Background: Pectus excavatum (PE), the most common congenital chest wall deformity, is increasingly treated with minimally invasive repair (MIRPE). However, postoperative complications such as bar displacement remain a significant challenge, occurring in approximately 9.5% of cases. While surgical modifications and stabilization techniques aim to reduce risks, bar displacement persists as a critical concern. Methods: This PROSPERO-registered systematic review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A search of PubMed, Scopus, and CINAHL through October 2024 identified studies evaluating bar displacement in PE patients undergoing MIRPE or alternative surgical approaches. The inclusion criteria focused on risk factors, stabilization techniques, and reoperation strategies. Data extraction and risk-of-bias assessments were independently conducted by multiple reviewers to ensure accuracy and quality. Results: Thirteen studies spanning 23 years were included. Bar displacement rates varied widely (0.9%–33.3%), with key risk factors including patient age, chest wall rigidity, bar length, and placement technique. Advanced stabilization methods—such as bridge fixation, shorter bars, multipoint fixation, and adjunct stabilizers—significantly reduced displacement rates. Common postoperative complications included wound infections, seromas, pleural effusions, and bar re-dislocation. Imaging modalities like chest X-rays and 3-dimensional computed tomography scans proved critical for early detection. Heterogeneity in stabilization approaches underscores a shift toward patient-specific strategies to optimize outcomes. Conclusion Tailored stabilization techniques are essential for successful PE correction.Although advancements in fixation methods have reduced displacement risks, standardized postoperative protocols and multicenter studies are needed to validate these innovations and improve long-term outcomes (PROSPERO: CRD42024595337).

Background: Pectus excavatum (PE), the most common congenital chest wall deformity, is increasingly treated with minimally invasive repair (MIRPE). However, postoperative complications such as bar displacement remain a significant challenge, occurring in approximately 9.5% of cases. While surgical modifications and stabilization techniques aim to reduce risks, bar displacement persists as a critical concern. Methods: This PROSPERO-registered systematic review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A search of PubMed, Scopus, and CINAHL through October 2024 identified studies evaluating bar displacement in PE patients undergoing MIRPE or alternative surgical approaches. The inclusion criteria focused on risk factors, stabilization techniques, and reoperation strategies. Data extraction and risk-of-bias assessments were independently conducted by multiple reviewers to ensure accuracy and quality. Results: Thirteen studies spanning 23 years were included. Bar displacement rates varied widely (0.9%–33.3%), with key risk factors including patient age, chest wall rigidity, bar length, and placement technique. Advanced stabilization methods—such as bridge fixation, shorter bars, multipoint fixation, and adjunct stabilizers—significantly reduced displacement rates. Common postoperative complications included wound infections, seromas, pleural effusions, and bar re-dislocation. Imaging modalities like chest X-rays and 3-dimensional computed tomography scans proved critical for early detection. Heterogeneity in stabilization approaches underscores a shift toward patient-specific strategies to optimize outcomes. Conclusion Tailored stabilization techniques are essential for successful PE correction.Although advancements in fixation methods have reduced displacement risks, standardized postoperative protocols and multicenter studies are needed to validate these innovations and improve long-term outcomes (PROSPERO: CRD42024595337).

Background: Pectus excavatum (PE), the most common congenital chest wall deformity, is increasingly treated with minimally invasive repair (MIRPE). However, postoperative complications such as bar displacement remain a significant challenge, occurring in approximately 9.5% of cases. While surgical modifications and stabilization techniques aim to reduce risks, bar displacement persists as a critical concern. Methods: This PROSPERO-registered systematic review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A search of PubMed, Scopus, and CINAHL through October 2024 identified studies evaluating bar displacement in PE patients undergoing MIRPE or alternative surgical approaches. The inclusion criteria focused on risk factors, stabilization techniques, and reoperation strategies. Data extraction and risk-of-bias assessments were independently conducted by multiple reviewers to ensure accuracy and quality. Results: Thirteen studies spanning 23 years were included. Bar displacement rates varied widely (0.9%–33.3%), with key risk factors including patient age, chest wall rigidity, bar length, and placement technique. Advanced stabilization methods—such as bridge fixation, shorter bars, multipoint fixation, and adjunct stabilizers—significantly reduced displacement rates. Common postoperative complications included wound infections, seromas, pleural effusions, and bar re-dislocation. Imaging modalities like chest X-rays and 3-dimensional computed tomography scans proved critical for early detection. Heterogeneity in stabilization approaches underscores a shift toward patient-specific strategies to optimize outcomes. Conclusion Tailored stabilization techniques are essential for successful PE correction.Although advancements in fixation methods have reduced displacement risks, standardized postoperative protocols and multicenter studies are needed to validate these innovations and improve long-term outcomes (PROSPERO: CRD42024595337).

Background: In acute ischemic stroke (AIS), the treatment window for thrombolytics is 4.5 hours from symptom onset. Tenecteplase, a modified tissue plasminogen activator, may be effective over an extended treatment window (4.5–24 hours). Hence, a meta-analysis was performed to evaluate tenecteplase use within an extended treatment window. Methods: Databases were searched for articles published before July 3, 2024. Randomized controlled trials (RCTs) that compared tenecteplase treatment in an extended treatment window with the current standard of care were included. The endpoints were excellent functional outcomes (modified Rankin Scale [mRS] 0–1) at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change at 24 hours and 7 days, and symptomatic intracranial hemorrhage (sICH) at 90 days. The pooled risk ratio (RR) and mean difference (MD) were calculated for categorical and continuous outcomes, respectively. Results: Four RCTs involving 1,629 patients with AIS were included. High-quality evidence indicated that tenecteplase achieved a higher likelihood of mRS 0–1 at 90 days (RR, 1.21; 95% confidence interval [CI], 1.06 to 1.38; P=0.004) and a lower NIHSS score change at 24 hours (MD, −0.84; 95% CI, −1.40 to −0.27; P=0.003) than that of the placebo. Low-quality evidence showed that tenecteplase reduced the NIHSS score change at 7 days (MD, −0.79; 95% CI, −1.56 to −0.03; P=0.04). No differences in sICH or mortality were observed. Conclusion Tenecteplase compared favorably with non-thrombolytic therapy in an extended treatment window. Future RCTs may establish tenecteplase as the standard of care for up to 24 hours.

Background: Large language models (LLMs) are increasingly used in medical and dental education to enhance clinical reasoning, patient communication, and academic learning. This study evaluates the effectiveness of four advanced LLMs— ChatGPT-4 (OpenAI), Claude 3.5 Sonnet (Anthropic), Microsoft Copilot, and Grok 3 (xAI)—in conveying fluoride-related dental knowledge. Methods: A cross-sectional comparative study was conducted using a mixed-methods approach. Each LLM answered 50 multiple- choice questions (MCQs) and 10 open-ended questions on fluoride chemistry, clinical applications, and safety concerns. Two blinded experts rated the open-ended responses on accuracy, depth, clarity, and evidence. Interrater reliability was assessed using Cohen’s kappa and Spearman’s correlation, and statistical analyses were performed using analysis of variance, Kruskal-Wallis, and post-hoc tests. Results: All models showed high MCQ accuracy (88%–94%). Claude 3.5 Sonnet achieved the highest scores in open-ended responses, especially for clarity (p=0.009). Minor differences in accuracy, depth, and evidence were not statistically significant. Overall, all LLMs performed strongly, with high interrater agreement supporting result reliability. Conclusion Advanced LLMs show strong potential as supportive tools in dental education and patient communication on fluoride use. Claude 3.5 Sonnet demonstrated superior linguistic clarity, enhancing its educational value. Continued evaluation and clinical oversight are crucial for their safe and effective integration into dentistry.

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M₄) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M₄ positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M₄ PET ligand that allows the non-invasive visualization of M₄ in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [¹⁸F] 12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [¹⁸F] 12 for the M₄-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [¹⁸F] 12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [¹⁸F] 12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [¹⁸F] 12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M₄ PET radioligand with promising attributes. The availability of a clinically validated M₄ PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023.The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogenactivated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp–like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.

Ivermectin is a US Food and Drug Administration (FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties. Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries, its potential therapeutic effect on pulmonary fibrosis (PF) has not been investigated. This study aimed to explore the ability of ivermectin (0.6 mg/kg) to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model. This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF. The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury, as manifested by the reduced infiltration of inflammatory cells, as well as decreased the inflammation and fibrosis scores. Intriguingly, ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-‍β1 (TGF-‍β1) and fibronectin protein expression, highlighting its anti-fibrotic activity. This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain (NOD)‍-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), with a subsequent decline in the interleukin‍-‍1β (IL‍-‍1β) level. In addition, ivermectin inhibited the expression of intracellular nuclear factor-‍κB (NF‍-‍κB) and hypoxia‑inducible factor‑1α (HIF‍-‍1α) proteins along with lowering the oxidative stress and apoptotic markers. Altogether, this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin. These beneficial effects were mediated, at least partly, via the downregulation of TGF-‍β1 and fibronectin, as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1α and NF-‍κB.
Animals ; Rats ; Anti-Inflammatory Agents ; Bleomycin/toxicity* ; Fibronectins/metabolism* ; Fibrosis ; Inflammasomes/metabolism* ; Ivermectin/adverse effects* ; NF-kappa B/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pulmonary Fibrosis/drug therapy*

Purpose: Optical coherence tomography (OCT) has the potential for in vivo clot composition characterization in difficult mechanical embolectomy cases. We performed an in vitro study to determine the OCT characteristics of red blood cells (RBCs) and fibrin rich clots. Materials and Methods: Analogues of 5 compositions of clots (5% to 95% RBCs from Group A to E) were created from human blood. The blood mixture was injected into the bifurcation of a 3D printed bifurcated silicone tube. The OPTISTM Integrated System (St. Jude Medical Inc.) was used to identify the magnitude of OCT signals from different compositions of clots. Martius Scarlett Blue trichrome (MSB) staining was performed to confirm the composition of RBCs and fibrin in each clot. Results: Group A and B showed less signal attenuation (less than 30%) from its surface to the inside, which indicated high penetration (low-back scattering). Group C indicated intermediate signal attenuation (60%) from its surface to inside the clots, in which signals were found even at the periphery of the clot. Group D and E were superficially signal rich with more signal attenuation (more than 80%) from its surface to the inside indicating low penetration (high-back scattering). Signal-free shadowing was shown in 3 clots in Group E. MSB staining indicated color change (from red in fibrin-rich clots to yellow in RBC-rich clots). Conclusion Different compositions of clots can be assessed using OCT. Fibrin-rich clots have homogeneous signals with high penetration, while RBC-rich clots can be recognized as superficially signal rich with low penetration.

We aimed to explore the population dynamics of snail in 3 sites of the White Nile in Sudan. More specifically, we aimed to investigate the annual patterns of snail populations that act as intermediate hosts of schistosomes and monthly snail infection rates and ecological characteristics presumably related to snail populations. We collected snails for 1 year monthly at 3 different shore sites in the vicinity of El Shajara along the White Nile river in Khartoum State, Sudan. In addition, we measured air and water temperatures, water turbidities, vegetation coverages, and water depths and current speeds. Most of the collected snails were Biomphalaria pfeifferi and Bulinus truncatus. The population densities of snails and their infection rates varied across survey sites. The collected snails liberated S. mansoni and S. haematobium cercariae as well as Amphistome and Echinostome cercariae. Infected snails were found during March-June. The ecological characteristics found to be associated with the absence of snails population were: high turbidity, deep water, low vegetation coverage (near absence of vegetation), high water temperature, and high current speed. To our knowledge, this is the first longitudinal study of the snail population and ecological characteristics in the main basin of the White Nile river.