para um diagnóstico definitivo. Embora apresentando diferentes graus de severidade assim como inicio de manifestação dos primeiros sintomas em diferentes alturas, toda a população com SD apresenta morfismo característico da face e do sistema esquelético, alterações do SNC e início precoce da doença de Alzheimer. As características dento-maxilo-faciais afetam o normal funcionamento do sistema estomatognático. A maioria possui um padrão braquifacial com um desenvolvimento mandibular no sentido anti-horário e manifesta má-oclusão sob uma vasta etiologia. Consequentemente ocorrem alterações a nível da estética, postura, mastigação, respiração e fonação. Apresentam inclusive um controlo de placa ineficaz e pobre higienização oral, sendo os procedimentos de prevenção importantes. A Ortodontia tem um papel de relevo no tratamento das má-oclusões que contribuem para as limitações do paciente. Ressalte-se a importância da sensibilização dos familiares para a necessidade de higienização bucal destes pacientes, bem como o conhecimento pelo médico dentista acerca das principais manifestações bucais que acometem os pacientes portadores, para que o tratamento adequado seja oferecido e a qualidade de vida desses indivíduos preservada.

The role of cellular prion protein in Alzheimer’s disease

Alzheimer’s disease (AD) is the most prevalent age-related neurodegenerative disease that leads to cognitive impairment and dementia. The major defined pathological hallmark of AD is the accumulation of amyloid beta (Aβ), a neurotoxic peptide, derived from beta and gamma-secretase cleavage of the amyloid precursor protein (APP). It has been described that cellular prion protein (PrPC) plays a role in the pathogenesis of Alzheimer disease. Although, the role of PrPC is still unclear, previous studies showed contradictious results. To elucidate this issue, the main objective of the present study is to investigate the influence of a knockout of the PRNP gene in 5XFAD mice, 5xFAD mice exhibited 5 mutations related to familial Alzheimer disease. These mice show an Aβ1-42 accumulation and an increased neuronal loss during aging. To create a bi-transgenic 5xFAD mice were crossed with Prnp0/0 Zurich 1 mice (prion protein knockout mice). We subjected two transgenic mice (5xFAD and Prnp0/05xFAD) at different ages (3, 9 and 12 months of age) to a battery of task to evaluate cognitive and motoric deficits and a biochemical analysis (ELISA, western blot and immunohistochemistry) to investigate the regulation and potential involvement of downstream signaling proteins in the Aβ induced toxicity process dependent of the PrPC concentration. The study revealed that the deficits induced by Aβ mediated toxicity appeared earlier in 5xFAD mice (9 months of age) than in Prnp0/05xFAD (12 months of age). Investigating the amount of amyloid beta in 5xFAD mice we observed a PrPC dependent regulation in 9 month-old animals of Aβ1−40 but not of the toxic form Aβ1−42. We did not found in Prnp0/05xFAD mice the up-regulation of P-Fyn, Fyn or Cav-1 as we found in 5xFAD mice. This suggests an important role of PrPC in Alzheimer’s disease as a promoter of toxic effect of Aβ oligomers. Our results may suggest the loss of PrPC delays the toxicity of amyloid beta. In conclusion, our data support a role of PrPC as a mediator of Aβ toxicity in AD by promoting early onset of disease.

Visual results with the use of prismatic lenses in the treatment of congenital nystagmus: a clinical case

Purpose: It is important to establish a differential diagnosis between the different types of nystagmus, in order to give the appropriate clinical approach to every situation and to improve visual acuity. The nystagmus is normally blocked when the eyes are positioned in a particular way. This makes the child adopt a posture of ocular torticollis that reduces the nistagmiformes movements, improving the vision in this position. A way to promote the blocking of the nystagmic movements is by using prismatic lenses with opposite bases, to block or minimize the oscillatory movements. This results in a vision improvement and it reduces the anomalous head position. There is limited research on the visual results in children with nystagmus after using prisms with opposing bases. Our aim is to describe the impact on the visual acuity (VA ) of theprescription prism lenses in a nystagmus patient starting at 3 months of age. Methods: Case report on thirty month old caucasian male infant, with normal growth and development for their age, with an early onset of horizontal nystagmus at 3 months of age. Ophthalmic examination included slit lamp examination, fundus, refractive study, electrophysiological and magnetic resonance tests, measurement of VA over time with the Teller Acuity Cards (TAC ) in the distance agreed for the age. At age ten months, the mother noted a persistent turn to the right of the child’s head, which became increasingly more severe along the months. There’s no oscillopcia. At 24 months, an atropine refraction showed the following refractive error: 0D.: -1,50, OS: -0,50 and prismatic lens adapting OD 8 Δ nasal base and OE 8 Δ temporal base. Results: Thirty month old child, with adequate development for their age, with onset of idiopatic horizontal nystagmus, at 3 months of age. Normal ocular fundus and magnetic ressoance without alterations, sub-normal results in electrophysiological tests and VA with values below normal for age. At 6 months OD 20/300; OE 20/400; OU 20/300. At 9 months OD 20/250; OE 20/300; OU 20/150 (TAC a 38 cm). At 18 months OD 20/200; OE 20/100; OU 20/80 (TAC at 38 cm), when the head is turned to the right and the eyes in levoversão, the nystagmus decreases in a “neutral” area. At 24 month, with the prismatic glasses, OD 20/200 OE 20/100, OU20/80 (TAC at 54 cm, reference value is 20/30 – 20/100 para OU e 20/40 – 20/100 monocular), there was an increase in the visual acuity. The child did visual stimulation with multimedia devices and using glasses. After adaptation of prisms: at 30 months VA (with Cambridge cards) OD e OE = 6/18. The child improved the VA and reduced the anomalous head position. There is also improvement in mobility and fine motricity. Conclusion: Prisms with opposing bases., were used in the treatment of idiopathic nystagmus. Said prisms were adapted to reduce the skewed position of the head, and to improve VA and binocular function. Monitoring of visual acuity and visual stimulation was done using electronic devices. Following the use of prismatic, the patient improved significantly VA and the anomalous head position was reduced.

The use of motivational interviews by nurses to promote health behaviors in adolescents: a scoping review protocol

Adolescents - defined as young people between 10 and 19 years of age1 - are, in general, a relatively healthy segment of the population.2 However, the developmental changes that take place during adolescence may affect their subsequent risk for diseases and for a variety of health-related behaviors. In fact, early onset of preventable health problems (e.g. obesity, malnutrition, STDs) and the engagement in health risk behaviors (e.g., sedentary life style, excessive alcohol consumption, unprotected sex) during adolescence, are likely to put them at greater risk for physical and mental health problems at a later stage in life. Moreover, health related problems and health risk behaviors may disrupt adolescents' physical and cognitive development and therefore may affect their ability to think and act in relation to decisions about their health in the future.1 In summary, health-related behaviors in adolescence, apart from their influence on the continuum of "health-disease", they also have the potential to influence future behaviors. In fact, several studies have shown that past behaviors are good predictors of future behaviors .3,4 Thus, promoting healthy practices during adolescence and taking measures to better protect young people from health risks are essential for the prevention of health problems in adulthood.5 According to the World Health Organization, the main problems affecting young people include mental health problems (such as behavioral disorders, eating disorders, suicide, anxiety or depression), the use of substances (illegal substances, alcohol and tobacco), interpersonal violence, nutrition (a proper nutrition consists of healthy eating habits and physical exercise), unintentional injuries (which are a leading cause of death and disability among young people, with road traffic injuries accounting for about 700 deaths per day), sexual and reproductive health (for example, risky sexual behaviors, early pregnancy and childbirth) and HIV (resulting from sexual transmission and drug injection).5,6 On the other hand, the number of children and youth with chronic health conditions has increased dramatically in the past four decades7 as larger numbers of chronically ill children survive beyond the age of 10.8 Despite the lack of data on adolescents' health making it difficult to determine the prevalence of chronic illnesses in this age group9, it is known that one in ten adolescents suffers from a chronic condition worldwide.10 In fact, national population based studies from Western countries show that 20-30% of teenagers have a chronic illness, defined as one that lasts longer than six months.8 The most prevalent chronic illness among adolescents is asthma and the one with the highest incidence is diabetes mellitus, particularly type II.9 Traditionally, healthcare professionals have been mainly investing in health education activities, through the transmission of knowledge with a view to creating habits, customs and behaviors, and promoting healthy lifestyles. However, empowering people does not only consist of giving them the right information11 , i.e. good information is not enough to cause people to make changes.12 The motivation or desire to change unhealthy behaviors and habits depends on many factors, namely intrinsic motivation, control over personal decisions, self-confidence and perception of effectiveness, personal ambivalence, and individualized assistance.12 Many professionals assume that supplying knowledge is sufficient for behavioral changes; however, even very good advice often fails to generate behavioral change. After all, people continue to engage in unhealthy behaviors despite clearly knowing what they should do and how to change. "What is lacking is the motivation to apply that knowledge".13, p.1233 In fact, behavioral change is a complex phenomenon with multiple determinants that also includes motivational variables. It is associated with ambivalent processes expressed in the dilemma between keeping the current status and moving on to new ways of acting. For example, telling adolescents that if they keep on engaging in a certain behavior, they are increasing the risk of developing a long-term condition such as cardiovascular disease, stroke or diabetes is rarely enough to trigger the desired behavioral change; people are more likely to change when they believe that the change is really effective and that they are able to implement it.12 Therefore, it is essential to provide specific training for "healthcare professionals to master motivational techniques, avoid confrontation with the users, and facilitate behavioral changes".14 In this context, motivating patients to make behavioral changes is also an important nursing task where change in lifestyle is a major element of patients' treatment and preventive interventions.15 One of the nurse's goals is to help improve a patient's health or help them to manage existing health conditions. Once nurses are in a position where they have to focus on accomplishing tasks and telling patients what needs to be accomplished16, the role of the nurse is expanding even more into the use of motivational strategies.17 MI is bringing nurses back to therapeutic communication and moving them closer to successful health promotion and disease management, by promoting behavior change and empowering their patients. As the nursing profession evolves, MI is seen as a challenge and the basis of nurse's interactions with individuals, families and communities.16, 17 In the same way, MI may be taken as an essential tool in the provision of nursing care to adolescents, being itself a workspace with possible therapeutic effects regarding problems, clarification of doubts, and development of skills.18 In fact, MI may be particularly applicable in work with adolescents because of their specific developmental stage. Adolescents attempt to establish their own autonomy and identity while struggling with social interactions and moral issues, which leads to ambivalence.19 Consistent with the developmental challenges during adolescence, "MI explicitly honors autonomy, people's right and irrevocable ability to decide about their own behavior"20 while allowing the person to explore possibilities for change of risky or maladaptive behaviours.19 MI can be defined as a directive, client-centred counselling style for eliciting behavior change by helping clients to explore and resolve ambivalence. It is most centrally defined not by technique but by its spirit as a facilitative style of interpersonal relationship.21 It is a set of strategies and techniques widely used in clinical practice based on the transtheoretical model of change. The Stages of Change model describes five stages of readiness—precontemplation, contemplation, preparation, action, and maintenance—and provides a framework for understanding behavior change.22 The MI has been widely tested and applied in different areas, such as modification of addictive behaviors, interventions with offenders in the context of justice, eating disorders, promotion of therapeutic adherence among chronic patients, promotion of learning in school settings or intervention with adolescents at risk.18,23 In general, clinical practice has been adopting the perspective of motivation as something relatively immutable, i.e., the adolescent is either motivated for change/treatment and, in these conditions, the professional's role is to help him/her, or the adolescent is not motivated and then change/treatment is not feasible. Alternatively the theoretical model underlying the MI technique postulates that the individual's adherence to change/treatment depends on his/her motivation, which can change throughout the therapeutic intervention. As several studies found positive results for effects of MI24-26 and its use by health professionals is encouraged23,27 nurses may play an important role in patients' process of change. As nurses have a crucial role in clinical contexts, they can facilitate the process of ending risk behaviors and/or adopting positive health behaviors through some motivational techniques, namely with adolescents. A considerable number of systematic reviews about MI already exist pointing to some benefits of its use in the treatment of a broad range of behavioral problems and diseases.13,28,29 Some of the current reviews focus on examining the effectiveness of MI for adolescents with diverse health risks/problems 30-32. However, to date there are no reviews that present and assess the evidence for the use of nurse-led MI in adolescents. Therefore, we have little knowledge of what works for whom (which adolescent subpopulation) under what circumstances (in which setting, for what problem) in relation to motivational interviewing by nurses. There is a clear need for scoping or mapping the use of MI by nurses with adolescents to identify evidence gaps and to inform opportunities for future development in nursing practice. On the other hand, information regarding nurse-led implemented and evaluated interventions, techniques and/or strategies used, contexts of application and adolescents subpopulation groups is dispersed in the literature33-36 which impedes the formulation of precise questions about the effectiveness of those interventions conducted by nurses and therefore the realization of a systematic review. In other words, it is known that different kind of motivational interventions have been implemented in different contexts by nurses, however does not exist a map about all the motivational techniques and/or strategies used. Furthermore the literature does not clarify which is the role of nurses at cross professional motivational intervention implemented programs and finally the outcomes and evaluation of interventions are unclear. Thus, the practical implication of this mapping will be clarifying all these aspects. Without this clarification is not possible to proceed to the realization of a systematic review about the effectiveness of the use of motivational interviews by nurses to promote health behaviors in adolescents, in a particular context and/or health risk behavior; or regarding the effectiveness of certain technique and/or strategy of MI. Consequently, there are important questions about the nature of the evidence in this area that need to be answered before formulating a precise question of effectiveness. This scoping review aims to respond to these questions. An initial search of the JBI Database of Systematic Reviews & Implementation Reports, Cochrane Database of Systematic Reviews, , Database of promoting health effectiveness reviews (DoPHER), The Campbell Library, Medline and CINAHL, has revealed that currently there is no Scoping Review (published or in progress) on the subject. In this context, this scoping review will examine and map the published and unpublished research around the use of MI by nurses implemented and evaluated to promote health behaviors in adolescents; to establish its current extent, range and nature and identify its feasibility, outcomes and gaps in the evidence defining research priorities in this field. This scoping review will be informed by the JBI methodology37 that suggests a five stage methodological framework for conducting scoping reviews which includes: identifying the research question, searching for relevant studies, selecting studies, charting data, collating, summarizing and reporting the results.

Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome

Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three unrelated consanguineous families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly, and the absence of seizures. We used homozygosity mapping and whole-exome sequencing to identify a homozygous nonsense mutation and an in-frame multiexon deletion in two families. A homozygous splice site mutation was identified by Sanger sequencing of SNX14 in a third family, selected purely by phenotypic similarity. This discovery confirms that these characteristic features represent a distinct and recognizable syndrome. SNX14 encodes a cellular protein containing Phox (PX) and regulator of G protein signaling (RGS) domains. Weighted gene coexpression network analysis predicts that SNX14 is highly coexpressed with genes involved in cellular protein metabolism and vesicle-mediated transport. All three mutations either directly affected the PX domain or diminished SNX14 levels, implicating a loss of normal cellular function. This manifested as increased cytoplasmic vacuolation as observed in cultured fibroblasts. Our findings indicate an essential role for SNX14 in neural development and function, particularly in development and maturation of the cerebellum.

Risco metabólico em crianças de 7 a 12 anos

Introdução – A frequência de dislipidemia em crianças e adolescentes tem vindo a aumentar rapidamente nos últimos anos, estando o seu aparecimento associado a fatores genéticos e ambientais. Este indicador, associado a outras doenças como a obesidade, constituem a síndrome metabólica e são considerados fatores de risco para doença cardiovascular e diabetes, que quando presentes na infância podem conduzir precocemente ao aparecimento destas doenças. Objetivos – Avaliar o perfil de indicadores de saúde de crianças no início de um Programa de Educação Contínua; Verificar os efeitos do Programa de Educação Contínua aplicado durante 36 meses (ginástica funcional, brincadeiras de rua e das aulas de natação), sobre os resultados dos exames iniciais de colesterol, triglicerídeos e do IMC. Métodos - Estudo quantitativo, exploratório e descritivo de corte transversal, realizado entre 2012 e 2015 numa amostra não probabilística por conveniência de 165 crianças, 70,0% da população-alvo. As crianças tinham entre 7 a 12 anos de idade, 40,59% entre 11 e 12 anos e 54% eram do sexo feminino. Eram beneficiárias de um plano de saúde que integrava um programa de intervenção (educação contínua e atividade física), designado Crescendo com Saúde e foram selecionadas através de critérios, como: dislipidemia (colesterol total e/ou triglicerídeos elevados), sobrepeso e/ou obesidade, e história familiar de HAS e DM. Os dados clínicos foram obtidos na consulta de enfermagem, utilizando-se a recolha de sangue para dosemanento do perfil lipídico no início do programa e a cada 6 meses e avaliação do IMC na fase inicial do programa e semanalmente. Para classificação do estado nutricional foram utilizados os pontos de corte da OMS (2007). Resultados – no início do programa 69% das crianças apresentavam hipercolesterolémia, 32% aumento do colesterol, 45% tinham excesso de peso (sobrepeso e obesidade) e 12% risco de sobrepeso. Após o programa de intervenção, das 53% crianças que participaram de forma regular, 29% apresentaram redução do colesterol, 16% dos triglicerídeos e o excesso de peso reduziu em 9%, aumentando contudo o risco de sobrepeso para 22%. Das que participaram de forma irregular, apenas 3% reduziram o perfil lipídico e 1% o estado nutricional. Conclusões – O programa de intervenção permitiu uma redução dos fatores de risco de doença metabólica e permitiu melhorar os hábitos das crianças estudadas e suas famílias. Estes resultados comprovam a eficácia a curto e médio prazo dos programas de intervenção na comunidade, e realçam o papel das intervenções preventivas de educação contínua e de atividade física regular, para o processo de redução dos indicadores de risco metabólico desde a infância. Palavra-chave: Crianças; Perfil lipídico; Obesidade; Programa de intervenção .

Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies

International audience

Aortic Intima-Media Thickness and Mean Platelet Volume in Children With Type 1 Diabetes Mellitus

Background: Diabetes mellitus type 1 is the most common endocrine metabolic disorder occurring in childhood and adolescence due to the autoimmune destruction of pancreatic beta cells as a result of various environmental factors interacting with an underlying genetic predisposition. Diabetes is a risk factor for early onset atherosclerosis, and the high mortality rate seen in these patients is partially related to cardiovascular diseases. Objectives: This study was conducted to compare mean platelet volume as a marker of early atherosclerosis with aortic intima-media thickness in children with type 1 diabetes and to identify its correlation with known cardiovascular risk factors. Patients and Methods: The study included 27 patients between age range of 6 and 17 years that were diagnosed with type 1 diabetes and 30 healthy children of the same age range who did not have any chronic disease. In both groups, we used the color Doppler ultrasound to measure children’s aortic intima-media thickness and identify their mean platelet volumes. Results: There was no significant difference between the groups regarding gender distribution, age, High-Density Lipoprotein (HDL) and Low-Density Lipoprotein (LDL) cholesterol levels (P > 0.05). Also no significant difference could be documented between the patient and control groups regarding the aortic intima-media thickness and mean platelet volume (P > 0.05). However, there was a significant correlation between aortic intima-media thickness and mean platelet volume (r = 0.351; P < 0.05). Conclusions: In the present study, there was no evidence of early atherosclerosis in children with type 1 diabetes. However, mean platelet volume having a significant correlation with aortic intima-media thickness may be useful as an early marker of atherosclerosis.

Southern Hemisphere Summer Mesopause Responses to El Niño-Southern Oscillation

In the Southern Hemisphere (SH) polar region, satellite observations reveal a significant upper-mesosphere cooling and a lower-thermosphere warming during warm ENSO events in December. An opposite pattern is observed in the tropical mesopause region. The observed upper-mesosphere cooling agrees with a climate model simulation. Analysis of the simulation suggests that enhanced planetary wave (PW) dissipation in the Northern Hemisphere (NH) high-latitude stratosphere during El Nino strengthens the Brewer-Dobson circulation and cools the equatorial stratosphere. This increases the magnitude of the SH stratosphere meridional temperature gradient and thus causes the anomalous stratospheric easterly zonal wind and early breakdown of the SH stratospheric polar vortex. The resulting perturbation to gravity wave (GW) filtering causes anomalous SH mesospheric eastward GW forcing and polar upwelling and cooling. In addition, constructive inference of ENSO and quasi-biennial oscillation (QBO) could lead to stronger stratospheric easterly zonal wind anomalies at the SH high latitudes in November and December and early breakdown of the SH stratospheric polar vortex during warm ENSO events in the easterly QBO phase (defined by the equatorial zonal wind at similar to 25 hPa). This would in turn cause much more SH mesospheric eastward GW forcing and much colder polar temperatures, and hence it would induce an early onset time of SH summer polar mesospheric clouds (PMCs). The opposite mechanism occurs during cold ENSO events in the westerly QBO phase. This implies that ENSO together with QBO could significantly modulate the breakdown time of SH stratospheric polar vortex and the onset time of SH PMC.

Association of SNPs in LCP1 and CTIF with hearing in 11 year old children:findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and the G-EAR consortium

BACKGROUND: The genetic basis of hearing loss in humans is relatively poorly understood. In recent years, experimental approaches including laboratory studies of early onset hearing loss in inbred mouse strains, or proteomic analyses of hair cells or hair bundles, have suggested new candidate molecules involved in hearing function. However, the relevance of these genes/gene products to hearing function in humans remains unknown. We investigated whether single nucleotide polymorphisms (SNPs) in the human orthologues of genes of interest arising from the above-mentioned studies correlate with hearing function in children. METHODS: 577 SNPs from 13 genes were each analysed by linear regression against averaged high (3, 4 and 8 kHz) or low frequency (0.5, 1 and 2 kHz) audiometry data from 4970 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth-cohort at age eleven years. Genes found to contain SNPs with low p-values were then investigated in 3417 adults in the G-EAR study of hearing. RESULTS: Genotypic data were available in ALSPAC for a total of 577 SNPs from 13 genes of interest. Two SNPs approached sample-wide significance (pre-specified at p = 0.00014): rs12959910 in CBP80/20-dependent translation initiation factor (CTIF) for averaged high frequency hearing (p = 0.00079, β = 0.61 dB per minor allele); and rs10492452 in L-plastin (LCP1) for averaged low frequency hearing (p = 0.00056, β = 0.45 dB). For low frequencies, rs9567638 in LCP1 also enhanced hearing in females (p = 0.0011, β = -1.76 dB; males p = 0.23, β = 0.61 dB, likelihood-ratio test p = 0.006). SNPs in LCP1 and CTIF were then examined against low and high frequency hearing data for adults in G-EAR. Although the ALSPAC results were not replicated, a SNP in LCP1, rs17601960, is in strong LD with rs9967638, and was associated with enhanced low frequency hearing in adult females in G-EAR (p = 0.00084). CONCLUSIONS: There was evidence to suggest that multiple SNPs in CTIF may contribute a small detrimental effect to hearing, and that a sex-specific locus in LCP1 is protective of hearing. No individual SNPs reached sample-wide significance in both ALSPAC and G-EAR. This is the first report of a possible association between LCP1 and hearing function.

Neurodegeneration and the m-AAA protease: pathogenic cascades in neurons and myelinating cells

The m-AAA protease is a hexameric complex involved in processing of specific substrates and turnover of misfolded polypeptides in the mitochondrial inner membrane. In humans, the m-AAA protease is composed of AFG3L2 and paraplegin. Mutations in AFG3L2 have been implicated in dominant spinocerebellar ataxia (SCA28) and recessive spastic ataxia-neuropathy syndrome (SPAX5). Mutations of SPG7, encoding paraplegin, are linked to hereditary spastic paraplegia. In the mouse, a third subunit AFG3L1 is expressed. Various mouse models recapitulate the phenotype of these neurodegenerative disorders, however, the pathogenic mechanism of neurodegeneration is not completely understood. Here, we studied several mouse models and focused on cell-autonomous role of the m-AAA protease in neurons and myelinating cells. We show that lack of Afg3l2 triggers mitochondrial fragmentation and swelling, tau hyperphosphorylation and pathology in Afg3l2 full-body and forebrain neuron-specific knockout mice. Moreover, deletion of Afg3l2 in adult myelinating cells causes early-onset mitochondrial abnormalities as in the neurons, but the survival of these cells is not affected, which is a contrast to early neuronal death. Despite the fact that myelinating cells have been previously shown to survive respiratory deficiency by glycolysis, total ablation of the m-AAA protease by deleting Afg3l2 in an Afg3l1 null background (DKO), leads to myelinating cell demise and subsequently progressive axonal demyelination. Interestingly, DKO mice show premature hair greying due to loss of melanoblasts. Together, our data demonstrate cell-autonomous survival thresholds to m-AAA protease deficiency, and an essential role of the m-AAA protease to prevent cell death independent from mitochondrial dynamics and the oxidative capacity of the cell. Thus, our findings provide novel insights to the pathogenesis of diseases linked to m-AAA protease deficiency, and also establish valuable mitochondrial dysfunctional mouse models to study other neurodegenerative diseases, such as tauopathies and demyelinating diseases.