Clinicopathological Significance of Exosomal Proteins CD9 and CD63 and DNA Mismatch Repair Proteins in Prostate Adenocarcinoma and Benign Hyperplasia

Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Introduction. Recently, it has been shown that exosomal biomarkers and DNA mismatch repair proteins (MMR) could play an important role in cancer risk stratification and prognosis assessment. The gold standard for prostate carcinoma (PCa) diagnosis is biopsy and histopathological examination. Thus, the complex evaluation of exosomal and MMR proteins could be beneficial for prostate cancer risk stratification and diagnostics. The aim of the current study was to evaluate and compare the expression of exosomal proteins CD9 and CD63 and MMR proteins in the tissue of patients with prostate benign hyperplasia (BPH) and PCa. Methods. The study was retrospective. Altogether, 92 patients with PCa and 20 patients with BPH (control group) were enrolled in the study. Exosomal and MMR protein expression was analyzed by immunohistochemistry (IHC). The follow-up for each PCa patient in our study lasted till disease progression and/or a maximum of 5 years. Results. Low-grade PCa was observed in 56 patients and high-grade PCa in 36 patients. CD63 expression was significantly higher in patients with high-grade PCa compared to those with low-grade PCa. CD9 expression was significantly downregulated in PCa patients compared to the control group. MMR protein expression deficiency was observed in 10 PCa patients. MMR proteins were maintained in all cases of BPH. The study found a negative correlation between MMR protein loss and PCa ISUP grade groups. Progression-free survival (PFS) in patients with MMR deficiency was significantly shorter than in patients with maintained MMR expression. Conclusions. CD9 protein expression was downregulated in PCa, compared to BPH, while CD63 protein expression was upregulated in high-grade PCa but downregulated in low-grade PCa. CD63 protein upregulation, CD9 downregulation, and loss of MMR protein characterized the shorter PFS of high-grade PCa patients. CD9, CD63, and MMR could be the routine immunohistochemical biomarkers for the diagnosis and risk stratification of PCa.publishersversionPeer reviewe

Oxidative stress parameters in Posttraumatic Stress Disorder risk group patients

Funding Information: The research is supported by European Social Foundation co-financing: Project for Doctoral students support, at Rîga Stradiòð University (No. 2009/0147/1DP/1.1.2.1.2/09/IPIA/ VIAA/009). The views expressed in this article are those of the authors and do not reflect the official policy or position of the Latvian government, Latvian National Armed Forces, Medical Support Centre of Latvian National Armed Forces or any of the institutions with which the authors are affiliated. The authors state no conflict of interest. All authors read and approved the final manuscript.Increased excitotoxity in response to stressors leads to oxidative stress (OS) due to accumulation of excess reactive oxygen/nitrogen species. Neuronal membrane phospholipids are especially susceptible to oxidative damage, which alters signal transduction mechanisms. The Contingent of International Operations (CIO) has been subjected to various extreme stressors that could cause Posttraumatic Stress Disorder (PTSD). Former studies suggest that heterogeneity due to gender, race, age, nutritional condition and variable deployment factors and stressors produce challenges in studying these processes. The research aim was to assess OS levels in the PTSD risk group in CIO. In a prospective study, 143 participants who were Latvian CIO, regular personnel, males, Europeans, average age of 27.4, with the same tasks during the mission, were examined two months before and immediately after a six-month Peace Support Mission (PSM) in Afghanistan. PCL-M questionnaire, valid Latvian language "Military" version was used for PTSD evaluation. Glutathione peroxidase (GPx), superoxide dismutase (SOD) and lipid peroxidation intensity and malondialdehyde (MDA) as OS indicators in blood were determined. Data were processed using SPSS 20.0. The MDA baseline was 2.5582 μM, which after PSM increased by 24.36% (3.1815 μM). The GPx baseline was 8061.98 U/L, which after PSM decreased by 9.35% (7308.31 U/L). The SOD baseline was 1449.20 U/gHB, which after PSM increased by 2.89% (1491.03 U/gHB). The PTSD symptom severity (total PCL-M score) baseline was 22.90 points, which after PSM increased by 14.45% (26.21 points). The PTSD Prevalence rate (PR) baseline was 0.0357, which after PSM increased by 147.06% (0.0882). We conclude that there is positive correlation between increase of OS, PTSD symptoms severity level, and PTSD PR in a group of patients with risk of PTSD - CIO. PTSD PR depends on MDA intensity and OS severity. OS and increased free radical level beyond excitotoxity, is a possible causal factor for clinical manifestation of PTSD.publishersversionPeer reviewe

Modular Point-of-Care Breath Analyzer and Shape Taxonomy-Based Machine Learning for Gastric Cancer Detection

Funding Information: The development of the analysis approach and its evaluation and analysis were supported by a postdoctoral grant within the Activity 1.1.1.2 “Post-doctoral Research Aid” co-funded by the European Regional Development Fund (postdoctoral project numbers: 1.1.1.2/VIAA/2/18/270 and 1.1.1.2/VIAA/3/19/495). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Background: Gastric cancer is one of the deadliest malignant diseases, and the non-invasive screening and diagnostics options for it are limited. In this article, we present a multi-modular device for breath analysis coupled with a machine learning approach for the detection of cancer-specific breath from the shapes of sensor response curves (taxonomies of clusters). Methods: We analyzed the breaths of 54 gastric cancer patients and 85 control group participants. The analysis was carried out using a breath analyzer with gold nanoparticle and metal oxide sensors. The response of the sensors was analyzed on the basis of the curve shapes and other features commonly used for comparison. These features were then used to train machine learning models using Naïve Bayes classifiers, Support Vector Machines and Random Forests. Results: The accuracy of the trained models reached 77.8% (sensitivity: up to 66.54%; specificity: up to 92.39%). The use of the proposed shape-based features improved the accuracy in most cases, especially the overall accuracy and sensitivity. Conclusions: The results show that this point-of-care breath analyzer and data analysis approach constitute a promising combination for the detection of gastric cancer-specific breath. The cluster taxonomy-based sensor reaction curve representation improved the results, and could be used in other similar applications.publishersversionPeer reviewe

Trading in influence: understanding and seperation from other criminal offences

Maģistra darbs ir veltīts tirgošanās ar ietekmi sastāva pazīmju analīzei un šī noziedzīga nodarījuma sastāva norobežošanai no citiem noziedzīgiem nodarījumiem. Darbā tiek veikta pastāvošā tiesiskā regulējuma un tiesību normas vēsturiskās attīstības analīze, tiek salīdzināti dažādu valstu tiesiskie regulējumi, kā arī veikts tirgošanās ar ietekmi piemērošanas prakses izvērtējums. Šajā maģistra darbā tiek piedāvātas turpmākajai diskusijai pazīmes, pēc kurām tirgošanos ar ietekmi ir iespējams nošķirt no kukuļošanas un lobēšanas.This master thesis is dedicated for analysis and understanding of trading in influence and its separation from other criminal offences. In this thesis author analyzes existing legal regulation and historical development of this legal norm, compares different criminal law regulations and conducts evaluation of legal practice in Latvia. Author initiates discussion and provides guidelines on how to separate trading in influence from bribery and lobbyism

NATO Achievements in Fight against Global Terrorism

Pēc teroristu uzbrukuma ASV 2001. gadā NATO valstis iedarbināja Ziemeļatlantijas līguma 5. panta mehānismu un pieteica kara globālajam terorismam. Darbā tiek vērtēts, vai militāra alianse, kas vēsturiski tikusi formēta cīņai pret valsti agresoru, spēj stāties pretī tik daudzveidīgiem un neparedzamiem draudiem kā terorisms. Tiek skaidrots, ar kādām metodēm visefektīvāk ir apkarot terorismu, un tiek aplūkotas NATO iespējas iesaistīties globālā terorisma draudu apkarošanā. Centrālais jautājums darbā ir, vai NATO komandētā militārā operācija Afganistānā palīdz samazināt teroristu aktivitāti pasaulē un iedibināt mieru šajā valstī. Darbā tiek izvirzīti 5 kritēriji – drošība, valsts rekonstrukcija, narkotiku apkarošana, demokratizācija un globālā terorisma izplatība. To analīze ļauj izdarīt secinājumus, vai NATO operācija Afganistānā nes panākumus cīņā ar starptautisko terorismu vai nenes.After terrorist attacks in 2001 international terrorism became one of the major threats to global security. The goal of this work is to answer whether military alliance is prepared to deal with this kind of threat. Authors like George Liska and Stephen Walt have written that alliances usually are formed to deal with aggressor states and to achieve balance of power in the world. However, in 21st century the threats have transformed. The central question in this work is about NATO’s military operation in Afghanistan, which is meant to be a powerful strike against terrorism. This work gives an answer on how effective NATO is doing campaign in Afghanistan and whether military intervention reduce the threats of terrorism

The Difference between Bribe Extortion and Request of Bribe

Bakalaura darbs ir veltīts divu kukuļņemšanas kvalificējošo pazīmju – kukuļa pieprasīšanas un kukuļa izspiešanas – izpētei un analīzei. Darba gaitā autors secina, ka praksē kriminālprocesa ietvaros ne vienmēr tiek visaptveroši analizēts jautājums, vai darbība, par kuru dots kukulis, bija likumīga vai nelikumīga, un vai valsts amatpersona apdraudēja personas likumīgās intereses vai nē, kas var novest pie kļūdainas noziedzīga nodarījuma kvalifikācijas. Ievērojot teorētiskās atziņas un apkopoto praksi par konkrēto tiesību normu piemērošanas apstākļiem, šajā darbā tiek analizēta un formulēta izpratne par pazīmēm, pēc kurām ir iespējams nošķirt abus minētos kukuļņemšanas veidus. Atslēgas vārdi: noziedzīgi nodarījumi valsts institūciju dienestā, kukuļošana, kukuļa pieprasīšana, kukuļa izspiešana.This bachelor thesis is dedicated to the research of two qualifying indicators of bribe-taking – request of bribe and extortion of bribe. In this thesis author concludes that in practice in criminal proceeding question, whether the activity for what the bribe was given was lawful or unlawful and whether the state official threatened the lawful interests, is not always analyzed in a comprehensive way and therefore it may lead to the incorrect qualification of criminal offence. Taking into account theoretical ideas and practice about the application of particular legal norms, analysis is made and comprehension is formulated about indicators, according to which a separation between these two types of bribe-taking can be made. Key words: criminal offences in state authority service, bribing, request of bribe, extortion of bribe

NATO Achievements in Fight against Global Terrorism

Pēc teroristu uzbrukuma ASV 2001. gadā NATO valstis iedarbināja Ziemeļatlantijas līguma 5. panta mehānismu un pieteica kara globālajam terorismam. Darbā tiek vērtēts, vai militāra alianse, kas vēsturiski tikusi formēta cīņai pret valsti agresoru, spēj stāties pretī tik daudzveidīgiem un neparedzamiem draudiem kā terorisms. Tiek skaidrots, ar kādām metodēm visefektīvāk ir apkarot terorismu, un tiek aplūkotas NATO iespējas iesaistīties globālā terorisma draudu apkarošanā. Centrālais jautājums darbā ir, vai NATO komandētā militārā operācija Afganistānā palīdz samazināt teroristu aktivitāti pasaulē un iedibināt mieru šajā valstī. Darbā tiek izvirzīti 5 kritēriji – drošība, valsts rekonstrukcija, narkotiku apkarošana, demokratizācija un globālā terorisma izplatība. To analīze ļauj izdarīt secinājumus, vai NATO operācija Afganistānā nes panākumus cīņā ar starptautisko terorismu vai nenes.After terrorist attacks in 2001 international terrorism became one of the major threats to global security. The goal of this work is to answer whether military alliance is prepared to deal with this kind of threat. Authors like George Liska and Stephen Walt have written that alliances usually are formed to deal with aggressor states and to achieve balance of power in the world. However, in 21st century the threats have transformed. The central question in this work is about NATO’s military operation in Afghanistan, which is meant to be a powerful strike against terrorism. This work gives an answer on how effective NATO is doing campaign in Afghanistan and whether military intervention reduce the threats of terrorism

A new method of local and systemic therapy in biliary tract surgery

Jaunas lokālās un sistēmiskās terapijas metodes žultsceļu ķirurģijā Laparoskopiska holecistektomija ir izvēles ārstēšanas metode žultsakmeņu slimības gadījumā. Galvenās problēmas pēcoperācijas periodā ir pēcoperācijas stress, sāpes, pēcoperācijas slikta dūša un vemšana. Viens no veidiem, kā samazināt centrālas nervu sistēmas aktivāciju, ir lokālās anestēzijas lietošana. Lokālā anestēzija bloķē aferentos nervu impulsus no operācijas lauka, mazinot centrālās nervu sistēmas un hipotalāma aktivāciju. Lokālā anestēzija arī palīdz samazināt sāpes pēcoperācijas periodā, uzlabot pēcoperācijas perioda gaitu un samazināt morbiditāti. Pētījuma mēs apskatam jaunu preventīvu intraoperatīvu žultspūšļa gultnes infiltrācijas metodi ar lokālās anestēzijas līdzekli pirms žultspūšļa disekcijas no aknām laparoskopiskās holecistektomijas laikā. Tiek apskatīta metodes pielietošana operācijas laikā, ietekme uz operāciju un pēcoperācijas periodu. Laparoskopiska holecistektomija, pēcoperācijas sāpēs, lokāla anestēzija.A new method of local and systemic therapy in biliary tract surgery Laparoscopic cholecystectomy is the best option for treatment in the case of symptomatic gallstone disease. The most common postoperative problem are pain, postoperative stress, postoperative nausea and vomiting. Stress reaction and pain are activated by afferent neural impulses from the operation field. Local anaesthetics can block afferent innervation, decrease central nervous system and hypothalamic activation The intra-operative use of local anaesthetics in the operation field can decrease postoperative pain, decrease analgesics consumption and increase patient comfort. In the current study, we investigate a new method of intraperitoneal local anaesthesia in gallbladder bed additional to general anaesthesia during laparoscopic cholecystectomy and evaluate its effect in the postoperative period. Laparoscopic cholecystectomy, postoperative pain, local anaesthetic

Application of Software SPRING and Method of Complete Bifurcation Groups for the Bifurcation Analysis of Nonlinear Dynamical System

The article is devoted to the parametrical analysis of periodic and chaotic oscillations in the nonlinear dynamical systems. Description of the systematic approach to the construction of bifurcation diagrams is offered to your attention. Considered approach allows us to build complete bifurcation diagrams. These diagrams allow to find and investigate regimes, analysis of which is inaccessible by traditional methods. Such approach is used in the method of complete bifurcation groups and realized in the software SPRING. Description of method of complete bifurcation groups and results of using of this method for the parametric analysis of the nonlinear dynamic systems is presented in this article

Clinicopathological Significance of Exosomal Proteins CD9 and CD63 and DNA Mismatch Repair Proteins in Prostate Adenocarcinoma and Benign Hyperplasia

Introduction. Recently, it has been shown that exosomal biomarkers and DNA mismatch repair proteins (MMR) could play an important role in cancer risk stratification and prognosis assessment. The gold standard for prostate carcinoma (PCa) diagnosis is biopsy and histopathological examination. Thus, the complex evaluation of exosomal and MMR proteins could be beneficial for prostate cancer risk stratification and diagnostics. The aim of the current study was to evaluate and compare the expression of exosomal proteins CD9 and CD63 and MMR proteins in the tissue of patients with prostate benign hyperplasia (BPH) and PCa. Methods. The study was retrospective. Altogether, 92 patients with PCa and 20 patients with BPH (control group) were enrolled in the study. Exosomal and MMR protein expression was analyzed by immunohistochemistry (IHC). The follow-up for each PCa patient in our study lasted till disease progression and/or a maximum of 5 years. Results. Low-grade PCa was observed in 56 patients and high-grade PCa in 36 patients. CD63 expression was significantly higher in patients with high-grade PCa compared to those with low-grade PCa. CD9 expression was significantly downregulated in PCa patients compared to the control group. MMR protein expression deficiency was observed in 10 PCa patients. MMR proteins were maintained in all cases of BPH. The study found a negative correlation between MMR protein loss and PCa ISUP grade groups. Progression-free survival (PFS) in patients with MMR deficiency was significantly shorter than in patients with maintained MMR expression. Conclusions. CD9 protein expression was downregulated in PCa, compared to BPH, while CD63 protein expression was upregulated in high-grade PCa but downregulated in low-grade PCa. CD63 protein upregulation, CD9 downregulation, and loss of MMR protein characterized the shorter PFS of high-grade PCa patients. CD9, CD63, and MMR could be the routine immunohistochemical biomarkers for the diagnosis and risk stratification of PCa