Local Defense Factors in Cleft-Affected Palate in Children before and during Milk Dentition Age : A Pilot Study

One of the most frequent congenital orofacial defects is the cleft lip and palate. Local tissue defense factors are known to be important in immune response and inflammatory and healing processes in the cleft tissue; however, they have only been researched in older children during mixed dentition. Thus, the aim of this study is to assess the distribution of LL-37, CD-163, IL-10, HBD-2, HBD-3, and HBD-4 in children before and during milk dentition. The unique and rare material of palate tissue was obtained from 13 patients during veloplastic surgeries during the time span of 20 years. Immunohistochemistry, light microscopy, semi-quantitative evaluation, and non-parametric statistical analysis were used. A significant decrease in HBD-3 and HBD-4 in the connective tissue was found, as well as several mutual statistically significant and strong correlations between HBD-2, HBD-3, HBD-4, and LL-37. Deficiency of HBD-3 and HBD-4 suggests promotion of chronic inflammation. The scarcity of HBD-4 could be connected to the different signaling pathways of dental pulp cells. Mutual correlations imply changes in the epithelial barrier, amplified healing efficiency, and increased antibacterial line of defense. Deprivation of changes in IL-10 quantity points to possible suppression of the factor. The presence of similar CD-163 immunoreactive substances produced by M2 macrophages was also observed.Peer reviewe

Structure of the Borrelia burgdorferi ATP-dependent metalloprotease FtsH in its functionally relevant hexameric form

Publisher Copyright: © 2023 The AuthorsATP-dependent proteases FtsH are conserved in bacteria, mitochondria, and chloroplasts, where they play an essential role in degradation of misfolded/unneeded membrane and cytosolic proteins. It has also been demonstrated that the FtsH homologous protein BB0789 is crucial for mouse and tick infectivity and in vitro growth of the Lyme disease-causing agent Borrelia burgdorferi. This is not surprising, considering B. burgdorferi complex life cycle, residing in both in mammals and ticks, which requires a wide range of membrane proteins and short-lived cytosolic regulatory proteins to invade and persist in the host organism. In the current study, we have solved the crystal structure of the cytosolic BB0789 166 - 614, lacking both N-terminal transmembrane α-helices and the small periplasmic domain. The structure revealed the arrangement of the AAA+ ATPase and the zinc-dependent metalloprotease domains in a hexamer ring, which is essential for ATPase and proteolytic activity. The AAA+ domain was found in an ADP-bound state, while the protease domain showed coordination of a zinc ion by two histidine residues and one aspartic acid residue. The loop region that forms the central pore in the oligomer was poorly defined in the crystal structure and therefore predicted by AlphaFold to complement the missing structural details, providing a complete picture of the functionally relevant hexameric form of BB0789. We confirmed that BB0789 is functionally active, possessing both protease and ATPase activities, thus providing novel structural-functional insights into the protein, which is known to be absolutely necessary for B. burgdorferi to survive and cause Lyme disease.Peer reviewe

Structural studies of chromosomally encoded outer surface lipoprotein BB0158 from Borrelia burgdorferi sensu stricto

Publisher Copyright: © 2023 The Author(s)Lyme disease, or also known as Lyme borreliosis, is caused by the spirochetes belonging to the Borrelia burgdorferi sensu lato complex, which can enter the human body following the bite of an infected tick. Many membrane lipid-bound proteins, also known as lipoproteins, are located on the surface of B. burgdorferi sensu lato and play a crucial role in the spirochete to interact with its environment, whether in ticks or mammals. Since the spirochete needs to perform various tasks, such as resisting the host's immune system or spreading throughout the organism, it is not surprising that numerous surface proteins have been found to be essential for B. burgdorferi sensu lato complex bacteria in causing Lyme disease. In this study, we have determined (at 2.4 Å resolution) and characterized the 3D structure of BB0158, one of the few chromosomally encoded outer surface proteins from B. burgdorferi sensu stricto. BB0158 belongs to the paralogous gene family 44 (PFam44), consisting of four other members (BB0159, BBA04, BBE09 and BBK52). The characterization of BB0158, which appears to form a domain-swapped dimer, in conjunction with the characterization of the corresponding PFam44 members, certainly contribute to our understanding of B. burgdorferi sensu stricto proteins.Peer reviewe

Self-Esteem and Occupational Factors as Predictors of the Incidence of Anxiety and Depression among Healthcare Workers during the COVID-19 Pandemic in Latvia

The prevalence of depression and anxiety among healthcare workers (HCWs) during the COVID-19 pandemic is high. The aim of the study is to identify the importance of self-esteem and occupational factors in association with the incidence of depression and anxiety among HCWs through a longitudinal cohort study during the COVID-19 pandemic in Latvia. Participants received seven questionnaires during the COVID-19 pandemic on demographic parameters, work-related information, and contact with COVID-19 patients, and three standardized questionnaires that evaluated symptoms of anxiety (GAD-7), depression (PHQ-9), and self-esteem (Rosenberg’s self-esteem scale). The Generalized Linear Mixed Model (GLMM) was used to identify factors associated with the incidence of depression and anxiety among HCWs. A total of 322 participants were included in the data analysis for depression and 352 for anxiety. HCWs with low self-esteem were 83% more likely to experience depression and 76% more likely to experience anxiety. Working at a general practitioner practice is associated with twice the risk of developing depression and anxiety. A 31% increase in the odds of depression is observed among HCWs with direct contact with COVID-19 patients. The organizational and government levels must look for opportunities to facilitate the mental health of HCWs to ensure better-quality healthcare.Peer reviewe

Ten-year safety and clinical benefit from open-label etanercept treatment in children and young adults with juvenile idiopathic arthritis

© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected]: CLIPPER2 was an 8-year, open-label extension of the phase 3b, 2-year CLIPPER study on the safety and efficacy of etanercept in patients with JIA, categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA) or PsA. METHODS: Participants with eoJIA (2-17 years old), ERA or PsA (each 12-17 years old) who received ≥1 etanercept dose (0.8 mg/kg weekly; maximum 50 mg) in CLIPPER could enter CLIPPER2. Primary end point was occurrence of malignancy. Efficacy assessments included proportions achieving JIA ACR 30/50/70/90/100 criteria and ACR inactive disease criteria, and clinical remission (ACR criteria) or Juvenile Arthritis DAS (JADAS) ≤1. RESULTS: Overall, 109/127 (86%) CLIPPER participants entered CLIPPER2 [n = 55 eoJIA, n = 31 ERA, n = 23 PsA; 99 (78%) on active treatment]; 84 (66%) completed 120 months' follow-up [32 (25%) on active treatment]. One malignancy (Hodgkin's disease in 18-year-old patient with eoJIA treated with methotrexate for 8 years) was reported; there were no cases of active tuberculosis or deaths. Numbers and incidence rates (events per 100 patient-years) of TEAEs (excluding infections/ISRs) decreased from 193 (173.81) in Year 1 to 9 (27.15) in Year 10; TE infections and serious infections also decreased. Over 45% of participants (n = 127) achieved JIA ACR50 responses from Month 2 onwards; 42 (33%) and 34 (27%) participants achieved JADAS and ACR clinical remission, respectively. CONCLUSIONS: Etanercept treatment up to 10 years was well tolerated, consistent with the known safety profile, with durable response in the participants still on active treatment. The benefit-risk assessment of etanercept in these JIA categories remains favourable. TRIAL REGISTRATION: ClinicalTrials.gov IDs: CLIPPER (NCT00962741); CLIPPER2 (NCT01421069).Peer reviewe

Investor Protection : Segregation of Assets

The article is devoted to the contemporary problems of the ownership rights on intermediated securities and investor protection. Authors provide brief introduction to the major aspects of the Latvian securities law, then they study peculiarities of US approach to the ownership rights on intermediated securities as well US techniques of investor protection in the context of segregation and separation of assets of investors as well as briefly review the insolvency regimes and return of the financial assets to the investors, customers of insolvent US regulated firms. In conclusion authors provide brief comparative summarizing of Latvian and US approaches. Objectives: The study aims at continuing development of the securities law theory, while its task is to characterise the problematic of investor protection especially in insolvency proceedings on example of US as well as to discuss some peculiarities ownership rights on intermediated securities from the point of view of US law and practice. Methods/Approach Scientific research methods - both comparative and analytical - is used in the process of drawing up of this article. Results: Authors come to conclusion that US investor protection system is more complex than Latvian, it uses the separation and segregation approaches, while Latvian system only segregation approach. Both systems do not excluding situations of shortfall in customer assets. Both systems recognize the pro-rata distribution of damages, but US system recognises various pro-rata approaches to the distribution of damages (from the defined amount of assets; from all the assets; from all the assets belonging to a specific category of customers), while Latvian law stays silent regarding this topic. Authors believe that modernisation of the law is required for the better protection of the customers in case of insolvency of investment service providers and obtaining of the greater certainty of the legal outcomes. Author suggest should to determine the prohibition to meet the claims of one class of assets at the expense of another class of assets during insolvency proceedings of investment service providers in case of shortfall in assetsPeer reviewe

Uz infrasarkano staru spektroskopijas balstīta klīniskā algoritma izmantošana mugurkaula operācijās un pēcoperācijas kognitīvie traucējumi. Promocijas darbs

The Doctoral Thesis was developed at Rīga Stradiņš University, Riga East Clinical University Hospital “Gaiļezers”, Latvia. Defence: at the public session of the Promotion Council of Clinical Medicine on 2023, June 12 at 13.00 via Zoom online platform.In patients undergoing spinal surgery in prone position, physiological changes can occur in multiple organ systems. Pressure on pelvis, abdomen and thorax reduces systemic venous return, thereby decreasing cardiac output and increasing pressure in vertebral blood vessels, thus promoting intraoperative bleeding. Concomitantly, lung compliance decreases. The latter noxious factors hamper blood flow and oxygen delivery to the brain. The brain is highly dependent on adequate oxygen delivery, thus, tissue injury, and even cell death may occur already 5 minutes after cerebral ischemia. Postoperative cognitive decline is a potential complication, which may lead to long-term consequences. The exact aetiology and pathophysiology of postoperative cognitive disturbances is not known. Despite intraoperative cerebral ischemia could be a contributing factor to consider, the brain remains one of the least monitored organs intraoperatively. The aim of the present study was to evaluate the effect of the intraoperative use of a near-infrared spectroscopy-based clinical algorithm on outcome, especially on postoperative cognitive decline. We included 64 adult patients, scheduled for elective spinal neurosurgery in the prone position. All the patients underwent general anaesthesia and regional cerebral oxygen saturation (rScO2) was monitored intraoperatively by means of an INVOS 4100 cerebral oximeter. Patients were randomised into a study group and a control group. In patients of the study group, a near-infrared spectroscopy-based clinical algorithm was used to restore adequate cerebral oxygen saturation when noticing a drop of 20 % from preoperative baseline of cerebral oxygen saturation, or a fall in regional cerebral oxygen saturation below an absolute value of 50 %. In the control group, intraoperative cerebral oxygen saturation was monitored blindly without using the near-infrared spectroscopy-based clinical algorithm. In both groups, before and after the surgery, cognitive function was evaluated using Montreal Cognitive Assessment Scale (MOCA). Preoperative haemoglobin (Hb) and haematocrit (Hct) concentrations also were noticed, as well as intraoperative mean arterial pressure (MAP), expiratory end-tidal carbon dioxide (EtCO2) levels, peripheral oxygen saturation (SpO2), intraoperative blood loss and length of operation. In our study, in three patients – two in the study group and one in the control group, intraoperative cerebral desaturation was observed. Two study group patients were 54 and 57 years old. In one study group patient, cerebral saturation fell for 29 % from baseline values and also under an absolute value of 50 %; in the other study group patient, we noticed a cerebral oxygen saturation drop of 27 % below preoperative baseline. The NIRS-based clinical algorithm was initiated. No changes in rScO2 were observed after the first step, which according to the algorithm, was an assurance of correct head positioning. The next step was a raise in mean arterial pressure in both patients, as assessed by ephedrine administration. After the second step rScO2 values raised above the threshold, and no further intervention was necessary. Mean arterial pressure in the patients at the time of cerebral desaturation was 95 mmHg and 62 mmHg, respectively vs. 124 mmHg and 104 mmHg preoperatively. None of the patients showed postoperative cognitive decline – MOCA score remained unchanged pre- and postoperatively. In one control group patient, in whom intraoperative cerebral desaturation occurred, but the NIRS-based clinical algorithm was not applied, we detected a rScO2 drop of 21 % from the preoperative baseline values. The patient was 24 years old and showed a postoperative MOCA score decline of 4 points (from 29 points preoperatively to 25 points postoperatively). In the present study, we found a correlation between lower intraoperative rScO2 values and higher patient age, larger intraoperative blood loss, higher preoperative mean arterial pressure and lower preoperative MOCA score. In our study, 45.5 % patients from the control group, where cerebral oximetry was monitored blindly, no NIRS algorithm was applied, showed postoperative cognitive decline, compared to the study group where postoperative cognitive decline was observed in 21.4 % of patients. No correlation was found between intraoperative cerebral oxygenation and postoperative cognitive function. However, patients, who had a rScO2 decrease of > 10 % in any stage of surgery experienced a lower median MOCA score after the surgery. Near-infrared spectroscopy together with NIRS-based clinical algorithm is useful to manage intraoperative cerebral oxygen desaturation and to avoid postoperative cognitive disturbances

Developing E-learning course "Circular Economy" in the Study process and Adult Education

Funding Information: This research has been published with the support of Latvian Council of Science (Latvia), a research project “Quadruple Helix Concept (QHC) as base of the next generation PPP model” (no. lzp-2020/1-0062). Funding Information: Riga Technical University (RTU) and the Ministry of Education and Science of Latvia have agreed on the use of state budget funds allocated to the Institute of Riga Technical University Riga Business School for the creation of an innovative study program in the field of information and communication technologies, Academic and scientific staff of Latvian universities and scientific institutions international training for the acquisition of high-level digital skills and knowledge transfer within the framework of the RTU project "Support for RTU international cooperation projects in research and innovation" (1.1.1.5/18/I/008), according to the Cabinet of Ministers' decision of 06.06.2017 regulations No. 315 "Activity program "Growth and employment" 1.1.1.5. the implementation rules of the first, second and third round of selection of project submissions of the event "Support for international cooperation projects in research and innovation". The trainees are Academic and scientific staff of the Latvian state higher education institutions, who, upon winning the competition, are granted funding for the purpose of increasing their qualifications - to improve their digital skills, improve the quality of teaching information and communication technologies, as well as to learn the latest methods in preparing and conducting the content of IT courses. Publisher Copyright: © 2023 EDP Sciences. All rights reserved.The educational process has changed; many more technologies and solutions are involved in preparing the subject and the study process. A degree of maturity in using digital tools has been reached, allowing the student to learn the subject whenever and wherever he or she wishes. The experience gained in the USA shows that in the case of successful development of an asynchronous course, in combination with really extended feedback, even content-compliant courses can be acquired in this way very successfully. The purpose of the article is to show a success story of developing a modern e-learning course, modernizing and digitizing their study courses. A complete cycle of "learn by doing"and "do by learning"approaches are being implemented for the first time. By support Erasmus+ project is developing an innovative, asynchronous online course on the topic of Circular Economy and will to improve teachers' digital pedagogical competencies by enabling them to provide a high-quality learning process. At all levels of education, it is essential to keep up with the requirements of the 21st Century and opportunities, to change previous thinking and accept digitization is the duty, mission and task of every teacher, student and administrator.Peer reviewe

The Role of the p16 and p53 Tumor Suppressor Proteins and Viral HPV16 E6 and E7 Oncoproteins in the Assessment of Survival in Patients with Head and Neck Cancers Associated with Human Papillomavirus Infections

Funding Information: This research was supported by the European Social Fund and the Latvian state budget within the frame of the project No. 8.2.2.0/20/l/004 “Support for involving doctoral students in scientific research and studies” at Riga Stradiņš University. The article processing charge was covered by Riga Stradinš University Department of Otorhinolaryngology. Publisher Copyright: © 2023 by the authors.The role of HPV in the survival prognosis of patients with head and neck squamous cell carcinoma, especially patients with laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC), is still somewhat ambiguous. The present study aimed to explore the significance of tumor suppressor proteins and HPV16 E6 and E7 oncoproteins in the assessment of survival in patients with oropharyngeal squamous cell carcinoma (OPSCC), LSCC, and HPSCC associated with high-risk (HR-) and low-risk (LR-) HPV infections. By utilizing molecular and immunohistochemical investigations of HNSCC samples and patient data, univariate and multivariate survival analyses were conducted. The presence of HPV DNA (LR- and HR-HPV) was associated with a better 5-year OS and DSS for OPSCC and LSCC. The IHC overexpression of HPV16 E6 protein and p16 protein was associated with better survival in the univariate (for OPSCC) and multivariate (OPSCC and HPSCC) survival analyses. The overexpression of p53 was associated with better survival in OPSCC. HPV infection plays a significant role in the tumorigenesis of HNSCC, and the immunohistochemical assessment of HPV16 E6 protein expression should be interpreted as a useful prognostic marker for OPSCC and HPSCC.Peer reviewe

Health-Related Quality of Life in Patients with McCune - Albright syndrome

Ārsta palīgsVeselības aprūpePhysician's AssistantHealth CareMcCune – Albright ir rets sindroms, un pagaidām nav statistikas datu par sindroma izplatību pasaulē, aptuvenā sastopamība svārstās no 1/100 000 līdz 1/1 000 000 (Holbrook et al., 2022). Pēc “Slimības profilakses un kontroles” datiem Latvijā ir sastopami pieci pacienti ar McCune – Albright sindromu (SPKC, 2022). Ļaujot pacientiem novērtēt savu dzīves kvalitāti, var atklāt problēmas, kuras mērķtiecīgi ir jānovērš, tas veidotu izpratni par nepieciešamību ieviest izmaiņas ārstēšanā un aprūpē, vai pat norādīt uz kādas terapijas neefektivitāti (Haraldstad et al., 2019). Pētījuma mērķis: Noskaidrot ar veselību saistītu dzīves kvalitāti pacientiem ar McCune Albright sindromu. Pētījuma jautājums: Kāda ir ar veselību saistīta dzīves kvalitāte pacientiem ar McCune– Albright sindromu? Pētījuma uzdevumi: 1. Noskaidrot, kādas fiziskās aktivitātes, tai skaitā arī ikdienas aktivitātes, pacientiem ar McCune - Albright sindromu ir visvairāk ietekmētas. 2. Noskaidrot, vai pastāv un cik bieži pacientiem ar McCune - Albright sindromu novēro emocionāla rakstura problēmas un vai tās ietekmē arī viņu sabiedrisko dzīvi. 3. Noteikt sāpju stiprumu pēdējo 4 nedēļu laikā. 4. Izvērtēt, pacientu ar McCune - Albright sindromu, pašsajūtu. Rezultāti: No visiem respondentiem sievietes piedalījās visvairāk – 88 % (n = 44), bet vīrieši 12 % (n = 6). Vecuma grupā no 48 gadiem līdz 62 gadiem rezultāti tika iegūti zemāki nekā pārējās vecuma grupās, bet viszemākais rezultāts no visiem dzīves kvalitātes rādītājiem bija emocionālais stāvoklis – 33,59 balles. Secinājumi: Pacientiem ar McCune – Albright sindromu ar veselību saistīti dzīves kvalitātes rādītāji nepārsniedz vidējo vērtību 50, norādot par zemāku dzīves kvalitāti nekā vispārējā populācijā. Kvalifikācijas darbs sastāv no 60 lapām, iekļautas 15 diagrammas, izmantoti 39 zinātniskās literatūras avoti, pievienoti 7 pielikumi.McCune-Albright syndrome is a rare condition, and currently there are no statistical data on the worldwide prevalence of the syndrome. The estimated prevalence ranges from 1 in 100,000 to 1 in 1,000,000 (Holbrook et al., 2022). According to data from the "Center for Disease Prevention and Control", in Latvia there are five patients with McCune-Albright syndrome (SPKC, 2022). By allowing patients to assess their quality of life, problems that need to be addressed can be identified, leading to an understanding of the need for changes in treatment and care, or even indicating the ineffectiveness of certain therapies (Haraldstad et al., 2019). Objective of the study: To determine the health - related quality of life in patients with McCune-Albright syndrome. Research question: What is the health - related quality of life in patients with McCune Albright syndrome? Research objectives: 1. Determine the physical activities, including daily activities, that are most affected in patients with McCune - Albright syndrome. 2. Determine if emotional problems are present and how often they impact the social life of patients with McCune - Albright syndrome. 3. Assess the intensity of pain experienced in the past 4 weeks. 4. Evaluate the well - being of patients with McCune - Albright syndrome. Results: Among all respondents, females accounted for the majority - 88% (n = 44), while males accounted for 12% (n = 6). In the age group from 48 to 62 years, the results were lower compared to other age groups, with the lowest result among all quality of life indicators being the emotional state - 33.59 points. Conclusions: Health - related quality of life indicators in patients with McCune - Albright syndrome do not exceed the average value of 50, indicating a lower quality of life compared to the general population. The qualification work consists of 60 pages, including 15 diagrams, 39 scientific literature sources were used, and 7 appendices are attached