Resumo em Inglês:

Living with chronic kidney disease (CKD) is associated with hardships for patients and their care-partners. Empowering patients and their care-partners, including family members or friends involved in their care, may help minimize burden and consequences of CKD-related symptoms to enable life participation. There is a need to broaden the focus on living well with kidney disease and re-engagement in life, including emphasis on patients being in control. The World Kidney Day (WKD) Joint Steering Committee has declared 2021 the year of “Living Well with Kidney Disease” in an effort to increase education and awareness on the important goal of patient empowerment and life participation. This calls for the development and implementation of validated patient-reported outcome measures to assess and address areas of life participation in routine care. It could be supported by regulatory agencies as a metric for quality care or to support labelling claims for medicines and devices. Funding agencies could establish targeted calls for research that address the priorities of patients. Patients with kidney disease and their care-partners should feel supported to live well through concerted efforts by kidney care communities including during pandemics. In the overall wellness program for kidney disease patients, the need for prevention should be reiterated. Early detection with prolonged course of wellness despite kidney disease, after effective secondary and tertiary prevention programs, should be promoted. WKD 2021 continues to call for increased awareness of the importance of preventive measures throughout populations, professionals, and policy makers, applicable to both developed and developing countries.

Resumo em Inglês:

Episodic angioedema with eosinophilia (EAE) is a rare condition characterized by recurrent attacks of angioedema and urticaria accompanied by a marked elevation of peripheral eosinophil count. We report the case of a young female patient diagnosed with EAE associated with urticarial vasculitis. A 40-year-old female patient was admitted to our institution due to recurrent episodes of cheek and eyelid angioedema in the previous year. Episodes of facial angioedema lasted for two months with spontaneous remission afterwards. In addition, she presented pruritic and painful skin eruptions of erythematous circles, which persisted for longer than 24 h, that were palpable, somewhat purplish, and more pronounced on the face, arms, and trunk. Laboratory investigation showed a sustained elevation of white cell counts with marked eosinophilia. Serum IgM, IgE, and IgA were normal; IgG was slightly elevated. C1-esterase inhibitor and tryptase test were normal. Reverse transcriptase-polymerase chain reaction was performed for detection of FIP1L1-PDGFRA and BCR-ABL rearrangements. None of these alterations were found. Skin biopsies were suggestive of urticarial vasculitis. The patient was submitted to esophagogastroduodenoscopy, which showed mild chronic gastritis, with no eosinophilic infiltration. Cardiac dimensions and function were normal. Abdominal ultrasound and total body CT-scan failed to show lymphadenopathy, organomegaly, and tumors. We report the first case of association between episodic angioedema with eosinophilia and urticarial vasculitis. It is possible that both conditions share a physiopathological mechanism, suggesting that it is not just a chance association.

Resumo em Inglês:

Endothelial dysfunction is a well-known component of the pathophysiology of heart failure (HF), with proven prognostic value. Dietary supplementation with whey protein (WP) has been widely used to increase skeletal muscle mass, but it also has vascular effects, which are less understood. This study aimed to evaluate the effects of WP supplementation on the systemic microvascular function of HF patients. This was a blinded, randomized, placebo-controlled clinical trial that evaluated the effects of 12-week WP dietary supplementation on systemic microvascular function, in patients with HF New York Heart Association (NYHA) classes I/II. Cutaneous microvascular flow and reactivity were assessed using laser speckle contrast imaging, coupled with pharmacological local vasodilator stimuli. Fifteen patients (aged 64.5±6.2 years, 11 males) received WP supplementation and ten patients (aged 68.2±8.8 years, 8 males) received placebo (maltodextrin). The increase in endothelial-dependent microvascular vasodilation, induced by skin iontophoresis of acetylcholine, was improved after WP (P=0.03) but not placebo (P=0.37) supplementation. Moreover, endothelial-independent microvascular vasodilation induced by skin iontophoresis of sodium nitroprusside, was also enhanced after WP (P=0.04) but not placebo (P=0.42) supplementation. The results suggested that dietary supplementation with WP improved systemic microvascular function in patients with HF.

Resumo em Inglês:

About 3000 tons of beans are not used in human food due to hardening. Several studies on bean-derived bioactive peptides have shown potential to treat some diseases, including those relying on oxidative dysfunctions. We assessed the effects of peptides extracted from hardened bean Phaseolus vulgaris (PV) on reactive oxygen species (ROS) and nitric oxide (NO) production, cytotoxic and cytoprotective effects in endothelial cells, and oxidonitrergic-dependent vasodilating effects. Extract was composed by peptide fraction <3 kDa (PV3) from hardened common bean residue. PV3 sequences were obtained and analyzed with bioinformatics. Human umbilical vein endothelial cells were treated with 10, 20, 30, and 250 µg/mL PV3. Oxidative stress was provoked by 3% H2O2. Cytotoxicity and cytoprotective effects were evaluated by MTT assay, whereas, ROS and NO were quantified using DHE and DAF-FM fluorescent probes by confocal microscopy. NO- and endothelium-dependent vasodilating effects of PV3 were assessed in isolated aortic rings. We found 35 peptides with an average mass of 1.14 kDa. There were no cell deaths with 10 and 20 μg/mL PV3. PV3 at 30 μg/mL increased cell viability, while cytotoxicity was observed only with 250 μg/mL PV3. PV3 at 10 μg/mL was able to protect cells from oxidative stress. PV3 also increased NO release without causing cell death. It also reduced relative ROS production induced by H2O2. PV3 vasodilating effects relied on endothelium-dependent NO release. PV3 obtained from low-commercial-value bean displays little cytotoxicity and exerts antioxidant effects, whereas it increases endothelial NO release.

Resumo em Inglês:

Epidermal growth factor receptor (EGFR) signaling and components of the fibrinolytic system, including urokinase-type plasminogen activator (uPA) and thrombomodulin (TM), have been implicated in tumor progression. In the present study, we employed cBioPortal platform (http://www.cbioportal.org/), cancer cell lines, and an in vivo model of immunocompromised mice to evaluate a possible cooperation between EGFR signaling, uPA, and TM expression/function in the context of cervical cancer. cBioPortal analysis revealed that EGFR, uPA, and TM are positively correlated in tumor samples of cervical cancer patients, showing a negative prognostic impact. Aggressive human cervical cancer cells (CASKI) presented higher gene expression levels of EGFR, uPA, and TM compared to its less aggressive counterpart (C-33A cells). EGFR induces uPA expression in CASKI cells through both PI3K-Akt and MEK1/2-ERK1/2 downstream effectors, whereas TM expression induced by EGFR was dependent on PI3K/Akt signaling alone. uPA induced cell-morphology modifications and cell migration in an EGFR-dependent and -independent manner, respectively. Finally, treatment with cetuximab reduced in vivo CASKI xenografted-tumor growth in nude mice, and decreased intratumoral uPA expression, while TM expression was unaltered. In conclusion, we showed that EGFR signaling regulated expression of the fibrinolytic system component uPA in both in vitro and in vivo settings, while uPA also participated in cell-morphology modifications and migration in a human cervical cancer model.

Resumo em Inglês:

Osteosarcoma is a highly malignant tumor that occurs in the bone. Previous studies have shown that multiple microRNAs (miRNAs) regulate the development of osteosarcoma. This study aimed to explore the role of miR-629-5p and its target gene, caveolin 1 (CAV1), in osteosarcoma development. To analyze the expression of miR-629-5p and CAV1 mRNA in osteosarcoma tissues and cell lines, qRT-PCR analysis was performed. Dual-luciferase reporter experiments were subsequently performed to validate the relationship between CAV1 and miR-629-5p. CCK8 assay was used to measure osteosarcoma cell proliferation, and wound-healing assay was performed to study their migratory phenotype. Our findings revealed that miR-629-5p was overexpressed in osteosarcoma tissues and cells, and thereby enhanced cell proliferation and migration. Further, we validated that miR-629-5p targets CAV1 mRNA directly. CAV1 expression, which was negatively correlated with miR-629-5p expression, was found to be downregulated in osteosarcoma tissue samples. Moreover, our data showed that an increase in CAV1 level led to a decline in osteosarcoma cell proliferation and migration, which could be rescued by miR-629-5p upregulation. Overall, our study confirmed that miR-629-5p promoted osteosarcoma proliferation and migration by directly inhibiting CAV1.

Resumo em Inglês:

Continuous industrial productivity and modern societies have resulted in excess artificial light. The altered circadian rhythm causes many diseases. During intrauterine life, the mother's maternal melatonin rhythm has a major role in influencing organ development. The aim of this study was to investigate the effect of maternal exposure to constant light on the structure and ultrastructure of neonatal skin. Twenty pregnant New Zealand rabbits were divided into two groups (n=10 each): control group (12-h light/dark) and constant light group (24-h light). Plasma maternal melatonin and corticosterone during pregnancy were determined. At the end of the experiment, the dorsal skin of the neonates of both groups was collected and prepared for histological, morphometric, and transmission electron microscopic study. Histological and morphometric results of skin of neonates from the constant light group revealed statistically significantly reduced epidermal thickness, decreased number of hair follicle, increased surface area of collagen, and decreased proliferating cell nuclear antigen (PCNA) positive cells. Ultrastructural examination showed wide intercellular spaces and disrupted desmosomal junctions in the epidermis. Earlier stages of hair follicles were also observed with indented shrunken nuclei, vacuolization, and swollen mitochondria. Dermal fibroblasts with dilated cisternae of rough endoplasmic reticulum containing electron-dense material were detected. Maternal melatonin was significantly reduced in the constant light group while maternal corticosterone showed no significant difference between groups. Therefore, normal maternal circadian rhythm is a key factor for the integrity of neonatal skin structure.

Resumo em Inglês:

The objective of this study was to examine the safety of multiple repeated percutaneous punctures of cisterna magna for collecting cerebrospinal fluid (CSF) and preliminarily determine the optimal time interval and volume at each collection. Sixty Wistar rats were randomly assigned to six groups: 10 d-0 μL, 10 d-100 μL (100 μL CSF collected at an interval of 10 days), 10 d-150 μL, 15 d-0 μL, 15 d-100 μL, and 15 d-150 μL. CSF was collected by percutaneous puncture of the cisterna magna at four time-points. Simultaneously, locomotor activity, cisterna magna pressure, and acetylcholine levels in the CSF were monitored. Compared with the 10 d-0 μL group, the escape latency by Morris water maze was significantly prolonged in the 10 d-100 μL and 10 d-150 μL groups (P<0.05). Compared with the 15 d-0 μL group, the indices of 15 d-100 μL and 15 d-150 μL groups had no significant differences. When compared with that at the first training, the exception of the 10 d-150 μL and 15 d-150 μL groups, significant differences in escape latency were found at the 6th attempt (P<0.05). Compared with baseline readings for each group, the cisterna magna pressure in the 10 d-150 μL group began to decrease significantly from the third measurement (P<0.05). The optimal time interval during four CSF collections (100 μL per collection) via cisterna magna percutaneous puncture was determined to be 15 days. The procedure did not significantly affect learning processes, performance, or other related indices.

Resumo em Inglês:

Physical performance is a multifactorial and complex trait influenced by environmental and hereditary factors. Environmental factors alone have been insufficient to characterize all outstanding phenotypes. Recent advances in genomic technologies have enabled the investigation of whole nuclear and mitochondrial genome sequences, increasing our ability to understand interindividual variability in physical performance. Our objective was to evaluate the association of mitochondrial polymorphic loci with physical performance in Brazilian elite military personnel. Eighty-eight male military personnel who participated in the Command Actions Course of the Army were selected. Total DNA was obtained from blood samples and a complete mitochondrial genome (mtDNA) was sequenced using Illumina MiSeq platform. Twenty-nine subjects completed the training program (FINISHED, ‘F'), and fifty-nine failed to complete (NOT_FINISHED, ‘NF'). The mtDNA from NF was slightly more similar to genomes from African countries frequently related to endurance level. Twenty-two distinct mtDNA haplogroups were identified corroborating the intense genetic admixture of the Brazilian population, but their distribution was similar between the two groups (FST=0.0009). Of 745 polymorphisms detected in the mtDNA, the position G11914A within the NADPH gene component of the electron transport chain, was statistically different between F and NF groups (P=0.011; OR: 4.286; 95%CI: 1.198-16.719), with a higher frequency of the G allele in group F individuals). The high performance of military personnel may be mediated by performance-related genomic traits. Thus, mitochondrial genetic markers such as the ND4 gene may play an important role on physical performance variability.

Resumo em Inglês:

The skin injury healing process involves the main phases of homoeostasis, inflammation, proliferation, and remodeling. The present study aimed to analyze the effects of low-level laser therapy (LLLT) on hematological dynamics, oxidative stress markers, and its relation with tissue healing following skin injury. Wistar rats were divided into control, sham, skin injury, and skin injury LLLT. The biochemical and morphological analyses were performed in the inflammatory (1 and 3 days) and regenerative phases (7, 14, and 21 days) following injury. The skin injury was performed in the dorsal region, between the intrascapular lines, using a surgical punch. LLLT (Al-Ga-In-P, λ=660 nm, energy density of 20 J/cm2, 30 mW power, and a time of 40 s) was applied at the area immediately after injury and on every following day according to the experimental subgroups. LLLT maintained hematocrit and hemoglobin levels until the 3rd day of treatment. Surprisingly, LLLT increased total leukocytes levels compared to control until the 3rd day. The effects of LLLT on mitochondrial activity were demonstrated by the significant increase in MTT levels in both inflammatory and regenerative phases (from the 1st to the 7th day), but only when associated with skin injury. The results indicated that LLLT modulated the inflammatory response intensity and accelerated skin tissue healing by a mechanism that involved oxidative damage reduction mostly at early stages of skin healing (inflammatory phase).

Resumo em Inglês:

Hypercalcemia is common in patients after kidney transplantation (KTx) and is associated with persistent hyperparathyroidism in the majority of cases. This retrospective, single-center study evaluated the prevalence of hypercalcemia after KTx. KTx recipients were evaluated for 7 years after receiving kidneys from living or deceased donors. A total of 301 patients were evaluated; 67 patients had hypercalcemia at some point during the follow-up period. The median follow-up time for all 67 patients was 62 months (44; 80). Overall, 45 cases of hypercalcemia were classified as related to persistent post-transplant hyperparathyroidism (group A), 16 were classified as “transient post-transplant hypercalcemia” (group B), and 3 had causes secondary to other diseases (1 related to tuberculosis, 1 related to histoplasmosis, and 1 related to lymphoma). The other 3 patients had hypercalcemia of unknown etiology, which is still under investigation. In group A, the onset of hypercalcemia after KTx was not significantly different from that of the other groups, but the median duration of hypercalcemia in group A was 25 months (12.5; 53), longer than in group B, where the median duration of hypercalcemia was only 12 months (10; 15) (P<0.002). The median parathyroid hormone blood levels around 12 months after KTx were 210 pg/mL (141; 352) in group A and 72.5 pg/mL (54; 95) in group B (P<0.0001). Hypercalcemia post-KTx is not infrequent and its prevalence in this center was 22.2%. Persistent hyperparathyroidism was the most frequent cause, but other important etiologies must not be forgotten, especially granulomatous diseases and malignancies.

Resumo em Inglês:

The aim of this study was to investigate the effects of multicomponent training on baroreflex sensitivity (BRS) and heart rate (HR) complexity of prefrail older adults. Twenty-one prefrail community-dwelling older adults were randomized and divided into multicomponent training intervention group (MulTI) and control group (CG). MulTI performed multicomponent exercise training over 16 weeks and CG was oriented to follow their own daily activities. The RR interval (RRi) and blood pressure (BP) series were recorded for 15 min in supine and 15 min in orthostatic positions, and calculation of BRS (phase, coherence, and gain) and HR complexity (sample entropy) were performed. A linear mixed model was applied for group, assessments, and their interaction effects in supine position. The same test was used to assess the active postural maneuver and it was applied separately to each group considering assessments (baseline and post-intervention) and positions (supine and orthostatic). The significance level established was 5%. Cardiovascular control was impaired in prefrail older adults in supine position. Significant interactions were not observed between groups or assessments in terms of cardiovascular parameters. A 16-week multicomponent exercise training did not improve HR complexity or BRS in supine rest or in active postural maneuver in prefrail older adults.