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A meeting was held by the Party committee of our factory in the middle of September, 1957, at which, in addition to factory workers, the director and dean of studies of secondary school No. 607, and representatives of the district department of public education were present. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the ability of selected microRNAs as biomarkers of atrial fibrillation (AF) in ischemic stroke patients in comparison with other established biochemical biomarkers. A prospective case-control study of consecutive ischemic stroke patients with AF admitted to a comprehensive stroke center was conducted. The control group consisted of patients with ischemic stroke with no AF detected on prolonged (at least 3 weeks) Holter ECG monitoring. As potential biomarkers of AF, we analyzed the plasma levels of microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) and 13 biochemical biomarkers at admission. The predictive accuracy of biomarkers was assessed by calculating the area under the receiver operating characteristic curve. The data of 117 patients were analyzed (61 with AF, 56 with no AF, 46% men, median age 73 years, median National Institutes of Health Stroke Scale 6). Biochemical biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and total triglycerides) were significantly associated with AF. NT-proBNP had the best diagnostic performance for AF with area under the receiver operating characteristic curve 0.92 (95%, CI 0.86-0.98); a cutoff value of >528 ng/L had a sensitivity of 79% and a specificity of 97%. None of the other biomarkers, including microRNAs, was associated with AF. Conventional biochemical biomarkers (NT-proBNP, high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and triglycerides), but not microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) were significantly associated with AF in our ischemic stroke cohort., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Liquid-liquid phase separation has emerged as a crucial mechanism driving the formation of membraneless biomolecular condensates, which play important roles in numerous cellular processes. These condensates, found both in the nucleus and cytoplasm, are formed through multivalent, low-affinity interactions between various molecules. P62-containing condensates serve, among other functions, as proteolytic hubs for the ubiquitin-proteasome system. In this study, we investigated the dynamic interplay between nuclear p62 condensates and promyelocytic nuclear bodies (PML-NBs). We show that p62 condensates stabilize PML-NBs under both basal conditions and following exposure to arsenic trioxide which stimulates their degradation. We further show that this effect on the stability of PML-NBs is due to sequestration of their ubiquitin E3 ligase RNF4 in the p62 condensates with subsequent rapid degradation of the ligase. The sequestration of the ligase is made possible by association between the proline-rich domain of the PML protein and the PB1 domain of p62, which results in the formation of a PML-NB shell around the p62 condensates. Importantly, these hybrid structures do not undergo fusion and mixing of their contents which leaves unsolved the mechanism of sequestration of RNF4 in the condensates. These findings suggest an additional possible mechanism of PML-NB as a tumor suppressor which is mediated via interactions between different biomolecular condensates., Competing Interests: Competing interests statement:The authors declare no competing interest.

The proteasome, the catalytic arm of the ubiquitin system, is regulated via its dynamic compartmentation between the nucleus and the cytoplasm, among other mechanisms. Under amino acid shortage, the proteolytic complex is translocated to the cytoplasm, where it stimulates proteolysis to supplement recycled amino acids for essential protein synthesis. This response is mediated via the mTOR pathway and the lack of the three aromatic amino acids Tyr, Trp, and Phe (YWF). mTOR activation by supplementation of the triad inhibits proteasome translocation, leading to cell death. We now show that tumoral inherent stress conditions result in translocation of the proteasome from the nucleus to the cytosol. We further show that the modulation of the signaling cascade governed by YWF is applicable also to non-starved cells by using higher concentration of the triad to achieve a surplus relative to all other amino acids. Based on these two phenomena, we found that the modulation of stress signals via the administration of YWF leads to nuclear proteasome sequestration and inhibition of growth of xenograft, spontaneous, and metastatic mouse tumor models. In correlation with the observed effect of YWF on tumors, we found - using transcriptomic and proteomic analyses - that the triad affects various cellular processes related to cell proliferation, migration, and death. In addition, Sestrin3-a mediator of YWF sensing upstream of mTOR-is essential for proteasome translocation, and therefore plays a pro-tumorigenic role, positioning it as a potential oncogene. This newly identified approach for hijacking the cellular "satiety center" carries therefore potential therapeutic implications for cancer., (© 2024. The Author(s).)

Purpose: This study aimed to evaluate the efficacy of a single-dose topical rifamycin application on postoperative complications after impacted lower third molar surgery., Materials and Methods: This prospective, controlled clinical study consisted of individuals with bilaterally impacted lower third molars that would be extracted for orthodontic reasons. The extraction sockets were irrigated with 3 ml/250 mg of rifamycin solution in Group 1, while in Group 2 (control group) the extraction sockets were irrigated with 20 ml of physiological saline. Pain intensity was measured daily for 7 days by using visual analog scale. Trismus and edema were evaluated preoperatively and on the postoperative days 2 and 7 by calculating the proportional changes in maximum mouth opening and mean distance between reference points of the face, respectively. Paired samples t-test, Wilcoxon signed rank test and Chi-square test were used to analyze the study variables., Results: 35 patients (19 female, 16 male) were included in the study. The mean age of all participants was 22.19±4.98. Alveolitis was observed in 8 patients, (6 in the control group, 2 in the rifamycin group). There was no statistically significant difference between groups in terms of trismus and swelling measurements on the 2nd and 7th postoperative days (p>0.05). VAS scores were significantly low in rifamycin group on postoperative days 1 and 4 (p<0.05)., Conclusion: Within the limits of the present study, topical rifamycin application reduced the incidence of alveolitis, prevented infection, and provided analgesic effect after surgical removal of impacted third molars., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Earthquakes disproportionately affect women and exacerbate gender and social inequalities. This study aims to investigate the psychological impact of the earthquake in Türkiye on women and the associated factors., Methods: This is a survey-based study. We collected data from 498 women residing in cities most affected by the earthquake., Results: Participants' mean age was 27.72 ± 5.4. Over 78% of the participants lost at least one family member, and 43.7% lost at least one child due to the earthquake. The mean average of Brief Symptom Inventory (BSI) scores was 100.8 (SD = 8.37), and the Global Severity Index was 1.9 (SD = 0.16). Regression analysis showed that higher education levels predicted poor outcomes across most BSI dimensions. Losing a family member and shelter and injury status were also predictors for several mental health outcomes of the BSI subscales., Conclusions: Earthquakes significantly impact women's well-being and may have a broader impact on the whole family. There is an urgent need to provide psycho-social interventions in the response and recovery phases of the crisis to meet the affected women's needs. This includes providing basic needs with attention to women-specific needs, restoring social networks, addressing gender-based violence and providing gender-sensitive specialized interventions for those who need further support., (© The Author(s) 2024. Published by Oxford University Press on behalf of Faculty of Public Health.)

Background and Objectives : The aim of this study was to investigate the efficacy of a single preoperative dose of deflazacort on pain, swelling, and trismus after impacted lower third molar surgery. Materials and Methods : This randomised, prospective, double-blind, split-mouth clinical study included 26 healthy individuals with bilaterally impacted lower third molars. Group 1 was given a placebo (single-dose vitamin C tablet), and group 2 was given a single 30 mg dose of deflazacort 1 h prior to surgery. Pain was evaluated using the visual analogue scale for 1 week postoperatively. Oedema (in mm) and trismus (in mm) were evaluated preoperatively and on postoperative days 2 and 7. The Mann-Whitney U test was applied for group analyses. p values < 0.05 were considered statistically significant. Results : Postoperative pain scores were significantly lower in the deflazacort group at the 6th and 12th hours after surgery ( p < 0.05). There were no significant differences in trismus between the groups at any time point ( p > 0.05). There was less oedema in the deflazacort group on postoperative days 2 and 7, without any statistically significant difference ( p > 0.05). Conclusions : A single preoperative dose of 30 mg deflazacort was found to be clinically effective in reducing pain and oedema after extraction of impacted lower third molars.

Introduction: Arrhythmogenic cardiomyopathy (AC) is an inherited cardiomyopathy characterized by fibro-fatty replacement of cardiomyocytes, leading to life-threatening ventricular arrhythmia and heart failure. Pathogenic variants of desmoglein2 gene (DSG2) have been reported as genetic etiologies of AC. In contrast, many reported DSG2 variants are benign or variants of uncertain significance. Correct genetic variant classification is crucial for determining the best medical therapy for the patient and family members., Methods: Pathogenicity of the DSG2 Ser194Leu variant that was identified by whole exome sequencing in a patient, who presented with ventricular tachycardia and was diagnosed with AC, was investigated by electron microscopy and immunohistochemical staining of endomyocardial biopsy sample., Results: Electron microscopy demonstrated a widened gap in the adhering junction and a less well-organized intercalated disk region in the mutated cardiomyocytes compared to the control. Immunohistochemical staining in the proband diagnosed with AC showed reduced expression of desmoglein 2 and connexin 43 and intercalated disc distortion. Reduced expression of DSG2 and Connexin 43 were observed in cellular cytoplasm and gap junctions. Additionally, we detected perinuclear accumulation of DSG2 and Connexin 43 in the proband sample., Conclusion: Ser194Leu is a missense pathogenic mutation of DSG2 gene associated with arrhythmogenic left ventricular cardiomyopathy., (© 2024 Wiley Periodicals LLC.)

Problems: This study was conducted to examine the association between posttraumatic stress disorder and mental health status of adolescents exposed to the worst disaster of the century., Methods: This study was descriptive, cross-sectional, and correlational. This research was conducted between March 31 and July 1, 2023. The study was conducted with earthquake survivors who migrated from Kahramanmaraş, the epicenter of the earthquake, and Adıyaman and Hatay, the other two cities where it was most effective, to Şanlıurfa. The study was conducted with a total of 947 adolescents. "Personal Information Form," "Child Posttraumatic Stress Reaction Index," and "Symptom Distress Check List- (SCL-90)" were used to collect data. Linear regression method was used in the analysis of the research. Path analysis was performed using PATH analysis., Findings: The mean age of the adolescents participating in the study was 16.69 ± 1.41 years. It was found that the Global Severity Index (GSI) of the adolescents was at the pathological level with a mean of 2.36 ± 0.68. Posttraumatic stress reactions of the adolescents who experienced the earthquake was found to explain 97.2% of their mental symptoms (anxiety, depression, somatization, anger-hostility, obsession-compulsion, interpersonal sensitivity, phobic anxiety, paranoid ideation, psychotic symptoms, other problems, and GSI) (p < 0.001). It was found that the age of the adolescents, total number of losses in the earthquake, the time they stayed under the rubble, the time they waited for siblings to be pulled from under the rubble and the state of having loss due to the earthquake explained 74.4% of the posttraumatic stress reactions (p < 0.001)., Conclusions: As a conclusion, it was found that the adolescents who experienced the earthquake experienced severe posttraumatic stress symptoms. It was also found that adolescents who experienced high levels of trauma symptoms showed pathological mental symptoms. After the earthquake, adolescents should be evaluated periodically in terms of posttraumatic stress symptoms. In the evaluations to be made, it is important to determine how adolescents are affected especially mentally. In this context, interventions should be implemented for the identified mental symptoms (anxiety, depression, somatization, etc.)., (© 2024 Wiley Periodicals LLC.)

Background: Hydatid cyst is a parasitic infection, often caused by Echinococcus granulosus . Although it is classified as a benign disease, cyst ruptures in the abdomen can be fatal. Ruptures occur spontaneously or after trauma. We aimed to report data from patients who underwent emergency surgery due to spontaneous intra-abdominal hydatid cyst rupture., Methods: Upon a retrospective review of the records at Department of General Surgery, Faculty of Medicine, Harran University, Şanlıurfa, Turkey, we found that 34 cases were operated on due to hydatid cyst rupture between January 2012 and October 2022. All patients were operated on in an emergency, and partial cystectomy, intra-abdominal irrigation, and drainage were performed using laparotomy. The patients were evaluated in terms of age, sex, symptoms, radiological findings, laboratory results, intraoperative findings, and postoperative follow-ups., Results: Twenty-two (64.7%) female and 12 (35.3%) male patients were enrolled. The mean age was 39.1 (±17.58) years. All patients experienced spontaneous rupture. The ruptured cyst was found in the liver in 32 patients (94%), the spleen in 1 patient (3%), and the pelvis in 1 patient (3%). The diagnosis was determined using ultrasonography in 12 (35.3%) patients, computed tomography in 21 (61.8%) patients, and magnetic resonance imaging in 1 (2.9%) patient. All patients exhibited acute abdomen and leukocytosis. The average length of hospital stay was 5.14 (±1.37) days., Conclusion: Hydatid cyst rupture should be considered in cases of acute abdomen, particularly in regions where the disease is endemic, as in our region. The ruptured hydatid cyst was primarily observed in the liver (94.11% of cases)., Competing Interests: Conflict of interest There are no conflicts of interest., (Copyright© 2024 Yönder et al. Published by Tehran University of Medical Sciences.)

The proteasome is responsible for removal of ubiquitinated proteins. Although several aspects of its regulation (e.g., assembly, composition, and post-translational modifications) have been unraveled, studying its adaptive compartmentalization in response to stress is just starting to emerge. We found that following amino acid starvation, the proteasome is translocated from its large nuclear pool to the cytoplasm-a response regulated by newly identified mTOR-agonistic amino acids-Tyr, Trp, and Phe (YWF). YWF relay their signal upstream of mTOR through Sestrin3 by disrupting its interaction with the GATOR2 complex. The triad activates mTOR toward its downstream substrates p62 and transcription factor EB (TFEB), affecting both proteasomal and autophagic activities. Proteasome translocation stimulates cytosolic proteolysis which replenishes amino acids, thus enabling cell survival. In contrast, nuclear sequestration of the proteasome following mTOR activation by YWF inhibits this proteolytic adaptive mechanism, leading to cell death, which establishes this newly identified pathway as a key stress-coping mechanism., Competing Interests: Declaration of interests I. Livneh and A.C. are co-founders and board members of Tripod Therapeutics, Ltd., (Copyright © 2023. Published by Elsevier Inc.)

Background: Heparanase, known to be involved in angiogenesis, cancer progression, and inflammation, was shown to form a complex with tissue factor (TF) via its procoagulant domain and to enhance the hemostatic system., Objectives: To reveal a potential role of heparanase procoagulant domain in nonhemostatic effects., Methods: Effects of peptides 16 and 16AC derived from the heparanase procoagulant domain, discovered by our group, were studied using the XTT proliferation assay, western blot analysis, and immunostaining in vitro and a mouse wound-healing model., Results: Procoagulant peptides induced increased proliferation, release of heparanase, and upregulation of heparanase, TF, tissue factor pathway inhibitor (TFPI), and TFPI-2 in U87, T47D, and MCF-7 tumor cell lines and in endothelial cells. These results were reversed by a peptide derived from TFPI-2 that inhibited the heparanse procoagulant domain-TF complex. Thrombin had a similar effect on tumor cell proliferation and heparanase release, although the impact of thrombin on cell proliferation was mediated by the heparanase procoagulant domain. A mouse model of full-thickness skin incision exhibited higher levels of heparanase, TF, TFPI, and TFPI-2 in the healing skin, mainly in the blood vessel wall and lumen in animals injected with the procoagulant peptides compared to controls. The cells transfected to overexpress full-length TF or TF devoid of the cytoplasmic domain demonstrated that the procoagulant domain conveyed intracellular signaling via TF., Conclusion: Heparanase procoagulant domain induces nonhemostatic effects via TF. The finding that TF serves as a receptor to heparanase supports the close direct relation between the hemostatic system and cancer progression., (© 2023 Published by Elsevier Inc. on behalf of International Society on Thrombosis and Haemostasis.)

Objectives: This study aimed to evaluate the effects of different concentrations of boric acid (BA) combined with chlorhexidine (CHX) mouthwash on postoperative complications and periodontal healing following impacted third molar surgery., Materials and Methods: A total of 80 patients were randomly divided into eight groups. The patients in the study groups received different concentrations of BA ranging from 0.1% to 2.5% combined with CHX or 2% BA mouthwash alone. The control group received CHX mouthwash alone. The scores of self-reported pain and jaw dysfunction, trismus, edema, number of analgesics used, and periodontal parameters were compared between the groups., Results: 2.5% BA + CHX group had significantly lower pain and facial swelling values during the follow-up period. 2% BA + CHX group reported significantly lower jaw dysfunction scores on the fourth and fifth postoperative days. The control group showed significantly higher values for pain, jaw dysfunction, and facial swelling than other groups. No significant differences were found between the groups regarding trismus, analgesic use, and periodontal variables., Conclusions: The combination of higher concentrations of BA with CHX was more effective in reducing pain, jaw dysfunction, and swelling following impacted third molar surgery than CHX mouthwash alone., Clinical Relevance: The combination of BA and CHX showed better results than the gold standard CHX mouthwash in reducing postoperative complications related to surgical removal of impacted third molars without any adverse effects. This new combination can be an effective alternative to traditional mouthwashes after impacted third molar surgery to ensure oral hygiene., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To assess the effects of naproxen sodium-codeine phosphate, naproxen sodium-dexamethasone, and naproxen sodium on myofascial pain., Methods: This randomized, double-blind prospective clinical study was conducted with patients who applied with the complaint of pain in the temporomandibular region. A total of 169 patients were randomly divided into four groups and received the following treatments: Group A: naproxen sodium 550 mg; Group B: naproxen sodium 550 mg + codeine phosphate 30 mg; Group C: naproxen sodium 550 mg + single-dose dexamethasone 8 mg, and Group D: paracetamol 500 mg., Results: Of the patients, 132 were female, and 37 were male, with a mean age of 27.04 ± 10.56 (18-69 years). Analgesic efficiency of the naproxen sodium-codeine phosphate group was the most effective at the 2nd week and 4th week ( p < 0.05)., Conclusion: Naproxen sodium-codeine phosphate might be preferred as an analgesic in similar cases with severe myofascial pain.

Housewives are individuals who assume the role of caregiver in the family in almost every society and experience serious psychological difficulties in line with this role. These psychological difficulties may develop due to the pathological relationships that women have, especially with their family members. In this context, the study aims to examine the mental health states of housewives within the framework of codependence and self-perceptions. This study, which was planned as descriptive, relational, and cross-sectional, by online questionnaire method, consists of 371 housewives. Personal information form, Codependency Assessment Tool (CODAT), social comparison scale (SCS), and the Symptom Checklist-90-Revised (SCL-90-R) were used to collect data. In the analysis of the research, a structural equation model was established by using SPSS 25 and AMOS 23 package programs. It was found that the mean age of the housewives included in the study was 35.19 ± 9.85 and 35.5% of the participants were university graduates, 13.2% lived in an extended family, 13.7% had a poor relationship with their spouse, and 51.5% were only responsible for housework. Besides, according to the results of the study, it was found that the total mean score of SCS was 75.16 ± 21.73, SCL-90-R was 1.96 ± 0.95, and CODAT was 76.16 ± 17.75. In the case of analysis, there was strong correlation between the mental status of housewives and both their codependency levels and their self-perceptions. It has been determined that increased levels of codependency and negative self-perception of housewives increase the psychological symptoms experienced., Competing Interests: Conflict of InterestThe author declares that he has done in the design, execution, and analysis of the paper, and that they have approved the final version. Additionally, there are no conflicts of interest in connection with this paper, and the material described is not under publication or consideration for publication., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: The study was conducted to determine the effect of the communication skills psychoeducation program on the self-esteem and communication skills of the care staff working in a rehabilitation center., Material and Method: The sample was 61 in the study, which was conducted in a quasi-experimental way with a single group pretest, posttest and follow-up pattern., Finding: At the end of the psychoeducation program, it was determined that the psychoeducation has a positive effect on the self-esteem and communication skills of the care staffs., Practice Implications: Implementation of this practice, which can be applied to all care staffs in the clinics or rehabilitation centers, with repeated measurements such as 6 or 12-month periods may contribute to the literature., (© 2022 Wiley Periodicals LLC.)

Purpose: The aim of this retrospective research is to compare frontal sinus dimensions in skeletal Class I, skeletal Class II, and skeletal Class III individuals and to evaluate the relationship of these dimensions with anterior skull base length and some cephalometric values., Materials and Methods: In this research, we used lateral cephalometric radiographs of 60 people aged 17 to 25. In individuals with skeletal Class I malocclusion, skeletal Class II malocclusion due to mandibular insufficiency, and skeletal Class III malocclusion due to mandibular excess, measurements of frontal sinus length and height as well as S-N, Co-A and Co- Gn lengths, ANB0, FMA0, SN-GoGn0 angles values were performed. The length between the highest point and the lowest point of the frontal sinus was calculated as the height of the frontal sinus, and the length between the most anterior and the most posterior points of the frontal sinus was calculated as the length of the frontal sinus., Results: The frontal sinus length and height were found to be higher in skeletal Class III individuals than in skeletal Class I and skeletal Class II individuals, however, there was no significant difference between skeletal Class I and Class II individuals., Conclusion: The increase in frontal sinus height and length correlated positively with the decrease in the ANB angle and the increase in the SN and Co-Gn lengths. The dimensions of the frontal sinus may be an indicator for the remaining mandibular growth potential., (Copyright © 2022 European Oral Research.)

Missense mutations in the p53 tumor suppressor abound in human cancer. Common (“hotspot”) mutations endow mutant p53 (mutp53) proteins with oncogenic gain of function (GOF), including enhanced cell migration and invasiveness, favoring cancer progression. GOF is usually attributed to transcriptional effects of mutp53. To elucidate transcription-independent effects of mutp53, we characterized the protein interactome of the p53R273H mutant in cells derived from pancreatic ductal adenocarcinoma (PDAC), where p53R273H is the most frequent p53 mutant. We now report that p53R273H, but not the p53R175H hotspot mutant, interacts with SQSTM1/p62 and promotes cancer cell migration and invasion in a p62-dependent manner. Mechanistically, the p53R273H-p62 axis drives the proteasomal degradation of several cell junction–associated proteins, including the gap junction protein Connexin 43, facilitating scattered cell migration. Concordantly, down-regulation of Connexin 43 augments PDAC cell migration, while its forced overexpression blunts the promigratory effect of the p53R273H-p62 axis. These findings define a mechanism of mutp53 GOF.

Membraneless condensates have recently caught the attention of biologists as hubs for cellular components required for catalysis of basic processes. Whether they are real has become the center of heated discussion where the main issues are their mechanism of assembly and function. A recent study describing these condensates as hubs for protein degradation by the ubiquitin system may shed a new light on this recent development in cell biology., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 Taylor & Francis Group, LLC.)

Degradation of a protein by the ubiquitin-proteasome system (UPS) is a multistep process catalyzed by sequential reactions. Initially, ubiquitin is conjugated to the substrate in a process mediated by concerted activity of three enzymes; the last of them-a ubiquitin ligase (E3)-belongs to a family of several hundred members, each recognizing a few specific substrates. This is followed by repeated addition of ubiquitin moieties to the previously conjugated one to generate a ubiquitin chain that serves as a recognition element for the proteasome, which then degrades the substrate. Ubiquitin is recycled via the activity of deubiquitinating enzymes (DUBs). It stands to reason that efficiency of such a complex process would depend on colocalization of the different components in an assembly that allows the reactions to be carried out sequentially and processively. Here we describe nuclear condensates that are dynamic in their composition. They contain p62 as an essential component. These assemblies are generated by liquid-liquid phase separation (LLPS) and also contain ubiquitinated targets, 26S proteasome, the three conjugating enzymes, and DUBs. Under basal conditions, they serve as efficient centers for proteolysis of nuclear proteins (e.g., c-Myc) and unassembled subunits of the proteasome, suggesting they are involved in cellular protein quality control. Supporting this notion is the finding that such foci are also involved in degradation of misfolded proteins induced by heat and oxidative stresses, following recruitment of heat shock proteins and their associated ubiquitin ligase CHIP., Competing Interests: The authors declare no competing interest.

Purpose: This study has been performed to investigate the effects of the interpersonal relational role analysis (IRRA) on the nursing students' anxiety levels and their interpersonal problem-solving orientation., Design and Methods: This study was conducted with randomized controlled, pre-test-post-test control group design and follow-up test patterns (n = 8)., Finding: Following the practice of IRRA sessions, the findings showed that IRRA has a positive effect on the anxiety levels and interpersonal problem-solving orientations of nursing students., Practice Implications: Implementation of this practice, which can also be employed by psychiatric nurses in the clinic, in other samples with repeated measurements, such as in 6-monthly or 12-monthly periods, could contribute to the literature., (© 2020 Wiley Periodicals LLC.)

Objectives: This multicenter study aimed to evaluate the effects of St. John's wort oil and virgin olive oil on the postoperative complications and compare this with chlorhexidine gluconate plus benzydamine hydrochloride mouthwash after the removal of impacted third molar., Methods: A total of 90 patients in need of impacted third molar surgery were included in this study. All included patients were randomly divided into 3 groups. The patients in group 1 received St. John's wort oil; the patients in group 2 received virgin olive oil, and those in group 3 received mouthwash containing chlorhexidine gluconate plus benzydamine hydrochloride. The self-reported pain and difficulty during jaw function, trismus, facial swelling, number of analgesics used during first postoperative week, and postoperative periodontal condition including plaque accumulation, bleeding on probing, and periodontal pocket depth were compared between the groups., Results: No significant differences were found regarding the study variables., Conclusions: The data of the present study supports that the use of essential oils provides efficient alternative to the gold standard chlorhexidine gluconate mouthwash in reducing postoperative complications and improving healing process without adverse effects after surgical removal of impacted third molars., Clinical Relevance: The use of essential oils showed similar results as the chlorhexidine gluconate mouthwash regarding swelling, mouth opening, pain, need for rescue medication, infectious complications (i.e., alveolar osteitis), and periodontal healing. Therefore, essential oils can be an alternative to routine mouthwashes to ensure oral hygiene after impacted third molar surgery.

Study Question: Does progestin have an effect on heparanase level and procoagulant activity?, Summary Answer: Progestin increases the heparanase level and procoagulant activity via the estrogen receptor and the magnitude of the effect depends on the progestin type., What Is Known Already: Users of combined oral contraceptives (COCs) containing third- and fourth-generation progestins have a higher risk of venous thrombosis compared to those employing second-generation progestins. Heparanase protein is capable of degrading heparan sulfate (HS) chains and enhancing activation of the coagulation system. We have previously demonstrated that estrogen enhances the expression and procoagulant activity of heparanase., Study Design, Size, Duration: Estrogen and progestin receptor positive breast carcinoma cell lines: EMT6, T47D and MCF-7 were compared to the MDA-231 breast carcinoma cell line devoid of these receptors. This observational study incorporated 45 users of third-generation COCs progestins, 21 users of fourth-generation COCs progestins and 28 individuals not using hormonal therapy and not pregnant per history., Participants/materials, Setting, Methods: Second-generation progestin-levonorgestrel, third-generation progestin-desogastrel (DSG), an estrogen receptor antagonist-ICI 182.780 and a progestin receptor antagonist-mifepristone, were added to cell lines. Heparanase level and procoagulant activity, HS levels, tissue factor (TF) activity and factor Xa levels were evaluated in the plasma of the study group., Main Results and the Role of Chance: Levonorgestrel and DSG increased heparanase levels in the cells and medium. The effect of DSG was more prominent and additive to that of estrogen. The effect was inhibited by ICI 182.780. In the plasma of COC users, heparanase procoagulant activity, HS levels, TF activity and factor Xa levels were significantly higher compared to controls. In COC pills containing the same dose of estrogen, the procoagulant effect of drospirenone was significantly stronger than that of DSG and gestodene., Limitations, Reasons for Caution: The limitations of the study include a small number of participants in each study group, although the results are statistically significant and evaluated by several different coagulation parameters., Wider Implications of the Findings: The study demonstrates a new mechanism through which progestin affects coagulation system activation and shows that this effect is progestin type-dependent. Development of a progestin derivative with an attenuated effect on heparanase procoagulant activity may reduce thrombotic risk., Study Funding/competing Interest(s): No external funding was sought for this study. Y.N. is named in a European patent application No. IL201200027 filed on 18 January 2012. Other authors have no conflict of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Warfarin use is limited by a low therapeutic index and significant interindividual variability of the daily dose. The most important factor predicting daily warfarin dose is individual genotype, polymorphisms of genes CYP2C9 (warfarin metabolism) and VKORC1 (sensitivity for warfarin). Algorithms using clinical and genetic variables could predict the daily dose before the initiation of therapy. The aim of this study was to develop and validate an algorithm for the prediction of warfarin daily dose in Czech patients., Methods: Detailed clinical data of patients with known and stable warfarin daily dose were collected. All patients were genotyped for polymorphisms in genes CYP2C9 and VKORC1 ., Results: Included patients were divided into derivation (n=175) and validation (n=223) cohorts. The final algorithm includes the following variables: Age, height, weight, treatment with amiodarone and presence of variant alleles of genes CYP2C9 and VKORC1 . The adjusted coefficient of determination is 72.4% in the derivation and 62.3% in the validation cohort (p<0.001)., Conclusions: Our validated algorithm for warfarin daily dose prediction in our Czech cohort had higher precision than other currently published algorithms. Pharmacogenetics of warfarin has the potential in the clinical practice in specialized centers., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Problem: This is a descriptive study to determine the levels of anger and aggression in street children with substance dependence., Methods: The study was conducted between October 2013 and March 2014 with 103 street children who use substances. Personal Information Form, Aggression Scale (AS), and Trait Anger and Anger Expression Styles Scale (STAXI) were used as data collection tools., Findings: The rate of the children reported that they lived on the streets due to the conflicts with the family was 67% and 35% of participants reported that they were exposed to violence on the street. The total score of AS was 146.78 ± 25.91, the mean score of the anger subscale of the STAXI was 31.05 ± 9.00 while the scores of the anger-in subscale and the anger-out subscale scores were 19.02 ± 4.55 and 23.04 ± 6.19, respectively. The total scores of AS had a significant positive correlation with both the trait anger and "anger-in" subscale scores. The results show that substance use negatively affected anger control in street children., Conclusion: The data demonstrated that the presence of continuous anger and turning the anger against oneself correlated with increased levels of aggression. Increasing the duration of living on the street, working on the street and being exposed to stressful situations in the street increased the "anger-in" scores., (© 2020 Wiley Periodicals, Inc.)

It has been demonstrated that the osteoconductivity, hydrophilicity, and biological capacity of titanium decreases over time, and this phenomenon was described as the biological aging of titanium. The aim of this study was to evaluate whether the age of sand-blasted and acid-etched (SLA) titanium dental implants (duration from the production date until the date of dental implant surgery) affects marginal bone resorption and implant survival. This nonrandom convenience-sample retrospective pilot study was carried out in 200 implants of 64 patients. Radiographic measurements were performed on intraoral periapical radiographs. Implants were divided into 2 age groups; group 1 = 0-3 months and group 2 = 36-41 months. A P value < .05 was considered statistically significant. Of the implants, 41% (n = 82) were between 0 and 3 months old, and 59% (n = 118) were between 36 and 41 months old. All (n = 200) of the implants survived and maintained their function. The mean mesial marginal resorption measurement was 0.60 ± 0.65 mm, and the mean distal marginal resorption was 0.77 ± 1.07 mm. There was no statistically significant difference between the amount of mesial and distal marginal bone resorption according to implant age (P > .05). In SLA surface titanium implants with adequate initial primary stability and a 3-month osseointegration period before loading, biological aging of titanium did not affect implant survival and marginal bone resorption.

Activity of heparanase, responsible for cleavage of heparan sulfate (HS), is strongly implicated in tumor metastasis. This is due primarily to remodeling of the extracellular matrix (ECM) that becomes more prone to invasion by metastatic tumor cells. In addition, heparanase promotes the development of blood and lymph vessels that mobilize disseminated cells to distant organs. Here, we provide evidence for an additional mechanism by which heparanase affects cell motility, namely the destruction of E-cadherin based adherent junctions (AJ). We found that overexpression of heparanase or its exogenous addition results in reduced E-cadherin levels in the cell membrane. This was associated with a substantial increase in the phosphorylation levels of E-cadherin, β-catenin, and p120-catenin, the latter recognized as a substrate of Src. Indeed, we found that Src phosphorylation is increased in heparanase overexpressing cells, associating with a marked decrease in the interaction of E-cadherin with β-catenin, which is instrumental for AJ integrity and cell-cell adhesion. Notably, the association of E-cadherin with β-catenin in heparanase overexpressing cells was restored by Src inhibitor, along with reduced cell migration. These results imply that heparanase promotes tumor metastasis by virtue of its enzymatic activity responsible for remodeling of the ECM, and by signaling aspects that result in Src-mediated phosphorylation of E-cadherin/catenins and loosening of cell-cell contacts that are required for maintaining the integrity of epithelial sheets., (Copyright © 2020 Cohen-Kaplan, Ilan and Vlodavsky.)

Apolipoprotein (APOE) ɛ4 is a well-known risk factor for late-onset Alzheimer's disease (AD), but other AD-related gene polymorphisms might also be important, such as the polymorphism within the brain-derived neurotrophic factor (BDNF) gene. Carriage of BDNF Val66Met has been associated with faster cognitive decline and greater hippocampal atrophy in cognitively normal elderly. Thus, we examined the effects of the concurrent presence of APOE and BDNF polymorphisms on cognitive functions and brain morphometry in amnestic mild cognitive impairment (aMCI) patients. 107 aMCI patients (mean age = 72.2) were recruited from the Czech Brain Aging Study and, based on APOE and BDNF genes polymorphisms, were divided into four groups: ɛ4-BDNFVal/Val (n = 37), ɛ4-BDNFMet (n = 19), ɛ4+BDNFVal/Val (n = 35), and ɛ4+BDNFMet (n = 16). All patients underwent clinical examination, magnetic resonance imaging, and complex neuropsychological battery. The combination of APOEɛ4+ and BDNF Met was associated with significantly worse memory performance in immediate and delayed recall compared to other polymorphism groups. We did not observe increased atrophy in areas related to memory function in the ɛ4+BDNFMet group. Our findings suggest that carriage of ɛ4+BDNFMet is associated with more pronounced memory dysfunction, a typical feature of early AD, but not with structural brain changes in aMCI patients. These findings suggest that in APOEɛ4/BDNF Met carriers, synaptic dysfunction affecting memory may precede pronounced structural changes.

Background: The apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory and spatial navigation deficits. The brain-derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment in APOEɛ4 carriers but its role in APOEɛ4-related spatial navigation deficits has not been established., Objective: We examined influence of APOE and BDNF Val66Met polymorphism combination on spatial navigation and volumes of selected navigation-related brain regions in cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (aMCI)., Methods: 187 participants (aMCI [n = 116] and CU [n = 71]) from the Czech Brain Aging Study were stratified based on APOE and BDNF Val66Met polymorphisms into four groups: ɛ4-/BDNFVal/Val, ɛ4-/BDNFMet, ɛ4+/BDNFVal/Val, and ɛ4+/BDNFMet. The participants underwent comprehensive neuropsychological examination, brain MRI, and spatial navigation testing of egocentric, allocentric, and allocentric delayed navigation in a real-space human analogue of the Morris water maze., Results: Among the aMCI participants, the ɛ4+/BDNFMet group had the least accurate egocentric navigation performance (p < 0.05) and lower verbal memory performance than the ɛ4-/BDNFVal/Val group (p = 0.007). The ɛ4+/BDNFMet group had smaller hippocampal and entorhinal cortical volumes than the ɛ4-/BDNFVal/Val (p≤0.019) and ɛ4-/BDNFMet (p≤0.020) groups. Among the CU participants, the ɛ4+/BDNFMet group had less accurate allocentric and allocentric delayed navigation performance than the ɛ4-/BDNFVal/Val group (p < 0.05)., Conclusion: The combination of APOEɛ4 and BDNF Met polymorphisms is associated with more pronounced egocentric navigation impairment and atrophy of the medial temporal lobe regions in individuals with aMCI and less accurate allocentric navigation in CU older adults.

Warfarin treatment is commonly started with a fixed loading dose that might be associated with an increased risk of bleeding. An individual maintenance dose can then be estimated based on a pharmacogenetic algorithm. Starting treatment with the estimated dose implies a longer time to reach the therapeutic range. Our goal was to compare the safety and efficacy of initiating warfarin treatment with a loading dose guided by pharmacogenetics versus a maintenance dose. The primary endpoint was time in the therapeutic range (TTR) in the first 10 days of treatment. Secondary endpoints were time to the first international normalized ratio (INR) in therapeutic range (2.0-3.0) and occurrence of serious adverse events. Consenting cardioembolic stroke patients were genotyped for CYP2C9 (cytochrome P450 2C9 gene) and VKORC1 (vitamin K epoxide reductase complex, subunit 1 gene) polymorphisms and a maintenance warfarin dose was estimated. Patients were randomized into two groups. The loading dose group (LDG) patients received twice the estimated dose in the first 2 days of treatment. The maintenance dose group (MDG) patients received the estimated dose directly from day one. The TTR in the first 10 days was significantly higher in the LDG than in the MDG (50.5% vs. 38.3%, p = 0.003). The time to the first INR in this range was significantly shorter in the LDG (5.24 vs. 7.3 days). There were no significant differences in the INR above this range or serious adverse events. Warfarin loading dose guided by pharmacogenetics after recent cardioembolic stroke improved the efficacy of warfarin initiation without increasing the risk of adverse events.

Introduction: Following years of controversy regarding screening for prostate cancer using prostate-specific antigen, evidence evolves towards a more restrained and preference-based use. This study reports the impact of landmark trials and updated recommendations on the incidence rate of prostate cancer screening by Swiss general practitioners., Methods: We performed a retrospective analysis of primary care data, separated in 3 time periods based on dates of publications of important prostate-specific antigen screening recommendations. 1: 2010-mid 2012 including 2 updates; 2: mid 2012-mid 2014 including a Smarter Medicine recommendation; 3: mid-2014-mid-2017 maintenance period. Period 2 including the Smarter Medicine recommendation was defined as reference period. We further assessed the influence of patient's age and the number of prostate-specific-antigen (PSA) tests, by the patient and within each time period, on the mean PSA concentration. Uni- and multivariable analyses were used as needed., Results: 36,800 men aged 55 to 75 years were included. 14.6% had ≥ 2 chronic conditions, 11.7% had ≥ 1 prostate-specific antigen test, (mean 2.60 ng/ml [SD 12.3]). 113,921 patient-years were covered. Data derived from 221 general practitioners, 33.5% of GP were women, mean age was 49.4 years (SD 10.0), 67.9% used prostate-specific antigen testing. Adjusted incidence rate-ratio (95%-CI) dropped significantly over time periods: Reference Period 2: incidence rate-ratio 1.00; Period 1: incidence rate-ratio 1.74 (1.59-1.90); Period 3: incidence rate-ratio 0.61 (0.56-0.67). A higher number of chronic conditions and a patient age between 60-69 years were significantly associated with higher screening rate. Increasing numbers of PSA testing per patient, as well as increasing age, were independently and significantly associated with an increase in the PSA value., Conclusion: Swiss general practitioners adapted screening behavior as early as evidence of a limited health benefit evolved, while using a risk-adapted approach whenever performing multiple testing. Updated recommendations might have helped to maintain this decrease. Further recommendations and campaigns should aimed at older patients with multimorbidity, to sustain a further decline in prostate-specific antigen screening practices., Competing Interests: The authors have declared that no competing interests exist.

Background: A comprehensive in-hospital patient management with reasonable and economic resource allocation is arguably the major challenge of health-care systems worldwide, especially in elderly, frail, and polymorbid patients. The need for patient management tools to improve the transition process and allocation of health care resources in routine clinical care particularly for the inpatient setting is obvious. To address these issues, a large prospective trial is warranted., Methods: The "Integrative Hospital Treatment in Older patients to benchmark and improve Outcome and Length of stay" (In-HospiTOOL) study is an investigator-initiated, multicenter effectiveness trial to compare the effects of a novel in-hospital management tool on length of hospital stay, readmission rate, quality of care, and other clinical outcomes using a time-series model. The study aims to include approximately 35`000 polymorbid medical patients over an 18-month period, divided in an observation, implementation, and intervention phase. Detailed data on treatment and outcome of polymorbid medical patients during the in-hospital stay and after 30 days will be gathered to investigate differences in resource use, inter-professional collaborations and to establish representative benchmarking data to promote measurement and display of quality of care data across seven Swiss hospitals. The trial will inform whether the "In-HospiTOOL" optimizes inter-professional collaboration and thereby reduces length of hospital stay without harming subjective and objective patient-oriented outcome markers., Discussion: Many of the current quality-mirroring tools do not reflect the real need and use of resources, especially in polymorbid and elderly patients. In addition, a validated tool for optimization of patient transition and discharge processes is still missing. The proposed multicenter effectiveness trial has potential to improve interprofessional collaboration and optimizes resource allocation from hospital admission to discharge. The results will enable inter-hospital comparison of transition processes and accomplish a benchmarking for inpatient care quality.

Background and Objective: Cutaneous metastases (CMs) account for 2% of skin tumors and their incidence varies between 0.7% and 9% in patients with cancer. The objective of this study was to describe and analyze the demographic, clinical, and histopathologic characteristics of CM in patients who visited 2 hospitals in the Santiago de Chile metropolitan region., Material and Method: We performed a retrospective, descriptive, analytical, observational, cross-sectional study. We reviewed the pathology reports, patient records, pathology slides, and dates of death for diagnosed cases of CM from the anatomic pathology departments of 2 hospitals in the Santiago de Chile metropolitan region between 2015 and 2017., Results: Ninety-six patients with CM were included in the study; 60.42% were women and 39.58% were men. The mean (SD) age was 67.95 (13.74) years, with a range of 28 to 96 years. The most common primary tumor was melanoma in 27.08% of cases (n=26), followed by breast cancer (18.75%, n=18), and adenocarcinoma (15.63%, n=15). The median time between diagnosis of the tumor and cutaneous metastasis was 9 months. Patients with CM of melanoma had a higher survival rate than patients with metastasis of other primary tumors (P<.05). A histopathologic study of 91 slides showed that diffuse infiltration of the tissue with tumor cells was the most common pattern and vascular invasion was rare., Conclusions: The results are similar to those found worldwide. CM is a rare manifestation of internal tumors. It presents mainly at an advanced age and is equally prevalent in both sexes., (Copyright © 2018 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Postoperative pain is one of the most common complications. The aim of this study is to evaluate the analgesic efficacies of dexketoprofen trometamol and two different dosages of dexketoprofen trometamol + thiocolchicoside combination in the impacted third molar tooth operation., Material and Methods: This randomized, double-blind study included 75 patients who did not have any disease. Patients were assigned to 3 groups. Group 1 received 25 mg dexketoprofen trometamol + 4 mg thiocholchicoside, Group 2 received 25 mg dexketoprofen trometamol +8 mg thiocholchicoside, and Group 3 received 25 mg dexketoprofen trometamol. In each group, the analgesic medication was administered twice a day, starting 1 hour before the operation. The level of pain was assessed with VAS., Results: Patient age varied from 18 to 36 years. Of all patients, 59.2% (n=42) were female and 40.8% (n=29) were male. Drug side effects were observed in 28.17% (n=20) of the patients. Mean 24th hour VAS score was lower in dexketoprofen trometamol + 8 mg thiocolchicoside group compared to dexketoprofen trometamol group (p<0.05). There was no statistically significant difference between the three groups regarding drug side effects (p>0.05)., Conclusions: Dexketoprofen trometamol + 8 mg thiocolchicoside combination has higher analgesic efficacy compared to dexketoprofen trometamol. More studies are needed to interpret the analgesic and anti-inflammatory effects of thiocholchicoside + dexketoprofen trometamol combination.

Almost 70 years after the discovery of the lysosome, and about four decades following the unraveling of ubiquitin as a specific "mark of death," the field of protein turnover-the numerous processes it regulates, the pathologies resulting from its dysregulation, and the drugs that have been developed to target them-is still growing exponentially. Accordingly, the need for new technologies and methods is ever growing. One interesting question in the field is the mechanism(s) by which the "predators become prey". We have reported recently that the 26S proteasome, the catalytic arm of the ubiquitin system, is degraded by the autophagy-lysosome machinery, in a process requiring specific ubiquitination of the proteasome, and subsequent recognition by the shuttle protein p62/SQSTM1. Studying the modification(s), recognition sites, engulfment, and breakdown of the 26S proteasome via such "proteaphagy" has required the use of microscopy, subcellular fractionation, 'classical biochemistry', and proteomics. In this chapter, we present the essentials of these protocols, with emphasis on the refinements we have introduced in order for them to better suit the particular study of proteaphagy., (© 2019 Elsevier Inc. All rights reserved.)

Background: Variable response after clopidogrel is well documented and may affect major adverse clinical events after stroke. Impact of CYP2C19 genetic polymorphisms is an established marker linked to variable response after clopidogrel. However, the association of certain genetic polymorphisms with prediction of major adverse clinical events following stroke still remains controversial, especially in Caucasians., Study Question: The primary aim was to evaluate the impact of CYP2C19 allele *2 in heterozygote form on major adverse clinical events in Caucasian poststroke survivors treated with clopidogrel. The secondary aim was to analyze the potential link between CYP2C19 genetic polymorphism and variable response after clopidogrel., Study Design: One hundred thirty patients of Caucasian origin following documented ischemic stroke were included. Platelet reactivity was assessed by light transmittance aggregometry (LTA) and matched with various CYP2C19 loss-of-function genetic polymorphisms and major adverse clinical events (composite of vascular deaths, stroke/transient ischemic attack, and myocardial infarction)., Results: Over the mean follow-up of 14.9 months, 19 patients experienced major adverse clinical events. The risk of major adverse clinical events was nearly 3-fold in loss-of-function allele carriers (hazard ratio = 2.904; 95% confidence interval, 1.083-7.786; P = 0.013), whereas the risk of ischemic stroke or transient ischemic attack alone was also higher (hazard ratio = 3.170; 95% confidence interval, 1.281-7.849; P = 0.034). Platelet activity was strongly associated with allele *2 status (rs = 0.21, P = 0.016) but not with other genetic polymorphisms. Carriers of allele*2 exhibited lower platelet response to adenosine diphosphate-mean LTA (30.1% vs. 42.0%; P = 0.017). There were no significant differences in LTA results with other agonists. Strong association of increase in adenosine diphosphate-induced aggregation with diabetes mellitus (rs = 0.20, P = 0.023), increasing age (rs = 0.23, P = 0.008), and conversely diminishing over increased weight (rs = 0.23, P = 0.009) was also detected. The carriers of other gene allele variants lack uniformed impact on variable response after clopidogrel., Conclusions: Even heterozygous CYP2C19*2 allele carriers among Caucasian patients after ischemic stroke had a higher risk of major adverse clinical events. The LTA, however, did not predict major adverse clinical events. The exact clinical utility of these findings is still uncertain and requires large outcome-driven randomized trial in Caucasians for proof of concept.

Henoch-Schönlein purpura (HSP) or IgA Vasculitis is the most common childhood vasculitis. The classic tetrad of signs and symptoms include palpable purpura, arthralgia, abdominal pain and renal disease. The occurrence of hemorrhagic bullae in children with HSP is rarely encountered. Objec tive: To report an unusual cutaneous manifestation of HSP in children., Case Report: A 14-year-old girl complained about a 2-week painful bullous rash in both lower extremities and multiple arthral gias. There was no history of abdominal pain or urinary symptoms. In both lower extremities, there were numerous palpable purpura and hemmorrhagic bullae. In light of clinical findings, laboratory tests and skin biopsy are requested. The histopathology described intraepidermal blisters, acanthosis, spongiosis and perivascular dermal infiltrate. Direct immunofluorescence (IFD) (+) for IgA. The diagnosis of bullous HSP was made and treatment with endovenous corticosteroids was initiated. Three days after overlapping to oral corticosteroids, new ecchymotic lesions appeared in both legs. Due to the persistence of cutaneous involvement and negative control tests, azathioprine was associa ted obtaining a good response., Conclusion: Although bullous lesions in HSP does not add morbidity, it is often an alarming phenomenon with multiple differential diagnoses. The anti-inflamatory effect of corticoids is likely to be beneficial in the treatment of patients with severe cutaneous involvement through inhibition of proinflammatory transcription factors and decreasing the production of the metalloproteinases.