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Competing Interests: The authors declare no conflicts of interest.

Background: Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies., Methods: We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes., Results: Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032)., Conclusion: This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: The objective of this study was to conduct an integrative review, addressing the key findings, biological functions, and clinical significance of these biomolecules in solid tumors., Methods: This document analyzes the main data on the involvement of snoRNAs in solid tumors. For this, Pubmed and Science direct were used, with keywords. Additionally, a search for the host gene was conducted using the snoDB tool, and its chromosomal location was identified using the Hugo Gene Nomenclature Committee (HGNC)., Results: According to research conducted in the literature, the majority of snoRNAs were found to be overexpressed and described as regulators of processes such as invasion, cellular proliferation, apoptosis, and migration. They are associated with clinical prognostic factors such as metastasis and worse survival., Conclusion: Therefore, it is essential to expand the investigation of snoRNAs in oncology across different types of tumors. The utilization of these biomolecules may pave the way for innovative clinical applications, such as their use in the early detection of neoplasms in non-invasive samples and as therapeutic targets. Broadening research on snoRNAs across various tumor types is crucial.

Competing Interests: The authors declare no conflicts of interest.

Cervical Cancer (CC) is one of the most prevalent neoplasms among women, considered the leading cause of gynecological death worldwide, and the fourth most common type of cancer. Regional metastasis is closely related to the low effectiveness of treatment, and validating biomarkers can optimize accuracy in diagnosis and prognosis. Among the potential biomarkers associated with disease metastasis are circular RNAs (circRNAs), whose altered expression has been linked to CC progression. In this context, this systematic review aims to compile information on the clinical-pathological significance and describe the biological function of circRNAs. Inclusion and exclusion criteria were used to include relevant literature, followed by in silico analysis. Additionally, we employed the UALCAN tools to search for host genes of circRNAs and expression data, miRTargetLink 2.0 to predict interactions of microRNA target genes and the Cytoscape software to predict possible interactions of microRNA target genes. According to the research, most circRNAs were found to be overexpressed and described as regulators of processes such as invasion, cell proliferation, apoptosis and migration. They were also implicated in clinical significance, including metastasis, TNM staging and microRNA interactions. CircRNAs may participate in critical processes in tumorigenesis; therefore, understanding the underlying molecular mechanisms of gene regulation in CC can contribute to the accuracy of diagnosis, prognosis and therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Matos, Silva, Barbosa, de Andrade, Santos Lages, Corrêa, Oliveira, Teixeira, da Silva, Fonseca, Teixeira-Júnior, Alves, Alencar Junior, Khayat and Pinho.)

The main goal of the present study was to analyze the expression profile of cyclin D1 in patients with PC, and to determine possible correlations with clinical and histopathological features. A survey was conducted with 100 patients diagnosed with PC, who were treated at two reference hospitals in São Luís, Maranhão, Brazil, between 2013 and 2017. A review of clinical, epidemiological, and histopathological data was performed, Human Papillomavírus (HPV) DNA was detected using polymerase chain reaction (PCR) and cyclin D1 expression analysis was performed using immunohistochemical techniques. The data revealed that the absence of cyclin D1 expression was significantly associated with HPV-positive histological subtypes ( p = 0.001), while its expression was associated with high-grade tumors ( p = 0.014), histological subtype ( p = 0.001), presence of sarcomatoid transformation ( p = 0.04), and perineural invasion ( p = 0.023). Patients with cyclin D1 expression exhibited lower disease-free survival compared to the cyclin D1-negative group, although the difference was not statistically significant. The results suggest that cyclin D1 may be a potential biomarker for PC, especially for poorer prognosis.

The Verbal Autopsy (VA) is a questionnaire about the circumstances surrounding a death. It was widely used in Brazil to assist in postmortem diagnoses and investigate excess mortality during the Coronavirus Disease 2019 (COVID-19) pandemic. This study aimed to determine the accuracy of investigating acute respiratory distress syndrome (ARDS) using VA. This is a cross-sectional study with prospective data collected from January 2020 to August 2021 at the Death Verification Service of Sao Luis city, Brazil. VA was performed for suspected COVID-19 deaths, and one day of the week was randomly chosen to collect samples from patients without suspected COVID-19. Two swabs were collected after death and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection. Of the 250 cases included, the VA questionnaire identified COVID-19-related ARDS in 67.2% (52.98% were positive for COVID-19). The sensitivity of the VA questionnaire was 0.53 (0.45-0.61), the specificity was 0.75 (0.64-0.84), the positive predictive value was 0.81 (0.72-0.88), and the negative predictive value was 0.44 (0.36-0.53). The VA had a lower-than-expected accuracy for detecting COVID-19 deaths; however, because it is an easily accessible and cost-effective tool, it can be combined with more accurate methods to improve its performance.

Osteoarthritis (OA) is a chronic degenerative disease that has a significant global impact. It is associated with aging and characterized by widespread joint destruction. Cuminaldehyde is a biologically active component of essential oils that has shown promise in the treatment of nociceptive and inflammatory diseases. This study investigated the effects of cuminaldehyde on an experimental model of osteoarthritis induced in rat knees. Cuminaldehyde was found to be as effective as indomethacin in reducing pain in all evaluated tests, including forced walking, functional disability of weight distribution on the legs, and spontaneous pain in animals with osteoarthritis. The knees of animals treated with cuminaldehyde had significantly higher radiographic and histopathological scores than those of animals that did not receive the treatment. Cuminaldehyde also modulated the production of pro-inflammatory cytokines. In vitro assays showed that cuminaldehyde preferentially inhibits COX-2 enzyme activity. In silico studies demonstrated that cuminaldehyde has satisfactory energy affinity parameters with opioid receptors and COX-2. These findings suggest that cuminaldehyde's anti-inflammatory activity is multifactorial, acting through multiple pathways. Its nociceptive activity occurs via central and peripheral mechanisms. Cuminaldehyde modulates the immune response of the inflammatory process and may be considered a leading compound for the development of new anti-inflammatory and analgesic drugs.

Several atypical forms of chikungunya fever (CHIK) have been described, including neurological, cardiac and renal involvement. These forms may be related to high morbidity and mortality rates. This scoping review based on the PubMed, Scopus, and WOS databases aims to identify and summarise all the available evidence regarding the clinical and histopathological presentations and risk factors associated with kidney injury related to CHIK, as well as the clinical impact. Thus, a total of 54 papers were selected from 1606 initial references after applying the defined inclusion criteria. Data on the association between kidney injury and CHIK are scarce, with studies only conducted in the acute phase of the disease, lacking further characterisation. Kidney injury incidence in hospitalised patients using the Kidney Disease Improving Global Outcomes criteria varies from 21% to 45%, being higher among patients with atypical and severe manifestations. Although acute kidney injury does not seem to be related to viraemia, it may be related to higher mortality. Few studies have described the renal histopathological changes in the acute phase of CHIK, with prevalent findings of acute interstitial nephritis with mononuclear infiltrate, glomerular congestion and nephrosclerosis. Only one study assessed the kidney function of patients in the subacute and chronic phases of CHIK. Additionally, individuals with comorbidities, including chronic kidney disease, may be among those with a greater risk of presenting worse outcomes when affected by CHIK. The results described herein may contribute to better understand the relationship between the kidneys and chikungunya virus., (© 2022 John Wiley & Sons Ltd.)

The respiratory tract is the main infection site for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in many admissions to intensive care centers in several countries. However, in addition to lung involvement, kidney injury caused by the novel coronavirus has proven to be a significant factor related to high morbidity and mortality, alarming experts worldwide. The number of deaths has drastically reduced with the advent of large-scale immunization, highlighting the importance of vaccination as the best way to combat the pandemic. Despite the undeniable efficacy of the vaccine, the renal side effects associated with its use deserve to be highlighted, especially the emergence or reactivation of glomerulopathies mentioned in some case reports. This study aimed to identify the main renal morphological findings correlated with COVID-19 infection and its vaccination, seeking to understand the pathophysiological mechanisms, main clinical features, and outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pacheco, Costa, Sousa, Salgado Filho N, Silva and Neves.)

Background: Although penile cancer (PC) is uncommon in developed countries, it is widespread in developing countries. The state of Maranhão (Northeast, Brazil) has the highest global incidence recorded for PC, and, despite its socioeconomic vulnerability, it has been attributed to human papillomavirus (HPV) infection. This study aimed to determine the histopathological features, the prevalence of HPV infection, and the immunohistochemical profile of PC in Maranhão., Methods: A retrospective cohort of 200 PC cases were evaluated. HPV detection was performed using nested-PCR followed by direct sequencing for genotyping. Immunohistochemistry (IHC) was performed using monoclonal antibodies anti-p16 INK4a , p53, and ki-67., Results: Our data revealed a delay of 17 months in diagnosis, a high rate of penile amputation (96.5%), and HPV infection (80.5%) in patients from Maranhão (Molecular detection). We demonstrated the high rate of HPV in PC also by histopathological and IHC analysis. Most patients presented koilocytosis (75.5%), which was associated with those reporting more than 10 different sexual partners during their lifetime (p = 0.001). IHC revealed frequent p16 INK4a overexpression (26.0%) associated with basaloid (p < 0.001) and high-grade tumors (p = 0.008). Interestingly, p16 appears not to be a better prognostic factor in our disease-free survival analysis, as previously reported. We also demonstrated high ki-67 and p53 expression in a subset of cases, which was related to worse prognostic factors such as high-grade tumors, angiolymphatic and perineural invasion, and lymph node metastasis. We found a significant impact of high ki-67 (p = 0.002, log-rank) and p53 (p = 0.032, log-rank) expression on decreasing patients' survival, as well as grade, pT, stage, pattern, and depth of invasion (p < 0.05, log-rank)., Conclusions: Our data reaffirmed the high incidence of HPV infection in PC cases from Maranhão and offer new insights into potential factors that may contribute to the high PC incidence in the region. We highlighted the possible association of HPV with worse clinical prognosis factors, differently from what was observed in other regions. Furthermore, our IHC analysis reinforces p16, ki-67, and p53 expression as important diagnosis and/or prognosis biomarkers, potentially used in the clinical setting in emerging countries such as Brazil., (© 2022. The Author(s).)

Competing Interests: All authors have nothing to disclose.

Introduction: Chikungunya virus was detected in cases of acute chikungunya fever in renal tissue. However, chikungunya virus-related kidney injury still lacks characterization, and it is unknown whether the kidneys are reservoirs for the virus. We sought to detect histopathological changes and viral antigens in renal tissue, and to evaluate kidney injury markers in different phases of chikungunya fever., Methods: Two groups were evaluated in this exploratory study: patients with biopsy-proven kidney injury established after chikungunya fever, and patients with post-chikungunya fever chronic joint manifestations without known kidney injury, in whom we actively searched for kidney injury markers., Results: In the first group, 15 patients had kidney injury 0.5-24 months after chikungunya fever. The most frequent histopathological diagnoses were glomerular lesions. No viral antigens were detected in renal tissue. High-risk genotypes were detected in patients with atypical hemolytic uremic syndrome and focal and segmental glomerulosclerosis. In the second group, 114 patients had post-chikungunya fever joint manifestations on average for 35.6 months. Mean creatinine and proteinuria were 0.9 mg/dl and 71.5 mg/day, respectively. One patient had isolated hematuria. There was no indication for renal biopsy in this group., Conclusions: Several histopathological features were found after chikungunya fever, without virus detection in renal tissue. These findings suggest that chikungunya virus may trigger kidney lesions with varying degrees of severity at different stages of infection. However, the probability that this virus replicates in the renal tissue seems unlikely., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Penile cancer (PC) still presents a health threat for developing countries, in particular Brazil. Despite this, little progress has been made on the study of markers, including molecular ones, that can aid in the correct management of the patient, especially concerning lymphadenectomy. As in other neoplasms, non-coding RNAs (ncRNAs) have been investigated for penile cancer, with emphasis on microRNAs, piRNAs (PIWI-interacting small RNAs), and long non-coding RNAs (LncRNAs). In this context, this review aims to assemble the available knowledge on non-coding RNA linked in PC, contributing to our understanding of the penile carcinogenesis process and addressing their clinical relevance. ncRNAs are part of the novel generation of biomarkers, with high potential for diagnosis and prognosis, orientating the type of treatment. Furthermore, its versatility regarding the use of paraffin samples makes it possible to carry out retrospective studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pinho, Silva, Teixeira-Júnior, Rocha, Batista, de Sousa, Calixto, Burbano, Souza and Khayat.)

The aim of this study was to analyze the glomerular and tubular alterations in dogs with terminal distemper through light microscopy, immunofluorescence, and electron microscopy. Thirteen animals with a molecular diagnosis of distemper and neurological signs were selected. As a control group, 10 clinically healthy animals with no manifestations or signs of disease and with negative tests for Ehrlichia sp., Anaplasma sp., and Babesia sp. were included in this study. Renal tissue was evaluated by light microscopy, topochemistry for DNA/chromatin, and video image analysis to detect the nuclear phenotypes of the renal tubular epithelial cells (RTECs), immunofluorescence, and transmission electron microscopy. Results showed that dogs with distemper exhibited anemia, hypergammaglobulinemia, and proteinuria. Creatinine in the distemper group was lower compared to the control group ( p = 0.0026), but there was no significant difference in relation to urea ( p = 0.9876). Although this alteration may be due to the smaller muscle mass observed in animals with distemper, it probably is not of clinical importance. Glomerular and tubular lesions were confirmed by light microscopy in 84.6% of these animals. Additional findings in the animals with distemper included deposition of different classes of immunoglobulins, particularly IgM in 92.3% of the cases, fibrinogen deposition in 69.2% of the cases as assessed by immunofluorescence, alterations in the nuclear phenotypes of the RTEC characterized by condensation of chromatin, loss of DNA and reduction in the nuclear shape, and the presence of subendothelial and mesangial electron-dense deposits. These findings confirm the existence of renal alterations related to terminal distemper., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Silva, Silva, Borin-Crivellenti, Alvarenga, Aldrovani, Braz, Aoki, Santana, Pennacchi and Crivellenti.)

Collapsing glomerulopathy (CG) is a clinicopathologic entity characterized by segmentar or global collapse of the glomerulus and hypertrophy and hyperplasia of podocytes. The Columbia classification of 2004 classified CG as a histological subtype of focal segmental glomerulosclerosis (FSGS). A growing number of studies have demonstrated a high prevalence of CG in many countries, especially among populations with a higher proportion of people with African descent. The present study is a narrative review of articles extracted from PubMed, Medline, and Scielo databases from September 1, 2020 to December 31, 2021. We have focused on populational studies (specially cross-sectional and cohort articles). CG is defined as a podocytopathy with a distinct pathogenesis characterized by strong podocyte proliferative activity. The most significant risk factors for CG include APOL1 gene mutations and infections with human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2. CG typically presents with more severe symptoms and greater renal damage. The prognosis is notably worse than that of other FSGS subtypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cutrim, Neves, Campos, Wanderley, Teixeira-Júnior, Muniz, Ladchumananandasivam, Gomes, Vasco, Brito, Lages, Salgado-Filho, Guedes, de Almeida, Magalhães, Araújo and Silva.)

Background: The introduction of tacrolimus (TAC) to clinical practice was essential to the establishment of transplantation as a therapy for patients with chronic renal disease. However, the higher interindividual variation of TAC metabolism has been an important limiting factor for its clinical use. Although the relationship between CYP3A5 polymorphisms and TAC pharmacokinetics (PK) is well established, the effects of other genetic variants on TAC metabolism, such as POR*28, still remain uncertain., Objective: The study aimed to evaluate the impact of POR variants on TAC PK in renal transplant patients with different CYP3A5 genotypes (expressers and non-expressers)., Methods: A total of 115 patients were included in this study. Genomic DNA was isolated from peripheral blood, and the real-time PCR technique was used to analyze the polymorphism POR rs1057868; C>T., Results: During the initial post-transplant period, variant allele carriers (*1/*28 and *28/*28) showed a lower TAC dose requirement than POR wild homozygotes (*1/*1). Regarding the influence of the different polymorphisms of POR within the CYP3A5 expresser and non-expresser groups, no differences were observed in any of the PK parameters analyzed during 12 months after transplantation., Conclusion: In the studied population, the variant allelic POR*28 was significantly associated with lower TAC dose requirements and higher Co/D ratio in the first-month post-transplant. However, the effects of this polymorphism on the CYP3A5 enzyme activity were not observed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Subclinical stage of ehrlichiosis is characterized by absence of clinical or laboratory alterations; however, it could lead to silent glomerular/tubular changes and contribute significantly to renal failure in humans and animals. The aim of this study was to evaluate glomerular and tubular alterations in dogs with subclinical ehrlichiosis. We evaluated renal biopsies of 14 bitches with subclinical ehrlichiosis and 11 control dogs. Samples were obtained from the left kidney, and the tissue obtained was divided for light microscopy, immunofluorescence, and transmission electron microscopy. Abnormalities were identified by light microscopy in 92.9% of dogs with ehrlichiosis, but not in any of the dogs of the control group. Mesangial cell proliferation and synechiae (46.1%) were the most common findings, but focal segmental glomerulosclerosis and ischemic glomeruli (38.4%), focal glomerular mesangial matrix expansion (30.7%), mild to moderate interstitial fibrosis and tubular atrophy (23%), and glomerular basement membrane spikes (23%) were also frequent in dogs with ehrlichiosis. All animals with ehrlichiosis exhibited positive immunofluorescence staining for immunoglobulins. Transmission electron microscopy from dogs with ehrlichiosis revealed slight changes such as sparse surface projections and basement membrane double contour. The subclinical phase of ehrlichiosis poses a higher risk of development of kidney damage due to the deposition of immune complexes., Competing Interests: The authors have declared that no competing interests exist.

Dengue fever and chikungunya are viral diseases that have spread rapidly throughout the world in recent decades. The occurrence of complications is well known, including prerenal acute kidney injury (AKI), which is usually thought to be caused by dehydration and fluid loss. Thrombotic microangiopathy (TMA) is an uncommon aggravation of dengue fever and chikungunya, with only a few cases described in the medical literature. The aim of this study is to present 3 cases of TMA associated with arboviral infection. Three patients with clinical history, laboratory test, and kidney biopsy results compatible with TMA were selected for the study, 2 of whom had a serological diagnosis of dengue fever and 1 of chikungunya. The 3 patients were followed up at the Federal University of Maranhão Hospital's Nephrology Service in 2018. A targeted gene panel sequencing (TGPS) plus multiple to atypical hemolytic uremic syndrome (aHUS) multiplex ligation-dependent probe amplification (MLPA) was performed in 2 of the patients and revealed in the patient 1 a heterozygous pathogenic variant in the gene THBD, as well as heterozygous deletions in CFH, CFHR1, and CFHR3. In the patient 2, there were heterozygous pathogenic variant in the genes CFI and CFB, in addition to heterozygous deletions in the genes CFHR1 and CFHR3. Both received treatment with eculizumab and undergone recovery of renal function. The third patient had TMA not classified as either aHUS or thrombotic thrombocytopenic purpura (TTP); he abandoned the treatment and returned to the service after 2 years for a dialysis emergency. Patients with arboviral infectious disease and changes that suggest TMA should have appropriate support to establish early diagnosis and useful treatment., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To compare tissue inflammatory response, foreign body reaction, fibroplasia, and proportion of type I/III collagen between closure of abdominal wall aponeurosis using polyglactin suture and intraperitoneal implant of polypropylene, polypropylene/polyglecaprone, and polyester/porcine collagen meshes to repair defects in the abdominal wall of rats., Methods: Forty Wistar rats were placed in four groups, ten animals each, for the intraperitoneal implant of polypropylene, polypropylene/polyglecaprone, and polyester/porcine collagen meshes or suture with polyglactin (sham) after creation of defect in the abdominal wall. Twenty-one days later, histological analysis was performed after staining with hematoxylin-eosin and picrosirius red., Results: The groups with meshes had a higher inflammation score (p < 0.05) and higher number of gigantocytes (p < 0.05) than the sham group, which had a better fibroplasia with a higher proportion of type I/III collagen than the tissue separating meshes (p < 0.05). There were no statistically significant differences between the three groups with meshes., Conclusions: The intraperitoneal implant of polypropylene/polyglecaprone and polyester/porcine collagen meshes determined a more intense tissue inflammatory response with exuberant foreign body reaction, immature fibroplasia and low tissue proportion of type I/III collagen compared to suture with polyglactin of abdominal aponeurosis. However, there were no significant differences in relation to the polypropylene mesh group.

Purpose: Genetic polymorphisms have been associated with variation in the metabolism of tacrolimus (TAC) in kidney transplant patients. This study is aimed at assessing the impact of allelic variants of CYP3A5 and PPARA genes on the pharmacokinetics (PK) of TAC in Brazilian kidney transplant recipients in the first-year post-transplant., Methods: A total of 127 patients were included for genetic evaluation. Genomic DNA was isolated from peripheral blood and real-time PCR was used to analyze the main polymorphisms described for the genes CYP3A5 (rs776746; C > G) and PPARA (rs4823613; A > G and rs4253728; G > A)., Results: CYP3A5 expressors showed a lower Co/dose ratio than non-expressors, with the median values of this parameter <1.01 ng/mL/mg in the first group at all evaluated times. Additionally, PPARA variant homozygotes had a lower Co/D ratio than wild allele carriers in the 12-month post-transplant period, with a median value of 0.65 ng/mL/mg. In the CYP3A5 expressers, the presence of the variant homozygous genotype PPARA was associated with a lower value of Co/D compared with the other genotypic groups at month 12., Conclusion: In the population under study, polymorphisms on CYP3A5 and PPARA were identified as determining and independent factors associated with the reduction of Co/D of TAC. Thus, the genotyping of these genetic variants may be a useful tool for the individualized prescription of TAC in kidney transplant patients.

This study aims to investigate the activity of n-hexane, ethyl acetate and butanol fractions obtained from Arrabidaea chica Verlot against MIA-induced osteoarthritis (OA). The antinociceptive potentials of each fraction were evaluated through a cyclooxygenase (COX) 1 and 2 inhibition test and an in vivo OA-model. In addition, toxicity assessments in the liver, spleen and kidney, as well as radiographic and histopathological knee analyses, were performed. The chemical composition of the n-hexane fraction was elucidated, and a molecular docking protocol was carried out to identify which compounds are associated with the detected bioactivity. The n-hexane A. chica fraction preferentially inhibits COX-2, with 90% inhibition observed at 10 µg/mL. The fractions also produced significant improvements in OA incapacity, motor activity and hyperalgesia parameters and in radiological knee conditions. However, concerning the histopathological evaluations, these improvements were only significant in the hexane and ethyl acetate fraction treatments, which resulted in better average scores, suggesting that these fractions slow OA-promoted joint injury progression. Histopathological organ analyses indicate that the fractions are not toxic to animals. Twenty compounds were identified in the n-hexane fraction, comprising fatty acids, terpenes and phytosterols. In silico analyses indicate the presence of favourable interactions between some of the identified compounds and the COX-2 enzyme, mainly concerning alpha-tocopherol (Vitamin E), squalene and beta-sitosterol. The findings indicate that A. chica fractions display analgesic, anti-inflammatory properties, are non-toxic and are able to slow OA progression, and may, therefore, be prioritized as natural products in OA human clinical trials.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause of death in the world and the third in Brazil. Mutations in the APC, DCC, KRAS and TP53 genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition., Methods: Ten paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene expression analysis. In addition, mutations in APC, KRAS and TP53 genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients., Results: Gene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change> 2, p< 0.05), between the adenoma and adenocarcinoma paired samples analyzed. Gene pathway analysis using the 689 DEG identified important cancer pathways such as remodeling of the extracellular matrix and epithelial-mesenchymal transition. Among these DEG, the ETV4 stood out as one of the most expressed in the adenocarcinoma samples, further confirmed in the adenocarcinoma set of samples from the TCGA database. Subsequent in vitro siRNA assays against ETV4 resulted in the decrease of cell proliferation, colony formation and cell migration in the HT29 and SW480 colorectal cell lines. DNA sequencing analysis revealed KRAS and TP53 gene pathogenic mutations, exclusively in the adenocarcinomas samples., Conclusion: Our study identified a set of genes with high potential to be used as biomarkers in CRC, with a special emphasis on the ETV4 gene, which demonstrated involvement in proliferation and migration.

Some studies have described that when the hemoglobin levels of chronic kidney disease (CKD) patients change, especially in those taking erythropoiesis-stimulating agents (ESA), they are associated with unfavorable outcomes such as increased morbidity and mortality, mainly due to cardiovascular events. This prospective cohort study included patients with end-stage renal disease currently undergoing hemodialysis. The initial 6-month clinical evaluation provided data of the variability in hemoglobin, associated blood parameters, and the use of erythropoietin. Subsequently, the patients were followed up for 78 months to evaluate mortality-associated factors. In total, 133 patients completed the 6-month follow-up with a mean age of 47.1 (±13.2) years. The majority were women (51.9%). Six-month hemoglobin levels were as follows: always low (18.0%), intermediate/target (1.5%), always high (0.8%), low-amplitude fluctuation/Hb low ( n = 37; 27.8%), low-amplitude fluctuation/Hb high (13.53%), and high-amplitude fluctuation (38.6%), among end-stage renal disease patients. At the end of 78 months, 50 (37.6%) patients died; 70% of deaths were attributed to cardiovascular etiologies. A high variability was observed in hemoglobin levels, which was not associated with mortality. Among all the variables evaluated, age, erythropoietin dose, and transferrin saturation were associated with a higher mortality. Thus, this study suggests that greater attention to erythropoietin doses and transferrin saturation levels may improve the survival of dialysis patients.

Kidney involvement appears to be frequent in coronavirus disease 2019 (COVID-19). Despite this, information concerning renal involvement in COVID-19 is still scarce. Several mechanisms appear to be involved in the complex relationship between the virus and the kidney. Also, different morphological patterns have been described in the kidneys of patients with COVID-19. For some authors, however, this association may be just a coincidence. To investigate this issue, we propose assessing renal morphology associated with COVID-19 at the renal pathology reference center of federal university hospitals in Brazil. Data will come from a consortium involving 17 federal university hospitals belonging to Empresa Brasileira de Serviços Hospitalares (EBSERH) network, as well as some state hospitals and an autopsy center. All biopsies will be sent to the referral center for renal pathology of the EBSERH network. The data will include patients who had coronavirus disease, both alive and deceased, with or without pre-existing kidney disease. Kidney biopsies will be analyzed by light, fluorescence, and electron microscopy. Furthermore, immunohistochemical (IHC) staining for various inflammatory cells (i.e., cells expressing CD3, CD20, CD4, CD8, CD138, CD68, and CD57) as well as angiotensin-converting enzyme 2 (ACE2) will be performed on paraffinized tissue sections. In addition to ultrastructural assays, in situ hybridization (ISH), IHC and reverse transcription-polymerase chain reaction (RT-PCR) will be used to detect Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) in renal tissue. For the patients diagnosed with Collapsing Glomerulopathy, peripheral blood will be collected for apolipoprotein L-1 (APOL1) genotyping. For patients with thrombotic microangiopathy, thrombospondin type 1 motif, member 13 (ADAMTS13), antiphospholipid, and complement panel will be performed. The setting of this study is Brazil, which is second behind the United States in highest confirmed cases and deaths. With this complete approach, we hope to help define the spectrum and impact, whether immediate or long-term, of kidney injury caused by SARS-CoV-2., (Copyright © 2020 Teixeira Júnior, Neves, Lages, Cunha, Muniz, Brito, Watanabe, Watanabe, Onuchic, Nunes, Coutinho Filho, Barcelos, Gatto, Monteiro, Polido, Motta, Leite, Guedes, Gomes, Valente, Israel, Ladchumananandasivam, de Farias, Marques, Uliano, Maramaldo, Neto, Luchi, Wanderley, Araújo, Salgado Filho and Silva.)

Introduction: Osteoporosis is defined as a systemic skeletal disease characterized by reduced bone mass and degeneration of bone tissue microarchitecture which leads to bone fragility and fracture risk. Annually, 100 to 200 million people around the world are at risk for osteoporotic fractures. One way to prevent osteoporosis fracture is by using medications such as bisphosphonates. Alendronate is the most prescribed bisphosphonate in the world. The objective of this article is to evaluate the effect of alendronate on bone fracture healing., Material and Methods: 15 adult male rats that were 60 days old were used, divided into three groups: A or Control, B (non-osteoporotic bones plus alendronate application) and C (osteoporotic bones plus alendronate application). Osteoporotic bones were compared with non-osteoporotic bones that underwent bone window creation and administration of alendronate sodium. These bones were submitted to radiographic and histological analysis., Results: All of Group A had complete bone healing, reaching the phase of bone remodeling. While in groups B and C, the rats were in the repair phase., Conclusions: The drug alendronate interferes with delayed fracture healing and delayed bone remodeling. The article advises that studies in humans are needed in order to assess whether the alendronate interferes with bone healing., (© 2020 Delhi Orthopedic Association. All rights reserved.)

Objective: Maranhão State-Northeast Brazil-has the world's highest incidence of penile cancer. This study describes the epidemiological, histopathological and clinical profile of patients stricken across that Brazilian state. The study is aimed at providing new data on neoplasia., Data Description: 402 men stricken with penile cancer were studied from January 2004 to December 2018. A retrospective stage was developed with collection of physical and electronic records. A prospective stage was performed with collection of clinical and epidemiological information through a questionnaire. The surgical material was looked into by a uropathologist, and the lesions were evaluated for macroscopic characteristics and various microscopic parameters. Three articles using this data have already been published.

A common criticism of the classification of lupus nephritis is the relative scarcity of information regarding tubular, interstitial, and vascular changes compared to the available information regarding glomerular changes, even though their potential for independent progression is known. This study reviewed the importance of less explored lesions by the current and widely used 2003 classification of lupus nephritis of the International Society of Nephrology/Renal Pathology Society (ISN/RPS), with emphasis on the tubulointerstitial, podocyte, and vascular lesions, increasingly recognised as being important in the pathogenesis and prognosis of the disease. Recognition of these lesions can help with therapeutic decision-making, thereby allowing better results for patients with systemic lupus erythematosus., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

Objective: To evaluate the prevalence of nondiabetic renal diseases (NDRDs) in renal biopsies of patients with diabetes mellitus (DM) in the University Hospital of Ribeirão Preto, São Paulo. Research Design and Methods . We conducted a retrospective study including kidney biopsies performed in diabetic patients between 1987 and 2013. We evaluated 79 biopsies during this period. The primary variable was the prevalence of NDRD in patients with DM. The secondary variables were the presence of systemic arterial hypertension (SAH), hematuria, time since diagnosis of DM, serum creatinine, and proteinuria levels. The cases were divided into the following groups: isolated diabetic nephropathy (DN-group I), isolated nondiabetic renal diseases (NDRD-group II), associated NDRD/DN (group III), and associated NDRD+NDRD/DN (group IV)., Results: Most of the patients (58.22%) presented only alterations arising from DN. NDRDs were present in 41.77% of the patients. Membranous glomerulonephritis (30.3%) and IgA nephropathy (24.24%) were the most prevalent NDRDs. We found no differences between female and male patients with NDRD when assessing the secondary variables. A time since diagnosis of five years or less revealed a statistical difference ( p = 0.0005) in the comparison between the isolated DN (group I) and the NDRD+NDRD/DN (group IV). The other secondary variables were not significant in the comparison of the groups., Conclusions: We concluded that the prevalence of NDRD is 41.77%. Membranous glomerulonephritis was the most prevalent NDRD in our study. We also conclude that the probability of the presence of NDRD with or without concomitant DN is greater for patients who had biopsies with a time since diagnosis of five years or less. A time since diagnosis of ten years or more does not allow the exclusion of the presence of NDRD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Diego Agra Souza et al.)

To determine the epidemiological, histopathological, and clinical characteristics of patients diagnosed with penile cancer in the Brazilian state of Maranhão, the region with the highest incidence worldwide. One hundred and sixteen penile cancer patients were interviewed from July 2016 to October 2018. The majority of patients lived in a rural area (57%), worked in farming (58%), had a low level of schooling or no schooling (90%), and were married or in a stable relationship (74%). The mean age was 60.4 ± 16.51 years (range, 23-93 years). Phimosis (66%), poor/moderate genital hygiene (73%), history of sexually transmitted infections (55%), and zoophilia (60%) were found in the majority of patients. Most patients had their first sexual encounter at 16.2 ± 2.8 years (range, 10-25 years), and 75% had >6 sexual partners. The most common initial symptom was pruritus (37%), and most patients waited to seek treatment (average time to treatment, 18.9 months; range, 2-84 months). Human papillomavirus (HPV)-related histologies were observed in 62% of patients. Most patients had histological grades II or III (87%), stage ≥T2 disease (84%), and lymphadenopathy at admission (42%). Penectomy was performed in 96% of patients. The population with penile cancer in the region of highest incidence in the world is marked by low socioeconomic status, high prevalence of HPV infection, and phimosis. The delay in seeking treatment is related to a very high rate of advanced cancer and aggressive surgical treatment. The high prevalence of young patients was also a striking feature.

Background: Inguinal lymph node involvement is the main prognostic factor in patients with penile cancer. However, there is a lack of marker/s for lymph node metastasis. microRNAs have been investigated as potential markers for prognosis of various types of cancer. Taking this into consideration, our main goal was to determine the association of miR-223-3p, miR-107, and miR-21-5p expression with clinicopathological characteristics, as well as presence of lymph node metastasis in patients with penile cancer., Methods: Formalin-fixed paraffin-embedded penile squamous cell carcinoma specimens from 50 patients, at diagnosis and prior to any cancer treatment, were obtained. Tissue samples comprising at least 70% malignant cells and adjacent non-tumor tissues were evaluated by using qRT-PCR for expression level of miR-223-3p, miR-107 and miR-21-5p. Additionally, molecular identification of HPV was performed by PCR, and the expression levels of PTEN were analyzed by immunohistochemistry., Results: Penile squamous cell carcinoma primary tumors presented higher expression of miR-223-3p, miR-107, and miR-21-5p when compared to non-tumor adjacent tissues. Upregulation of miR-223-3p was associated lymph node metastasis. Higher expression of miR-107 was associated with worsening of prognosis (as observed by histological grade II and III, tumors bigger than 2.0 cm, stage III and IV, and lower disease-free survival). In addition, higher expression of miR-107 and miR-21-5p was correlated to the absence of PTEN protein expression., Conclusions: Our data demonstrate that higher expression of miR-223-3p, miR-107, and miR-21-5p is correlated with poor prognosis in penile cancer. The upregulation of these microRNAs potentially affect critical cancer pathways and may be important for the prognosis and response to therapy in penile cancer.

To analyze possible clinical-pathological parameters and predictors of lymph node metastasis and evaluate the impact of lymphadenectomy in the survival of these patients.A retrospective study of patients diagnosed with penile cancer and submitted to regional lymphadenectomy at two reference hospitals in Maranhão, Northeast, Brazil, an area where the disease has a high incidence. We described here clinical and histopathological characteristics of patients diagnosed between January 2009 and September 2017.Fifty-five patients with an average age of 55.4 years (range: 25-84 years) were analyzed, with 24.4 months being the average time between the onset of symptoms and start of treatment. Among patients without palpable lymph nodes at the first examination, 51% were affected by inguinal metastasis. In the multivariate analysis, the presence of angiolymphatic invasion (P = .029) and absence of koilocytosis (P = .001) were found to be predictive factors for lymph node metastasis. Patients submitted to prophylactic lymphadenectomy presented with a disease-free period of 25.4 months (±5.81), whereas those who underwent therapeutic lymphadenectomy presented with a disease-free period of 19.9 months (±3.12).Angiolymphatic invasion and absence of koilocytosis appeared to be predictive factors for lymph node metastasis. Therefore, the submission of patients with metastatic risk to prophylactic lymphadenectomy may improve their survival. Thus, prophylactic lymphadenectomy in patients at risk for inguinal metastasis may create a positive impact in survival rates.

Background: Oculosporidiosis (ocular rhinosporidiosis) accounts for 15% of cases of rhinosporidiosis, which is a chronic granulomatous disease and is endemic in India and Sri Lanka. In Brazil, the climatic and hydrographic similarities to these endemic areas and the presence of riverside populations contributes to an increase in the incidence of rhinosporidiosis particularly in the State of Maranhão. This study, therefore, aimed to identify the number of diagnosed cases of oculosporidiosis and describe its the clinical epidemiology, laboratory, histopathology, and therapeutic characteristics., Methods: The study is descriptive, observational, and cross-sectional, and reports the prevalence and clinical epidemiological characteristics of oculosporidiosis in the State of Maranhão, Brazil. A retrospective analysis of the paper and electronic records for a period from 1999 to 2017 was conducted in the University Hospital of Federal University of Maranhão (HU-UFMA), located in the northeastern region of Brazil., Results: Thirty patients were diagnosed with rhinosporidiosis, eight of them had oculosporidiosis and seven of these met the criteria to be included in the study. Of the cases (23.3% of all 30), five were men (71.4%) and two women (28.5%), with an average age of 16.4 ± 15.6 years. In terms of race, four patients (57.1%) declared themselves white and three (42.9%) as brown. The north of the state, the mesoregion, had the most diagnosed cases accounting for 57.1% of the total. Left eye was the most affected site, reported in six patients (85.7%), while the conjunctiva was affected in all patients. Rhinosporidiosis and papilloma were the predominant diagnostic hypotheses (28.5 and 28.5%, respectively), followed by chronic scleritis, granuloma, and chalazion (14.25, 14.25, and 14.25%, respectively). All these cases were treated with lesion excision, and only two patients (28.5%) progressed with recurrence., Conclusion: It was verified that there was a male predominance, with only one eye reported as an infected site, with no bilateral involvement. The younger age group (between 1 and 2 years of age) was more affected by oculosporidiosis, and histopathological examination was necessary for a conclusive diagnosis.