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

Different in Vivo Reactivity Profile in Health Care Workers and Patients with Spina Bifida to Internal and External Latex Glove Surface-Derived Allergen Extracts

BACKGROUND: Allergy to natural rubber latex is a well-recognized health problem, especially among health care workers and patients with spina bifida. Despite latex sensitization being acquired in health institutions in both health care workers and patients with spina bifida, differences in allergen sensitization profiles have been described between these two risk groups. OBJECTIVE: To investigate the in vivo reactivity of health care workers and patients with spina bifida to extracts of internal and external surfaces of latex gloves and also to specific extracts enriched in major allergens for these risk groups. METHODS: Gloves from different manufacturers were used for protein extraction, and salt precipitation and hydrophobic interaction chromatography (HIC) were applied to obtain the enriched latex extracts. The major latex allergens were quantified by an enzyme immunoassay. The extracts obtained were tested in 14 volunteers using skin prick tests (SPT). RESULTS: Latex glove extracts enriched in the hydrophobic allergens that are most often seen in patients with spina bifida were obtained by selective precipitation, whereas HIC produced extracts enriched in the hydrophilic allergens commonly found in health care workers. The health care workers had positive SPTs to glove extracts from internal surfaces and to the hydrophilic allergen-enriched extracts. By contrast, patients with spina bifida had larger skin reactions both to external glove extracts and to the extracts enriched with the hydrophobic major allergens for this risk group. Despite the protein concentration of these extracts being less than half the concentration of the commercial extract, the weal-and-flare reactions were of similar magnitude. CONCLUSION: Using novel latex extracts, our study showed a different in vivo reactivity pattern in health care workers and in patients with spina bifida to extracts of the internal and external surfaces of gloves, which suggests that sensitization may occur by different routes of exposure, and that this influences the allergen reactivity profiles of these risk group

Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HRE

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with clinical and etiological heterogeneity and a complex genetic contribution. Clinical, neuropathological, and genetic evidence revealed that ALS and frontotemporal dementia (FTD) are in part of a single disease continuum. Genetic causes have been identified in sporadic (SALS) and familial patients (FALS) and the recurrent genetic factor underlying ALS and FTD is the C9orf72 hexanucleotide repeat expansion (HRE). However, in our population, the concomitance of ALS and FTD cannot be explained by C9orf72 HRE in many FALS and SALS cases. Our aim is to further understand the genetic basis of ALS in Portuguese patients. 34 patients with FALS or SALS-FTD, negative for C9orf72 HRE, were screened for rare variants in a panel of 29 relevant genes by next-generation sequencing. We detected 15 variants in 11 genes, one classified as pathogenic in TARDBP, two as likely pathogenic in TARDBP and PRPH, and the others as variants of unknown significance (VUS). Gene variants, including VUS, were found in 41.2% FALS patients and 40% SALS-FTD. In most patients, no potential pathogenic variants were found. Our results emphasize the need to enhance the efforts to unravel the genetic architecture of ALS-FTD.info:eu-repo/semantics/publishedVersio

Physical Interactions With Bacteria and Protozoan Parasites Establish the Scavenger Receptor SSC4D as a Broad-Spectrum Pattern Recognition Receptor

Since the pioneering discoveries, by the Nobel laureates Jules Hoffmann and Bruce Beutler, that Toll and Toll-like receptors can sense pathogenic microorganisms and initiate, in vertebrates and invertebrates, innate immune responses against microbial infections, many other families of pattern recognition receptors (PRRs) have been described. One of such receptor clusters is composed by, if not all, at least several members of the scavenger receptor cysteine-rich (SRCR) superfamily. Many SRCR proteins are plasma membrane receptors of immune cells; however, a small subset consists of secreted receptors that are therefore in circulation. We here describe the first characterization of biological and functional roles of the circulating human protein SSC4D, one of the least scrutinized members of the family. Within leukocyte populations, SSC4D was found to be expressed by monocytes/macrophages, neutrophils, and B cells, but its production was particularly evident in epithelial cells of several organs and tissues, namely, in the kidney, thyroid, lung, placenta, intestinal tract, and liver. Similar to other SRCR proteins, SSC4D shows the capacity of physically binding to different species of bacteria, and this opsonization can increase the phagocytic capacity of monocytes. Importantly, we have uncovered the capacity of SSC4D of binding to several protozoan parasites, a singular feature seldom described for PRRs in general and here demonstrated for the first time for an SRCR family member. Overall, our study is pioneer in assigning a PRR role to SSC4D.This work was funded by National Funds through FCT– Fundação para a Ciência e a Tecnologia, I.P., under the projects SRecognite Infect-ERA/0003/2015 and UIDB/04293/ 2020. Individual funding to JT was provided by FCT through CEECIND/02362/2017. MC, RS, and MS were recipients of studentships from FCT, respectively, SFRH/BD/116791/2016, SFRH/BD/110691/2015, and SFRH/BD/133485/2017. This paper is dedicated to our colleague and friend Rui Appelberg (1960-2020). The authors acknowledge the support of the i3S Scientific Platform BioSciences Screening, member of the national infrastructure PPBI–Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122) and PT-OPENSCREEN. Tissue sections were kindly provided by Amaro Frutuoso, Department of Complementary Means of Diagnosis and Therapy, Service of Pathology, Hospital Pedro Hispano, Matosinhos

Produtos de contraste iodados

A aplicação na medicina dos produtos de contraste iodados é uma realidade com a qual a generalidade dos médicos deve estar familiarizada. Através de uma abordagem sucinta, o presente artigo pretende simplificar a compreensão dos diversos tipos de contraste, suas propriedades, utilidade clínica e reacções adversas

Impact of montelukast as add on treatment to the novel coronavirus pneumonia (COVID-19): protocol for an investigator-initiated open labeled randomized controlled pragmatic trial

Background: Montelukast, a safe drug widely use in asthmatic patients, may be an adjuvant in the treatment of Covid-19, either by improving lung injury and inflammation, or by acting as an anti-viral drug. We aim to assess the efficacy and safety of montelukast as add-on treatment in patients with Covid-19. Methods: We propose a randomized, controlled, parallel, open-label trial involving 160 hospitalized adult patients with confirmed Covid-19. Patients will be randomly assigned in a 1:1 ratio to receive either montelukast 10 mg, once a day for 14 days, in addition to standard of care (SoC), or SoC alone. SoC will follow the best practice for treating these patients, according to updated recommendations. The primary outcome is time to recovery. Participants will be assessed using diary cards to capture data on treatment-related improvements in an 8-point ordinal scale. Secondary endpoints will include changes in respiratory and inflammatory parameters, and adverse events. This phase IV clinical trial will take place at the University Hospital of São João, Porto. EudraCT number: 2020-001747-21. Results: This study intends to generate scientific evidence on efficacy and safety of montelukast as add-on treatment in Covid-19. The results will be essential to improve clinical outcomes which remains to be determined. Conclusion: Montelukast has been suggested as a potential drug with 2 main actions on Covid-19. The validation of montelukast as an adjuvant treatment may improve lung injury, inflammation, and symptoms leading to a better prognosis. The use of this drug may fulfil the existing gap on therapeutic options

Flow cytometry and targeted immune transcriptomics identify distinct profiles in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors with or without interferon-α

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Selective ablating urologic cancers with cold atmospheric plasma

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The effect of cold atmospheric plasma in bladder cancer cell

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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