Renal amyloid-A amyloidosis in cats: Characterization of proteinuria and biomarker discovery, and associations with kidney histology.

BACKGROUND: Amyloid A (AA) amyloidosis is a protein misfolding disease arising from serum amyloid A (SAA). Systemic AA amyloidosis recently was shown to have a high prevalence in shelter cats in Italy and was associated with azotemia and proteinuria. OBJECTIVES: Investigate urine protein profiles and diagnostic biomarkers in cats with renal AA amyloidosis. ANIMALS: Twenty-nine shelter cats. METHODS: Case-control study. Cats with renal proteinuria that died or were euthanized between 2018 and 2021 with available necropsy kidney, liver and spleen samples, and with surplus urine collected within 30 days before death, were included. Histology was used to characterize renal damage and amyloid amount and distribution; immunohistochemistry was used to confirm AA amyloidosis. Urine protein-to-creatinine (UPC) and urine amyloid A-to-creatinine (UAAC) ratios were calculated, and sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) and liquid chromatography-mass spectrometry (LC-MS) of proteins were performed. RESULTS: Twenty-nine cats were included. Nineteen had AA amyloidosis with renal involvement. Cats with AA amyloidosis had a higher UPC (median, 3.9; range, 0.6-12.7 vs 1.5; 0.6-3.1; P = .03) and UAAC ratios (median, 7.18 × 10-3 ; range, 23 × 10-3 -21.29 × 10-3 vs 1.26 × 10-3 ; 0.21 × 10-3 -6.33 × 10-3 ; P = .04) than unaffected cats. The SDS-AGE identified mixed-type proteinuria in 89.4% of cats with AA amyloidosis and in 55.6% without AA amyloidosis (P = .57). The LC-MS identified 63 potential biomarkers associated with AA amyloidosis (P < .05). Among these, urine apolipoprotein C-III was higher in cats with AA amyloidosis (median, 1.38 × 107 ; range, 1.85 × 105 -5.29 × 107 vs 1.76 × 106 ; 0.0 × 100 -1.38 × 107 ; P = .01). In the kidney, AA-amyloidosis was associated with glomerulosclerosis (P = .02) and interstitial fibrosis (P = .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Renal AA amyloidosis is associated with kidney lesions, increased proteinuria and increased urine excretion of SAA in shelter cats. Additional studies are needed to characterize the role of lipid transport proteins in the urine of affected cats.

Successful treatment of methotrexate intolerance in juvenile idiopathic arthritis using eye movement desensitization and reprocessing - treatment protocol and preliminary results.

BACKGROUND: Methotrexate (MTX), commonly used in juvenile idiopathic arthritis (JIA), frequently has to be discontinued due to intolerance with anticipatory and associative gastrointestinal adverse effects. Eye Movement Desensitization and Reprocessing (EMDR) is a psychological method where dysfunctional experiences and memories are reprocessed by recall combined with bilateral eye movements. The objective of this study was to assess efficacy of EMDR for treatment of MTX intolerance in JIA patients. METHODS: We performed an open prospective study on consecutive JIA patients with MTX intolerance. Intolerance was determined using the Methotrexate Intolerance Severity Score (MISS) questionnaire prior to treatment, directly after treatment and after four months. Health-related quality of life was determined using the PedsQL prior to and four months after treatment. Patients were treated according to an institutional EMDR protocol with 8 sessions over two weeks. Changes in MISS and PedsQL were analyzed using non-parametric statistics. RESULTS: Eighteen patients with MTX intolerance (median MISS at inclusion 16.5, IQR = 11.75-20.25) were included. Directly after treatment, MTX intolerance symptoms were significantly improved (median MISS 1 (IQR = 0-2). After four months, median MISS score was at 6.5 (IQR = 2.75-12.25, p = 0.001), with 9/18 patients showing MISS scores ≥6. Median PedsQL after 4 months improved significantly from 77.6% to 85.3% (p = 0.008). CONCLUSION: MTX intolerance in children with JIA was effectively treated using an EMDR protocol, with lasting effect over a period of 4 months. EMDR treatment can potentially increase quality of life of affected patients and enable continued MTX treatment.

O que move o nosso trabalho? A experiência do consultor da saúde da criança e aleitamento materno em apoiar as ações nos territórios / What moves our work? The experience of child health consultant and breastfeeding support actions in the region

Este artigo relata a experiência da consultoria na área de saúde da criança e aleitamento materno (Coordenação-Geral de Saúde da Criança e Aleitamento Materno) do Ministério da Saúde nos estados do Acre, Espírito Santo, Minas Gerais, Rio de Janeiro e Rondônia, na contribuição para a implementação das ações de saúde da criança nesses territórios. O texto traz os desafios enfrentados na implantação da consultoria nos estados, como ocorreu a formação desse consultor e suas ações no território, bem como sua atuação nas redes de atenção à saúde. O resultado desse trabalho deu-se na transformação desse consultor, bem como no aumento das ofertas à saúde da criança no território e avanços a partir da elaboração e aprovação da Política Nacional de Saúde da Criança, construída de forma coletiva

This article reports the experience of consulting in child health and breastfeeding (CGSCAM) of the Ministry of Health in the states of Acre, Espírito Santo, Minas Gerais, Rio de Janeiro and Rondônia, in contributing to the implementation of child health actions in these territories. The text presents the challenges faced in the implementation process of consultancy in the states, how the training of those consultants was carried out and their actions in the territories, as well as their performance in health care networks. The result of this work took place in the transformation of the consultants, as well as in the increasing of the offers to child health in the territory and advances from the preparation and approval of the National Child Health Policy, built collectively

Cartografia, grupalidade e cuidado: operadores conceituais do processo de formação da Estratégia Brasileirinhas e Brasileirinhos Saudáveis / Cartography, groupality and care: conceptual operators of the process of formation of the Estratégia Brasileirinhas e Brasileirinhos Saudáveis

A partir da experiência da Estratégia Brasileirinhas e Brasileirinhos Saudáveis, pretende-se descrever e sistematizar sua proposta de formação no campo da saúde, encarnada aqui no processo de formação dos consultores estaduais de saúde da criança. Para tal,desenvolveu-se uma metodologia baseada em três operadores conceituais, dinamicamente interligados: a cartografia como processo de entrada, conhecimento e reconhecimento do território, a grupalidade como dispositivo de ação e o cuidado em sua dimensão ética.Sublinha-se o modo de fazer específico que prioriza a inclusão da dimensão sensível no processo de formação...

This article aims at describing and synthesizing, within the experience of the Estratégia Brasileirinhas e Brasileirinhos Saudáveis, the proposal of training in the health field, incarnated here in the process of training state consultants for child health. For this purpose, a methodology was developed based in three conceptual operators dynamically interlinked: cartography as aprocess of entry, knowledge and recognition of the territory; groupality as an action device; and care in its ethical dimension. We highlight the specific way of doing that prioritizes the inclusion of the sensible dimension in the training process...

Heavy metal removal in anaerobic semi-continuous stirred tank reactors by a consortium of sulfate-reducing bacteria.

Removal of heavy metals by an enriched consortium of sulfate-reducing bacteria (SRB) was evaluated through the abundance of SRB, sulfate reduction, sulfide production and heavy metal precipitation. Five parallel anaerobic semi-continuous stirred tank reactors (CSTR, V = 2 L) (referred as R1-R5) were fed with synthetic wastewater containing mixtures of Cu(2+), Zn(2+), Ni(2+), and Cr(6+) in the concentrations of 30, 60, 90, 120, and 150 mg L(-1) of each metal and operated with a hydraulic retention time of 20 days for 12 weeks. The loading rates of each metal in R1-R5 were 1.5, 3, 4.5, 6, and 7.5 mg L(-1) d(-1), respectively. The results showed that there was no inhibition of SRB growth and that heavy metal removal efficiencies of 94-100% for Cu(2+), Zn(2+), Ni(2+), and Cr(6+) were achieved in R1-R3 throughout the experiment and in R4 during the first 8 weeks. The toxic effect of heavy metals on the SRB consortium was revealed in R5, in which no SRB could survive and almost no heavy metal precipitation was detected after four weeks of operation.

Purinergic receptor-stimulated IP3-mediated Ca2+ release enhances neuroprotection by increasing astrocyte mitochondrial metabolism during aging.

Astrocytes play an essential role in the maintenance and protection of the brain, which we reported was diminished with age. Here, we demonstrate that activation of a purinergic receptor (P2Y-R) signaling pathway, in astrocytes, significantly increases the resistance of astrocytes and neurons to oxidative stress. Interestingly, P2Y-R activation in old astrocytes increased their resistance to oxidative stress to levels that were comparable with stimulated young astrocytes. P2Y-R enhanced neuroprotection was blocked by oligomycin and by Xestospongin C, inhibitors of the ATP synthase and of inositol (1,4,5) triphosphate (IP3) binding to the IP3 receptor, respectively. Treatment of astrocytes with a membrane permeant analog of IP3 also protected astrocytes against oxidative stress. These data indicate that P2Y-R enhanced astrocyte neuroprotection is mediated by a Ca2+-dependent increase in mitochondrial metabolism. These data also reveal a signaling pathway that can rapidly respond to central energy needs throughout the aging process.

Ca2+ signaling, mitochondria and sensitivity to oxidative stress in aging astrocytes.

Age-related changes in astrocytes that could potentially affect neuroprotection have been largely unexplored. To test whether astrocyte function was diminished during the aging process, we examined cell growth, Ca2+ signaling, mitochondrial membrane potential (DeltaPsi) and neuroprotection of NGF-differentiated PC12 cells. We observed that cell growth was significantly slower for astrocytes cultured from old (26-29 months) mice as compared to young (4-6 months) mice. DeltaPsis in old astrocytes were also more depolarized (lower) than in young astrocytes and old astrocytes showed greater sensitivity to the oxidant tert-butyl hydrogen peroxide (t-BuOOH). ATP-induced Ca2+ responses in old astrocytes were consistently larger in amplitude and more frequently oscillatory than in young astrocytes, which may be attributable to lower mitochondrial Ca2+ sequestration. Finally, NGF-differentiated PC12 cells that were co-cultured with old astrocytes were significantly more sensitive to t-BuOOH treatment than co-cultures of NGF-differentiated PC12 cells with young astrocytes. Together, these data demonstrate that astrocyte physiology is significantly altered during the aging process and that the astrocyte's ability to protect neurons is compromised.

Phylogenetic relationships and generic delimitation in subtribe Arctotidinae (Asteraceae: Arctotideae) inferred by DNA sequence data from ITS and five chloroplast regions.

Asteraceae are the largest family in southern Africa. Elucidating its origins and radiation in the region requires well-supported species-level phylogenies of the lineages. This paper presents a phylogenetic framework for subtribe Arctotidinae, which have a southern and eastern African-Australian distribution centered in the winter-rainfall region of South Africa. DNA sequence data from five chloroplast fragments (ndhF, psbA-trnH, rps16, trnS-trnfM, and trnT-trnF) and the nuclear ITS region were analyzed separately and in combination using parsimony and Bayesian methods. The data sets comprised exemplars from 18 ingroup species, representing the five currently accepted genera, and four outgroup species from Gorteriinae. All analyses indicated Arctotis and Haplocarpha are polyphyletic as presently circumscribed. The Australian-endemic Cymbonotus lawsonianus was placed within a strongly supported clade also containing A. arctotoides from South Africa and H. schimperi from eastern Africa. Retention of Dymondia and resurrection of Landtia at generic level are strongly supported. The phylogenetic hypotheses indicate the subtribe might have originated in temperate southern or eastern Africa, or it was ancestrally widespread in southern Africa and has diversified vicariously. The derived placement of C. lawsonianus indicates long-distance dispersal from southern Africa to Australia occurred.

How we teach on a 'Return to General Practice' course.

This article describes a course, for doctors returning to general practice, modelled on Harden's 10 questions when planning a curriculum. The course has been running in the West Midlands region of the United Kingdom for the past four years.

Final de analise a luz de uma experiencia de Albert Camus

Este artigo versa sobre o tema do final da analise, abordando o percurso feito por Freud, ate as proposicoes de Lacan sobre o tema. Finalizamos com uma breve analise de alguns ditos de Albert Camus, atraves dos quais nos interrogamos se nao ha ai um testemunho da experiencia de dessubjetivacao e de destituicao do Outro consistente imaginariamente, pertinentes a um final de analise