Clinical Efficacy of Extracellular Vesicle Therapy in Periodontitis: Reduced Inflammation and Enhanced Regeneration.

Periodontitis, a prevalent inflammatory condition, affects the supporting structures of teeth, leading to significant oral health challenges. Traditional treatments have primarily focused on mechanical debridement, antimicrobial therapy, and surgery, which often fail to restore lost periodontal structures. Emerging as a novel approach in regenerative medicine, extracellular vesicle (EV) therapy, including exosomes, leverages nano-sized vesicles known for facilitating intercellular communication and modulating physiological and pathological processes. This study is a proof-of-concept type that evaluates the clinical efficacy of EV therapy as a non-surgical treatment for stage I-III periodontitis, focusing on its anti-inflammatory and regenerative potential. The research involved seven patients undergoing the therapy, and seven healthy individuals. Clinical parameters, including the plaque index, bleeding on probing, probing depth, and attachment level, were assessed alongside cytokine levels in the gingival crevicular fluid. The study found significant improvements in clinical parameters, and a marked reduction in pro-inflammatory cytokines post-treatment, matching the levels of healthy subjects, underscoring the therapy's ability to not only attenuate inflammation and enhance tissue regeneration, but also highlighting its potential in restoring periodontal health. This investigation illuminates the promising role of EV therapy in periodontal treatment, advocating for a shift towards therapies that halt disease progression and promote structural and functional restoration of periodontal tissues.

Harnessing the Stem Cell Niche in Regenerative Medicine: Innovative Avenue to Combat Neurodegenerative Diseases.

Regenerative medicine harnesses the body's innate capacity for self-repair to restore malfunctioning tissues and organs. Stem cell therapies represent a key regenerative strategy, but to effectively harness their potential necessitates a nuanced understanding of the stem cell niche. This specialized microenvironment regulates critical stem cell behaviors including quiescence, activation, differentiation, and homing. Emerging research reveals that dysfunction within endogenous neural stem cell niches contributes to neurodegenerative pathologies and impedes regeneration. Strategies such as modifying signaling pathways, or epigenetic interventions to restore niche homeostasis and signaling, hold promise for revitalizing neurogenesis and neural repair in diseases like Alzheimer's and Parkinson's. Comparative studies of highly regenerative species provide evolutionary clues into niche-mediated renewal mechanisms. Leveraging endogenous bioelectric cues and crosstalk between gut, brain, and vascular niches further illuminates promising therapeutic opportunities. Emerging techniques like single-cell transcriptomics, organoids, microfluidics, artificial intelligence, in silico modeling, and transdifferentiation will continue to unravel niche complexity. By providing a comprehensive synthesis integrating diverse views on niche components, developmental transitions, and dynamics, this review unveils new layers of complexity integral to niche behavior and function, which unveil novel prospects to modulate niche function and provide revolutionary treatments for neurodegenerative diseases.

Cytokine Dynamics in Autism: Analysis of BMAC Therapy Outcomes.

Autism spectrum disorder (ASD) has recently been linked to neuroinflammation and an aberrant immune response within the central nervous system. The intricate relationship between immune response and ASD remains elusive, with a gap in understanding the connection between specific immune mechanisms and neural manifestations in autism. In this study, we employed a comprehensive statistical approach, fusing both overarching and granular methods to examine the concentration of 16 cytokines in the cerebrospinal fluid (CSF) across each autologous bone marrow aspirate concentrate (BMAC) intrathecal administration in 63 male and 17 female autism patients. Following a six-month period post the third administration, patients were stratified into three categories based on clinical improvement: Group 1- no/mild (28 subjects), Group 2-moderate (16 subjects), and Group 3-major improvement (15 subjects). Our integrated analysis revealed pronounced disparities in CSF cytokine patterns and clinical outcomes in autism subjects pre- and post-BMAC transplantation. Crucially, our results suggest that these cytokine profiles hold promise as predictive markers, pinpointing ASD individuals who might not exhibit notable clinical amelioration post-BMAC therapy.

Potential Impact of Polymorphisms in Toll-like Receptors 2, 3, 4, 7, 9, miR-146a, miR-155, and miR-196a Genes on Osteoarthritis Susceptibility.

Osteoarthritis (OA) is a progressive inflammatory disease of synovial joints and a leading cause of disability among adults. Inflammation-related genes, including genes for Toll-like receptors (TLRs), are tightly controlled by several microRNAs that, in addition to their pivotal role in the epigenetic regulation of target genes, are ligands for TLR activation and downstream signaling. Thus, we evaluated the association between OA risk and genetic variants in TLR2, TLR3, TLR4, TLR7, TLR9, and microRNAs that regulate TLRs signaling miR146a, miR155, and miR196a2. Our study group consisted of 95 surgically treated OA patients and a control group of 104 healthy individuals. Genetic polymorphisms were determined using TaqMan real-time PCR assays (Applied Biosystems). Adjusted logistic regression analysis demonstrated that polymorphisms in TLR4 rs4986790 (OR = 2.964, p = 0.006), TLR4 rs4986791 (OR = 8.766, p = 0.00001), and TLR7 rs385389 (OR = 1.579, p = 0.012) increased OA risk, while miR-196a2 rs11614913 (OR = 0.619, p = 0.034) was significantly associated with decreased OA risk. Our findings indicate that polymorphisms in the TLR4 and TLR7 genes might increase OA risk and suggest a novel association of miR-196a2 polymorphism with decreased OA susceptibility. The modulation of TLRs and miRNAs and their cross-talk might be an attractive target for a personalized approach to OA management.

Stem Cell Homing in Intrathecal Applications and Inspirations for Improvement Paths.

A transplanted stem cell homing is a directed migration from the application site to the targeted tissue. Intrathecal application of stem cells is their direct delivery to cerebrospinal fluid, which defines the homing path from the point of injection to the brain. In the case of neurodegenerative diseases, this application method has the advantage of no blood-brain barrier restriction. However, the homing efficiency still needs improvement and homing mechanisms elucidation. Analysis of current research results on homing mechanisms in the light of intrathecal administration revealed a discrepancy between in vivo and in vitro results and a gap between preclinical and clinical research. Combining the existing research with novel insights from cutting-edge biochips, nano, and other technologies and computational models may bridge this gap faster.

Bone Marrow Aspirate Concentrate versus Platelet Rich Plasma or Hyaluronic Acid for the Treatment of Knee Osteoarthritis.

Background: In the last decade, regenerative therapies have become one of the leading disease modifying options for treatment of knee osteoarthritis (OA). Still, there is a lack of trials with a direct comparison of different biological treatments. Our aim was to directly compare clinical outcomes of knee injections of Bone Marrow Aspirate Concentrate (BMAC), Platelet-rich Plasma (PRP), or Hyaluronic acid (HA) in the OA treatment. Methods: Patients with knee pain and osteoarthritis KL grade II to IV were randomized to receive a BMAC, PRP, and HA injection in the knee. VAS, WOMAC, KOOS, and IKDC scores were used to establish baseline values at 1, 3, 6, 9, and 12 months. All side effects were reported. Results: A total of 175 patients with a knee osteoarthritis KL grade II-IV were randomized; 111 were treated with BMAC injection, 30 with HA injection, and 34 patients with PRP injection. There were no differences between these groups when considering KL grade, BMI, age, or gender. There were no serious side effects. The mean VAS scores after 3, 7, 14, and 21 days showed significant differences between groups with a drop of VAS in all groups but with a difference in the BMAC group in comparison to other groups (p < 0.001). There were high statistically significant differences between baseline scores and those after 12 months (p < 0.001) in WOMAC, KOOS, KOOS pain, and IKDC scores, and in addition, there were differences between these scores in the BMAC group in comparison with other groups, except for the PRP group in WOMAC and the partial IKDC score. There were no differences between the HA and PRP groups, although PRP showed a higher level of clinical improvement. Conclusions: Bone marrow aspirate concentrate, Leukocyte rich Platelet Rich Plasma, and Hyaluronic acid injections are safe therapeutic options for knee OA and provide positive clinical outcomes after 12 months in comparison with findings preceding the intervention. BMAC could be better in terms of clinical improvements in the treatment of knee OA than PRP and HA up to 12 months. PRP provides better outcomes than HA during the observation period, but these results are not statistically significant. More randomized controlled trials and high quality comparative studies are needed for direct correlative conclusions.

An insight into osteoarthritis susceptibility: Integration of immunological and genetic background.

Osteoarthritis (OA) is a progressive degenerative disease that affects all synovial joints, causing the disability of the main locomotor diarthrodial joints. OA pathogenesis is caused by a complex interplay between a number of genetic and environmental risk factors, involved in the early onset and progression of this chronic inflammatory joint disease. Uncovering the underlying immunological and genetic mechanisms will enable an insight into OA pathophysiology and lead to novel and integrative approaches in the treatment of OA patients, together with a reduction of the disease risk, or a delay of its onset in susceptible patients.

Do knee injection portals affect clinical results of bone marrow aspirate concentrate injection in the treatment of osteoarthritis? A prospective randomized controlled study.

Aim: To explore the effect that the location of needle placement has on efficacy and tolerability of bone marrow aspirate concentrate injections during treatment of knee osteoarthritis. Methods: Bone marrow aspirate concentrate injections were administered to 111 patients via superolateral, anteromedial or anterolateral portals. Pain was assessed by visual analog scale before and 3, 7, 14 and 21 days after intervention. Knee function was assessed by Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score and International Knee Documentation Committee scores before and 1, 3, 6, 9 and 12 months after intervention. Results: Significant differences in Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score and International Knee Documentation Committee scores were observed 12 months post intervention compared with baseline (p < 0.001 for all comparisons). No significant differences in outcome or pain scores were observed among groups. Conclusion: All portals demonstrated similar clinical benefits up to 12 months after intervention. Trial registration number: ClinicalTrials.gov (NCT03825133).

A painful symphony: the presence of overuse syndrome in professional classical musicians / Una sinfonía dolorosa: la presencia del síndrome de uso excesivo en músicos clásicos profesionales

Musculoskeletal problems are common in instrumental musicians. Little is known about the factors that place musicians at risk, and the ways in which musicians can prevent these problems. Overuse syndrome is the most reported diagnosis among instrumental musicians suffering from playing related musculoskeletal injuries. The study group comprised 50 musicians employed in Symphony Orchestra of the Serbian National Theatre of Novi Sad. Out of the 50 musicians, 30 (60 %) are male and 20 (40 %) female. Higher frequencies of the presence of musculoskeletal symptoms were neck, region of trapezius, back, shoulder, wrist, hand and arm. A larger number of musicians (81.8 %) had perception of high demand of the profession. This investigation with professional classical musicians should show the music-medical interest.

Los problemas musculo-esqueléticos son comunes en los músicos instrumentales. Poco se sabe sobre los factores que ponen en riesgo a los músicos y las formas en que los ellos pueden prevenir estos problemas. El síndrome de uso excesivo es el diagnóstico más informado entre los músicos instrumentales que sufren lesiones musculo-esqueléticas relacionadas al uso de instrumentos musicales. El grupo de estudio estuvo compuesto por 50 músicos de la Orquesta Sinfónica del Teatro Nacional Serbio de Novi Sad. De los 50 músicos, 30 (60 %) eran hombres y 20 (40 %) mujeres. La frecuencia más alta de presencia de síntomas musculoesqueléticos se produjo en el cuello, músculo trapecio, espalda, hombro, muñeca, mano y brazo. Un mayor número de músicos (81,8 %) tuvo una percepción de alta demanda de la profesión. Esta investigación con músicos clásicos profesionales debería ser de interés médico-musical.

Prevalence of third coronary artery: variation or constant coronary artery? / Prevalencia de la tercera arteria coronaria: ¿variación o arteria coronaria constante?

Third coronary artery or supernumerary coronary artery is a direct branch from right aortic sinus and it supplies pulmonary conus and upper part of right ventricle. Third coronary artery is an important bridge for collateral circulation between right and left coronary system. The aim of this study was to determine the number of arteries that origin from right aortic sinus, their frequency and position. The study included 55 adult human hearts collected from Department of Anatomy. The hearts were morphologically studied by gross dissection for the prevalence and topographical anatomy of supernumerary coronary arteries. Out of 55 hearts, 26 (47.3 %) had one right coronary artery, 23 (41.8 %) had two right coronary arteries, and 6 (10.9 %) had three coronary arteries. The supernumerary arteries arises from the right aortic sinus. Right supernumerary coronary arteries may be present in about 52.7 % of the Serbian population. Interpretation of signs and symptoms of coronary occlusion should therefore consider possible contribution of this blood vessels.

La tercera arteria coronaria o arteria coronaria supernumeraria es una rama directa del seno aórtico derecho y su ministra el cono pulmonar y la parte superior del ventrículo derecho. La tercera arteria coronaria es importante para la circulación colateral entre el sistema coronario derecho e izquierdo. El objetivo de este estudio fue determinar el número de arterias de origen del seno aórtico derecho, su frecuencia y posición. El estudio incluyó 55 corazones humanos adultos pertenecientes al Departamento de Anatomía. Los corazones se estudiaron morfológicamente mediante disección macroscópica para determinar la prevalencia y la anatomía topográfica de las arterias coronarias supernumerarias. De 55 corazones, 26 (47,3 %) tenían una arteria coronaria derecha, 23 (41,8 %) tenían dos arterias coronarias derechas, y 6 (10,9 %) tenían tres arterias coronarias. Las arterias supernumerarias surgen del seno aórtico derecho. Las arterias coronarias supernumerarias derechas pueden estar presentes en aproximadamente el 52,7 % de la población serbia. La interpretación de los signos y síntomas de la oclusión coronaria debería considerar la posible contribución de estos vasos sanguíneos.

An anatomical study of the lumbar external foraminal ligaments: appearance at MR imaging.

PURPOSE: The purpose of this study was to examine the MRI appearance of the ligaments within the external space of the lumbar intervertebral foramen by correlating MR images with the corresponding anatomic dissection of the cadaver lumbar spine. METHODS: This was a two part study. Part I of the anatomic study consisted of the dissection of lumbar specimens from one embalmed adult male cadaver. At each lumbar level the external ligamentous structures were identified and their origin, insertion and position were determined. Part II of the study consisted of the anatomical analysis of the external transforaminal ligaments in the 180 lumbar intervertebral foramina on the MR images (1.5 T) in the sagittal plane. The diagnostic procedure was performed on 18 individuals from 18 to 25 years of age. RESULTS: The external transforaminal ligaments were observed at all levels and from both sides in the lumbar intervertebral foramen. The presence of the superior corporotransverse ligament was found in 45.56% intervertebral foramina, while the inferior corporotransverse ligament was found in 61.67% intervertebral foramina in the MRI. CONCLUSION: Our results confirm that external transforaminal ligaments are common structures in the intervertebral foramen. The results of this study show that the external transforaminal ligaments can be clearly visualized in MR images. It is crucial to have previous knowledge of the cadaveric specimens to recognize the transforaminal ligaments in MR images. The presence of these ligaments is clinically important because the ligaments could be the cause of nerve root compression or the low back pain syndrome.

Scaphoid fractures in children.

INTRODUCTION: Scaphoid fractures are rare in childhood. Diagnosis is very difficult to establish because carpal bones are not fully ossified. In suspected cases comparative or delayed radiography is used, as well as computerized tomography, magnetic resonance imaging, ultrasound and bone scintigraphy. Majority of scaphoid fractures are treated conservatively with good results. In case of delayed fracture healing various types of treatment are available. OBJECTIVE: To determine the mechanism of injury, clinical healing process, types and outcome of treatment of scaphoid fractures in children. METHODS: We retrospectively analyzed patients with traumatic closed fracture of the scaphoid bone over a ten-year period (2002-2011).The outcome of the treatment of"acute"scaphoid fracture was evaluated using the Mayo Wrist Score. RESULTS: There were in total 34 patients, of mean age 13.8 years, with traumatic closed fracture of the scaphoid bone, whose bone growth was not finished yet. Most common injury mechanism was fall on outstretched arm--76% of patients. During the examined period 31 children with "acute" fracture underwent conservative treatment, with average immobilization period of 51 days. Six patients were lost to follow-up. In the remaining 25 patients, after completed rehabilitation, functional results determined by the Mayo Wrist Score were excellent. CONCLUSION: Conservative therapy of "acute" scaphoid fractures is an acceptable treatment option for pediatric patients with excellent functional results.

Treatment of complex tibial plateau fractures using Ilizarov technique.

Complex tibial plateau fractures are most commonly caused by high-energy trauma and they are often associated with severe soft tissue injuries that can frequently result in severe complications. Ilizarov external circular fixation is an ideal method of treatment for high- energy fractures of the tibial plateau when extensive soft tissue dissection and internal fixation are contraindicated. Our research included 50 consecutive patients and clinical features of the patients were evaluated during the follow up period using the following instruments: Gustillo-Anderson, Sc- hatzker and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/ OTA) classification methods. Bony results were evaluated using the Association of the Study and Application of the Method ofIlizarov (ASAMI) protocol. The mean functional recovery scores were obtained by the modified functional evaluation system of Karlstrom-Olerud. All fractures healed successfully. Circular fixators could be removed without anesthesia for type IV fractures at 16 weeks (range 12-21) and for type V-VI at 18 weeks (range 15-26) after the operation. According to ASA- MI bone results, there were 39 (78%) excellent, 7 (14%) good, 3 (6%) fair results and 1 (2%) poor result. Analysis of data obtained by the Karlstrom-Olerud functional evaluation system in this study yielded a mean value of 24.7 after six months, which implies recovery. Functional recovery at 12 months after surgery revealed satisfactory recovery with a mean value of 27.7, whereas the mean sco- re of 29.8 recorded at the last evaluation suggested good functional status. The treatment of patients with open and closed multiple intra-articular fractures of proximal tibia applying Ilizarov apparatus showed good functional outcome, which had positive impact on our patients' quality of life.

[Humeral lengthening: case report].

INTRODUCTION: Difference in length of upper extremities has mainly esthetic significance and is therefore not so often a subject of operative treatment, compared to lower extremities. CASE OUTLINE: We are presenting a case of a 16-year-old patient in whom a shortening of 9 cm of the right humerus was determined at the end of growth. This shortening was the result of surgical treatment of solitary bone cyst at the proximal end of the humerus done at the age of 10 years. In order to correct the length of the humerus we applied distraction osteogenesis with a compressive-distracting device according to Mitkovic (Traffix), and we achieved the lengthening of 7.5 cm. During the period of distraction we encountered the following complications: minimal suppuration at the site of the wedges that was successfully resolved with intensive local treatment, while pain and paresthesias along the N. radialis were resolved with a temporarily slowing of the distraction process. Fixation with a plate, i.e. bone grafting was not necessary, and final functional and esthetic result was excellent. CONCLUSION: Successful lengthening of the shortened humerus can be achieved with a unilateral compressive-distracting device according to Mitkovic as its application up to a complete bone reconstruction does not require additional plate fixation or bone grafting. The patient was capable of performing usual daily activities during application of the device.

Ectopic adrenocortical tissue: an incidental finding during inguinal surgery in children.

Adrenal rests are usually unrecognized during operation, and the incidence of ectopic adrenal cortical tissue in pediatric patients during inguinal surgery procedures is unknown. We performed 3028 groin surgical explorations in 2680 patients aged 1 month to 17 years. Ectopic adrenal tissue was found in 69 inguinal operations (2.2%): 37 during 1.524 orchiopexy (2.4%), 23 during 1.115 herniectomy (2.0%), and 9 during 389 hydrocoela operation (2.3%). Statistically there were no significant differences among those three groups. No adrenal rests were detected in females. Although a few reported cases with hormonal activity of ectopic adrenocortical tissue (EACT), the recommendation is to remove them if found.

[Pediatric femur fractures, epidemiology and treatment].

BACKGROUND/AIM: Femur fractures in children most often occur as a consequence of traffic accidents, during play and sport activities, and due to different pathological states. Diagnosis is rather simple and it includes physical and radiographical examination. Femur fractures treatment in children can be operative and unoperative, depending on several facts: age, localisation and type of fracture, joint injuries of soft tissues, the presence of other injuries (in polytrauma), economical and social aspects, ect. The aim of this study was to present epidemiological characteristics of pediatric femur fractures, that is in the stage of development, including a special analysis of the used treatment techniques, as well as the comparison of the obtained data with those from the literature. METHODS: The evaluation included following parameters: age, gender, cause, localisation and type of femur fracture, applied treatment and hospitalisation duration. RESULTS: Among the presented 143 patients with femur fracture, 109 were boys and 34 were girls (3.2:1 ratio; p = 0.0001). Average age for both genders was 8.6 years, and no difference between boys and girls were found for the age (p = 0.758). In total, the most common fracture was diaphyseal fracture of femur in 93 (65.03%) patients. The second was proximal fracture in 30 (20.98%) patients, and the last distal fracture of the femur in 20 (13.99%) patients (p = 0.0001). Three main causes of femur fracture can be distinguished: during play and sport activities in 67 (46.8%) children, in traffic accidents in 64 (44.8%) children, and pathological fractures in 12 (8.4%) children. Inoperative treatment was applied in 82 (57.3%) patients, and operative one in 61 (42.7%) patients. The most common treatment was traction, in 71 (49.6%) patients, followed by immobilization by hip spica cast mostly in young children. Intramedullar elastic nailing was applied in 16 (11.2%) cases, and intra-medullar rigid nailing (Küntscher) in 19 (13.3%) cases. Significantly longer hospitalization period was detected after traction (21 days) comparing to other ways of treatment, mainly operative or hip spica cast (5 to 10 days). CONCLUSION: In young children the standard treatment was hip spica cast after traction. Intramedullar elastic nailing is a modern trend accepted as standard in our approach to femur fracture treatment in children.

Osteoid osteoma: fluoroscopic guided percutaneous excision technique - our experience.

Osteoid osteoma is a small benign bone lesion. It generally affects children and young adults. Traditional treatment of osteoid osteoma includes excision either by wide resection, or by the removal of the nidus using curettes and burrs after opening the overlying cortex. Newly developed techniques involve percutaneous ablation of the tumor by computed tomography-guided core-drill excision and destruction of the nidus by thermocoagulation. Fluoroscopic guided percutaneous extirpation and drilling resection procedures have been performed at the Institute for Health Care of Children and Youth, Pediatric Surgery Clinic in Novi Sad, Serbia. Some modifications in the methods were made and implemented, which resulted in an excellent cost-benefit ratio, shorter period of hospitalization, and faster recovery. The aim of this paper is to present the experience gained in the treatment of osteoid osteomas in the last 5 years at the Pediatric Surgery Clinic in Novi Sad and to describe the modifications to the percutaneous biopsy technique of osteoid osteoma that have been implemented.

[Ultrasonographic differentiation of painful hip in developmental age].

INTRODUCTION: The most common diseases in the group of painful hip are transient synovitis, rheumatoid arthritis, infective (septic) arthritis, Perthes disease and slipping of the upper femoral epiphysis. METHODOLOGY: The algorhythm covers the first and control examinations in certain time intervals (after: 3-7, 7-15, 21-30 days; as well as 2-4 months). RESULTS AND DISCUSSION: The most frequent feature of painful hip is transient synovitis with 65%, Perthes disease with 13%, septic arthritis with 6%, rheumatoid arthritis and slipping of the upper femoral epiphysis with 2.5%. The ratio boys and girls was 2.3:1. The average age in the group of the painful hip was 6.8 years, in the group of TS 6.5 years. The most frequent clinical signs were limping in 84.2% and hip pain in 79.6%. Through the follow up period the difference of the anterior capsular distance was established for symptomatic hip: the average value on the first exam was 8.1 mm, and on the final exam 4.7 mm 3.6 mm. In transient synovitis, there was no difference in measured values of the anterior and lateral femoral head distance for both hips. The medial duration of synovial effusion, measured ultrasonographically, was 10.6 days, and the duration of the clinical signs was 8.7 days. The prolongated synovitis was recorded in 17.6%, and Perthes disease in 8.4%. The average value of anterior capsular distance in these patients was 5.4 mm. In group of Perthes disease the values of anterior capsular distance during control examinations showed increase that implicated the lateralisation or extrusion of the femoral head. The values of anterior distance of the femoral head were without significant difference. CONCLUSION: The ultrasonography should be the method of choice in painful hip differentiation regardless of the age. The ultrasonography can replace radiography safely in the primary diagnostic procedure as well as through the control examination.