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Abstract New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. In this manuscript we characterize 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv-exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target. We show that humAb 826827 blocks the invasion of human reticulocytes using Pv clinical isolates and inhibits sporozoite invasion of human hepatocytes in vitro (IC50 of 0.3 – 3.7 µg/mL). Inoculation of human liver transgenic (FRG-humHep) female mice with humAb 826827 significantly reduces liver infection in vivo. The crystal structure of rPvAMA1 bound to 826827 shows that 826827 partially occupies the highly conserved hydrophobic groove in PvAMA1 that binds its known receptor, RON2. We have isolated a potent humAb that is isolate-transcendent, blocks both pre-erythrocytic and blood stage infection, and could be a potential therapy for Pv.

Abstract Plasmodium vivax is the most widespread of the different Plasmodium species able to infect humans and is responsible for most malaria cases outside Africa. An effective, strain-transcending vaccine that alleviates or suppresses erythrocyte invasion would be a game-changer in eliminating vivax malaria. Recently, the binding of P. vivax Reticulocyte Binding Protein 2b (PvRBP2b) to human Transferrin receptor (TfR1) has been described as essential for reticulocyte invasion, making this parasite protein an appealing vaccine candidate. Here, using P. vivax Cambodian clinical isolates in robust ex vivo invasion assays, we show that anti-PvRBP2b polyclonal and monoclonal antibodies that inhibit binding of PvRBP2b to TfR1 do not block P. vivax invasion into reticulocytes even at high concentrations. Anti-TfR1 antibodies do not inhibit P. vivax invasion either. Combinations at high concentrations of human monoclonal antibodies targeting different PvRBP2b epitopes do not inhibit invasion. Combinations of anti-PvRBP2b with anti-PvDBP do not enhance invasion inhibition caused by anti-PvDBP alone. We also show that the invasion of Cambodian P. vivax is trypsin-resistant while TfR1 is trypsin-sensitive, and we demonstrate that TfR1 is not recycled following trypsin treatment. We determined the PvRBP2b sequence of all isolates used in the invasion assays and analyzed polymorphism within epitopes recognized by anti-PvRBP2b antibodies. We show that polymorphism does not explain the absence of neutralization. Anti-PvRBP2b polyclonal antibodies recognized all four isolates tested in immunofluorescence assays while not inhibiting P. vivax invasion. Overall, our results demonstrate that PvRBP2b binding to TfR1 is not essential for invasion into reticulocytes of P. vivax Cambodian strains questioning the relevance of PvRBP2b as vaccine candidate.

Цель. Изучение функциональных особенностей изолированного сердца при постинфарктном ремоделировании миокарда с целью выявления компенсаторных и декомпенсаторных патогенетических механизмов сердечной недостаточности (СН). Материал и методы. Инфаркт миокарда был воспроизведен у белых лабораторных крыс при двукратном введении изопротеренола (ИИМ). Функциональный статус левого желудочка (ЛЖ) изолированного сердца оценивали в конце модели (исходно) и через 4 недели (период становления ремоделирования миокарда), определив при этом инотропизм миокарда при действии эндотелина 1 (ET-1), в том числе на фоне нагрузок обьёмом и давлением, толерантность к ишемии и реперфузии, а также коронарную реактивность на действие различных стимулов (ацетилхолин, брадикинин, аденозин, эпоксиэйкозатриены). Результаты. Постинфарктное ремоделирование миокарда сопровождалось реверсией отрицательного инотропного эффекта сердца на действие EТ-1 в положительный ответ, что сочеталось повышением систолического давления ЛЖ и минутного обьёма до 10%. Этот положительный эффект был выявлен наряду с увеличением значения -dP/dTmax и +dP/dTmax, показателей изоволюмического расслабления и сокращениясердца, до 9,3%, что привело к улучшению гетеро- и гомеометрической регуляции сердца и оптимизации адаптации сердца к гемодинамическим нагрузкам, в том числе на фоне премедикации EТ-1. Выявлено также улучшение эндотелий зависимой коронарной реактивности, в результате чего функциональный коронарный резерв увеличивался до 43% под действием ацетилхолина, аденозина и брадикинина. Примечательно, что на фоне постинфарктного ремоделирования миокарда снижается коронарнодилатирующий эффект брадикинина опосредованного рецепторами В1 и увеличивается эффект эндотелиальных В2-рецепторов. В то же время обнаружено повышение толерантности миокарда к ишемии (30 мин) и реперфузии (45 мин), вследствие чего величина конечно-диастолического давления ЛЖ была достоверно ниже показателя ИИМ.Выводы. 1. Связь функционального статуса сердца с постинфарктном ремоделированием миокарда характеризуется улучшением инотропизма миокарда и появлением положительного ответа на действие ЕТ-1, проявляющегося увеличением систолического давления и минутного обьёма ЛЖ. 2. Положительный инотропный эффект сопровождался увеличением скорости изоволюмического расслабления и сокращения сердца, что приводило к улучшению гомеометрической регуляции и адаптации сердца к нагрузке сопротивлением. 3. Важным патофизиологическим маркером постинфарктной СН является преобладание коронарнодилатирующего эффект брадикинина, опосредованного В1-рецепторами, при том, как преобладание коронарнодилатирующего эффект брадикинина, опосредованного В2-рецепторами, является предиктором положительного постинфарктного ремоделирования миокарда и улучшения течения СН.

Scop: Aprecierea ratei infarctului miocardic fără elevarea segmentului ST cu artere coronare non-obstructive (NSTE- MINOCA) și analiza comparativă a datelor clinice și de management cu infarctul miocardic fără elevarea segmentului ST cu artere coronare obstructive (NSTEMI-CAD). Material și metode: În studiu au fost incluși 494 pacienți cu diagnosticul de infarct miocardic fără supradenivelarea segmentului ST (NSTEMI). Pacienții au fost repartizați în 2 loturi de cercetare în funcție de prezența obstrucției pe arterele coronare: lotul I - 35 de pacienți cu infarct miocardic cu artere coronare non-obstructive (MINOCA) și lotul II - 459 de pacienți cu infarct miocardic cu artere coronare obstructive (MI-CAD). Rezultate: Rata MINOCA în lotul NSTEMI studiat a fost de 7.08%. Ponderea factorilor de risc: fumat, diabet zaharat (DZ), HTA a fost mai mare în lotul MI-CAD vs MINOCA. Markerii necrozei miocardice au avut valori crescute în MI- CAD vs MINOCA: troponina cantitativă - 8.58±0.89 vs 2.8 ±1.3, CK-MB 20.7 ±1.78 vs 13.97±2.6 ng/L, p

Oral cancer contributes to approximately 3–10% of all cancer mortality worldwide, and its incidence is continuously increasing due to environmental conditions and harmful habits of the modern lifestyle [...]

Background and objectives: Erythrocyte sedimentation rate test guides dentists in the suspicion of inflammatory reactions or infections of the dental focus. In 1981, Kondi mentioned that any delay after blood sampling for the purpose of determining the ESR can lead to a false shortening of the result. The literature indicates that failure to determine within 1 hour and remixing of blood are not recommended. The objectives of our study were to verify the stability of the determinations within 4 hours after storage at room temperature and after 12 hours of refrigeration, involving also the remixing manoeuvre. Materials and Methods:The study was performed in the “St. SpiridonˮHospital of Iași, Romania, on 75 samples, taking also into account the rejected samples presenting source of error. Results: The study showed that 4 (5.33%) samples had an inadequate volume, 3 (4%) showed erythrocyte and fibrin in suspension, preventing the interpretation of the result, whereas the clot was identified in 4 (5.33%) samples. Following 4 hours after the first determination, respectively after 12 hours of refrigeration, rebalancing at room temperature and remixing, forout of the 64 (85.33%) determinations the results were comparable showing a close correlation (r = 0.988 / 0.993 / 0.990, p

Thrombocytopenia represents one of the most frequent causes of addressability for a hematological consultation. The purpose of the study is to establish a correlation between the degree of thrombocytopenia and the appearance of the mucocutaneous bleeding, with a therapeutic purpose. Materials and method: Our study is a retrospective observational study and was carried out on a group of 100 patients who were referred to the Hematology Clinic of Sp. St. Spiridon, Iași for a period of 12 months and who presented with isolated thrombocytopenia on admission. Other coagulopathy evolving with thrombocytopenia were excluded. To establish the correlation between the decrease in the number of platelets and the appearance of the hemorrhagic skin-mucosal syndrome, statistical methods were used – F Test – Two sample for Variance. Results and discussions: Thrombocytopenia was defined as the value of platelets below 150,000\mmc. 5 grades of thrombocytopenia were established: grade I (TR=150,000-100,000/mmc), grade II (TR= 100,000-50,000/mmc), grade III (TR=50,000-20,000/mmc), grade IV (TR= 20,000 -10,000/mmc), grade V (TR below 10,000/mmc)40% of the patients included in the study presented thrombocytopenia gr. I, 24% – grade II, 15% – grade III, 6% – grade IV and 15% presented severe thrombocytopenia (grade V). The mucocutaneous bleeding was manifested by: petechiae and ecchymosis, epistaxis, bleeding in the oral cavity (gingival bleeding, hemorrhagic bullae), menometrorrhagia, hematuria, melena. There is a statistical correlation between the number of platelets and the occurrence of mucocutaneous bleeding: p=0.000121 (p less than 0.001). The first clinical manifestations of the mucocutaneous bleeding appeared at the value of 70,000/mmc. No statistical correlation was obtained between the age of the patients and the number of platelets (p=0.0352). Conclusions: The occurrence of mucocutaneous bleeding is directly related to the decrease in the number of platelets. The oral cavity usually is involved in bleeding caused by the decrease in the number of platelets and requires a multidisciplinary approach.

Aim of the study Eugenol, a phenolic compound commonly found in plants like clove and bay leaves, has garnered significant attention in the field of dentistry due to its diverse pharmacological properties. In dentistry, eugenol is frequently employed in various forms, such as in polymerized cement with zinc oxide for restorative purposes. Its applications extend to endodontic cements like zinc oxide-eugenol formulations, which are commonly used in dental procedures. So far, according to our knowledge, no study in the literature has approached formulations based on iron oxide nanoparticles and eugenol, this study being the first. Materials and methods In the present study, it was developed for the first time a formulation based on iron oxide nanoparticles obtained through the combustion method, embedded on its surface with eugenol. The prepared formulation was characterized through electron microscopy investigations, followed by further in vitro evaluation as concerned with their biosafety use on a healthy murine epidermal cell line. Results The results obtained showed that the naked iron oxide nanoparticles are biocompatible and safe to use on the healthy murine epidermal cell line, while the eugenol compound exhibits a dose-dependent cytotoxicity reaching until a value of ~17% at the highest tested dose (100 μg/mL). In addition, the cytotoxicity of eugenol decreased when this was embedded on the iron oxide nanoparticles surface, recording a value of 11% at the highest concentration tested. Conclusions In conclusion, the in vitro studies on such type of formulation in dentistry and dental medicine highlight their multifaceted applications of iron oxide nanoparticles as well as eugenol, emphasizing their potential for advancing dental treatments and diagnostics.

COVID-19 and influenza are highly contagious respiratory viral diseases and priority global public health concerns. We conducted a retrospective observational study of COVID-19 and/or influenza hospitalized cases, during 2023. We identified 170 influenza cases, 150 COVID-19 cases and 3 co-infections. Overall, 29.10% of patients had at least one COVID-19 vaccine dose and 4.6% received the seasonal Flu vaccine. The demographic data found older patients in the COVID-19 group and a higher index of the comorbidities, mainly due to chronic heart diseases, hypertension, and diabetes. Fever, chills, and rhinorrhea were more frequently related to influenza, while cough was prevalent in COVID-19. Antibiotics were more used in influenza than COVID-19, either pre-hospital or in-hospital. The mortality rate within the first 30 days from the onset of the respiratory infection was higher in influenza compared to COVID-19. We concluded that the COVID-19 clinical picture in hospitalized patients is changing to influenza-like symptoms. The evolution is variable, related to chronic comorbidities, but influenza had more frequent severe forms. All through 2023, due to poor vaccination rates, COVID-19 and influenza have continued to cause numerous hospitalizations, and a new strategy for efficient vaccinations is required.

Oral hygiene plays a crucial role in preventing dental diseases, but tooth brushing alone is insufficient for cleaning hard-to-reach interdental spaces. Aim: This comparative study investigates the effectiveness of two types of dental floss (nylon and silicone) in cleaning interproximal spaces as adjuncts to tooth brushing. Material and Methods: The study involved 20 final-year students from the Faculty of Dental Medicine in Iași, who met specific criteria, including having more than 30% of their tooth surfaces covered with plaque and interdental bleeding. Clinical assessments were conducted at three stages (initial, intermediate, and final) using the Quigley-Hein Plaque Index, O’Leary Index, Approximal Plaque Index (API), and Sulcular Bleeding Index (SBI). Results: Silicone dental floss showed greater efficiency in reducing plaque and gingival bleeding, as indicated by lower scores in the final evaluation compared to nylon floss. Conclusions: The findings suggest that silicone floss provides superior comfort, durability, and effectiveness, making it a preferable choice for consistent oral hygiene practices. These results underline the importance of incorporating adjunctive tools, such as dental floss, into daily oral care routines for optimal dental and gingival health.

Dental caries is a multifactorial, dynamic disease that affects dental hard tissues, being initiated by acidic products from oral biofilms. The etiology and pathophysiology of dental caries are extremely complex. It is widely accepted that changes in the local microecology and disruption of tooth re/demineralization could cause dental caries. Moreover, saliva, fluoride application, dietary sugars and preventive behaviors could also influence it. In recent decades, a combination of drug-release and controlled-release systems for the purpose of caries prevention has gradually attracted attention. These could help maintain the concentration of anti-caries agents in situ through sustained drug release. Such local application has many advantages, such as high efficacy and few systemic effects. Thus, in recent years, there has been an increasing amount of research on drug delivery systems for different stages of dental caries.

In the context of increasing economic interdependence, tax reform has become critical on the international agenda due to widespread tax avoidance by multinational companies and digital giants. The OECD has proposed tax reforms to address these challenges, aiming for a fairer distribution of tax revenues among countries. This paper examines the necessity and impact of implementing the OECD's tax reforms within the EU, considering the diverse tax systems of member states. The analysis reveals an upward trend in profits transferred to tax havens globally. EU tax havens like the Netherlands, Ireland, and Luxembourg are significant recipients of these profits. The OECD reforms, by reallocating profits and establishing a minimum tax, are expected to reduce the attractiveness of these havens. The impact will vary: less developed EU countries may lose foreign investment opportunities, while more developed countries could benefit from increased tax revenues and fairer profit distribution.

This study investigates the impact of tax avoidance on Romania's economy, specifically its relationship with GDP, comparing Romania's situation to other EU member states. The research utilizes a quantitative methodology, analyzing data from 2015 to 2020 through statistical methods, including regression analysis. The findings indicate a substantial increase in profits transferred from Romania to tax havens, rising from 4 billion USD in 2015 to 7 billion USD in 2020, with a peak of 8 billion USD in 2019. The share of profits lost as a percentage of GDP ranged from 2.25% to 3.19%, with an average of 2.63%. Transfers to non-EU tax havens increased significantly, while those to EU tax havens remained constant. Regression analysis shows a positive and significant relationship between GDP growth and profits lost, with an increase of 0.039904 units of profits lost for each additional unit of GDP. These results highlight the economic impact of tax avoidance and underline the need for effective policy measures to address this issue.

Veziculele extracelulare (EV) sunt o familie de particule/vezicule prezente în sânge și fluide corporale, delimitate de un strat dublu lipidic și care nu se pot replica, adică nu conțin un nucleu functional. Acestea poartă o varietate de molecule importante în medierea comunicării celulare, modulând astfel procese celulare cruciale, cum ar fi homeostazia, inducerea/ atenuarea inflamației și promovarea reparației. [1]Existența lor, suspectată inițial în 1946 și confirmată în 1967, a determinat o creștere bruscă a numărului de publicații științifice, a interesului pentru EV și aplicațiile lor potențiale în înțelegerea mecanismelor care stau la baza diferitelor boli, cum ar fi cancerul, bolile cardiovasculare, metabolice, neurologice și infecțioase, printre altele, care au dezvăluit un rol pentru EV ca biomarkeri candidați promițători pentru diagnostic, prognostic și chiar instrumente terapeutice, în bolile cardiovasculare (CV) și alte boli [2].Populația veziculelor derivate din trombocite (pEV) este cea mai mare printre alte tipuri de EV din circulație.Caracteristicile fizice ale membranei celulare și încărcătura biologică definesc rolul pivot al veziculelor derivate din trombocite în patogeneza bolilor cardiovasculare (CV).pEV-urile sunt, așadar, jucători cheie în mediarea reacțiilor inflamatorii și de coagulare care implică endoteliul, trombocitele, celulele musculare netede și celulele inflamatorii și contribuie astfel la dezvoltarea aterosclerozei și angiogenezei, dereglării microcirculației coronariene în contiguitate cu disfuncția endotelială [3]. În plus, EV joacă un rol esențial în repararea țesuturilor, angiogeneză și neovascularizare prin cascade de semnalizare intracelulară. De fapt, EV-urile mediază semnale autocrine și paracrine care sunt capabile să reconstruiască micro-mediul homeostatic din inimă și vase [4].Această revizuire își propune să ofere o scurtă privire de ansamblu asupra biogenezei, caracteristicilor microparticulelor plachetare cu un accent special pe implicarea lor în bolile cardiovasculare, dar, mai ales, pe legătura dintre tromboză, disfuncție endoteliala și inflamație. Tot aici trecem în revistă experimentele timpurii, rezumăm constatările cheie care au propulsat domeniul, descriem creșterea unei comunități organizate de EV și discutăm starea actuală a domeniului.

O mare majoritate (până la 70%) dintre pacienții supuși angiografiei coronariene din cauza anginei și a semnelor de ischemie miocardică nu au artere coronare obstructive. Studiile efectuate în ultimele decenii au evidențiat că disfuncția coronariană microvasculară (DCM) și vasospasmul epicardic sunt mecanismele fiziopatologice de bază ale bolii coronariene cronice (BCC) non-obstructive, iar în funcție de mecanismul subiacent se diferențiază trei endotipuri clinice: angina microvasculară, vasospastică și mixtă. Este demonstrat că diagnosticul corect și tratamentul personalizat în funcție de endotipul BCC non-obstructive este asociat cu o calitate mai bună a vieții și un prognostic mai favorabil pe termen lung.Pacienții cu BCC non-obstructivă necesită un control la fel de bun al factorilor lor de risc cardiovascular ca și pacienții cu obstrucția arterelor coronare. Statinele și inhibitorii enzimei de conversie ai angiotensinei (IECA) au efecte benefice la majoritatea pacienților. Tratamentul anti-anginal de prima linie sunt betablocantele și/sau blocante ale canalelor de calciu, în funcție de mecanismul subiacent (disfuncție coronariană microvasculară sau vasospastică). Medicamentele de linia a doua sunt ivabradina, ranolazina și nicorandilul, iar inhibitorii de rho-kinaza și antagoniștii receptorilor de endotelină reprezintă potențiale medicamente pentru tratamentul pacienților cu BCC non-obstructivă în viitor.

Introducere. Deși în ultimele decenii s-au realizat progrese notabile în managementul pacienților cu infarct miocardic fără supradenivelarea segmentului ST (NSTEMI), rata mortalității intraspitalicești rămâne ridicată. Aceasta depinde de un șir de factori: demografici, antropometrici, temporali, socio-economici, etnici și altele. Astfel, decelarea unui algoritm de factori cu valoare predictivă asupra riscului mortalității intraspitalicești se anunță un reper important în contextul gestionării corespunzătoare a acestora. Scopul studiului a fost evaluarea factorilor de prognostic asociați cu moartea intraspitalicească la pacienții cu NSTEMI revascularizați prin intervenție coronariană percutană cu stent (PCI). Materiale și metode. În studiu observațional realizat în perioada 2020-2023 au fost incluși 550 de pacienți cu NSTEMI revascularizați prin PCI. În baza evidențelor clinice și paraclinice de la admitere (date demografice, factorii de risc cardiovascular, istoricul bolii cardiovasculare, comorbidități, prezentarea clinică, clasa Killip, date de laborator, electrocardiograma, ecocardiograma selectate din chestionarul de 180 de puncte) s-au selectat predictorii plauzibili ai mortalității în contextul estimării comparative a 2 loturi: primul - lotul celor decedați (n=23; 4,18%) și al doilea – lotul pacienților care au supraviețuit (n=527, 95,82%).Rezultate. Vârsta medie a pacienților decedați era de 71,39± 2,05 ani vs 66,24±0,45 ani, p71 ani, FCC peste 90 bătăi/min, insuficiența cardiacă avansată, valori majorate ale NT proBNP, creatinina crescută, Scorul GRACE peste 143 de puncte, raportul neutrofile-limfocite peste 6,607, precum și prezența comorbidități cum este boală obstructivă cronică pulmonară (BPCO).

Geophilus zagreus sp. nov., a troglomorphic geophilid endemic to the Movile Cave sulfidic groundwater ecosystem, is described and illustrated. It is distinguished from other European Geophilus species by a high number of coxal pores on the ventral side of the coxa of the last pair of legs. Its affinities with the other two troglobitic species of the genus are discussed. The mitochondrial COI barcode is sequenced for the new species and phylogenetic analysis is carried out to elucidate its placement within Geophilus. Other syntopic Chilopoda from Movile cave are listed.https://www.zoobank.org/urn:lsid:zoobank.org:act:D549ACAF-5DE4-403E-8D1A-5E6232A635E7