Aetiological molecular identification of sexually transmitted infections that cause urethral discharge syndrome and genital ulcer disease in Brazilian men: a nationwide study.

BACKGROUND: Little is known about the aetiology of urethral discharge syndrome (UDS) and genital ulcer disease (GUD) in Brazil due to limited access to laboratory tests and treatment based mainly on the syndromic approach. OBJECTIVES: To update Brazilian treatment guidelines according to the current scenario, the first nationwide aetiological study for UDS and GUD was performed. METHODS: Male participants with urethral discharge (UD) and/or genital ulcer (GU) reports were enrolled. Sample collection was performed by 12 sentinel sites located in the five Brazilian regions. Between 2018 and 2020, 1141 UD and 208 GU samples were collected in a Universal Transport Medium-RT (Copan). A multiplex quantitative PCR kit (Seegene) was used to detect UD: Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), M. hominis (MH), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Ureaplasma parvum (UP), U. urealyticum (UU) and another kit to detect GU: cytomegalovirus (CMV), Haemophilus ducreyi (HD), herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), lymphogranuloma venereum (LGV), Treponema pallidum (TP) and varicella-zoster virus (VZV). RESULTS: In UD samples, the frequency of pathogen detection was NG: 78.38%, CT: 25.6%, MG: 8.3%, UU: 10.4%, UP: 3.5%, MH: 3.5% and TV: 0.9%. Coinfection was assessed in 30.9% of samples, with 14.3% of NG/CT coinfection. The most frequent pathogen identified in GU was HSV2, present in 40.8% of the samples, followed by TP at 24.8%, LGV and CMV at 1%, and HSV1 at 0.4%. Coinfection of TP/HSV2 was detected in 4.4% of samples. VZV and HD were not detected. In 27.7% of the GU samples, no pathogen was detected. CONCLUSION: This study provided the acquisition of unprecedented data on the aetiology of UDS and GUD in Brazil, demonstrated the presence of a variety of pathogens in both sample types and reaffirmed the aetiologies known to be most prevalent globally.

Insulin-like growth factor-1 short-period therapy stimulates bone marrow cells in obese swiss mice.

Bone marrow cells (BMCs) from obese Swiss mice fed with Western diet show mitochondrial dysfunction. Obesity interferes with BMCs disrupting energetic metabolism, stimulating apoptosis, and reducing cell proliferation since adipose tissue releases inflammatory adipokines into the medullar microenvironment. These changes lead to reduction of BMC differentiation capacity and hematopoiesis impairment, a process responsible for blood cell continuous production through hematopoietic stem cells (HSCs). This work aimed to analyze the effects of IGF-1 therapy on BMC viability in Western diet-induced obesity, in vivo. We observed that after only 1 week of treatment, obese Swiss mice presented reduced body weight and visceral fat and increased mitochondrial oxidative capacity and coupling, indicating mitochondrial function improvement. In addition, IGF-1 was able to reduce apoptosis of total BMCs, stem cell subpopulations (hematopoietic and mesenchymal), and leukocytes, restoring all progenitor hematopoietic lineages. The treatment also contributed to increase proliferative capacity of hematopoietic stem cells and leukocytes, keeping the hematopoietic and immune systems balanced. Therefore, we conclude that IGF-1 short period therapy improved BMC survival, proliferation, and differentiation capacity in obese Swiss mice.

Non-invasive Predictors of Esophageal Varices With a High Risk of Bleeding in Pediatric Cirrhotic Patients.

OBJECTIVES: To evaluate non-invasive predictive factors of varices with a high risk of bleeding in pediatric cirrhotic patients. METHODS: This retrospective, cross-sectional study included data from 158 children with cirrhosis, median age of 5.38 years (interquartile [IQ] 2.08-11.52 years), and no history of upper gastrointestinal bleeding. Patients underwent an endoscopy to screen for esophageal varices. Varices with a high risk of bleeding were defined as those with a medium to large caliber, presence of red spots, or the presence of gastric varices and identified as high-risk varices (HRV). Laboratory and clinical factors were evaluated as possible predictors of HRV. RESULTS: HRV were detected in 30 children (19%) after the first endoscopy. In the multivariate analysis, only the risk score (RS), as described by Park et al, and the aspartate aminotransferase-to-platelet ratio index (APRi) were predictive of HRV. The best non-invasive predictor of HRV was the RS with an area under the receiver operating characteristic curve of 0.764. When used a cut-off point of -1.2, the sensitivity of the RS was 90% and specificity was 53%. The use of RS or APRi correctly identified 96% of children with HRV. CONCLUSIONS: The described predictors allow the correct identification of patients with HRV. The association of RS >-1.2 or APRi >1.4 has a good sensitivity to identify HRV and to prevent unnecessary endoscopy in about one-third of children with no HRV.

A global functional analysis of missense mutations reveals two major hotspots in the PALB2 tumor suppressor.

While biallelic mutations in the PALB2 tumor suppressor cause Fanconi anemia subtype FA-N, monoallelic mutations predispose to breast and familial pancreatic cancer. Although hundreds of missense variants in PALB2 have been identified in patients to date, only a few have clear functional and clinical relevance. Herein, we investigate the effects of 44 PALB2 variants of uncertain significance found in breast cancer patients and provide detailed analysis by systematic functional assays. Our comprehensive functional analysis reveals two hotspots for potentially deleterious variations within PALB2, one at each terminus. PALB2 N-terminus variants p.P8L [c.23C>T], p.Y28C [c.83A>G], and p.R37H [c.110G>A] compromised PALB2-mediated homologous recombination. At the C-terminus, PALB2 variants p.L947F [c.2841G>T], p.L947S [c.2840T>C], and most strikingly p.T1030I [c.3089C>T] and p.W1140G [c.3418T>C], stood out with pronounced PARP inhibitor sensitivity and cytoplasmic accumulation in addition to marked defects in recruitment to DNA damage sites, interaction with BRCA2 and homologous recombination. Altogether, our findings show that a combination of functional assays is necessary to assess the impact of germline missense variants on PALB2 function, in order to guide proper classification of their deleteriousness.

Contributions of HOX genes to cancer hallmarks: Enrichment pathway analysis and review.

Homeobox genes function as master regulatory transcription factors during development, and their expression is often altered in cancer. The HOX gene family was initially studied intensively to understand how the expression of each gene was involved in forming axial patterns and shaping the body plan during embryogenesis. More recent investigations have discovered that HOX genes can also play an important role in cancer. The literature has shown that the expression of HOX genes may be increased or decreased in different tumors and that these alterations may differ depending on the specific HOX gene involved and the type of cancer being investigated. New studies are also emerging, showing the critical role of some members of the HOX gene family in tumor progression and variation in clinical response. However, there has been limited systematic evaluation of the various contributions of each member of the HOX gene family in the pathways that drive the common phenotypic changes (or "hallmarks") and that underlie the transformation of normal cells to cancer cells. In this review, we investigate the context of the engagement of HOX gene targets and their downstream pathways in the acquisition of competence of tumor cells to undergo malignant transformation and tumor progression. We also summarize published findings on the involvement of HOX genes in carcinogenesis and use bioinformatics methods to examine how their downstream targets and pathways are involved in each hallmark of the cancer phenotype.

Insulin-like growth factor-1 short-period therapy improves cardiomyopathy stimulating cardiac progenitor cells survival in obese mice.

BACKGROUND AND AIMS: Cardiovascular diseases are the main cause of mortality in obesity. Despite advanced understanding, the mechanisms that regulate cardiac progenitor cells (CPC) survival in pathological conditions are not clear. Low IGF-1 plasma levels are correlated to obesity, cardiomyopathy and CPC death, so this work aimed to investigate IGF-1 therapeutic potential on cardiomyopathy and its relationship with the survival, proliferation and differentiation of CPC in Western diet-induced obesity. METHODS AND RESULTS: Male Swiss mice were divided into control group (CG, n = 8), fed with standard diet; and obese group (OG, n = 16), fed with Western diet, for 12 weeks. At 11th week, OG was subdivided to receive a daily subcutaneous injection of human recombinant IGF-1 (100 µg.Kg-1) for seven consecutive days (OG + IGF1, n = 8). Results showed that IGF-1 therapy improved the metabolic parameters negatively impacted by western diet in OG, reaching levels similar to CG. OG + IGF-1 also demonstrated restored heart energetic metabolism, fibrosis resolution, decreased apoptosis level, restored cardiac gap junctions and intracellular calcium balance. Cardiomyopathy improvement was accompanied by increased CPC survival, proliferation and newly cardiomyocytes formation related to increased pAkt/Akt ratio. CONCLUSION: These results suggest that only one week of IGF-1 therapy has cardioprotective effects through Akt pathway upregulation, ensuring CPC survival and differentiation, contributing to heart failure rescue.

Bone marrow mononuclear cell transplantation rescues the glomerular filtration barrier and epithelial cellular junctions in a renovascular hypertension model.

NEW FINDINGS: What is the central question of this study? Can a single bone marrow mononuclear cell (BMMC) transplant into the subcapsular region of kidney improve cellular communication and adhesion, while restoring renal tissue cytoarchitecture and function during renovascular hypertension? What is the main finding and its importance? The BMMC transplantation restored connexin 40 expression and led to recovery of N- and E-cadherin levels within 15 days. It was observed, for the first time, that BMMC transplantation restores expression of nephrin, a component of the glomerular filtration barrier related to podocytes and the glomerular basal membrane. ABSTRACT: Stem cell therapy has emerged as a potential treatment for renal diseases owing to the regenerative potential of stem cells. However, a better understanding of the morphological and functional changes of damaged renal cells in the presence of transplanted stem cells is needed. The aim of this study was to investigate cell-cell communication and adhesion in renal parenchyma, with analysis of fibrosis, to evaluate renal morphology and function after bone marrow mononuclear cell (BMMC) transplantation in two-kidney-one-clip rats. The BMMC therapy significantly decreased blood pressure and renin expression, improved renal morphology and restored the glomerular filtration barrier, with remodelling of podocytes. In addition, there was a reduction in fibrosis, and connexin 40 and nephrin expression were significantly increased after 7 and 15 days of transplantation. Plasma creatinine, urea and total protein levels were restored, and proteinuria was reduced. Furthermore, N- and E-cadherin expression was increased soon after BMMC therapy. Green fluorescent protein-positive BMMCs were found in the renal cortex 24 and 48 h after transplantation into the renal subcapsule, and at 7 and 15 days after transplantation, these cells were observed throughout the renal medulla, indicating cellular migration. Therefore, these data suggest that transplanted BMMCs improve cell-cell communication and adhesion between damaged cells, which is accompanied by a recovery of renal morphology and function.

Transplantation of bone marrow-derived MSCs improves renal function and Na++K+-ATPase activity in rats with renovascular hypertension.

Renovascular hypertension (RVH) is a progressive disease, leading to chronic kidney disease when untreated and no specific treatment is available. Therefore, development of new therapeutic modalities is imperative. RVH is triggered by renal artery stenosis and subsequent renin-angiotensin-aldosterone system activation; it can be experimentally induced by the 2 Kidneys-1 Clip (2K1C) model. This study investigates the therapeutic potential of renal subcapsular mesenchymal stem cell (MSC) infusion in 2K1C rats. Renal morphological and functional changes were analyzed, including Na++K+-ATPase activity and expression, renin angiotensin-converting enzyme (ACE) and angiotensin-II type 1 (AT1R) and type 2 (AT2R) receptors expression. 2K1C rats developed hypertension accompanied by renin upregulation (clipped kidney) and renal Na++K+-ATPase activity and expression reduction. MSC therapy decreased systolic blood pressure, renin, ACE, and AT1R, upregulated AT2R and podocin expression and restored renal Na++K+-ATPase activity and expression. In addition, MSC improved renal morphology, reduced fibrosis and TGF-ß expression in the clipped kidney, decreased proteinuria and restored protein plasma levels. In conclusion, transplantation into a renal subcapsule is an efficient route and MSC is a good candidate for cell therapy, which may represent an interesting approach for chronic kidney disease treatment.

Factors Associated With Bleeding Secondary to Rupture of Esophageal Varices in Children and Adolescents With Cirrhosis.

OBJECTIVE: Bleeding of esophageal varices is the main cause of morbidity and mortality in children with portal hypertension. It is important to understand the factors related with a bleeding episode to evaluate more effective primary prophylaxis. The present study aims to describe the endoscopic and laboratory findings associated with upper gastrointestinal bleeding (UGIB) secondary to esophageal varices. METHOD: A cross-sectional study with 103 children and adolescents with cirrhosis, divided into a group that had experienced an episode of upper UGIB (35 patients) and a group without a history of UGIB (68 patients), was carried out. The esophageal and gastric varices were classified, and the portal hypertensive gastropathy, laboratory findings, and Child-Pugh classification were measured. RESULTS: Factors observed in univariate analysis to be associated with UGIB were the presence of esophageal varices of medium caliber or larger, portal hypertensive gastropathy, presence of red spots on esophageal varices, Child-Pugh class B or C, and hypoalbuminemia (P < 0.05). After multivariate logistic regression analysis, the significant factors were the presence of red spots on esophageal varices and the presence of gastric varices. When separated the autoimmune hepatitis, nonbiliary atresia patients (all patients except the patients with biliary atresia), and biliary atresia groups the findings in the univariate analysis were the presence of esophageal varices of medium or larger caliber, presence of red spots on varices, and presence of gastric varices in the autoimmune hepatitis patients and nonbiliary atresia patients and presence of red spots on esophageal varices, presence of gastric varices, and Child-Pugh classification B or C in biliary atresia group (P < 0.05). After multivariate logistic regression analysis, no statistical significance was found for any factor analyzed in any groups. CONCLUSIONS: The presence of gastric varices and red spots on esophageal varices were related to episodes of UGIB secondary to rupture of esophageal varices. When these findings are observed, indications for endoscopic primary prophylaxis should be evaluated. More studies are, however, necessary to better understand this problem.

Bone marrow mononuclear cell transplantation improves mitochondrial bioenergetics in the liver of cholestatic rats.

Mitochondrial dysfunction has been associated with liver cholestatis. Toxic bile salt accumulation leads to chronic injury with mitochondrial damage, ROS increase and apoptosis, resulting in liver dysfunction. This study aimed to analyze mitochondrial bioenergetics in rats with hepatic fibrosis induced by bile duct ligation (BDL) after BMMNC transplantation. Livers were collected from normal rats, fibrotic rats after 14 and 21 days of BDL (F14d and F21d) and rats that received BMMNC at 14 days of BDL, analyzed after 7 days. F21d demonstrated increased collagen I content and consequently decrease after BMMNC transplantation. Both F14d and F21d had significantly reduced mitochondrial oxidation capacity and increased mitochondrial uncoupling, which were restored to levels similar to those of normal group after BMMNC transplantation. In addition, F21d had a significantly increase of UCP2, and reduced PGC-1α content. However, after BMMNC transplantation both proteins returned to levels similar to normal group. Moreover, F14d had a significantly increase in 4-HNE content compared to normal group, but after BMMNC transplantation 4-HNE content significantly reduced, suggesting oxidative stress reduction. Therefore, BMMNC transplantation has a positive effect on hepatic mitochondrial bioenergetics of cholestatic rats, increasing oxidative capacity and reducing oxidative stress, which, in turn, contribute to liver function recover.

Cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser.

Low-level infrared laser is considered safe and effective for treatment of muscle injuries. However, the mechanism involved on beneficial effects of laser therapy are not understood. The aim was to evaluate cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser at therapeutic fluences. C2C12 myoblast cultures at different (2 and 10 %) fetal bovine serum (FBS) concentrations were exposed to low-level infrared laser (808 nm, 100 mW) at different fluences (10, 35, and 70 J/cm(2)) and evaluated after 24, 48, and 72 h. Cell viability was evaluated by WST-1 assay; reactive oxygen species (ROS), apoptosis, and necrosis were evaluated by flow cytometry. Cell viability was decreased atthe lowest FBS concentration. Laser exposure increased the cell viability in myoblast cultures at 2 % FBS after 48 and 72 h, but no significant increase in ROS was observed. Apoptosis was decreased at the higher fluence and necrosis was increased at lower fluence in myoblast cultures after 24 h of laser exposure at 2 % FBS. No laser-induced alterations were obtained at 10 % FBS. Results show that level of reactive oxygen species is not altered, at least to those evaluated in this study, but low-level infrared laser exposure affects cell viability, apoptosis, and necrosis in myoblast cultures depending on laser fluence and physiologic conditions of cells.

Sexual function of women surviving cervical cancer.

OBJECTIVE: The objective of this study was to evaluate the sexual function of survivors of cervical cancer (CC) in comparison to the control group of women without a history of cancer. METHODS: This was an observational, analytical, case-control study. In the cancer group, women subjected to CC treatment of at least 3 months in the past were included (n = 37). For each survivor, one random selection from a base population control group was made (n = 37) of a woman without a history of cancer and with similar socioeconomic and demographic characteristics. The sexual function was evaluated through the female sex function index (FSFI) instrument. Data collection occurred through the application of questions in a face-to-face interview. RESULTS: In the cancer group, 64.9 % related vaginal stenosis or shortening; 59.5 % were not sexually active and of those which had sexual relations, 80 % showed dysfunction. The total FSFI score varied between 9.60 and 35.10 in the cancer group and 23.90 and 36.00 in the control group. The means of the cancer group were statistically inferior (P < 0.05) to the control group in all the FSFI domains and in the total score. The mean total score was 21.72 in the cancer group, classified as sexual dysfunction when considering a score of 26 as the cutoff point. CONCLUSION: CC treatment was found to have a negative impact on the sexual function of women. Further, sexual function should be monitored routinely by interdisciplinary teams to provide comprehensive care with the objective of an improved quality of life post-cancer.

Central role of PAFR signalling in ExoU-induced NF-κB activation.

ExoU is an important virulence factor in acute Pseudomonas aeruginosa infections. Here, we unveiled the mechanisms of ExoU-driven NF-κB activation by using human airway cells and mice infected with P. aeruginosa strains. Several approaches showed that PAFR was crucially implicated in the activation of the canonical NF-κB pathway. Confocal microscopy of lungs from infected mice revealed that PAFR-dependent NF-κB activation occurred mainly in respiratory epithelial cells, and reduced p65 nuclear translocation was detected in mice PAFR-/- or treated with the PAFR antagonist WEB 2086. Several evidences showed that ExoU-induced NF-κB activation regulated PAFR expression. First, ExoU increased p65 occupation of PAFR promoter, as assessed by ChIP. Second, luciferase assays in cultures transfected with different plasmid constructs revealed that ExoU promoted p65 binding to the three κB sites in PAFR promoter. Third, treatment of cell cultures with the NF-κB inhibitor Bay 11-7082, or transfection with IκBα negative-dominant, significantly decreased PAFR mRNA. Finally, reduction in PAFR expression was observed in mice treated with Bay 11-7082 or WEB 2086 prior to infection. Together, our data demonstrate that ExoU activates NF-κB by PAFR signalling, which in turns enhances PAFR expression, highlighting an important mechanism of amplification of response to this P. aeruginosa toxin.

Th1 immune response to H. pylori infection varies according to the age of the patients and influences the gastric inflammatory patterns.

To compare children and adults in respect to the effect of H. pylori infection on the gastric concentrations of cytokines linked to innate and Th1 immune response, as well as to investigate the changes in the gastric concentrations of the studied cytokines according to the age. We studied 245 children (142 H. pylori-negative and 103 H. pylori-positive) and 140 adults (40 H. pylori-negative and 100 H. pylori-positive). The gastric concentrations of cytokines representative of the innate and Th1 response were higher in the H. pylori-positive than in the -negative children and adults. The gastric concentrations of IL-1α and TNF-α were significantly higher, while those of IL-2, IL-12p70 and IFN-γ were lower in the infected children than in the infected adults. In the infected children, the gastric concentration of IL-1α, IL-2, IL-12p70 and IFN-γ increased, whereas in adults, the gastric concentrations of IFN-γ and IL-12p70 decreased with the aging. Increased gastric concentration of Th1 associated cytokines correlated with increased degree of gastritis that is the background lesion for the development of the H. pylori associated severe diseases. Concluding, Th1 response to H. pylori infection varies according to the age and seems to have determinant implication in the H. pylori infection outcomes.

Impaired mitochondrial function and reduced viability in bone marrow cells of obese mice.

Bone marrow cells (BMCs) are the main type of cells used for transplantation therapies. Obesity, a major world health problem, has been demonstrated to affect various tissues, including bone marrow. This could compromise the success of such therapies. One of the main mechanisms underlying the pathogenesis of obesity is mitochondrial dysfunction, and recent data have suggested an important role for mitochondrial metabolism in the regulation of stem cell proliferation and differentiation. Since the potential use of BMCs for clinical therapies depends on their viability and capacity to proliferate and/or differentiate properly, the analysis of mitochondrial function and cell viability could be important approaches for evaluating BMC quality in the context of obesity. We therefore compared BMCs from a control group (CG) and an obese group (OG) of mice and evaluated their mitochondrial function, proliferation capacity, apoptosis, and levels of proteins involved in energy metabolism. BMCs from OG had increased apoptosis and decreased proliferation rates compared with CG. Mitochondrial respiratory capacity, biogenesis, and the coupling between oxidative phosphorylation and ATP synthesis were significantly decreased in OG compared with CG, in correlation with increased levels of uncoupling protein 2 and reduced peroxisome proliferator-activated receptor-coactivator 1α content. OG also had decreased amounts of the glucose transporter GLUT-1 and insulin receptor (IRß). Thus, Western-diet-induced obesity leads to mitochondrial dysfunction and reduced proliferative capacity in BMCs, changes that, in turn, might compromise the success of therapies utilizing these cells.

Use of technologies by nurses to promote breastfeeding: a scoping review.

OBJECTIVE: To map evidence on technologies used by nurses to promote breastfeeding in Health Services. METHOD: This is a scoping review, based on the recommendations of the Joanna Briggs Institute and following the PRISMA Extension for Scoping Reviews, carried out in 2022. The searches took place in seven databases, using the following combined descriptors: "nurse", "technology", "breastfeeding", and "health services". RESULTS: Fifteen articles were found, the first from 2000 and the last from 2022, all published in English with a predominance of productions in the United States of America (n = 5) and Brazil (n = 3). The link was the technology present in most studies (n = 11). However, with regard to classification, educational and hard technologies were the most used in promotion strategies (n = 14 and n = 12), respectively. CONCLUSION: The articles showed a variety of technologies used to promote breastfeeding in health services, and thus, contributing for the maintenance and duration of breastfeeding.

Bone marrow cell transplantation is associated with fibrogenic cells apoptosis during hepatic regeneration in cholestatic rats.

Liver fibrosis is accompanied by hepatocyte death and proliferation of α-SMA(+) fibrogenic cells (activated hepatic stellate cells and myofibroblasts), which synthesize extracellular matrix components that contribute to disorganization of the hepatic parenchyma and loss of liver function. Therefore, apoptosis of these fibrogenic cells is important to hepatic regeneration. This study aimed to analyze the effect of cell therapy using bone marrow mononuclear cell (BMMNC) transplantation on α-SMA expression and on apoptosis of hepatic cells during liver fibrosis induced by bile duct ligation (BDL). Livers were collected from normal rats, fibrotic rats after 14 and 21 days of BDL, and rats that received BMMNC at 14 days of BDL and were analyzed after 7 days. Apoptosis in fibrogenic cells was analyzed by immunoperoxidase, confocal microscopy, and Western blotting, and liver regeneration was assessed by proliferating cell nuclear antigen staining. Results showed that caspase-3 and proliferating cell nuclear antigen expression were significantly increased in the BMMNC-treated group. Additionally, confocal microscopy analysis showed cells coexpressing α-SMA and caspase-3 in these animals, suggesting fibrogenic cell death. These results suggest a novel role for BMMNC in liver regeneration during fibrotic disease by stimulating fibrogenic cells apoptosis and hepatocyte proliferation, probably through secretion of specific cytokines that modulate the hepatic microenvironment toward an antifibrogenic balance.

Bone marrow mononuclear cell transplantation increases metalloproteinase-9 and 13 and decreases tissue inhibitors of metalloproteinase-1 and 2 expression in the liver of cholestatic rats.

Liver fibrosis results from chronic injury followed by activation of macrophages and fibrogenic cells like myofibroblasts and activated hepatic stellate cells. These fibrogenic cells express α-smooth muscle actin (α-SMA) and produce excessive extracellular matrix (ECM), with disorganization and loss of function of hepatic parenchyma. It is known that increased levels of metalloproteinases (MMPs) in liver fibrosis are associated with reduction of the pathologic ECM and fibrosis resolution. Recently, it has been shown that bone marrow mononuclear cells (BMMNCs) may reduce collagen and α-SMA expression, and ameliorate liver function in cholestatic rats. Therefore, this study aimed to analyze MMP-2, MMP-9 and MMP-13, and tissue inhibitors of MMPs (TIMPs)-1 and TIMP-2 in the liver of cholestatic rats transplanted with BMMNC. Animals were divided into normal rats, cholestatic rats obtained after 14 and 21 days of bile duct ligation (BDL), and rats obtained after 14 days of BDL that received BMMNCs and were killed after 7 days. MMP and TIMP expression was assessed by Western blotting, along with α-SMA, CD68 and CD11b expression by confocal microscopy. Western blotting analysis showed that 14-day BDL animals had significantly reduced amounts of MMP-2 and MMP-13, but increased amounts of MMP-9 compared to normal rats. After 21 days of BDL, overall MMP amounts were decreased and TIMPs were increased. BMMNC transplantation significantly increased MMP-9 and MMP-13, and decreased TIMP expression. Increased MMP activity was confirmed by zymography. MMP-9 and MMP-13 were expressed by macrophages near fibrotic septa, suggesting BMMNC may stimulate MMP production in fibrotic livers, contributing to ECM degradation and hepatic regeneration.

Endoscopic and pharmacological secondary prophylaxis in children and adolescents with esophageal varices.

OBJECTIVE: The aim of this study was to describe the results of endoscopic secondary prophylaxis, alone or in combination with propranolol, used to prevent upper gastrointestinal bleeding (UGIB) in children and adolescents with esophageal varices. METHODS: This observational study followed 43 patients younger than 18 years who received secondary prophylaxis between August 2001 and December 2009. Sclerotherapy and/or band ligation were performed, and propranolol was used when no contraindications were present. The rebleeding rate, number of endoscopic sessions required for variceal eradication, rate of varix recurrence, the occurrence of varices at the gastric fundus, and the occurrence of portal hypertensive gastropathy were evaluated. RESULTS: Endoscopic prophylaxis in combination with propranolol was performed in 25 patients (58.1%) and endoscopic prophylaxis alone was performed in 18 patients (41.9%). Esophageal varices were eradicated in all of the patients after a median of 3 sessions. Varices recurred in 22 patients (51.2%). Rebleeding occurred in 13 patients (30.2%). Fundal varices and portal hypertensive gastropathy developed in 31% and 61.9% of patients, respectively. No deaths related to the endoscopic procedure or UGIB occurred. No statistically significant differences in any of the studied variables were observed when comparing endoscopic prophylaxis with propranolol and endoscopic prophylaxis alone. CONCLUSIONS: No significant differences were observed between sclerotherapy and band ligation. Secondary prophylaxis was effective in eradicating esophageal varices. The use of propranolol did not affect the results of the endoscopic prophylaxis. Furthermore, randomized studies will be necessary to assess the best form of prevention during childhood.

Women's perception about the discovery of breast cancer amid the covid-19 pandemic.

BACKGROUND: Breast cancer is considered a health problem at a worldwide level. In Brazil, the South and Southeast regions have the highest mortality rates. Understanding how they dealt with the diagnostic of a stigmatized disease amid the COVID-19 pandemic and its potential repercussions, may enable healthcare professionals to of life. Thus, this study is aimed at understanding the perception of women about the discovery of breast cancer and the impact of the disease on their lives. METHODS: A qualitative study, with the participation of forty women with breast cancer, under chemotherapy treatment. It was performed in a hospital specialized in oncology, in Juiz de Fora, Brazil, in 2020 and 2021. Data collection was carried out with semi-structured interviews, which were analyzed with Bardin Content Analysis. RESULTS: Based on the central theme "Discovery of the disease", these categories were developed: "Discovery" and "Impact of the disease". A large part of women noticed a change in the breast, even before routine checks. Upon the impact of cancer diagnosis, negative feelings arise, then going through a process of acceptance and coping. Some barriers were faced due to the COVID-19 pandemic, which caused delays in the diagnostic and impact caused by social isolation. Family, friends, and healthcare professionals integrated an important supporting network in order to help coping with the disease. CONCLUSION: The consequences of a breast cancer diagnosis can be devastating. It is necessary that healthcare professionals know and embrace the feelings, beliefs, and values as a part of the aspects related to health. Valuing the supporting network of women suffering from the disease may favor the process of accepting and coping with the neoplasm. The COVID-19 pandemic is highlighted as an obstacle to be overcome specially when it comes to diagnostic assistance and availability of a support network. In that sense, it is worth mentioning the importance of a healthcare team able to offer full assistance, with quality. The need of further studies to determine the impact of the pandemic in the long run.