Adding Evidence to the Role of NEUROG1 in Congenital Cranial Dysinnervation Disorders

Congenital cranial dysinnervation disorders (CCDDs) are a heterogeneous group of neurodevelopmental phenotypes caused by a primary disturbance of innervation due to deficient, absent, or misguided cranial nerves. Although some CCDDs genes are known, several clinical phenotypes and their aetiologies remain to be elucidated. We describe a 12-year-old boy with hypotonia, developmental delay, sensorineural hearing loss, and keratoconjunctivitis due to lack of corneal reflex. He had a long expressionless face, severe oromotor dysfunction, bilateral agenesis/severe hypoplasia of the VIII nerve with marked atresia of the internal auditory canals and cochlear labyrinth malformation. Trio-exome sequencing identified a homozygous loss of function variant in the NEUROG1 gene (NM_006161.2: c.202G > T, p.Glu68*). NEUROG1 is considered a causal candidate for CCDDs based on (i) the previous report of a patient with a homozygous gene deletion and developmental delay, deafness due to absent bilateral VIII nerves, and severe oromotor dysfunction; (ii) a second patient with a homozygous NEUROG1 missense variant and corneal opacity, absent corneal reflex and intellectual disability; and (iii) the knockout mouse model phenotype which highly resembles the disorder observed in humans. Our findings support the growing compelling evidence that loss of NEUROG1 leads to a very distinctive disorder of cranial nerves development.info:eu-repo/semantics/publishedVersio

The Role of Ophthalmic Imaging in Central Nervous System Degeneration in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disorder that can involve any organ system. Central nervous system involvement can be a severe life threatening complication, ultimately resulting in severe neurodegenerative changes. Magnetic resonance imaging suggests that neurodegeneration, which may have deleterious effects on brain function, may occur early in SLE and experimental models suggest that neuroprotection may be feasible and beneficial. The retina is an extension of the brain. Recent ophthalmic imaging technologies are capable of identifying early changes in retinal and choroidal morphology and circulation that may reflect CNS degeneration. However, their utility in monitoring CNS involvement in SLE has been poorly studied as these have only been performed in small cohorts, in a cross-sectional design, non-quantitatively and without correlation to disease activity. The authors aim to review the current understanding of neurodegeneration associated with SLE, with particular focus on the visual pathway. We describe the neuropathology of the visual system in SLE and the evidence for retinal and choroidal neurodegenerative and microvascular changes using optical coherence tomography technology. We aim to describe the potential role of optical imaging modalities in NPSLE diagnosis and their likely impact on the study of neuronal function.info:eu-repo/semantics/publishedVersio

Retinal Neurodegeneration in Diabetic Patients Without Diabetic Retinopathy

PURPOSE: To compare the thickness of all retinal layers between a nondiabetic group and diabetic patients without diabetic retinopathy (DR). METHODS: Cross-sectional study, in which all subjects underwent an ophthalmic examination including optical coherence tomography. After automatic retinal segmentation, each retinal layer thickness (eight separate layers and overall thickness) was calculated in all nine Early Treatment Diabetic Retinopathy Study (ETDRS) areas. The choroidal thickness (CT) also was measured at five locations. Generalized additive regression models were used to analyze the data. RESULTS: A total of 175 patients were recruited, 50 nondiabetic subjects and 125 diabetic patients without DR, stratified into three groups according to diabetes duration: group I (10 years, n = 31). Overall, groups I and III of diabetic patients had a decrease in the photoreceptor layer (PR) thickness, when compared with the nondiabetic subjects in six ETDRS areas (P < 0.0007). Patients with more recent diagnosis (group I) had thinner PR than those with moderate duration (group II). Interestingly, patients with longer known disease (group III) had the thinnest PR values. There were no overall differences in the remaining retinal parameters. CONCLUSIONS: Retinal thickness profile is not linear throughout disease duration. Even in the absence of funduscopic disease, PR layer in diabetic patients seems to differ from nondiabetic subjects, thus suggesting that some form of neurodegeneration may take place before clinical signs of vascular problems arise.info:eu-repo/semantics/publishedVersio

The Roosevelt – Rondon expedition marmoset (Mico marcai) : unveiling the conservation status of a data deficient species

The Roosevelt-Rondon Expedition marmoset, Mico marcai, was collected in 1914 and to date, all information on this species comes from three skins brought back by the Expedition and two additional skins collected in the 1990s. It is no surprise then that M.marcai has been classified as Data Deficient (DD). Given that Mico marcai’s suspected range sits on the path of the advancing Brazilian “Arc-of-Deforestation”, it is urgent that relevant data be collected to assess this taxon. Here we present the first comprehensive field data on the distribution, population size and threats on M. marcai with the goal of removing the species from the DD category. From 2012 to 2015, we surveyed for the species in 11 localities, in and around the Marmelos-Aripuanã interfluve, and estimated density using distance sampling on 10 transects. We also used spatial predictive modelling to project the amount of habitat that will be lost within its range in 18 years under different deforestation scenarios. We found marmosets in 14 localities and calculated its Extent of Occurrence to be 31,073 km2. We walked 271 km and detected 30 marmoset groups, allowing us to estimate their density to be 8.31 individuals/km2 and a total population of 258,217.71 individuals. By a “Business as usual” scenario, 20,181 km2 of habitat will be lost in three marmoset generations (~18 years), compromising 33% of the species’ range. Accordingly, M. marcai should be classified as globally Vulnerable under category A3c. Following our study, we propose the Amazonian marmosets, genus Mico, should undergo similar re-assessment as their ranges all fall in the path of the Arc-of-Deforestation. Keywords: Amazonian marmosets, Conservation Status, Data Deficient, Habitat Loss, Southern Amazoni

Retinal Structural Changes in Preterm Children without Retinopathy of Prematurity

Purpose: The aim of this study was to compare all retinal layers' thickness in full-term and preterm children without retinopathy of prematurity (ROP). Methods: Cross-sectional study including two groups of patients: group 1 children with history of preterm gestation without ROP (gestational age < 37 weeks) and group 2 healthy children with history of full-term gestation. All subjects underwent an ophthalmic examination including spectral domain-optical coherence tomography. After automatic retinal segmentation, each retinal layer thickness (eight separate layers and overall thickness) was calculated in all nine Early Treatment Diabetic Retinopathy Study areas. Demographic, systemic, gestational, and birth data were collected. Generalized additive regression models were used to analyze the data. Results: Fifty-one children (51 eyes) were recruited, 19 full-term and 32 preterm children, mean age at ophthalmic examination of 10.58 (4.21) and 14.13 (3.16), respectively. In multivariable analysis, the preterm group's retinal thickness was significantly decreased in total retina nasal outer sector, ganglion cell layer (GCL), and inner plexiform layer (IPL), specifically GCL temporal outer (p = 0.010), GCL superior outer (p = 0.009), IPL temporal outer (p = 0.022), and IPL superior outer (p = 0.004), when compared with full-term group. From the variables compared only with birth head circumference that influenced the models, a non-linear association was identified and consequently modeled with splines through a generalized additive model. Conclusion: This study suggests that preterm children without ROP have structural retinal alterations, mostly in GCL and IPL in outer areas of the macula. Therefore, it is crucial to question gestational history since these retinal changes may be found later in life leading to useless investigation.info:eu-repo/semantics/publishedVersio

Choroidal Binarization Analysis: Clinical Application

Introduction: Image processing of optical coherence tomography scans through binarization techniques represent a non-invasive way to separately asses and measure choroidal components, in vivo. In this review, we systematically search the scientific literature regarding binarization studies published so far. Methods: A systematic research was conducted at PubMed database, including English literature articles for all of the following terms in various combinations: binarization, choroid/al, enhanced depth spectral domain/swept source optic coherence tomography, and latest publications up to November 2018 were reviewed. Results: Thirty-seven articles were included and analyzed regarding studied disease, binarization method, studied variables, and outcomes. Most of the studies have focused on the more common retinal pathologies, such as age-related macular degeneration, central serous chorioretinopathy and diabetic retinopathy but binarization techniques have also been applied to the study of choroidal characteristics in ocular inflammatory diseases, corneal dystrophies and in postsurgical follow-up. Advantages and disadvantages of binarization techniques are also discussed. Conclusion: Binarization of choroidal images seems to represent a promising approach to study choroid subcomponents in an increasingly detailed manner.info:eu-repo/semantics/publishedVersio

Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumab

Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab.Agência financiadora Merck Sharp and Dohme, Lda, Portugal MK8259-22info:eu-repo/semantics/publishedVersio

Compromiso organizacional y satisfacción laboral: un estudio exploratorio en unidades de salud familiar portuguesas

Explorou-se a relação entre compromisso organizacional e satisfação laboral nos colaboradores de unidades de saúde familiar. Participaram seis unidades de saúde familiar do norte de Portugal e 105 profissionais (médico, enfermeiros e secretários clínicos). Utilizaram-se as adaptações portuguesas da Escala do Compromisso Organizacional de Meyer & Allen (1997) e do Questionário de Satisfação com o Trabalho (Spector, 1985). Os resultados sugerem associação positiva entre compromisso organizacional e satisfação laboral. Os profissionais estão moderadamente satisfeitos e comprometidos com as unidades de saúde familiar, sendo a natureza do trabalho, a relação com os colegas e a comunicação os aspectos mais satisfatórios, e as recompensas o mais insatisfatório. A componente afetiva do compromisso evidencia-se, salientando o envolvimento e a identificação dos profissionais com o projeto unidades de saúde familiar. O modelo de regressão linear revelou-se significativo, o compromisso organizacional explica 22,7% da variância da satisfação com o trabalho. Para esta amostra, o compromisso organizacional prediz a satisfação com o trabalho.This study explored the relationship between organizational commitment and job satisfaction among workers in family health units. Six family health units in the North of Portugal participated, including 105 health professionals (physicians, nurses, and clinical secretaries). The study used the Portuguese adaptations of the Organizational Commitment Scale by Meyer & Allen (1997) and the Job Satisfaction Survey (Spector, 1985). The results suggest a positive association between organizational commitment and job satisfaction. The professionals are moderately satisfied and committed to the family health units; the most satisfactory aspects are the nature of the work, relationship to coworkers, and communication, while pay is the most unsatisfactory. The affective component of the commitment appears, highlighting the professionals' involvement in (and identification with) the family health units project. The linear regression model proved significant, and organizational commitment explains 22.7% of the variance in job satisfaction. For this sample, organizational commitment predicts job satisfaction.Instituto Nacional de Saúde Dr Ricardo Jorgeinfo:eu-repo/semantics/publishedVersio

Short-term versus long-term changes in the benthic communities of a small coastal lagoon: implications for ecological status assessment

The characteristic high variability and low predictability of coastal lagoons, due to strong changes in marine and freshwater inputs, make these ecosystems an interesting casestudy. The small Melides landlocked coastal lagoon in SW Portugal is a paradigmatic example, with a biological community highly stressed by these phenomena. Benthic macroinvertebrate samples were collected in 1998/99 and 2009 and each year, in different seasons and addressing different environmental conditions influenced by the connection to the sea and rainfall regime. Major spatial and temporal patterns in benthic communities were investigated using some invertebrate attributes (e.g. community composition, density, species richness and diversity). A very low taxonomic species richness and diversity was found in the Melides lagoon and only a much reduced number of species occurred along all sampling periods and in both sampling campaigns. Although the colonization events play a crucial role, the persistence of the observed species was mainly associated to abiotic factors, such as salinity, temperature and dissolved oxygen. Despite the potential reduction in anthropogenic pressure, by the construction of a sewage treatment plant and a reduction of urban occupation, the ecological status did not improve and the high level of natural environmental variably in the lagoon seems to be the dominant stressor influencing benthic invertebrate communitie

The resolution of acute inflammation induced by cyclic AMP is dependent on annexin A1

Annexin A1 (AnxA1) is a glucocorticoid-regulated protein known for its anti-inflammatory and pro-resolving effects. We have shown previously that the cAMP-enhancing compounds rolipram (ROL; a PDE4 inhibitor) and Bt2cAMP (a cAMP mimetic) drive caspase-dependent resolution of neutrophilic inflammation. In this follow-up study, we investigated whether AnxA1 could be involved in the pro-resolving properties of these compounds using a model of LPS-induced inflammation in BALB/c mice. The treatment with ROL or Bt2cAMP at the peak of inflammation shortened resolution intervals, improved resolution indices, and increased AnxA1 expression. In vitro studies showed that ROL and Bt2cAMP induced AnxA1 expression and phosphorylation, and this effect was prevented by PKA inhibitors, suggesting the involvement of PKA in ROL-induced AnxA1 expression. Akin to these in vitro findings, H89 prevented ROL- and Bt2cAMP-induced resolution of inflammation, and it was associated with decreased levels of intact AnxA1. Moreover, two different strategies to block the AnxA1 pathway (by using N-t-Boc-Met-Leu-Phe, a nonselective AnxA1 receptor antagonist, or by using an anti-AnxA1 neutralizing antiserum) prevented ROL- and Bt2cAMP-induced resolution and neutrophil apoptosis. Likewise, the ability of ROL or Bt2cAMP to induce neutrophil apoptosis was impaired in AnxA-knock-out mice. Finally, in in vitro settings, ROL and Bt2cAMP overrode the survival-inducing effect of LPS in human neutrophils in an AnxA1-dependent manner. Our results show that AnxA1 is at least one of the endogenous determinants mediating the pro-resolving properties of cAMP-elevating agents and cAMP-mimetic drug