Autoimmunity Overlaps Primary Biliary Cirrhosis: a Not Straightforward Diagnosis

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Levetiracetam-induced psychosis in a Filipino female diagnosed with anti-N-methyl-D-aspartate receptor encephalitis: a case report

Levetiracetam (LEV), an SV2A inhibitor is a widely available anti-epileptic drug that is used to treat a range of partial and generalized seizure and juvenile myoclonic epilepsy. It is generally well tolerated and deemed safe due to the absence of drug-to-drug interaction. Despite its safety, there are adverse effects that can lead to the discontinuation of this anti-seizure medication. Some of the reported infrequent adverse effects are mood-related changes including agitation, depression, anxiety and suicidal ideations that can be observed after initiation or rapid up titration of the medication. The mechanism for this is still unknown but there are certain theories that attempted to determine the association. Risk factors reported were female sex, temporal lobe involvement and history of psychiatric disorder. In this case report, we present a 30-year-old female without history of psychiatric illness diagnosed with anti N-methyl-D-aspartate receptor (NMDAR) encephalitis who presented with seizure and was started on LEV for seizure control. She developed aggression and suicidal ideations secondary to initiation and up-titration of LEV. The symptoms resolved after discontinuation of the said medication.

O desenvolvimento dos caminhos-de-ferro em Portugal e no Brasil: Uma análise comparativa e morfológica dos territórios atravessados por estas infraestruturas

O desenvolvimento dos caminhos-de-ferro desempenhou desde o século XIX um papel importante na estruturação do território. A sua implementação deu a conhecer diversas soluções bem como distintos ciclos de desenvolvimento socioeconómico, nos vários pontos do globo onde esta ocorreu. Em Portugal, os caminhos-de-ferro constituíram o primeiro elemento estruturador do território, desvinculado das rotas marítimas e fluviais, a estabelecer-se de forma sistemática a interligar o país. No Brasil, os caminhos-de-ferro estruturaram e transformaram um território em parte virgem de ocupação, favorecendo a expansão urbana do litoral em direção ao interior do país. Foram os lucros provindos do comércio de bens coloniais, à priori operado por via hídrica, que motivaram a construção ferroviária nos dois países. Este comércio estendeu-se para o sistema ferroviário e iniciou a estruturação do território a partir de uma nova infraestrutura com uma lógica distinta. Este trabalho expõe, de forma inédita, através da análise conjunta, os resultados desta conduta nos dois países, inseridos em contextos diferentes. Assim, através de uma análise comparativa dos processos de evolução e desenvolvimento físico-territorial das linhas férreas portuguesas e brasileiras entre 1850 e 2015, busca-se aqui contribuir para a pertinência do estudo do impacto das infraestruturas ferroviárias na transformação morfológica dos territórios por elas atravessados. A aplicação do método seguido por este estudo permitiu identificar a relação dos investimentos na estrutura ferroviária e a estruturação da paisagem das regiões atravessadas por estas infraestruturas. Consequentemente, é-nos possível aferir, para os dois casos de estudo: (i) os traçados propostos nas tentativas de criação de planos ferroviários; e (ii) as repercussões deste novo meio de transporte no território, em especial na estruturação ou reestruturação de centralidades. Os resultados deste trabalho permitem-nos concluir que, em ambos os casos, a estruturação do território foi condicionada pela vontade do capital privado e pela legislação criada para a construção ferroviária e o planeamento dos transportes. Em Portugal resultou no reforço de ligações já existentes entre as cidades do interior com Lisboa e Porto . No Brasil, os caminhos-de-ferro foram responsáveis pela criação de centros urbanos e de áreas de produção agropecuária e industrial, factor que condicionou um compromisso ambiental com áreas florestadas ou de preservação. Finalmente, o desenvolvimento dos caminhos-de-ferro, teve um papel fundamental na organização da comunicação entre os centros urbanos. Ressalva-se, consequentemente, a necessidade da integração desta temática aos estudos da forma e da paisagem urbana.info:eu-repo/semantics/publishedVersio

ACTIVIDAD DE ANTISEPTICOS EN Malassezia pachydermatys AISLADA DE OIDO EXTERNO EN PERROS Y GATOS

Se estudiaron en agar Sabouraud dextrosado, muestras obtenidas del conducto auditivo externo de 80 perros y 22 gatos aparentemente sanos. El examen micológico directo y las características morfofisiológicas y bioquímicas, permitieron determinar la presencia de Malassezia pachydermatis en el 61,3% de las muestras provenientes de perros y en el 13,6% de los gatos. La susceptibilidad de esta levadura se determinó en medios sólidos, por el método de dilución in vitro frente a soluciones de yodo, timerosal y violeta de genciana. Todas las cepas fueron inhibidas en las siguientes concentraciones: Yodo 1.0 g/l; Timerosal 0,0125 g/l y Violeta de genciana a 0,0078 g/l, lo que representa su dilución comercial diluida 641 veces

Prolonged Hospitalizations in an Internal Medicine Ward

Introdução: As enfermarias de Medicina Interna acolhem doentes complexos, com múltiplas comorbilidades, idosos, frágeis, dependentes, frequentemente com problemas sociais, podendo condicionar internamentos longos. Pretende-se caracterizar a população com internamentos prolongados (IPs), avaliando se foram adequados à situação clínica ou relacionados com questões socioeconómicas. Métodos: Estudo retrospetivo realizado durante o ano de 2014 numa enfermaria de Medicina Interna e que incluiu doentes com internamentos superiores a 20 dias. Os IPs foram classificados como apropriados pela complexidade do quadro clínico, intercorrências ou iatrogenias, e inapropriados se relacionados com falta de condições pós-alta. Resultado: Cento e setenta e sete IPs (10,4% do total de internamentos); 53 homens, idade média 76 anos. Média de internamento 33,8 dias; 39% tiveram previamente alta clínica - dias de alta protelada: 1653. À admissão, 36% parcial- e 17% totalmente dependentes. Comorbilidades: hipertensão (75%), doença cerebrovascular (52%), diabetes (35%), demência (28%). Diagnósticos principais mais prevalentes: acidente vascular cerebral (21%), pneumonia (14%), neoplasia (11%); 14% com necessidade de cuidados intensivos/intermédios. Em 64% o factor de prolongamento preponderante foi clinicamente apropriado - 77% pela complexidade e 15% por infecções nosocomiais. Foram referenciados à Rede Nacional de Cuidados Continuados 23%. Mortalidade 13,0%. Nos 36 meses pós-alta, 59% foram internados, 23% apresentaram IPs e 57 doentes faleceram - mortalidade 37% aos 3 anos. Conclusão: Os doentes com IPs são heterogéneos em relação aos diagnósticos e necessidades específicas. Apesar de 36% dos IPs ser condicionada pelas condições pós-alta, a maioria foi apropriada à gravidade, complexidade clínica ou intercorrências no internamento.info:eu-repo/semantics/publishedVersio

An unusual association of diffuse adenomyomatosis with dysplastic adenoma in chronic calculous cholecystitis: case presentation

<p>Abstract</p> <p>Background</p> <p>Gallbladder adenomyomatosis is an epithelial proliferation and hypertrophy of the muscularis mucosae of the gallbladder. Rokitansky-Aschoff sinuses are a characteristic of this condition. The segmental adenomyomatosis has a higher risk of developing into gallbladder carcinoma, especially in the fundal region of elderly patients.</p> <p>We report the case of a patient affected by chronic calculous cholecystitis with diffuse adenomyomatosis associated with dysplastic adenoma.</p> <p>Case presentation</p> <p>An 81-year-old woman presented at our hospital with a 1-year history of intermittent pain localized at the right upper abdominal quadrant, without diffusion to any other body part. On physical examination the abdomen was soft, not distended, and tender to palpation in the right upper quadrant. Murphy sign was negative. Laboratory tests were normal. The patient was scheduled for a laparoscopic cholecystectomy, and neither endoscopic ultrasonographic scan nor magnetic resonance imaging was performed. The operation, performed after obtaining informed consent, was uncomplicated and the intra-operative pathological examination showed no malignancy. The definitive pathological examination of the gallbladder showed: multiple stones of cholesterol origin; diffuse mucosal adenomyomatosis; and a 1.1 cm pedunculated mass localized at the fundus, whose surface was lumpy. This mass was diagnosed as an adenoma with multiple areas of severe dysplasia.</p> <p>Conclusions</p> <p>The adenoma of the gallbladder, together with the dysplasia, represents a biological carcinogenetic model. Carcinoma has rarely been reported in adenomyomatosis. Degenerative risk suggests surgery should be mandatory when there is a concomitant presence of large adenoma and adenomyomatosis.</p

Knock-Down of Cathepsin D Affects the Retinal Pigment Epithelium, Impairs Swim-Bladder Ontogenesis and Causes Premature Death in Zebrafish

The lysosomal aspartic protease Cathepsin D (CD) is ubiquitously expressed in eukaryotic organisms. CD activity is essential to accomplish the acid-dependent extensive or partial proteolysis of protein substrates within endosomal and lysosomal compartments therein delivered via endocytosis, phagocytosis or autophagocytosis. CD may also act at physiological pH on small-size substrates in the cytosol and in the extracellular milieu. Mouse and fruit fly CD knock-out models have highlighted the multi-pathophysiological roles of CD in tissue homeostasis and organ development. Here we report the first phenotypic description of the lack of CD expression during zebrafish (Danio rerio) development obtained by morpholino-mediated knock-down of CD mRNA. Since the un-fertilized eggs were shown to be supplied with maternal CD mRNA, only a morpholino targeting a sequence containing the starting ATG codon was effective. The main phenotypic alterations produced by CD knock-down in zebrafish were: 1. abnormal development of the eye and of retinal pigment epithelium; 2. absence of the swim-bladder; 3. skin hyper-pigmentation; 4. reduced growth and premature death. Rescue experiments confirmed the involvement of CD in the developmental processes leading to these phenotypic alterations. Our findings add to the list of CD functions in organ development and patho-physiology in vertebrates

Late Onset Neuromyelitis Optica Spectrum Disorders (LONMOSD) from a Nationwide Portuguese Study: Anti-AQP4 Positive, Anti-MOG Positive and Seronegative Subgroups

Introduction: Several neuroimmunological disorders have distinct phenotypes according to the age of onset, as in multiple sclerosis or myasthenia gravis. It is also described that late onset NMOSD (LONMOSD) has a different phenotype. Objective: To describe the clinical/demographic characteristics of the LONMOSD and distinguish them from those with early onset (EONMOSD). Methods: From a nationwide Portuguese NMOSD study we analyzed the clinical/demographic characteristics of the LONMOSD. Results: From the 180 Portuguese patients 45 had disease onset after 50 years old, 80% were female. 23 had anti-AQP4 antibodies (51.1%), 13 anti-MOG antibodies (28.9%) and 9 were double seronegative (20.0%). The most common presenting phenotypes in LONMOSD were transverse myelitis (53.3%) and optic neuritis (26.7%), without difference from EONMOSD (p = 0.074). The mean EDSS for LONMOSD was 6.0 (SD=2.8), after a mean follow-up time of 4.58 (SD=4.47) years, which was significantly greater than the mean EDSS of EONMOSD (3.25, SD=1.80)(p = 0.022). Anti-AQP4 antibodies positive LONMOSD patients had increased disability compared to anti-MOG antibodies positive LONMOSD (p = 0.022). The survival analysis showed a reduced time to use a cane for LONMOSD, irrespective of serostatus (p<0.001). Conclusions: LONMOSD has increased disability and faster progression, despite no differences in the presenting clinical phenotype were seen in our cohort.info:eu-repo/semantics/publishedVersio

Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 patients

SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID-19. We investigated whether the specific immune responses in the peripheral blood of 276 patients were associated with the severity and progression of COVID-19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56–CD16+ NK-cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID-19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic interventionThe study was funded by grants SAF2017- 82886-R to FS-M from the Ministerio de Economía y Competitividad, and from “La Caixa Banking Foundation” (HR17-00016) to FS-M. Grant PI018/01163 to CMC and grant PI19/00549 to AA were funded by Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain. SAF2017-82886-R, PI018/01163 and PI19/00549 grants were also co-funded by European Regional Development Fund, ERDF/FEDER. This work has been funded by grants Fondo Supera COVID (CRUE-Banco de Santander) to FSM, and “Ayuda Covid 2019” from Comunidad de Madri

A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Introduction. Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods. We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, aminoacid residues and single nucleotide polymorphisms was undertaken. Results. The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two aminoacid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions. Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition