Pathogenesis and methods of diagnosis of chronic kidney disease in cats: retrospective analysis (1981–2007)

The aim: to conduct a retrospective analysis of literature sources on the pathogenesis and methods of diagnosis of chronic kidney disease in cats. Materials and methods. The research was conducted by the method of scientific literature open-source analysis: PubMed, Elsevier, electronic resources of the National Library named after V.I. Vernadsky (1981–2007). Results. Chronic kidney disease is a common reason for cat owners to go to veterinary clinics. The term “chronic kidney disease” has a broader meaning than the more limited and not very specific name – chronic renal failure; it is also used to indicate the preazotemic stage of the disease. Chronic kidney disease is characterized by a gradual deterioration of the clinical condition of animals due to progressive decline in renal function. An idea of the pathogenesis and methods of diagnosis of chronic kidney disease in the period from 1981 to 2007 is presented. Conclusions. According to the results of retrospective analysis of literature sources for the period from 1981 to 2007, the basis was identified aspects of the pathogenesis of chronic kidney disease in domestic cats, which have not lost relevance today. The main link during chronic kidney disease in cats is the development of hyperazotemia and, as a consequence, endogenous intoxication of the body, which develops gradually and leads to the death of the animal. The morphological basis of chronic kidney disease in cats is the development of diffuse nephrosclerosis, which is reflected in the results of clinical, biochemical and instrumental studies. According to biochemical analysis of blood, in cats recorded an increase in urea and creatinine, the results of clinical studies of urine showed a decrease in its relative density, as well as the development of proteinuria, the appearance of erythrocytes and cylinders. According to the results of hematological research, anemic syndrome develops due to decreased erythropoietin synthesis. With age in cats, ultrasound examination of the kidneys reveals a decrease in their volume due to uniform sclerosis of the parenchyma: it is determined by its thinning and increased echogenicity due to the accumulation of connective tissue components, which is a sign of nephrosclerosis. Although kidney biopsy is the most informative method of diagnosing chronic kidney disease, it has many contraindications, which does not allow its use in the routine diagnosis of nephropathy in domestic cats. its thinning and increase in echogenicity due to the accumulation of connective tissue components, which is a sign of nephrosclerosis, is determined. Although kidney biopsy is the most informative method of diagnosing chronic kidney disease, it has many contraindications, which does not allow its use in the routine diagnosis of nephropathy in domestic cats. Its thinning and increase in echogenicity due to the accumulation of connective tissue components, which is a sign of nephrosclerosis, is determined

Distributions of extinction times from fossil ages and tree topologies: the example of mid-Permian synapsid extinctions

Given a phylogenetic tree that includes only extinct, or a mix of extinct and extant taxa, where at least some fossil data are available, we present a method to compute the distribution of the extinction time of a given set of taxa under the Fossilized-Birth-Death model. Our approach differs from the previous ones in that it takes into account (i) the possibility that the taxa or the clade considered may diversify before going extinct and (ii) the whole phylogenetic tree to estimate extinction times, whilst previous methods do not consider the diversification process and deal with each branch independently. Because of this, our method can estimate extinction times of lineages represented by a single fossil, provided that they belong to a clade that includes other fossil occurrences. We assess and compare our new approach with a standard previous one using simulated data. Results show that our method provides more accurate confidence intervals. This new approach is applied to the study of the extinction time of three Permo-Carboniferous synapsid taxa (Ophiacodontidae, Edaphosauridae, and Sphenacodontidae) that are thought to have disappeared toward the end of the Cisuralian (early Permian), or possibly shortly thereafter. The timing of extinctions of these three taxa and of their component lineages supports the idea that the biological crisis in the late Kungurian/early Roadian consisted of a progressive decline in biodiversity throughout the Kungurian.

Cellular Resilience as a Potential Predictor of Lifespan

The progressive decline of resilience during the aging process across multiple functional systems suggests basic biological mechanisms of regulation. We exploited a primary cell model to identify markers of cellular resilience or the ability of cells in culture to respond and return to homeostasis following acute challenge including metabolic, oxidative, or proteostatic stress. Using primary fibroblasts from minimally-invasive skin biopsies of genetically heterogeneous mice, we are able to determine individual cellular resilience as well as the normal lifespan and healthspan of each donor. Our studies suggest donor age and sex affect cellular resilience and that this measure of resilience can predict functional outcomes in some interventional studies. While longevity studies continue, these studies point to a potential highly important marker of healthspan and longevity as well as a model to delineate the biology of resilience in animal and translational models.

Successful Exogenous Expression of ATP8, a Mitochondrial Encoded Protein, From the Nucleus In Vivo

Replicative errors, inefficient repair, and proximity to reactive oxygen species production sites make the mitochondrial DNA (mtDNA) susceptible to damage with time. mtDNA mutations accumulate with age and accompany a progressive decline in organelle function. We lack molecular biology tools to manipulate mtDNA, thus we explore the possibility in vivo of utilizing allotopic expression, or the re-engineering mitochondrial genes and expressing them from the nucleus, as an approach to rescue defects arising from mtDNA mutations. This study uses a mouse model with a mutation in the mitochondrial ATP8 gene that encodes a protein subunit of the ATP synthase. We generated a transgenic mouse with an epitope-tagged recoded and mitochondrial-targeted ATP8 gene expressed from the nucleus. Our results show that the allotopically expressed ATP8 protein in the transgenic mice is robustly expressed across all tested tissues, successfully transported into the mitochondria, and incorporated into ATP synthase. We are currently evaluating if allotopic expression of ATP8 will functionally rescue the behavioral and bioenergetic defects in ATP8 mutant mice. Translating allotopic expression technology into a mammal and demonstrating systemic functional rescue will lend credence to utilizing allotopic expression as a gene therapy in humans to repair physiological consequences of mtDNA defects that may accumulate with age.

Segmenting the Bottom of the Pyramid Consumers: Theoretical Approach

The Bottom of the Pyramid (BOP) market deserves further attention from researchers. The purpose of the paper is to profile the psychographic and behavioral heterogeneity within the BOP market in India employing a theoretical approach. We use constructs of the Theory of planned behavior (TPB) to identify distinct BOP segments. It segments the BOP market in the context of durable goods, non-durable goods, and services. The findings demonstrate the presence of three consumer segments, each of the durable and non-durable goods. In the context of services, the findings show the existence of four segments of BOP consumers. This study offers insights into application of behavioral theories for segmentation, which could help with behavioral change of BOP consumers to use high-quality products and services. Further, it is significant because the BOP market has witnessed a progressive decline in size as a large segment of the BOP market is being transformed into the middle class. Comprehension of the cognitive and behavioral tendencies of each consumer segment would strategically help in retaining the brand loyal BOP customers when they upgrade to the middle class.

Aging-Related Changes in Erythropoietic Activity and Iron Metabolism in a Mouse Model of Congenital Erythrocytosis with Human Gain-of-Function Erythropoietin Receptor

We previously created and characterized a mouse model of congenital erythrocytosis with low erythropoietin (EPO) levels from a gain-of-function mutation of the human erythropoietin receptor gene (mtHEPOR) (Divoky et al. PNAS. 2001; 98:986; Divoky et al. JMM Berl. 2016; 94:597). These mice develop fetal erythrocytosis, followed by transient amelioration of erythrocytosis in perinatal life, and reappearance at 3-6 weeks of age. Similarly, erythrocytosis is observed in heterozygous mtHEPOR patients postnatally but not at birth. We previously reported dynamic changes of the erythron with iron homeostasis during ontogenesis in these mice (Kralova et al. Blood 2017; 130: 170). We observed that while perinatal mtHEPOR mice exhibit relative iron deficiency, aged mice had iron overload. Here, we evaluated developmentally-determined factors associated with hyperactivation of EPOR signaling which could cause a transition from iron deficiency (neonates) to hyperferremia and increased iron deposition (aged mice). To assess the consequences of different levels of EPOR-JAK2-STAT5 signaling, we studied hetero- and homozygous mtHEPOR mice that differ in their severity of erythrocytosis. We found that prenatally and perinatally, mtHEPOR hetero- and homozygous mice have increased erythroferrone (Erfe) transcripts and reduced hepcidin, consistent with the known inverse correlation between Erfe and hepcidin and in accordance with increased numbers of immature erythroid progenitors in the fetal hepatic circulation. At birth, previously normal Epo expression decreased and remained low in adulthood. Iron deficiency, observed in mtHEPOR hetero- and homozygotes at postnatal day 7, was likely related to increased iron consumption by augmented erythropoiesis at this stage. Postnatally, hepcidin levels increased in mutant mice, accompanied by low Erfe induction and iron accumulation in the liver and spleen as reflected by the upregulation of hepatic Bmp6 expression in mature adult (aged ~6.5 months) and old (~16 months) mtHEPOR homozygotes. We hypothesized that this could be a consequence of diminished iron consumption due to a progressive decline of erythropoiesis in mtHEPOR mice, possibly mediated by premature aging of erythroid progenitors with cell-autonomously increased proliferative history and/or increased inflammation. Indeed, young mutant erythrocytes had decreased erythrocyte survival and expression of a senescent marker CD47, an inhibitor of erythrocytes' phagocytosis. Additionally, a progressive decline in the percentage of Ter119-positive bone marrow cells and immature erythroblasts was observed in mtHEPOR hetero- and homozygotes with aging. Clonogenic assays of old mice revealed suppression of early (BFU-E) and late (CFU-E) erythroid progenitors and myeloid bias of hematopoiesis, paralleled by the up-regulation of PU.1 expression, elevation of platelet counts, and an increase in megakaryocytes chiefly in the bone marrow of mtHEPOR homozygotes. Serum levels of inflammatory cytokines did not indicate systemic inflammation; however, induced transcripts of IL-6, Inf-γ, Tgf-β, and Tnf-α, mainly in mtHEPOR homozygotes showed local bone marrow inflammatory stress. These data indicate progressive attenuation of erythroid drive in mtHEPOR homozygotes, and less so in mtHEPOR heterozygotes, paralleled by a decline in hematocrit levels with aging. In response to attenuated erythropoietic activity, iron consumption was reduced in mtHEPOR mice, leading to iron accumulation in the liver and spleen accompanied by markedly increased hepcidin synthesis. Our data suggest that even in the absence of systemic inflammation, albeit with possible paracrine inflammatory signals, known to affect bone marrow remodeling and hematopoietic aging, life-lasting prolonged activation of EPOR-JAK2-STAT5 signaling promoted exhaustion of erythroid progenitors and resulted in an age-related decline of accelerated erythropoiesis in this mouse model of congenital erythrocytosis with human gain-of-function EPOR. Grant support: Czech grant agencies projects GA17-05988S, NV19-07-00412 and LTAUSA17142, Palacky University project IGA_LF_2021_004. Disclosures No relevant conflicts of interest to declare.

Prediction of biological age by morphological staging of sarcopenia in Caenorhabditis elegans

Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with aging, it may represent a valuable healthspan marker. Given the commonalities with human muscle structure and facile visualization possibilities, C. elegans represents an attractive model for studying the relationship between sarcopenia and healthspan. However, classical visual assessment of muscle architecture is subjective and has low throughput. To resolve this, we have developed an image analysis pipeline for the quantification of muscle integrity in confocal microscopy images from a cohort of aging myosin::GFP reporter worms. We extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed establishing a linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted knockdown of the daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and may foster the development of image-based screens to identify modulators that mitigate age-related muscle frailty and thus improve healthspan in C. elegans.

Self-perception of nurses’ competence in family assessment and intervention

Objective. To describe nurses’ self-perception of competence in family assessment and intervention Methods. A sample of 551 Portuguese primary care nurses was selected. A Likert-type questionnaire with 11 items corresponding to the areas of care proposed by the Dynamic Model of Family Assessment and Intervention (MDAIF) was administered. Each item consists of 7 optional responses; a score equal to or greater than 4 denotes competence. Results. The nurses perceived themselves as competent in areas of care belonging to the development dimension of the MDAIF (parental role, adaptation to pregnancy, and family planning), as well as in the caregiver role (which belongs to the functional dimension). There was a progressive decline in self-perception of competence over the stages of the nursing process. Conclusion. In this study, crucial aspects related to nurses’ self-perception of their competence in family assessment and intervention were observed, and need to be addressed in the training of nurses in all areas of care included in the Model. This should facilitate awareness of the competences needed to provide the best care for families.

Olfactory Dysfunction in Huntington’s Disease

Olfactory dysfunction is a common symptom in patients with neurodegenerative disorders, including Huntington’s disease (HD). Understanding its pathophysiology is important in establishing a preventive and therapeutic plan. In this literature review, we cover the physiology of olfaction, its role in neurodegeneration, and its characteristics in patients with HD. In the general population, olfactory dysfunction is present in 3.8–5.8%and the prevalence increases significantly in those older than 80 years. For HD, data regarding prevalence rates are lacking and the scales used have been inconsistent or have been restructured due to concerns about cross-cultural understanding. Pathogenic huntingtin deposits have been found in the olfactory bulb of individuals with HD, although no studies have correlated this with the grade of olfactory impairment. Olfactory dysfunction is present in both premanifest and manifest patients with HD, showing a progressive decline over time with more severe deficits at advanced stages. No specific treatment for olfactory impairment in HD has been proposed; identifying and avoiding potential medications that cause olfactory dysfunction, as well as general safety recommendations remain the basis of the therapeutic strategy.