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    Bronchopulmonary dysplasia in children: etiological factors and clinical-paraclinical diagnosis: Summary of the Ph.D. Thesis in Medical Sciences: 322.01 - Pediatrics and neonatology

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    Structura tezei: Teza este expusă pe 134 pagini de text și include: introducere, 3 capitole, sinteza rezultatelor obţinute, concluzii generale, recomandări practice, sursele bibliografice 217 şi 7 anexe. Materialul ilustrativ conţine 37 de tabele și 27 figuri. Cuvinte-cheie: displazie bronhopulmonară, prematuri, factori de risc, radiografia cutiei toracice, CT pulmonară. Scopul lucrării. Evaluarea factorilor etiologici și diagnosticul clinico-paraclinic la copiii prematuri cu displazie bronhopulmonară pentru elaborarea criteriilor de prognostic al maladiei Obiective cercetării: 1) Studierea factorilor de risc și cauzali în displazia bronhopulmonară la copii; 2) Evaluarea manifestărilor clinice la copiii cu displazie bronhopulmonară; 3) Cercetarea modificărilor imagistice pulmonare la copiii cu displazie bronhopulmonară; 4) Elaborarea criteriilor de prognostic pentru realizarea displaziei bronhopulmonare și severității bolii la copiii născuți prematur. Noutatea și originalitatea științifică. a constat în axarea cercetării științifice pe stabilirea determinantelor și a factorilor predictivi la copii cu displazie bronhopulmonară, cu evidențierea unor particularități ale formelor clinice. A fost realizat un studiu observațional analitic de cohortă printr-o abordare etiologică multifactorială a displaziei bronhopulmonare la copiii cu istoric de naștere prematură. Cercetarea a furnizat date autohtone privind factorii de risc în displazia bronhopulmonare la copiii prematuri internați la IMSP Institutul Mamei și Copilului, precum și date referitoare la sechelele bronhopulmonare în displazia bronhopulmonară. Cercetarea a oferit date noi despre semnificația patogenilor în displazia bronhopulmonară, ne-a permis să obținem rezultate provond corelarea acestora cu gradul de prematuritate, greutatea, vârsta de gestație și nivelul de O2. Au fost studiați factorii de risc, particularitățile clinice și imagistice în funcție de severitatea DBP la copii. Semnificația teoretică. a cercetării constă în aprofundarea cunoștințelor privind mecanismele etiopatogenice implicate în dezvoltarea displaziei bronhopulmonare (DBP) la copiii prematuri, printr-o abordare complexă și integrativă a factorilor determinanți. Studiul a contribuit la îmbogățirea cadrului teoretic existent, prin identificarea și clasificarea factorilor de risc și a celor predictivi în funcție de severitatea bolii, precum și prin evidențierea relației dintre factorii perinatali, infecțioși și necesarul de suport respirator. Rezultatele obținute au adus un aport semnificativ în înțelegerea relațiilor dintre prematuritate, agresiunile postnatale (infecții, oxigenoterapie, ventilație mecanică) și dezvoltarea sechelelor bronhopulmonare, oferind un cadru conceptual care poate susține dezvoltarea unor modele predictive și ghiduri de monitorizare a copiilor cu risc crescut de DBP. Valoarea aplicativă. Au fost elaborate programe cu criterii de diagnostic timpuriu și de prognostic pentru evoluţia displaziei bronhopulmonare la copii. În sprijinul practicienilor din domeniu, a fost propus un algoritm bine structurat de diagnostic de laborator al displaziei bronhopulmonare, care permite o detectare timpurie a acestei entități nosologice. Aplicarea acestui algoritm facilitează evaluarea impactului DBP asupra morbidității respiratorii pediatrice, contribuind la intervenții mai rapide și mai eficiente în practica clinică. Implementarea rezultatelor. Rezultatele studiului au fost integrate în activitatea practică a clinicii de pneumologie din cadrul IMSP Institutl Mamei și Copilului. De asemenea, aceste rezultate au fost valorificate în procesul didactic al Departamentului de Pediatrie de la USMF „Nicolae Testemițanu” și au contribuit la actualizarea protocolului clinic național (PCN-393) privind „Displazia bronhopulmonară la copii.” Aceste inițiative subliniază aplicabilitatea practică a cercetării în îmbunătățirea îngrijirii pacienților și formarea profesională continuă.Structure of the thesis: The thesis is presented on 134 pages and comprises the following sections: introduction, 3 chapters, synthesis of obtained results, general conclusions, practical recommendations, bibliography with 217 titles, and 7 annexes. The illustrative material includes 37 tables and 27 figures. Keywords: bronchopulmonary dysplasia, preterm infants, risk factors, chest X-ray, pulmonary CT. Aim of the research: To evaluate the etiological factors and clinical-paraclinical diagnosis of bronchopulmonary dysplasia (BPD) in preterm infants to develop prognostic criteria for the disease. Research objectives: 1) To study the risk and causal factors involved in bronchopulmonary dysplasia in children; 2) To evaluate the clinical manifestations of children with bronchoulmonary dysplasia; 3) To investigate pulmonary imaging changes in children with bronchopulmonary dysplasia; 4) To develop prognostic criteria for the evolution and severity of bronchopulmonary dysplasia in preterm infants. Scientific novelty and originality: The scientific novelty focuses on identifying determinants and predictive factors in children with bronchopulmonary dysplasia, highlighting specific clinical forms. An analytical observational cohort study was conducted through a multifactorial etiological approach to BPD in children with a history of prematurity. The research provided original national data regarding risk factors for BPD in preterm infants hospitalized at the IMSP Institute of Mother and Child, as well as data related to bronchopulmonary sequelae in BPD. New insights were gained regarding the role of pathogens in BPD, enabling a deeper correlation with the degree of prematurity, birth weight, gestational age, and oxygen therapy level. Risk factors, clinical features, and imaging characteristics were analyzed according to the severity of BPD in children. Theoretical significance: The theoretical significance of the research lies in the in-depth exploration of the etiopathogenic mechanisms involved in the development of BPD in preterm infants, using a comprehensive and integrative approach to the determining factors. The study enriched the existing theoretical framework by identifying and classifying risk and predictive factors based on disease severity and highlighting the relationship between perinatal, infectious factors and the need for respiratory support. The findings significantly contributed to the understanding of the relationship between prematurity, postnatal insults (infections, oxygen therapy, mechanical ventilation), and the development of bronchopulmonary sequelae, offering a conceptual framework that can support the development of predictive models and follow-up guidelines for children at high risk of BPD. Practical value: Programs were developed with clear criteria for early diagnosis and prognosis of the evolution of bronchopulmonary dysplasia in children. For practitioners, a well-structured laboratory diagnostic algorithm was proposed to enable the earliest possible detection of this nosological entity. The application of this algorithm facilitates the assessment of BPD’s impact on pediatric respiratory morbidity, contributing to faster and more effective clinical interventions. Implementation of results: The results of the study were implemented in the clinical practice of the Pneumonology Clinic within the IMSP Institute of Mother and Child. Additionally, these findings were incorporated into the educational process at the Department of Pediatrics, “Nicolae Testemițanu” State University of Medicine and Pharmacy, and contributed to the update of the National Clinical Protocol (PCN-393) on “Bronchopulmonary Dysplasia in Children.” These initiatives highlight the practical applicability of the research in improving patient care and continuous professional development.Структура диссертации: Работа изложена на 134 страницах и включает: введение, 3 главы, синтез полученных результатов, общие выводы, практические рекомендации, библиографический указатель с 217 источниками и 7 приложениями. Иллюстративный материал включает 37 таблиц и 27 рисунков. Ключевые слова: бронхолёгочная дисплазия, недоношенность, факторы риска, рентгенография грудной клетки, КТ лёгких. Цель исследования: Оценка этиологических факторов и клинико-параклинической диагностики у недоношенных детей с бронхолёгочной дисплазией для разработки прогностических критериев заболевания. Задачи исследования: 1) Изучить причинные и предрасполагающие факторы БЛД у детей; 2) Оценить клинические проявления у детей с БЛД; 3) Исследовать изменения лёгочной визуализации при БЛД у детей; 4) Разработать критерии прогноза течения и степени тяжести БЛД у недоношенных детей. Научная новизна и оригинальность: Новизна исследования заключается в акценте на выявлении детерминант и прогностических факторов у детей с бронхолёгочной дисплазией, с выделением особенностей клинических форм заболевания. Проведено аналитическое обсервационное когортное исследование с мультифакторным этиологическим подходом к изучению БЛД у детей с историей преждевременных родов. Работа предоставила оригинальные отечественные данные о факторах риска БЛД у недоношенных детей, госпитализированных в ИМСМ «Институт матери и ребёнка», а также информацию о бронхолёгочных осложнениях при БЛД. Были получены новые данные о роли патогенов в развитии БЛД и установлены значимые корреляции с уровнем недоношенности, массой тела, гестационным возрастом и уровнем кислородной терапии. Изучены клинико-визуализационные особенности БЛД в зависимости от степени её тяжести. Теоретическая значимость: Работа углубляет знания о этиопатогенетических механизмах развития БЛД у недоношенных детей посредством комплексного и интегративного анализа определяющих факторов. Исследование дополняет существующую теоретическую базу за счёт классификации факторов риска и прогноза в зависимости от тяжести заболевания, а также установления взаимосвязи между перинатальными, инфекционными факторами и потребностью в респираторной поддержке. Полученные результаты способствуют лучшему пониманию связи между недоношенностью, постнатальными агрессиями (инфекции, оксигенотерапия, искусственная вентиляция лёгких) и развитием бронхолёгочных осложнений, формируя концептуальную основу для разработки прогностических моделей и протоколов мониторинга детей с высоким риском БЛД. Практическая значимость: Разработаны программы с чёткими критериями ранней диагностики и прогноза течения БЛД у детей. Практикующим специалистам предложен структурированный лабораторный алгоритм диагностики БЛД, позволяющий выявлять заболевание на ранней стадии. Применение этого алгоритма способствует более быстрой и эффективной оценке влияния БЛД на педиатрическую респираторную заболеваемость и оптимизации клинических вмешательств. Внедрение результатов: Полученные данные внедрены в клиническую практику пульмонологического отделения ИМСМ «Институт матери и ребёнка» и в учебный процесс кафедры педиатрии ГУМФ. Результаты исследования учтены при обновлении национального клинического протокола по бронхолёгочной дисплазии у детей, что подтверждает их практическую значимость

    Telomere shortening as a mechanism for the induction of neurodegenetative diseases

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    Background. Telomeres are considered the "cellular biological clock" because their length could determine the possible number of cell divisions. Telomerase plays a role in maintaining telomere length. Telomerase ensures de novo addition of nitrogenous base sequences such as TTAGGG at the 3' end, protecting the chromosome end from double-strand breaks and preventing the DNA damage response (DDR). Objective of the study. Identifying the mechanisms by which the progressive shortening of telomeres in nerve cells activates processes leading to neuronal senescence, with the aim of improving diagnosis and developing effective treatment methods. Materials and Methods. To achieve the proposed objective, a literature review was conducted using 10 bibliographic sources from electronic libraries such as PubMed, MedScape, Hindawi, and ScienceDirect. Results. Telomerase is active in young neural cells or neural precursor cells, but as they differentiate into mature neurons, its activity progressively decreases, affecting neuronal differentiation and stopping neurogenesis. In the absence of telomerase, telomere shortening can reach critical lengths, triggering a DDR-type response. This process induces the activation of ataxia-telangiectasia mutated kinase and other signaling proteins such as p53 and p21. The p53 protein plays a role in halting the cell cycle by activating p21, which inhibits cyclin-dependent kinase 2 and blocks the phosphorylation of the retinoblastoma protein (Rb). Hypophosphorylated Rb blocks E2 factor, a transcription factor, preventing the expression of genes necessary for cell division and causing cell cycle arrest in the G1 phase, leading to replicative senescence. Senescent cells secrete a senescence-associated secretory phenotype, which contributes to chronic inflammation and the spread of senescence in neighboring tissues. Chronic inflammation accelerates the accumulation of toxic proteins, such as beta-amyloid in Alzheimer’s or alpha-synuclein in Parkinson’s, promoting neuronal death and disease progression. Conclusion: Telomere shortening in nerve cells induces senescence and chronic inflammation, accelerating neurodegeneration in diseases such as Alzheimer's and Parkinson's. Future therapies could aim at controlled activation of telomerase, the use of senolytic cells to eliminate senescent cells, and blocking senescence-associated secretory phenotype to reduce inflammation. These approaches could help slow down the neurodegenerative process and contribute to the development of more effective treatments

    Flexible and rigid bronchoscopy: advantages and disadvantages

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    Rezumat: Ultimii ani au fost marcați de progrese semnificative în pediatrie, inclusiv endoscopia pediatrică, care a condus spre realizari importante în diagnosticarea, tratamentul și prevenirea bolilor respiratorii la copii. În lucrarea se discută atât despre avantajele, cât și dezavantajele diferitelor tipuri de bronhoscopie, o gamă largă de aplicare a acestora în diverse cazuri clinice. Informațiile privind indicațiile și contraindicațiile bronhoscopiei sunt sistematizate. Este definit algoritmul de alegere a metodei optime de cercetare, care oferă cea mai completă gamă posibilă de informații de interes. Articolul este ilustrat cu imagini endoscopice pentru o percepție mai completă și mai voluminoasă a textului.Summary: Recent years have been marked by marked progress in paediatric science, including paediatric endoscopy, which has led to significant advances in the diagnosis, treatment and prevention of respiratory diseases in children. The paper discusses both advantages and disadvantages of different types of bronchoscopy, a wide range of their application in various clinical cases. Information about indications and contraindications to bronchoscopy is systematised. The algorithm of choosing the optimal method of research, which gives the fullest possible range of information of interest, is defined. The article is illustrated with endoscopic images for a more complete and voluminous perception of the text

    Mimicking the host: gene addition via adeno-associated virus (AAV) to reduce rejection in organ transplants

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    Background.Organ transplantation is a crucial medical advancement, offering life-saving treatment for patients with end-stage organ failure. Despite significant progress, graft rejection remains a major cause of transplant failure. The immune system often attacks the transplanted organ as a foreign body, complicating long-term success. Although immunosuppressive therapies help reduce rejection risk, they have serious side effects, such as increased susceptibility to infections, malignancies, and organ toxicity.Recent research focuses on genetic engineering to address graft rejection. One promising approach is using Adeno-Associated Virus (AAV) vectors to deliver immune-modulatory genes to transplanted organs. AAV-based gene delivery can potentially promote immune tolerance by regulating T-cell activation. Genes like CTLA-4Ig or PD-L1 can be introduced to help the transplanted organ integrate into the recipient’s immune system, reducing rejection likelihood. Materials/Methods. A systematic review was conducted using PubMed, Scopus, and Web of Science (2000–2024). Peer-reviewed studies on AAV-mediated gene addition for reducing transplant rejection in English were included, while non-peer-reviewed and irrelevant articles were excluded. Findings were synthesized into key themes such as organ transplant rejection, immunosuppressive therapy, host immune profile, and AAV-mediated gene therapy. Results. AAV-mediated gene addition, especially the delivery of CTLA-4Ig, has shown promise in reducing organ transplant rejection by inhibiting T-cell activation. AAV vectors, particularly AAV8 and AAV9, target liver cells and express CTLA-4Ig in hepatocytes, modulating immune responses. However, challenges persist, including variable transduction efficiency, immune responses against AAV vectors, and short gene expression duration. Pre-existing immunity against AAV vectors can limit gene delivery, and potential side effects such as immune reactions and genotoxicity remain concerns. Self-complementary AAV vectors reduce integration risks. Conclusion. Advancements in vector design and gene therapy techniques may revolutionize organ transplantation. AAV-mediated gene addition could offer an alternative to traditional immunosuppressive therapies, improving long-term transplant success and reducing side effects. The goal is personalized gene therapy that mimics the host's immune profile, promoting long-term graft acceptance without lifelong immunosuppressive drugs. Continued research and clinical trials will be essential to fully realize AAV-based therapies in transplantation

    CBCT – Gold standard in the imaging diagnosis of dental caries

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    Introducere. Prima cerință pentru efectuarea unui tratament stomatologic eficace este formularea unui diagnostic corect și complet. Metodele radiologice, precum radiografia retroalveolară, ortopantomografia (OPT), tomografia computerizată cu fascicul conic (CBCT) oferă informații importante referitoare la topografia defectului carios și gradul de implicare a țesuturilor dure dentare. Scopul lucrării. Compararea acurateței examenului OPT față de CBCT în identificarea leziunilor carioase. Materiale și metode. Un clinician a examinat mai întâi OPT-urile și apoi tomografiile a 7 pacienți care au efectuat ambele metode de diagnostic. Prezența sau absența cariilor au fost consemnate prin „0” și respectiv „1”, obținând perechi de parametri dihotomici pentru fiecare leziune identificată pe OPT și/sau CBCT. Gradul de acord între cele două metode a fost calculat prin coeficientul kappa al lui Cohen. Rezultate. Un grad de acord substanțial a fost obținut între interpretarea OPT-urilor și imaginilor CBCT (k=0.72, p<0.05). Examenul CBCT a avut o acuratețe superioară, identificând toate leziunile carioase. Metoda OPT a fost eficace în identificarea cariilor primare proximale, dar mai puțin eficace în detectarea cariilor secundare. Un alt avantaj a fost posibilitatea vizualizării exacte a relației cariilor profunde cu camera pulpară. Concluzie. Examenul CBCT oferă o acuratețe superioară față de OPT în evaluarea leziunilor carioase, însă cea din urmă rămâne o metodă viabilă de screening datorită costului redus și dozei mici de radiație.Background. The primary requirement for effective dental treatment is the establishment of a correct and comprehensive diagnosis. Radiological methods such as periapical radiography, orthopantomography (OPT), and cone beam computed tomography (CBCT) provide essential information regarding the topography of carious defects and the extent of involvement of hard dental tissues. Objective of the study. To compare the accuracy of OPT examination versus CBCT in detecting carious lesions. Materials and Methods. A clinician first examined the OPT images and subsequently analyzed the CBCT scans of seven patients who underwent both diagnostic methods. The presence or absence of caries was recorded as “0” and “1,” respectively, generating paired dichotomous parameters for each lesion identified on OPT and/or CBCT. The level of agreement was assessed using Cohen’s kappa coefficient. Results. A substantial degree of agreement was observed between the interpretation of OPT and CBCT images (k = 0.72, p < 0.05). CBCT demonstrated superior accuracy, identifying all carious lesions. The OPT method was effective in detecting primary proximal caries but less effective in identifying secondary caries. Another advantage of CBCT was its ability to precisely visualize the relationship between deep carious lesions and the pulp chamber. Conclusion. CBCT examination provides superior accuracy compared to OPT in the assessment of carious lesions. However, OPT remains a viable screening method due to its lower cost and reduced radiation dose

    Correlations between echocardiographic findings and SPECT CT as a predective tool for chronic thromboembolic pulmonary hypertension in post-pulmonary embolism patients

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    Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe but potentially treatable complication of pulmonary embolism (PE). SPECT CT has emerged as a non-invasive modality capable of detecting residual perfusion defects, potentially improving early risk stratification. Current guidelines rely on echocardiographic and hemodynamic assessment for CTEPH diagnosis, but these methods may lack sensitivity in early-stage disease. Objective: To investigate the predictive value of RV echocardiographic findings and SPECT CT in identifying PE survivors at risk of developing CTEPH and to assess its role in guiding therapeutic interventions. Methods: It is a prospective study that enrolled PE survivors who had completed standard anticoagulation period (3-6 months). Patients underwent structured follow-up, including clinical assessment (dyspnea score, 6-minute walk test), echocardiography, biochemical markers (NTproBNP), and SPECT CT imaging. Correlations between SPECT CT findings, right ventricular dysfunction, and pulmonary hemodynamics were analyzed using multivariate logistic regression on SPSS program. Results: Among 86 enrolled patients, 30 underwent complete imaging workup, revealing persistent perfusion defects in 60% of symptomatic individuals. Of these, 43% exhibited echocardiographic markers suggestive of chronic thromboembolic pulmonary hypertension (CTEPH), with significant associations between perfusion abnormalities and elevated NT-proBNP levels (p<0.001). Echocardiographic findings suggest a strong correlation between TAPSE/PSAP rapport and the NTproBNP test (p<0,001), RV strain changes (p<0,02) and high probability of pulmonary hypertension (p<0,001). The severity of perfusion defects on SPECT CT correlated strongly with thoracic pain (p<0,03) and high probability of pulmonary hypertension (p<0.03). No statistical significant correlation found between SPECT CT changes and RV strain (p<0,9), 3D RVEF results (p<0,1) or TAPSE/PSAP rapport (p<0,08). Conclusions: SPECT CT may represent a valuable imaging modality in early detection of post-PE sequelae, identifying patients with high probability of pulmonary hypertension who may benefit from more diagnostic tests or/and interventional and improving long-term cardiovascular outcomes. However, additional prospective scientific studies are required to draw definitive conclusions regarding its clinical utility and optimal integration into post-PE management

    Polichistoza renală la copil

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    „Chronic myeloid leukemia: contemporary insights into the epidemiological, clinical-biological profile, diagnosis and treatment”. Author: Vasile Musteaţă

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    Schizofrenia. Metode de intervenție

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    În acest material vom afla informații prețioase despre schizofrenie, pornind de la clasificare, detalii epidemiologice până la screening și strategii terapeutice pe termen lung

    Stem cell transplantation in infertility treatment: new perspectives in regenerative medicine

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    Background. Female infertility is a multifactorial condition caused by factors such as ovarian dysfunction, endometrial disorders, hormonal imbalances, and age-related decline in reproductive potential. Stem cell transplantation offers a promising approach to regenerate reproductive tissues, restore ovarian function, and enhance endometrial receptivity. Objective of the study. To evaluate the potential of stem cell transplantation in treating female infertility and identify the mechanisms by which stem cells promote tissue regeneration and fertility restoration. Material and Methods. This study synthesizes literature from articles published between 2020-2025, selected from PubMed, NCBI and MPDI. Results. Stem cell therapies, especially for ovarian and endometrial dysfunction, show significant promise. Embryonic stem cells (ESCs) can differentiate into germ cells, offering infertility solutions, but their use is limited by ethical concerns. Induced pluripotent stem cells (iPSCs) can differentiate into gametes, showing potential for fertility restoration, although their clinical use is restricted by genomic instability. Mesenchymal stem cells (MSCs), particularly from bone marrow and menstrual blood, have demonstrated therapeutic potential in treating ovarian failure and endometrial dysfunction. These cells aid in tissue repair, restore hormonal function, and promote angiogenesis. Studies in animals show improvement in ovarian function, endometrial thickness, and egg development. Amniotic fluid stem cells (AFSCs) regenerate oocytes and prevent follicular atresia. Amnion-derived mesenchymal stem cells (AmDMSCs) support ovarian recovery by reducing apoptosis and enhancing granulosa cell proliferation. Placenta-derived mesenchymal stem cells (PDMSCs) improve folliculogenesis through the PI3K/Akt pathway. Adipose tissue-derived stem cells (ADMSCs) enhance ovarian function through neovascularization. Ovarian stem cells (OSCs) hold promise for fertility restoration in cases of premature ovarian failure. Spermatogonial stem cells (SSCs) have been used experimentally to restore male fertility, especially after chemotherapy-induced infertility. Conclusion. Stem cell-based therapies offer significant potential for treating female infertility, particularly in ovarian and endometrial dysfunctions. Further research is needed to optimize protocols, address risks like immune rejection and tumor formation, and confirm clinical safety and efficacy

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