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IntroductionKnee osteoarthritis (OA) significantly impacts the quality of life of those afflicted, with many patients eventually requiring surgical intervention. While Total Knee Arthroplasty (TKA) is common, it may not be suitable for younger patients with unicompartmental OA, who might benefit more from High Tibial Osteotomy (HTO). Effective patient education is crucial for informed decision-making, yet most online health information has been found to be too complex for the average patient to understand. AI tools like ChatGPT may offer a solution, but their outputs often exceed the public's literacy level. This study assessed whether a customised ChatGPT could be utilized to improve readability and source accuracy in patient education on Knee OA and tibial osteotomy.MethodsCommonly asked questions about HTO were gathered using Google's “People Also Asked” feature and formatted to an 8th-grade reading level. Two ChatGPT-4 models were compared: a native version and a fine-tuned model (“The Knee Guide”) optimized for readability and source citation through Instruction-Based Fine-Tuning (IBFT) and Reinforcement Learning from Human Feedback (RLHF). The responses were evaluated for quality using the DISCERN criteria and readability using the Flesch Reading Ease Score (FRES) and Flesch-Kincaid Grade Level (FKGL).ResultsThe native ChatGPT-4 model scored a mean DISCERN score of 38.41 (range 25–46), indicating poor quality, while “The Knee Guide” scored 45.9 (range 33–66), indicating moderate quality. Cronbach's Alpha was 0.86, indicating good interrater reliability. “The Knee Guide” achieved better readability with a mean FKGL of 8.2 (range 5–10.7, ±1.42) and a mean FRES of 60 (range 47–76, ±7.83), compared to the native model's FKGL of 13.9 (range 11–16, ±1.39) and FRES of 32 (range 14–47, ±8.3). These differences were statistically significant (p

Background Head-to-head data for bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF; B) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF; D) are lacking in the context of rapid antiretroviral therapy (ART) initiation. This study, BIC-T&T, evaluates the efficacy and tolerability of B vs D in a UK test‐and‐treat setting. Setting BIC-T&T was a randomised, open-label, multi-centre, study in which participants initiated ART within 14 days after confirmed HIV‐1 diagnosis before baseline laboratory. Methods The primary endpoint is the virological response (HIV RNA < 50copies/mL) at week 12 by time-weighted average change in log10 HIV RNA recorded in viral load assays from treatment initiation to week 12, using two-sample Wilcoxon rank-sum test. Results 36 participants were randomised: 94% were male, 53% white; mean (SD) age was 35 years (11.8). Baseline mean (±SD) log10 HIV-RNA was 4.79 (± 0.87) log10 copies/mL and CD4 505 (±253) cells/mm3. The mean (±SD) time from confirmed HIV diagnosis to ART initiation was 7.9 (± 3.7) days. The time-weighted mean decrease in log10 HIV RNA from treatment initiation to week 12 was significantly greater in B in comparison to D (3.1 vs. 2.6 log10 copies/mL, p

Abstract Background Human genetic contribution to HIV progression remains inadequately explained. The type 1 interferon (IFN) pathway is important for host control of HIV and variation in type 1 IFN genes may contribute to disease progression. This study assessed the impact of variations at the gene and pathway level of type 1 IFN on HIV-1 viral load (VL). Methods Two cohorts of antiretroviral (ART) naïve participants living with HIV (PLWH) with either early (START) or advanced infection (FIRST) were analysed separately. Type 1 IFN genes (n = 17) and receptor subunits (IFNAR1, IFNAR2) were examined for both cumulated type 1 IFN pathway analysis and individual gene analysis. SKAT-O was applied to detect associations between the genotype and HIV-1 study entry viral load (log10 transformed) as a proxy for set point VL; P-values were corrected using Bonferroni (P G) was associated with study entry VL (p = 0.0020, beta = 0.32; G associated with higher study entry VL than A) in single SNP association analyses. The findings were not reproduced in FIRST participants. Conclusion Across 19 type 1 IFN genes, only IFNW1 was associated with HIV-1 study entry VL in a cohort of ART-naïve individuals in early stages of their infection, however, this was no longer significant in sensitivity analyses that controlled for population structures using LME.

Abstract Background Rare disease registries (RDRs) are valuable tools for improving clinical care and advancing research. However, they often vary qualitatively, structurally, and operationally in ways that can determine their potential utility as a source of evidence to support decision-making regarding the approval and funding of new treatments for rare diseases. Objectives The goal of this research project was to review the literature on rare disease registries and identify best practices to improve the quality of RDRs. Methods In this scoping review, we searched MEDLINE and EMBASE as well as the websites of regulatory bodies and health technology assessment agencies from 2010 to April 2023 for literature offering guidance or recommendations to ensure, improve, or maintain quality RDRs. Results The search yielded 1,175 unique references, of which 64 met the inclusion criteria. The characteristics of RDRs deemed to be relevant to their quality align with three main domains and several sub-domains considered to be best practices for quality RDRs: (1) governance (registry purpose and description; governance structure; stakeholder engagement; sustainability; ethics/legal/privacy; data governance; documentation; and training and support); (2) data (standardized disease classification; common data elements; data dictionary; data collection; data quality and assurance; and data analysis and reporting); and (3) information technology (IT) infrastructure (physical and virtual infrastructure; and software infrastructure guided by FAIR principles (Findability; Accessibility; Interoperability; and Reusability). Conclusions Although RDRs face numerous challenges due to their small and dispersed populations, RDRs can generate quality data to support healthcare decision-making through the use of standards and principles on strong governance, quality data practices, and IT infrastructure.

Abstract Background Unicompartmental knee arthroplasty (UKA) procedures are considered to be more technically demanding than conventional total knee arthroplasty (TKA), requiring a longer learning curve and more expert surgical skills. Despite some clear advantages of UKA over TKA (such as lesser blood loss, greater bone stock, greater knee performances, etc.), UKA evidenced a greater rate of revision. Object This study investigated the learning curve of Persona Partial Knee (PPK) arthroplasty for primary medial UKA performed by a single, non-designer surgeon. PPK is a fixed-bearing, compartment-specific implant. The primary outcome of interest for this study was to evaluate the learning curve of the surgical duration. The secondary outcome of interest was to evaluate the learning curve of radiological implant positioning. Methods Patients who underwent primary medial UKA using PPK (Zimmer-Biomet, Warsaw IN, USA) were prospectively enrolled for the study. All surgeries were performed by a single, non-designer surgeon experienced in knee and hip arthroplasty. The primary outcome of interest was to evaluate the surgical duration. The secondary outcome of interest was to evaluate the implant positioning. The learning curve was estimated using an appropriate nonlinear polynomial regression model with a lower Akaike Information Criterion (AIC). Results One hundred twenty five patients were enrolled in the study. 59% of them (74 of 125 patients) were women. The patients’ mean age at the time of surgery was 70.1 ± 9.5 years and their mean body mass index (BMI) was 27.8 ± 4.2 kg/m2. Curve stabilisation of the surgical time was at the 94th patient, of the tibial angle at the 47th patient, of the tibial slope at the 54th patient, of the anterior protrusion at the 29th patient, and of the posterior protrusion at the 51st patient. Conclusions The learning curve for component positioning was achieved in approximately 50 cases. The curve of the surgical time achieved a plateau at 94 Persona Partial Knee. Additionally, the factors directly correlated with earlier stabilization of the learning curve in terms of component positioning were: male gender, younger age, right side, and larger components.

The Notch pathway is an evolutionarily preserved signaling pathway involved in a variety of vital cell functions. Additionally, it is one of the key regulators of inflammation, and controls the differentiation and function of different cells. Moreover, it was found to be involved in skeletal development and bone remodeling process. This review provides an overview of the involvement of the Notch signaling pathway in the pathogenesis of alveolar bone resorption in different forms of pathological conditions such as apical periodontitis, periodontal disease, and peri-implantitis. In vitro and in vivo evidence have confirmed the involvement of Notch signaling in alveolar bone homeostasis. Nonetheless, Notch signaling system, along with complex network of different biomolecules are involved in pathological process of bone resorption in apical periodontitis, periodontitis, and peri-implantitis. In this regard, there is a substantial interest to control the activity of this pathway in the treatment of disorders associated with its dysregulation. This review provides knowledge on Notch signaling and outlines its functions in alveolar bone homeostasis and alveolar bone resorption. Further investigations are needed to determine whether inhibition of the Notch signaling pathways might be beneficial and safe as a novel approach in the treatment of these pathological conditions.

Background: Subacute thyroiditis (SAT) is characterized by profound inflammation and fluctuations in thyroid hormones which may affect the hemostasis balance. This study investigates sex-specific associations between thyroid status, inflammation and hemostasis biomarkers in SAT. Methods: We included 52 patients (40 women and 12 men) treated with non-steroidal anti-inflammatory drugs (NSAID) or methylprednisolone (MPS). Free thyroxine (fT4), thyroid stimulating hormone, C-reactive protein, complete blood count and routine hemostasis parameters were assessed. Results: Both men and women were in hyperthyroid state and had comparable levels of inflammatory biomarkers. A shortened activated partial thromboplastin time (aPTT) was observed in 16.7% of the men and 10% of the women (p = 0.562), and a shortened prothrombin time (PT) was observed in 33% of the men and 12.5% of the women (p = 0.094). In men, aPTT positively correlated with fT4 (r = 0.627; p < 0.05), while PT positively correlated with leukocyte-based inflammatory indices in women (p < 0.05). NSAID-treated patients had lower aPTTs and platelet counts than those treated with MPS (p < 0.05). Principal component analysis extracted “proinflammatory”, “prothrombotic” and “antithrombotic” factors, but the “proinflammatory” factor was the independent predictor of elevated fT4 in women (OR = 2.705; p = 0.036). Conclusions: Our data demonstrated sex-specific associations of thyroid status and inflammatory biomarkers with hemostasis parameters in SAT. Routine hemostasis screening tests may help in monitoring the changes in the hemostasis system over the course of SAT.

In this paper, we present opportunities with the uses of origami and technology, in our case GeoGebra, in teaching formal geometric definitions for fifth-grade primary school students (11-12yrs). Applying origami in mathematical lessons is becoming to be recognized as a valuable tool for improving students' mathematical knowledge. In previous studies, we developed origami and technology activities for high-school mathematics, but we wanted to explore if such approach would work in primary school as well. For this reason, we chose a flat origami model ?f the crane and we used this model to introduce students to basic geometrical notions and definitions, such as points, lines, intersections of lines and angles. To complement mathematical ideas from paper folding we also employed mathematical software GeoGebra, to further ideas and extend students' mathematical toolkits. However, to be able to use software, students would already need basic conceptions of geometric definitions and then the use of the software clearly add to solidifying their knowledge. We believe that the combination hands-on activities and technology could contribute to discovery learning and enhancing students' understanding of geometric definitions and operations.

Abstract Background The data on polyetheretherketone (PEEK) influence on the peri-implant soft tissues in clinical settings are deficient. The aims of this pilot study were to analyze and compare soft tissues’ response to PEEK and titanium (Ti) healing abutments (HA) by means of histological and immunohistochemical analyses. Methods A total of 22 implants with PEEK or Ti HA were placed in 11 patients, applying the “split-mouth” study design. Three months later, soft tissue specimens were harvested from 20 implants for histology in order to qualitatively detect the inflammatory cells’ presence, to semi-qualitatively analyze the inflammation intensity and to assess the inflammatory responses type by immunohistochemical analysis using LCA, CD3, CD20 and CD68 antibodies. Results Epithelial infiltrate followed by an intensive inflammation in sub-epithelium was observed in 100% around PEEK HA. A number of LCA+ and CD 68+ cells was significantly higher in PEEK comparing to Ti group (p = 0.001 and p = 0.020, respectively), while CD 20+ and CD3+ counted cells were found in a significantly higher amount in Ti than in PEEK group (p = 0.006 and p = 0.010, respectively). Conclusion PEEK HA seems to evoke the more intense tissue inflammatory response demonstrated predominantly by histocytes’ and plasmacytes’ activation, while Ti HA triggers the inflammatory reaction of lower intensity, dominantly mediated by B-cells. Trial registration The study registered at ClinicalTrials.gov (NCT04436939).

This study aimed to determine how guanidinoacetic acid (GAA) or its combined administration with betaine (B) or creatine (C) influences the cardiac function, morphometric parameters, and redox status of rats subjected to high-intensity interval training (HIIT). This research was conducted on male Wistar albino rats exposed to HIIT for 4 weeks. The animals were randomly divided into five groups: HIIT, HIIT + GAA, HIIT + GAA + C, HIIT + GAA + B, and HIIT + GAA + C + B. After completing the training protocol, GAA (300 mg/kg), C (280 mg/kg), and B (300 mg/kg) were applied daily per os for 4 weeks. GAA supplementation in combination with HIIT significantly decreased the level of both systemic and cardiac prooxidants ([O.sup.-.sub.2], [H.sub.2][O.sub.2], N[O.sup.-.sub.2], and thiobarbituric acid reactive substances) compared with nontreated HIIT (p < 0.05). Also, GAA treatment led to an increase in glutathione and superoxide dismutase levels. None of the treatment regimens altered cardiac function. A larger degree of cardiomyocyte hypertrophy was observed in the HIIT + GAA group, which was reflected through an increase of the crosssectional area of 27% (p < 0.05) and that of the left ventricle wall thickness of 27% (p < 0.05). Since we showed that GAA in combination with HIIT may ameliorate oxidative stress and does not alter cardiac function, the present study is a basis for future research exploring the mechanisms of cardioprotection induced by this supplement in an HIIT scenario. Key words: guanidinoacetic acid, creatine, betaine, high-intensity interval training, cardioprotection Cette etude visait a etablir comment l'acide guanidinoacetique (GAA) ou son administration en association avec de la betaine (B) ou de la creatine (C) a une influence sur le fonctionnement du coeur, les parametres morphometriques et l'etat redox chez le rat auquel on administre un entrainement physique par intervalle a haute intensite (ou HIIT pour << high-intensity interval training >>). Nous avons mene cette etude chez des rats Wistar albinos males exposes au HIIT pendant 4 semaines. Nous avons reparti aleatoirement tous les animaux dans cinq groupes : HIIT, HIIT + GAA, HIIT + GAA + C, HIIT + GAA + B, HIIT + GAA + C + B. Une fois le protocole d'entrainement physique avec GAA (300 mg/kg) termine, nous avons administre C (280 mg/kg) et B (300 mg/kg) quotidiennement par voie orale pendant 4 semaines. La supplementation en GAA en association avec le HIIT entrainait une diminution nettement plus marquee des taux des prooxydants generaux comme cardiaques ([O.sub.2]-, H2[O.sub.2], N[O.sub.2]-, TBARS) que le HIIT seul (p < 0,05). De plus, l'administration de GAA a mene a une augmentation des taux de GSH et de SOD. Aucune des conditions experimentales n'a entraine de modification du fonctionnement du coeur. Nous avons observe une hypertrophie des cardiomyocytes plus marquee dans le groupe HIIT + GAA, avec une augmentation de l'aire de la section transversale de 27 % (p < 0,05) et de l'epaisseur de la paroi du ventricule gauche de 27 % (p < 0,05). Puisque nous avons montre que l'association du GAA avec le HIIT pourrait permettre d'attenuer le stress oxydatif et qu'elle n'a pas d'effet sur le fonctionnement du coeur, la presente etude constitue le fondement de futures recherches portant sur les modes d'action de la cardioprotection qu'engendre ce supplement au scenario du HIIT. [Traduit par la Redaction] Mots-cles : acide guanidinoacetique, creatine, betaine, entrainement physique par intervalle a haute intensite, cardioprotection, 1. Introduction For decades, physical exercise has been recognized both as a healthy habit and as a useful strategy for reduction of cardiovascular risk factors, thus preserving cardiovascular health. Regular [...]

Background: The immune-inflammatory response is the basis of the pathophysiology of SARS-Cov-2 infection. In severe cases of COVID-19 uncontrolled systemic inflammatory response causes multiorgan dysfunction (MODS), as the most common immediate cause of death. Unfavorable outcome of the COVID-19 most often occurs in elderly patients. The aim of the study was to establish parameters with prognostic significance in severe cases of COVID-19 according to life years, laboratory markers of sepsis and MODS, as well as the number of peripheral CD4+ and CD8+T lymphocytes in 20 consecutively selected critically ill patients.Results: Eleven subjects were male, 9 female, mean age 73.45 ± 11.59, among which the oldest patient was 94 and the youngest 43 years. All the patients met the sepsis and MODS criteria. Increased age and low CD4+ and CD8+T cell counts were identified as independent predictors of death. Only the two youngest patients (43 and 50 years old) survived 28 days, and they are the only ones with a CD4 lymphocyte count above 500 cells/mm3.Conclusion: Senescence of the immune system is mostly characterized by reduced regenerative capacity of adaptive immunity with diminished ability to respond to new antigens and a manifested proinflammatory phenotype. Additional reduction of protective capacity by further deterioration of T cell quantity and quality due to sepsis itself and mutual interaction of senescent T cells and vascular endothelial cells in the induction of cytokine storm represent two complementary vicious cycles in the development of sepsis-related multiorgan dysfunction.

A challenging task in routine practice is finding the distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is to conduct a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, succinate dehydrogenase B (SDHB) expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS < 4) and 54 potentially malignant (PASS ≥ 4). We found no notable difference between intratumoral MVD and potentially malignant behavior. The group of potentially malignant tumors is significantly larger in size, has lower intratumoral MVD, and a decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1.02 and 1.22, respectively). Most tumors maintain SDHB expression, only 6 cases (5.2%) showed a loss of expression (4 of them in PASS < 4 group and 2 in PASS ≥ 4). PASS score is easily available for assessment and complemented with markers of biological behavior to complete the risk stratification algorithm. Size is directly related to PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential.

Oxidative stress represents the pathophysiological basis for most disorders, including reproductive issues. Polycystic ovary syndrome (PCOS) is heterogeneous endocrine disorder of women characterized primarily by irregular menstrual cycles, hyper-androgenism, and ovulatory dysfunction. In the last decades, PCOS was recognized as a systemic silent inflammation and an oxidative disturbance-related disorder, exerting multifaceted symptoms, including metabolic. PCOS treatment should involve a personalized approach tailored to individual symptoms; however, the results are often unsatisfactory. Various supplementary treatments have been proposed to assist in the management and alleviation of PCOS symptoms. Cinnamon and ginger, known for millennia as herbs used in spices or traditional medicine for the treatment of various diseases, are of interest in this study. The aim of this study is to evaluate and investigate the effects of cinnamon and ginger in PCOS patients. Using relevant keywords we searched through PubMed/MEDLINE, Science Direct, Google Scholar and Web of science to find animal studies, pre-clinical, and clinical studies which were then reviewed for usage. Out of all of the reviewed studies a total of 65 studies were included in this review article. Cinnamon and ginger can affect hormonal status, lipid profile, obesity, and insulin resistance by mitigating oxidative stress and inflammation. Generally, based on current clinical evidence, it was revealed that supplementation with cinnamon or ginger had a useful impact in patients with PCOS. This review summarizes the antioxidative effects of ginger and cinnamon in PCOS treatment, highlighting their potential benefits in other oxidative stress-related pathologies.