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Severe complex neglected infantile Blount disease acute correction by Ilizarov frame: A case report.International Journal of Surgery Case... Jun 2024Blount disease is a disorder causing three proportions of deformity, including varus deformity, procurvatum deformity, and internal tibial rotational deformity. The...
INTRODUCTION
Blount disease is a disorder causing three proportions of deformity, including varus deformity, procurvatum deformity, and internal tibial rotational deformity. The standardized treatment remains controversial despite extensive reviews. The application of Ilizarov external fixators for circumspect corrections is established. The SCARE 2023 criteria have been followed in reporting the case report.
CASE PRESENTATION
We present the case of a nine-year-old girl who's complaining about bowing on both of her knees. From the examination, we found that the metaphyseodiaphyseal angle of both knees was 50 degrees. On the right knee, there is 125 degrees of procurvatum deformity and 115 degrees of deformity on the left knee. After performing deformity correction with the Ilizarov application, there's clinical improvement in the patient.
CLINICAL DISCUSSION
Some experts advise using physeal distraction to manage the deformity in order to achieve correction. The limited popularity of physeal distraction technique may be attributed to the risks of premature closure of the growth plate that we manage to avoid. The Ilizarov frame provides maximum adjustability for aligning all planes, making it suitable for treating severe deformities. Secure fixation, improved patient mobility, being able to assess patient alignment in a functional standing position, and precision.
CONCLUSION
Acute correction and fixation using circular frames as a treatment option for Blount disease show positive outcomes without any significant complications.
PubMed: 38917699
DOI: 10.1016/j.ijscr.2024.109909 -
PLoS Computational Biology Jun 2024Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed...
Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed reduction in recurrent arrhythmias through antiarrhythmic drug therapy, the precise mechanisms underlying their effectiveness in treating ischemic heart disease remain unclear. Moreover, there is a lack of specialized drugs designed explicitly for the treatment of myocardial ischemic arrhythmia. This study employs an electrophysiological simulation approach to investigate the potential antiarrhythmic effects and underlying mechanisms of various pharmacological agents in the context of ischemia and myocardial infarction (MI). Based on physiological experimental data, computational models are developed to simulate the effects of a series of pharmacological agents (amiodarone, telmisartan, E-4031, chromanol 293B, and glibenclamide) on cellular electrophysiology and utilized to further evaluate their antiarrhythmic effectiveness during ischemia. On 2D and 3D tissues with multiple pathological conditions, the simulation results indicate that the antiarrhythmic effect of glibenclamide is primarily attributed to the suppression of efflux of potassium ion to facilitate the restitution of [K+]o, as opposed to recovery of IKATP during myocardial ischemia. This discovery implies that, during acute cardiac ischemia, pro-arrhythmogenic alterations in cardiac tissue's excitability and conduction properties are more significantly influenced by electrophysiological changes in the depolarization rate, as opposed to variations in the action potential duration (APD). These findings offer specific insights into potentially effective targets for investigating ischemic arrhythmias, providing significant guidance for clinical interventions in acute coronary syndrome.
PubMed: 38917196
DOI: 10.1371/journal.pcbi.1012244 -
PloS One 2024To date, several types of airway stents are available to treat central airway obstructions. However, the ideal stent that can overcome anatomical, mechanical and...
To date, several types of airway stents are available to treat central airway obstructions. However, the ideal stent that can overcome anatomical, mechanical and microbiological issues is still awaited. In addition, therapeutic effect and self-elimination of these stents are desirable properties, which pose an additional challenge for development and manufacturing. We aimed to create a prototype bioresorbable tracheal stent with acceptable clinical tolerance, fit and biocompatibility, that could be tested in a rabbit model and in the future be further optimized to enable drug-elution and ensure local therapeutic effect. Twenty-one New Zealand White Rabbits received five different types of bioresorbable tracheal stents, 3D-printed from poly(D,L-lactide-co-ε-caprolactone) metacrylates. Various configurations were tested for their functionality and improved until the best performing prototype could undergo detailed in vivo assessment, regarding clinical tolerance, migration and biocompatibility. Previously tested types of 3D printed stents in our preliminary study required improvement due to several problems, mainly related to breakage, unreliable stability and/or migration within the trachea. Abandoned or refined pre-prototypes were not analyzed in a comparative way. The final best performing prototype stent (GSP2 (Group Stent Prototype 2), n = 8) allowed a transoral application mode and showed good clinical tolerance, minimal migration and acceptable biocompatibility. The good performance of stent type GSP2 was attributed to the helix-shaped surface structure, which was therefore regarded as a key-feature. This prototype stent offers the possibility for further research in a large animal model to confirm the promising data and assess other properties such as bioresorption.
Topics: Animals; Rabbits; Printing, Three-Dimensional; Stents; Trachea; Absorbable Implants; Materials Testing; Biocompatible Materials; Prosthesis Design; Polyesters
PubMed: 38917158
DOI: 10.1371/journal.pone.0300847 -
PloS One 2024Typhoid fever, caused by Salmonella enterica serovar typhi, presents a substantial global health threat, particularly in regions with limited healthcare infrastructure....
Typhoid fever, caused by Salmonella enterica serovar typhi, presents a substantial global health threat, particularly in regions with limited healthcare infrastructure. The rise of multidrug-resistant strains of S. typhi exacerbates this challenge, severely compromising conventional treatment efficacy due to over activity of efflux pumps. In our study, a comprehensive exploration of two fundamental aspects to combat MDR in S. typhi is carried out; i.e. employing advanced bioinformatics analyses and AlphaFold AI, We successfully identified and characterised a putative homologue, ABC-TPA, reminiscent of the P-glycoprotein (P-gp) known for its role in multidrug resistance in diverse pathogens. This discovery provides a critical foundation for understanding the potential mechanisms driving antibiotic resistance in S. typhi. Furthermore, employing computational methodologies, We meticulously assessed the potential of lignans, specifically Schisandrin A, B, and C, as promising Efflux Pump Inhibitors (EPIs) against the identified P-gp homologue in S. typhi. Noteworthy findings revealed robust binding interactions of Schisandrin A and B with the target protein, indicating substantial inhibitory capabilities. In contrast, Schisandrin C exhibited instability, showing varied effectiveness among the evaluated lignans. Pharmacokinetics and toxicity predictions underscored the favourable attributes of Schisandrin A, including prolonged action duration. Furthermore, high systemic stability and demanished toxicity profile of SA and SB present their therapeutic efficacy against MDR. This comprehensive investigation not only elucidates potential therapeutic strategies against MDR strains of S. typhi but also highlights the relevance of computational approaches in identifying and evaluating promising candidates. These findings lay a robust foundation for future empirical studies to address the formidable challenges antibiotic resistance poses in this clinically significant infectious diseases.
Topics: Salmonella typhi; Drug Resistance, Multiple, Bacterial; Lignans; Anti-Bacterial Agents; Bacterial Proteins; Humans; Microbial Sensitivity Tests; Computational Biology
PubMed: 38917154
DOI: 10.1371/journal.pone.0303285 -
JCI Insight Jun 2024The number of adults living with cystic fibrosis (CF) has already increased significantly due to drastic improvements in life expectancy attributable to advances in...
The number of adults living with cystic fibrosis (CF) has already increased significantly due to drastic improvements in life expectancy attributable to advances in treatment including the development of highly effective modulator therapy. Chronic airway inflammation in cystic fibrosis (CF) contributes to morbidity and mortality and aging processes like 'inflammaging' and cell senescence impact CF pathology. Our results show that single cell RNA sequencing data, human primary bronchial epithelial cells from non-CF and CF donors, a CF bronchial epithelial cell line, and Cftr knockout (Cftr-/-) rats all demonstrated increased cell senescence markers in the CF bronchial epithelium. This was associated with upregulation of fibroblast growth factor receptors (FGFRs) and mitogen-activated protein kinase (MAPK) p38. Inhibition of FGFRs, specifically FGFR4 and to some extent FGFR1 attenuated cell senescence and improved mucociliary clearance, which was associated with MAPK p38 signaling. Mucociliary dysfunction could also be improved using a combination of senolytics in a CF ex vivo model. In summary, FGFR/MAPK p38 signaling contributes to cell senescence in CF airways, which is associated with impaired mucociliary clearance. Therefore, attenuation of cell senescence in the CF airways might be a future therapeutic strategy improving mucociliary dysfunction and lung disease in an aging CF population.
PubMed: 38916962
DOI: 10.1172/jci.insight.174888 -
JMIR Formative Research Jun 2024Large-scale crisis events such as COVID-19 often have secondary impacts on individuals' mental well-being. University students are particularly vulnerable to such...
BACKGROUND
Large-scale crisis events such as COVID-19 often have secondary impacts on individuals' mental well-being. University students are particularly vulnerable to such impacts. Traditional survey-based methods to identify those in need of support do not scale over large populations and they do not provide timely insights. We pursue an alternative approach through social media data and machine learning. Our models aim to complement surveys and provide early, precise, and objective predictions of students disrupted by COVID-19.
OBJECTIVE
This study aims to demonstrate the feasibility of language on private social media as an indicator of crisis-induced disruption to mental well-being.
METHODS
We modeled 4124 Facebook posts provided by 43 undergraduate students, spanning over 2 years. We extracted temporal trends in the psycholinguistic attributes of their posts and comments. These trends were used as features to predict how COVID-19 disrupted their mental well-being.
RESULTS
The social media-enabled model had an F1-score of 0.79, which was a 39% improvement over a model trained on the self-reported mental state of the participant. The features we used showed promise in predicting other mental states such as anxiety, depression, social, isolation, and suicidal behavior (F1-scores varied between 0.85 and 0.93). We also found that selecting the windows of time 7 months after the COVID-19-induced lockdown presented better results, therefore, paving the way for data minimization.
CONCLUSIONS
We predicted COVID-19-induced disruptions to mental well-being by developing a machine learning model that leveraged language on private social media. The language in these posts described psycholinguistic trends in students' online behavior. These longitudinal trends helped predict mental well-being disruption better than models trained on correlated mental health questionnaires. Our work inspires further research into the potential applications of early, precise, and automatic warnings for individuals concerned about their mental health in times of crisis.
PubMed: 38916951
DOI: 10.2196/52316 -
Neurologia I Neurochirurgia Polska Jun 2024We aimed to compare knowledge, opinions, and clinical experiences among Czech, Slovak, and Italian neurologists to identify potential educational gaps and unify...
AIM OF STUDY
We aimed to compare knowledge, opinions, and clinical experiences among Czech, Slovak, and Italian neurologists to identify potential educational gaps and unify understanding.
CLINICAL RATIONALE FOR STUDY
Functional neurological disorder (FND) is a disabling condition characterised by motor, sensory, or cognitive symptoms which are incompatible with other neurological disorders. Novel diagnostic and treatment approaches have improved FND management. However, the extent of their adoption, and any differences or similarities across European communities, remain to be established.
MATERIAL AND METHODS
Members of the Czech and Slovak Neurological Societies were invited via e-mail to participate in a 14- -item web-based survey investigating their approach to FND. This data was compared to results from a previous study involving 492 Italian neurologists.
RESULTS
232 questionnaires were completed by Czech and Slovak neurologists (CZ-SK). Similarities were found between CZ- -SK and Italian neurologists in their preference for the term 'FND' over other psychological-related terms and in explaining symptoms as due to abnormal functioning of the nervous system rather than attributing them to mental illness. However, only fewer than 5% in both groups thought that simulation was highly unlikely. Both groups reported relying on positive signs (e.g. inconsistency, distractibility) according to the current diagnostic criteria, but also a tendency to perform additional tests to exclude other causes. However, some differences were observed: Italian neurologists placed a greater emphasis on psychological factors including litigation. CZ-SK neurologists were more likely to suggest physiotherapy as a treatment option and to provide educational intervention for patients and their relatives.
CONCLUSIONS
Overall, our findings suggest that although Czech, Slovak, and Italian neurologists have adopted some new developments in the field of FND, significant gaps still exist in their understanding and common practices regarding conceptualisation, diagnosis, and treatment.
CLINICAL IMPLICATIONS
Our results suggest that promoting knowledge through postgraduate curricula and teaching courses for neurologists is necessary to optimise patient management in various European countries.
PubMed: 38916493
DOI: 10.5603/pjnns.99264 -
Frontiers in Endocrinology 2024Type 2 diabetes (T2D) is a polygenic metabolic disorder characterized by insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While... (Review)
Review
Type 2 diabetes (T2D) is a polygenic metabolic disorder characterized by insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While the decline in insulin production and secretion was previously attributed to apoptosis of insulin-producing β-cells, recent studies indicate that β-cell apoptosis rates are relatively low in diabetes. Instead, β-cells primarily undergo dedifferentiation, a process where they lose their specialized identity and transition into non-functional endocrine progenitor-like cells, ultimately leading to β-cell failure. The underlying mechanisms driving β-cell dedifferentiation remain elusive due to the intricate interplay of genetic factors and cellular stress. Understanding these mechanisms holds the potential to inform innovative therapeutic approaches aimed at reversing β-cell dedifferentiation in T2D. This review explores the proposed drivers of β-cell dedifferentiation leading to β-cell failure, and discusses current interventions capable of reversing this process, thus restoring β-cell identity and function.
Topics: Humans; Insulin-Secreting Cells; Cell Dedifferentiation; Diabetes Mellitus, Type 2; Animals; Cell Differentiation; Apoptosis; Insulin Secretion
PubMed: 38915897
DOI: 10.3389/fendo.2024.1414447 -
BioRxiv : the Preprint Server For... Jun 2024The most discriminative and revealing patterns in the neuroimaging population are often confined to smaller subdivisions of the samples and features. Especially in...
The most discriminative and revealing patterns in the neuroimaging population are often confined to smaller subdivisions of the samples and features. Especially in neuropsychiatric conditions, symptoms are expressed within micro subgroups of individuals and may only underly a subset of neurological mechanisms. As such, running a whole-population analysis yields suboptimal outcomes leading to reduced specificity and interpretability. Biclustering is a potential solution since subject heterogeneity makes one-dimensional clustering less effective in this realm. Yet, high dimensional sparse input space and semantically incoherent grouping of attributes make post hoc analysis challenging. Therefore, we propose a deep neural network called semantic locality preserving auto decoder (SpaDE), for unsupervised feature learning and biclustering. SpaDE produces coherent subgroups of subjects and neural features preserving semantic locality and enhancing neurobiological interpretability. Also, it regularizes for sparsity to improve representation learning. We employ SpaDE on human brain connectome collected from schizophrenia (SZ) and healthy control (HC) subjects. The model outperforms several state-of-the-art biclustering methods. Our method extracts modular neural communities showing significant (HC/SZ) group differences in distinct brain networks including visual, sensorimotor, and subcortical. Moreover, these biclustered connectivity substructures exhibit substantial relations with various cognitive measures such as attention, working memory, and visual learning.
PubMed: 38915715
DOI: 10.1101/2024.06.08.598092 -
BioRxiv : the Preprint Server For... Jun 2024Arterial thrombosis, which represents a critical complication of cardiovascular diseases, is a leading cause of death and disability worldwide with no effective bioassay...
Arterial thrombosis, which represents a critical complication of cardiovascular diseases, is a leading cause of death and disability worldwide with no effective bioassay for clinical prediction. As a symbolic feature of arterial thrombosis, severe stenosis in the blood vessel creates a high-shear, high-gradient flow environment that effectively facilitates platelet aggregation towards vessel occlusion even with platelet amplification loops inhibited. However, no approach is currently available to comprehensively characterize the size, composition and platelet activation status of thrombi forming under this biorheological condition. Here, we present a thrombus profiling assay that monitors the multi-dimensional attributes of thrombi forming in conditions mimicking the physiological scenario of arterial thrombosis. Using this platform, we demonstrate that different receptor-ligand interactions contribute distinctively to the composition and activation status of the thrombus. Our investigation into hypertensive and older individuals reveals intensified biomechanical thrombogenesis and multi-dimensional thrombus profile abnormalities, demonstrating a direct contribution of mechanobiology to arterial thrombosis and endorsing the diagnostic potential of the assay. Furthermore, we identify the hyperactivity of GPIbα-integrin α β mechanosensing axis as a molecular mechanism that contributes to hypertension-associated arterial thrombosis. By studying the interactions between anti-thrombotic inhibitors and hypertension, and the inter-individual variability in personal thrombus profiles, our work reveals a critical need for personalized anti-thrombotic drug selection that accommodates each patient's pathological profile.
PubMed: 38915705
DOI: 10.1101/2024.06.11.598290