Abstract
Background and Aims
C3 glomerulopathy (C3G) is a rare diagnosis, characterized by dysregulation of the alternative pathway of complement, classically presenting in children and young adults. ...Recently, it has been reported the association between the production of a monoclonal protein and the development of C3G, affecting a larger age span.
Method
We report the case of a 53-year-old male patient, that attended the emergency department due to persistent holocranial headache. He was an IV drug abuser with a history of treated Hepatitis C infection and free lambda light chain monoclonal protein, being studied by the Haematology Department. On admission, he was hypertensive (187/98 mmHg), and labs showed an acute on chronic kidney disease (serum creatinine 2.35 mg/dL from a basal of 1.5 mg/dL) with an active urinary sediment (38 erythrocytes/field, with dysmorphia), a urinary protein/creatinine ratio of 626 mg/g, and C3 consumption (0.52 g/L). The patient was admitted, and a kidney biopsy was performed.
Results
Further lab results confirmed a serum IgG Lambda monoclonal protein. Autoantibodies screening (ANCAs, ANAs, Anti-GBM), ASLO and Rheumatoid Factor were negative. Cryoglobulinemia was detected, and the cryoprecipitate's immunofixation revealed monoclonal proteins IgG Lambda and IgM Kappa. HCV viral load was negative. Bone marrow biopsy revealed a small population (< 3%) of plasma cells with Lambda light chain restriction. Kidney biopsy's light microscopy showed increased mesangial matrix and cells, endocapillary hypercellularity, and some glomeruli with lobulated appearance. Five out of 15 glomeruli presented fibrocellular crescents. Immunofluorescence showed C3 dominant staining on capillary walls and in the mesangium, with absent IgG and light chain deposits. A presumptive diagnosis of C3 glomerulopathy was made and the patient was empirically started on corticosteroids (3 pulses of intravenous methylprednisolone, followed by oral prednisolone 1mg/Kg/day), which was followed by paraprotein-directed chemotherapy with bortezomib, cyclophosphamide and dexamethasone (VCD). The patient is currently on the third VCD cycle, presenting both renal and haematological responses: recovery of serum creatinine to basal levels (1.54 mg/dL), resolution of haematuria and proteinuria, normalisation of C3 levels. Serum immunofixation is currently negative for monoclonal protein, with normal serum immunoglobulin levels. Electron microscopy revealed electron-dense deposits in the mesangium, and mesangium-capillary transition, supporting the diagnosis of C3 glomerulonephritis. Genetic testing of complement-related genes revealed a rare missense variation of unknown significance (c.4855A>C) on the C3 gene, that has been previously reported in association with C3 glomerulopathy and atypical Haemolytic-Uremic syndrome.
Conclusion
This case represents a monoclonal gammopathy associated-C3 glomerulonephritis with a favourable response to paraprotein-directed chemotherapy. Although the association between monoclonal gammopathy and C3G rests on epidemiologic findings, experimental evidence suggests that several monoclonal proteins have complement dysregulation features, which may enhance alternate complement pathway activation.
Our patient's response is in line with observational data that have shown improved renal outcomes in patients who achieve a haematological response following clone-directed chemotherapy, which further supports the role of monoclonal gammopathy in C3G pathogenesis 1.
Interestingly, the genetic variation identified in our patient might have provided a favourable genetic background for the development of C3G, which is thought to rely upon a complex interaction of triggering events, such as a monoclonal gammopathy, and underlying complement abnormalities, such as genetic variants in complement genes.
Abstract Objectives: analyse the relation between the nutritional status of children with 0 to 60 months in São Tome and Principe (STP) and their mothers. Methods: characterization of the nutritional ...status of 1,169 children for the weight / length ratio (W/L) (≤24months) and Body Mass Index (BMI) for age (>24months) and their mothers. The Chi Square or Fisher tests were used for the study on the relation between the nutritional status of the mother and children, as appropriate. Results: fifty-five percent (55%) of the children are female (median = 21 months). There was a high percentage of global acute malnutrition in the children aged0≤24months (30.2%) and 24≤60months (22%) as well as global chronic malnutrition (32% and 41.1% respectively). We observed a high percentage of overweight /obese mothers (31.6%), with 16.5% of them being of a low height. We observed a significantly higher percentage of children with global acute malnutrition 47.5%) when compared with that which was reported for children of normal mothers (27.9%) or overweight /obese (22%) (p<0,001) mothers. Conclusions: It was observed a high prevalence of acute and chronic global malnutrition in the children studied and a high prevalence of overweight /obese mothers. We observed a statistically significant association between maternal and acute global malnutrition of the children.
Bothrops snakes are responsible for more than 70 % of snakebites every year in Brazil and their venoms cause severe local and systemic damages. The pharmacological properties of medicinal plants have ...been widely investigated in order to discover new alternative treatments for different classes of diseases including neglected tropical diseases as envenomation by snakebites. In this work, we have investigated the ability of Vochysia haenkeana stem barks extract (VhE) to neutralize the neuromuscular effects caused by Bothropstoxin-I (BthTX-I), the major phospholipase A
(PLA
) myotoxin from B. jararacussu venom.
The biological compounds of VhE were analysed under thin layer chromatography (TLC) and its neutralizing ability against BthTX-I was assessed through twitch-tension recordings and histological analysis in mouse phrenic nerve-diaphragm (PND) preparations. The antimicrobial activity of VhE was assessed against S. aureus, E. coli and P. aeruginosa strains. The aggregation activity of VhE was analysed under protein precipitation assay.
VhE showed the presence of phenolic compound visualized by blue trace under TLC. VhE abolished the neuromuscular blockade caused by BthTX-I applying the pre-toxin incubation treatment and partially neutralized the BthTX-I action under post-toxin incubation treatment; VhE contributed slightly to decrease the myotoxicity induced by BthTX-I. The neutralizing mechanism of VhE may be related to protein aggregation. VhE showed no antimicrobial activity.
V. haenkeana extract which has no antimicrobial activity exhibited neutralizing ability against the neuromuscular blockade caused by BthTX-I and also contributed to decrease its myotoxicity. Protein aggregation involving phenolic compounds may be related in these protective effects.
Formalization of Ring Theory in PVS de Lima, Thaynara Arielly; Galdino, André Luiz; Avelar, Andréia Borges ...
Journal of automated reasoning,
12/2021, Letnik:
65, Številka:
8
Journal Article
Recenzirano
This paper presents a PVS development of relevant results of the theory of rings. The PVS theory includes complete proofs of the three classical isomorphism theorems for rings, and characterizations ...of principal, prime and maximal ideals. Algebraic concepts and properties are specified and formalized as generally as possible allowing in this manner their application to other algebraic structures. The development provides the required elements to formalize important algebraic theorems. In particular, the paper presents the formalization of the general algebraic-theoretical version of the Chinese remainder theorem (CRT) for the theory of rings, as given in abstract algebra textbooks, proved as a consequence of the first isomorphism theorem. Also, the PVS theory includes a formalization of the number-theoretical version of CRT for the structure of integers, which is the version of CRT found in formalizations. CRT for integers is obtained as a consequence of the general version of CRT for the theory of rings.
•Physical and mechanical performance of cement-based renders.•Fly ash, expanded cork granules and expanded clay contents variation.•Thermal mortars with distinct EN 998 classes allow deferent ...applications.•Suitable values for thermal conductivity, mechanical and water resistance.
In recent decades, there has been a demand for new cladding solutions with higher thermal efficiency. Mortars with an improved thermal performance are one such solution. The biggest challenge in developing these mortars consists in achieving a lower thermal conductivity, while still maintaining an appropriate mechanical and water resistance performance with a low environmental impact.
The aim of this study is to analyse the physical and mechanical performance of 20 cement-based coating mortars (renders) with different contents of a SCM – supplementary cementitious material (fly ash) used to replace cement, and of two insulating aggregates (expanded cork granules, expanded clay or a mix of both) replacing sand.
The reduction of cement binder and sand aggregate contents led to lower thermal conductivity and a decrease of the mechanical properties. However, the balance between the physical and mechanical performance allows different applications, reaching thermal mortars with distinct EN 998 classes: (i) thermal conductivity T1 or T2; (ii) compressive strength CSI or CSII; (iii) water capillary absorption W0 or W1.
Os sistemas educacionais não estavam preparados para confrontar as excepcionalidades decorrentes da pandemia da COVID-19 e buscaram alternativas para minimizar os impactos na aprendizagem dos alunos ...depositando suas esperanças no ensino remoto. Embora a alteração do modelo de ensino tenha impactado integralmente públicos diversos, alunos acometidos pelo Transtorno do Espectro Autista (TEA) enfrentaram desafios maiores durante o processo de adaptação à nova realidade de ensino. Neste sentido, a identificação dos desafios e impactos gerados pela pandemia da COVID-19 no desenvolvimento escolar de alunos com TEA regularmente matriculados em uma escola pública de educação básica do município de São José do Alegre/Minas Gerais foi realizada mediante a aplicação de um questionário a uma professora regente e de apoio, além de cinco pais responsáveis por estas crianças e adolescentes. As professoras consideraram que a pandemia impactou moderadamente a aprendizagem dos seus alunos autistas, observando pouco avanço na capacidade de aprender. Contudo, para a maioria dos pais a pandemia interferiu negativamente, pois observaram grande retrocesso na aprendizagem dos seus filhos. Na percepção da professora regente, o principal desafio ao ensino esteve relacionado ao processo de ensino-aprendizagem que necessitou ser amplamente ressignificado para atender as condições restritivas do momento. Já para a professora de apoio, o desafio foi estabelecer um contato efetivo com os alunos para estimular a realização das atividades. Os pais foram unânimes em considerar o estabelecimento de uma nova rotina de estudos para os seus filhos como o principal desafio. Diante dos novos desafios, as professoras apostam na manutenção do vínculo com os alunos e na mediação da aprendizagem como formas de minimizar os impactos. A intensificação do diálogo, mediação constante e maior paciência são as principais atitudes experimentadas pelos pais para minimizar os possíveis danos ao desenvolvimento escolar dos seus filhos autistas durante a pandemia do novo coronavírus.
Abstract Background and Aims The Kidney Donor Profile Index (KDPI) was introduced in the United States in 2014 to support clinicians' decision-making regarding the acceptance or decline of potential ...donors. In Portugal, there is no valid stratification score to assist physicians in accepting or declining an organ offer. Our study aims to characterize a cohort of Portuguese kidney transplant recipients and donors and evaluate the correlation between KDPI and long-term graft survival. The results are interpreted considering the nuances of the Portuguese allocation system, which favors an age-matched donor-recipient allocation. Method We conducted an observational single-center retrospective cohort study, which included patients who received a deceased donor kidney transplant at our unit between January 2013 and December 2015. We excluded patients for whom the donor KDPI index was unavailable for retrieval. Besides the KDPI index, we collected data regarding the receptor's demographic, clinical, and immunological characteristics, as well as graft and recipient survival. The primary outcome was death-censored survival, and follow-up ended on the 31st of December 2023. The secondary outcome was survival with a functioning graft. Survival estimates were obtained using Kaplan-Meier curves. We performed univariate and multivariate survival analysis with log-rank tests and Cox proportional-hazards regression models. Results We selected 364 deceased-donor kidney recipients and 212 kidney donors. The mean KDPI was 60% and 53.3% of donors were classified as expanded criteria. The kidney recipients were predominantly male (68.4%), with a mean age of 50.16 years and an average of 4 HLA mismatches. Median follow-up was 102 months. Considering recipient characteristics according to pre-defined KDPI strata (≤ 20%, 21-85%, > 85%), recipients from higher KDPI were significantly older, with a mean age of 40.6, 48.8, and 61.1 years, respectively (p < 0.001), and had a higher average body mass index (p = 0.041). There were no significant differences regarding the number of HLA mismatches (p = 0.624) or the proportion of hypersensitized patients (p = 0.253) between classes. During follow-up, 16.8% patients presented graft failure and 9.9% died with a functioning graft. Cumulative death-censored graft survival at 5, 8, and 10 years was 87.7%, 87.1%, and 84.4% respectively. The cumulative percentage of patients living with a functioning graft at 5, 8, and 10 years was 83.6%, 76.7%, and 68.6%. Death-censored graft survival was lower in recipients of donors with higher KDPI (Fig. 1), although it did not reach statistical significance (p-value = 0.166). The number of HLA mismatches (p = 0.592) or the recipient's age (p = 0.513) did not significantly impact death-censored graft survival, whereas delayed graft function (DGF) was the variable with the strongest association in univariate analysis (p < 0.001). In a multivariate Cox regression model, KDPI (HR 1.02, p = 0.005) and DGF (HR 3.2, p < 0.001) correlated with graft loss, while older recipients (HR 0.971, p = 0.019) seemed to have a protective effect over death-censored survival. Patient survival with a functioning graft was significantly associated with KDPI strata (p = 0.008; Fig. 2), the recipient's age (p = 0.006), and DGF (p < 0.001) in univariate analysis. Considering KDPI kidneys ≥ 90%, 10-year cumulative death-censored survival was 67.9%. Conclusion In our sample, despite not reaching statistical significance, there was a trend for improved death-censored graft survival in patients with lower KDPI, which further emulates the results of other European cohorts. Nevertheless, the 10-year cumulative death-censored survival of higher KDPI kidneys (≥ 90%) was remarkable, showing that long-term acceptable outcomes can be achieved. The impact of KDPI on patient survival with a functioning graft is probably overestimated, given the bias introduced by the Portuguese matching system, which rewards an “old-for-old” donor-recipient allocation.
In Hymenoptera, homozygosity at the sex locus results in the production of diploid males. In social species, these pose a double burden by having low fitness and drawing resources normally spent for ...increasing the work force of a colony. Yet, diploid males are of academic interest as they can elucidate effects of ploidy (normal males are haploid, whereas the female castes, the queens and workers, are diploid) on morphology and life history. Herein we investigated expression levels of ten caste-related genes in the stingless bee Melipona quadrifasciata, comparing newly emerged and 5-day-old diploid males with haploid males, queens and workers. In diploid males, transcript levels for dunce and paramyosin were increased during the first five days of adult life, while those for diacylglycerol kinase and the transcriptional co-repressor groucho diminished. Two general trends were apparent, (i) gene expression patterns in diploid males were overall more similar to haploid ones and workers than to queens, and (ii) in queens and workers, more genes were up-regulated after emergence until day five, whereas in diploid and especially so in haploid males more genes were down-regulated. This difference between the sexes may be related to longevity, which is much longer in females than in males.
Introduction: Contemporary dental care must be comprehensive, aimed not only at dental treatment but also at assessing the patient's health status. In this sense, hospital dentistry is gaining ...importance in the multidisciplinary health team, which is essential for the therapy and quality of life of hospitalized patients. Objective: A systematic review was carried out to highlight the main functions and importance of the dental surgeon in the hospital environment and intensive care units. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from January to February 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 89 articles were found, 45 articles were evaluated in full and 15 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 25 studies with a high risk of bias and 31 studies that did not meet GRADE and AMSTAR2. Most studies did not show homogeneity in their results, with X2=75.8%>50%. It was concluded that it is necessary to train and qualify the entire hospital team and the dental surgeon so that oral health is offered to patients, as well as knowing the impact caused by oral problems on the systemic health of patients and implementing specific protocols on the subject in all aspects. The dentist must promote the general health of the hospitalized individual, based on interdisciplinary planning developed together with other health professionals, as well as assess the patient's main needs and contribute to the quality of life of these individuals. According to the literature consulted, we can conclude how important the role of the dentist is as an integral part of the multidisciplinary healthcare team in ICU, as their presence could minimize such problems in hospitalized patients. Its insertion in hospitals would contribute to the maintenance of the patient's oral and general health, as well as the use of appropriate procedures during their hospitalization.
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