Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can ...therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.
In this work we report the synthesis, crystal structures, and magnetic behavior of 2p–3d–4f heterospin systems containing the nitroxide radical 4-azido-2,2,6,6-tetramethylpiperidine-1-oxyl radical ...(N3tempo). These compounds were synthesized through a one-pot reaction by using Cu(hfac)2, Ln(hfac)3 (hfac = hexafluoroacetylacetonate, Ln = DyIII, TbIII or GdIII), and the N3tempo radical. Depending on the stoichiometric ratio used, the synthesis leads to penta- or trimetallic compounds, with molecular formulas Cu3Ln2(hfac)8(OH)4(N3tempo) (Ln = Gd, Tb, Dy) and CuLn2(hfac)8(N3tempo)2(H2O)2 (Ln = Gd, Dy). The magnetic properties of all compounds were investigated by direct current (dc) and alternating current (ac) measurements. The ac magnetic susceptibility measurements of TbIII- and DyIII-containing compounds of both families revealed slow relaxation of the magnetization, with magnetic quantum tunneling in zero field.
Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. Diagnosing MM presents considerable challenges, involving the ...identification of plasma cells in cytology examinations on hematological slides. At present, this is still a time-consuming manual task and has high labor costs. These challenges have adverse implications, which rely heavily on medical professionals' expertise and experience. To tackle these challenges, we present an investigation using Artificial Intelligence, specifically a Machine Learning analysis of hematological slides with a Deep Neural Network (DNN), to support specialists during the process of diagnosing MM. In this sense, the contribution of this study is twofold: in addition to the trained model to diagnose MM, we also make available to the community a fully-curated hematological slide dataset with thousands of images of plasma cells. Taken together, the setup we established here is a framework that researchers and hospitals with limited resources can promptly use. Our contributions provide practical results that have been directly applied in the public health system in Brazil. Given the open-source nature of the project, we anticipate it will be used and extended to diagnose other malignancies.
Combined allergic rhinitis and asthma syndrome (CARAS) is an allergic airway inflammatory disorder orchestrated by the type 2 immune response. The close gut-lung relationship has been described, ...however, the effect of gut-modulating agents such as probiotics in allergic airway disorder is unclear. Thus, the goal of this study was to evaluate theLimosilactobacillus fermentumsupplementation in animals with CARAS. Therefore, BALB/c mice were ovalbumin (OVA) -sensitized and -challenged after being supplemented withL. fermentum. Animals, previously probiotic supplemented, showed a decrease (p < 0.05) of inflammatory cell migration, mainly eosinophil, into the nasal (NALF) and the bronchoalveolar (BALF) fluids as well as reduction of the allergic signs such as sneezing, nasal rubbings, and nasal hyperreactivity induced by histamine as compared with non-supplemented animals. In the systemic context,L. fermentumreduced eosinophilia and the serum levels of OVA-specific IgE. The altered histological aspects of nasal and lung tissues of animals with CARAS were effectively ameliorated byL. fermentum. In the BALF, the immunomodulatory effect was due to the decreasing of type 2 and 3 cytokines (IL-4, IL-13, IL-5 and IL-17A) dependent on type 1 (IFN-γ) and Treg (IL-10) cytokine increasing. Indeed,L. fermentumimproved the FOXP3 activation. Additionally, these effects correlate with the amplification of the gut response as increasing short-chain fatty acids (SCFAs) levels, gut epithelium barrier (ZO-1) maintenance, and colon tissue integrity. These data pointed out that animals’ probiotic supplemented presented immunomodulatory responses in CARAS experimental model by activating the intracellular transduction signal underlying the IL-10 gene transcription.
The importance of capabilities and resources for portfolio management and business strategy has been recognized in the management literature. Despite that, little attention has been given to ...integrate the notions of capabilities and resources in enterprise architecture descriptions. One notable exception is a recent proposal to extend the ArchiMate framework and language to include capability and resources and thus improve ArchiMate׳s coverage of portfolio management. This paper presents an ontological analysis of the concepts introduced in that proposal, focusing in particular on the resource, capability and competence concepts. We provide an account for these concepts in terms of the Unified Foundational Ontology (UFO). The analysis allows us to identify semantic issues in the proposal and suggests well-founded recommendations for improvements. We revise the proposed metamodel in order to address the identified problems, thereby improving the semantic clarity and usefulness of the proposed language extension. Two real-world cases are modeled with the resulting metamodel to show the applicability of the constructs and relations in an industrial setting.
•We present an ontological analysis of resource, capability and competence for EA.•We found 13 issues on the original proposal with the ontological analysis.•We refactor the original metamodel to address the identified problems.•We present two use cases using the improved extension.•Our recommendations should lead to improved resource and capability oversight.
Newcastle disease virus (NDV) can infect over 250 bird species with variable pathogenicity; it can also infect humans in rare cases. The present study investigated an outbreak in feral pigeons in São ...Paulo city, Brazil, in 2019. Affected birds displayed neurological signs, and hemorrhages were observed in different tissues. Histopathology changes with infiltration of mononuclear inflammatory cells were also found in the brain, kidney, proventriculus, heart, and spleen. NDV staining was detected by immunohistochemistry. Twenty-seven out of thirty-four tested samples (swabs and tissues) were positive for Newcastle disease virus by RT-qPCR test, targeting the M gene. One isolate, obtained from a pool of positive swab samples, was characterized by the intracerebral pathogenicity index (ICPI) and the hemagglutination inhibition (HI) tests. This isolate had an ICPI of 0.99, confirming a virulent NDV strain. The monoclonal antibody 617/161, which recognizes a distinct epitope in pigeon NDV strains, inhibited the isolate with an HI titer of 512. A complete genome of NDV was obtained using next-generation sequencing. Phylogenetic analysis based on the complete CDS F gene grouped the detected isolate with other viruses from subgenotype VI.2.1.2, class II, including one previously reported in Southern Brazil in 2014. This study reports a comprehensive characterization of the subgenotype VI.2.1.2, which seems to have been circulating in Brazilian urban areas since 2014. Due to the zoonotic risk of NDV, virus surveillance in feral pigeons should also be systematically performed in urban areas.
The present study evaluates the proteome of early antral follicles from Ovis aries. Fifty follicles were collected from ovaries of adult ewes and extracted proteins were trypsin-digested, desalted ...and analyzed by LC-MS/MS. Genes were screened for potential modulation by miRNAs and protein data, subjected to functional enrichment analysis. Label-free mass spectrometry allowed the identification of 2503 follicle proteins, confirming vimentin, actin, lamin, heat shock proteins and histones as the most abundant ones. In silico analyses indicated that miRNAs modulate the expression of genes coding proteins of the sheep follicles involved in cell cycle, cell differentiation, aging, apoptosis, cell death, adipocyte differentiation, cell division. The most important biological processes associated with the follicle proteins were innate immune response, translation, adaptive immune response and protein folding, while molecular functions linked to the proteome of sheep antral follicles related to metal ion binding, ATP binding, oxygen binding, RNA binding and GTP binding, among others. Upload of 2503 Uniport accession codes through DAVID platform matched 1274 genes, associated with translation, metabolic process, proteolysis involved in cellular protein catabolic process, zona pellucida receptor complex and others. KEEG pathways analysis indicated genes correlated with ovine follicular development, with major pathways listed as carbon metabolism, biosynthesis of amino acids, glutathione metabolism, oxidative phosphorylation, fatty acid degradation and oocyte meiosis. This represents a comprehensive atlas of proteins expressed in sheep early antral follicles and will contribute to future identification of biomarkers for follicular development and oocyte maturation.
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•First proteome atlas (2,503 proteins) of early antral follicles from Ovis aries.•Main follicle proteins were structural proteins, chaperones and histones.•Follicle proteins linked to metabolism, zona pellucida receptor, oxidative phosphorylation, fatty acid degradation, meiosis.•Data contribute to future identification of follicular development markers in the ovine species.
Multiple medications in common use have been considered for the treatment of Covid-19. In this double-blind, randomized, placebo-controlled trial, ivermectin that was administered within 7 days after ...Covid-19 symptom onset was shown not to be of any clinical benefit.
There are no previous randomized trials comparing surgical to conservative treatment for post-traumatic elbow stiffness. The aim of our study was to compare elbow range of motion (ROM) and clinical ...outcomes among patients undergoing surgical treatment or a standardized rehabilitation for post-traumatic elbow stiffness.
Randomized clinical trial of patients with post-traumatic elbow stiffness for more than 6 months who failed conventional physical therapy for 4 months. Patients were randomized into 2 treatment groups. The conservative group underwent the rehabilitation protocol associated with the use of orthoses (static progressive for extension and dynamic for flexion) and continuous passive motion. The surgical group underwent surgical release by a posterior approach without triceps detachment, followed by a rehabilitation protocol similar to the conservative group. The primary outcome of the study was flexion-extension ROM at 6 months of follow-up. Secondary outcomes included the visual analog scale for pain, the Mayo Elbow Performance Score, the Disabilities of the Arm, Shoulder, and Hand score, absolute and relative increase in flexion-extension ROM, and complication rates.
Thirty patients were analyzed in the study, 15 in each group. The mean elbow flexion-extension ROM at the end of 6 months of follow-up was 108° in the surgical group and 88° in the conservative group (P = .002). The mean absolute and the relative increase of elbow flexion-extension at 6 months were, respectively, 17° and 27% in the conservative group and 41° and 59% in the surgical group (P < .001).
Surgical elbow release associated with the rehabilitation protocol resulted in a greater flexion-extension ROM, as well as a greater absolute and relative increase compared with rehabilitation alone at 6 months of follow-up. The groups did not differ regarding clinical scores and complication rates.
To assess the prevalence, nature, and associated phenotypes of ATP13A2 gene mutations among patients with juvenile parkinsonism (onset <21 years) or young onset (between 21 and 40 years) Parkinson ...disease (YOPD).
We studied 46 patients, mostly from Italy or Brazil, including 11 with juvenile parkinsonism and 35 with YOPD. Thirty-three cases were sporadic and 13 had positive family history compatible with autosomal recessive inheritance. Forty-two had only parkinsonian signs, while four (all juvenile-onset) had multisystemic involvement. The whole ATP13A2 coding region (29 exons) and exon-intron boundaries were sequenced from genomic DNA.
A novel homozygous missense mutation (Gly504Arg) was identified in one sporadic case from Brazil with juvenile parkinsonism. This patient had symptoms onset at age 12, levodopa-responsive severe akinetic-rigid parkinsonism, levodopa-induced motor fluctuations and dyskinesias, severe visual hallucinations, and supranuclear vertical gaze paresis, but no pyramidal deficit nor dementia. Brain CT scan showed moderate diffuse atrophy. Furthermore, two Italian cases with YOPD without atypical features carried a novel missense mutation (Thr12Met, Gly533Arg) in single heterozygous state.
We confirm that ATP13A2 homozygous mutations are associated with human parkinsonism, and expand the associated genotypic and clinical spectrum, by describing a homozygous missense mutation in this gene in a patient with a phenotype milder than that initially associated with ATP13A2 mutations (Kufor-Rakeb syndrome). Our data also suggest that ATP13A2 single heterozygous mutations might be etiologically relevant for patients with YOPD and further studies of this gene in Parkinson disease are warranted.
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