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Journal of Inflammation Research 2024Osteitis is more prevalent in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), making the disease refractory and prone to recurrence. However, the...
OBJECTIVE
Osteitis is more prevalent in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), making the disease refractory and prone to recurrence. However, the pathophysiologic mechanism of osteitis formation in CRS has not been fully elucidated, and this study aimed to further elucidate the association of eosinophils and type 2 inflammatory mediators with osteitis in patients with CRSwNP.
METHODS
This retrospective study collected clinical data on 125 cases of CRSwNP. The participants were categorized into two groups based on the presence or absence of osteitis in their sinus CT scan. The groups were classified as the osteitis group and the non-osteitis group. The clinical baseline data, type 2 inflammatory mediators, and eosinophils were compared between the two groups. The correlation between these factors and the Global Osteitis score scale (GOSS) was also evaluated.
RESULTS
There were 69 cases in the osteitis group and 56 cases in the non-osteitis group of CRSwNP patients. The prevalence of concomitant asthma (P=0.009), SNOT-22 score, LUND-MAKAY score, and LUND-KEDENY score were significantly higher in the osteitis group than in the non-osteitis group (All P values were < 0.001); the absolute values of IL-13 (P<0.001), periosteal proteins (P<0.001), and tissue eosinophils (P < 0.05) were significantly higher in the osteitis group as compared with the non-osteitis group. Logistic regression analysis showed that IL-13 and periosteal proteins were risk factors for CRSwNP osteitis (P<0.001). ROC curve analysis revealed that IL-13 had the highest predictive value (AUC=0.786) with a cut-off value of 5.8059 pg/mL, the sensitivity of 58.0%, and a specificity of 89.3% respectively.
CONCLUSION
Osteitis could indicate the more severe symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), and elevated IL-13, periosteal proteins, and tissue eosinophils are risk factors for osteitis formation in patients with CRSwNP.
PubMed: 38939122
DOI: 10.2147/JIR.S466944 -
Frontiers in Bioengineering and... 2024Anterior communicating artery (ACoA) aneurysms are more prone to rupture compared to aneurysms present in other cerebral arteries. We hypothesize that systemic blood...
Identifying hemodynamic factors associated with the rupture of anterior communicating artery aneurysms based on global modeling of blood flow in the cerebral artery network.
Anterior communicating artery (ACoA) aneurysms are more prone to rupture compared to aneurysms present in other cerebral arteries. We hypothesize that systemic blood flow in the cerebral artery network plays an important role in shaping intra-aneurysmal hemodynamic environment thereby affecting the rupture risk of ACoA aneurysms. The majority of existing numerical studies in this field employed local modeling methods where the physical boundaries of a model are confined to the aneurysm region, which, though having the benefit of reducing computational cost, may compromise the physiological fidelity of numerical results due to insufficient account of systemic cerebral arterial hemodynamics. In the present study, we firstly carried out numerical experiments to address the difference between the outcomes of local and global modeling methods, demonstrating that local modeling confined to the aneurysm region results in inaccurate predictions of hemodynamic parameters compared with global modeling of the ACoA aneurysm as part of the cerebral artery network. Motivated by this finding, we built global hemodynamic models for 40 ACoA aneurysms (including 20 ruptured and 20 unruptured ones) based on medical image data. Statistical analysis of the computed hemodynamic data revealed that maximum wall shear stress (WSS), minimum WSS divergence, and maximum WSS gradient differed significantly between the ruptured and unruptured ACoA aneurysms. Optimal threshold values of high/low WSS metrics were determined through a series of statistical tests. In the meantime, some morphological parameters of aneurysms, such as large nonsphericity index, aspect ratio, and bottleneck factor, were found to be associated closely with aneurysm rupture. Furthermore, multivariate logistic regression analyses were performed to derive models combining hemodynamic and morphological parameters for discriminating the rupture status of aneurysms. The capability of the models in rupture status discrimination was high, with the area under the receiver operating characteristic curve reaching up to 0.9. The findings of the study suggest that global modeling of the cerebral artery network is essential for reliable quantification of hemodynamics in ACoA aneurysms, disturbed WSS and irregular aneurysm morphology are associated closely with aneurysm rupture, and multivariate models integrating hemodynamic and morphological parameters have high potential for assessing the rupture risk of ACoA aneurysms.
PubMed: 38938980
DOI: 10.3389/fbioe.2024.1419519 -
Cureus Jun 2024Solid organ transplant recipients are prone to developing a wide range of complications associated with the procedure itself, as well as with immunosuppressants....
Solid organ transplant recipients are prone to developing a wide range of complications associated with the procedure itself, as well as with immunosuppressants. Guillain-Barré syndrome, which is part of the spectrum of inflammatory neuropathies, is not expected to occur early after organ transplant when immunosuppression is at its highest point. We describe the clinical case of a patient who underwent an urgent liver transplant due to acute liver failure secondary to drug-induced liver injury and developed Guillain-Barré syndrome early after the transplant.
PubMed: 38938905
DOI: 10.7759/cureus.63304 -
JACS Au Jun 2024Computational study of the effect of drug candidates on intrinsically disordered biomolecules is challenging due to their vast and complex conformational space. Here, we...
Computational study of the effect of drug candidates on intrinsically disordered biomolecules is challenging due to their vast and complex conformational space. Here, we developed a comparative Markov state analysis (CoVAMPnet) framework to quantify changes in the conformational distribution and dynamics of a disordered biomolecule in the presence and absence of small organic drug candidate molecules. First, molecular dynamics trajectories are generated using enhanced sampling, in the presence and absence of small molecule drug candidates, and ensembles of soft Markov state models (MSMs) are learned for each system using unsupervised machine learning. Second, these ensembles of learned MSMs are aligned across different systems based on a solution to an optimal transport problem. Third, the directional importance of inter-residue distances for the assignment to different conformational states is assessed by a discriminative analysis of aggregated neural network gradients. This final step provides interpretability and biophysical context to the learned MSMs. We applied this novel computational framework to assess the effects of ongoing phase 3 therapeutics tramiprosate (TMP) and its metabolite 3-sulfopropanoic acid (SPA) on the disordered Aβ42 peptide involved in Alzheimer's disease. Based on adaptive sampling molecular dynamics and CoVAMPnet analysis, we observed that both TMP and SPA preserved more structured conformations of Aβ42 by interacting nonspecifically with charged residues. SPA impacted Aβ42 more than TMP, protecting α-helices and suppressing the formation of aggregation-prone β-strands. Experimental biophysical analyses showed only mild effects of TMP/SPA on Aβ42 and activity enhancement by the endogenous metabolization of TMP into SPA. Our data suggest that TMP/SPA may also target biomolecules other than Aβ peptides. The CoVAMPnet method is broadly applicable to study the effects of drug candidates on the conformational behavior of intrinsically disordered biomolecules.
PubMed: 38938816
DOI: 10.1021/jacsau.4c00182 -
International Journal of Dentistry 2024To determine the minimum dentin thickness in the mesial and distal walls of the mesiobuccal (MB) and mesiolingual (ML) canals of the mandibular first molars using...
AIM
To determine the minimum dentin thickness in the mesial and distal walls of the mesiobuccal (MB) and mesiolingual (ML) canals of the mandibular first molars using cone-beam computed tomography (CBCT).
MATERIALS AND METHODS
CBCT examinations of 624 mandibular first molars from an Indian subpopulation were analyzed. The mesial and distal minimum dentin thickness was evaluated in 1 mm intervals apical to the furcation area. Independent -test was used to analyze the data ( = 0.05). Using Cohen's kappa coefficient, the interexaminer and intraexaminer reliability was evaluated.
RESULTS
The mesial dentin thickness was significantly higher than the distal dentin thickness for MB and ML canals (=0.01). The average dentin thickness in the distal and mesial plane of the MB canal was 1.15 ± 0.15 mm and 1.52 ± 0.19 mm at the 1 mm level and 0.83 ± 0.13 and 1.08 ± 0.18 at the 5 mm level, respectively. For the ML canal, the average dentin thickness in the distal plane and the mesial plane was 1.24 ± 0.18 mm and 1.44 ± 0.21 at the 1 mm level and 0.91 ± 0.16 and 1.01 ± 0.17 at the 5 mm level, respectively. Statistical analysis between the MB and ML canals showed significant differences in the dentin thickness at 4 and 5 mm levels in both the distal and the mesial planes (=0.01). In more than 85% of the cases, the minimum dentin thickness was seen at the 5 mm level in both the distal and mesial planes in MB and ML canals.
CONCLUSION
The distal planes of the mesiolingual and mesiobuccal canals were thinner in most cases, making the distal surface more prone to iatrogenic perforations. Considerably, at 4 and 5 mm from the furcation, the distal wall was significantly thinner than the mesial walls. Understanding the anatomy of the danger zone in the mesial roots of the mandibular first molars may serve to minimize the risk of endodontic mishaps such as strip perforations.
PubMed: 38938693
DOI: 10.1155/2024/8823070 -
JACC. Advances Dec 2023Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications.
BACKGROUND
Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications.
OBJECTIVES
The purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients.
METHODS
COVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression.
RESULTS
Of 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; < 0.0001) and were in more advanced physiological stage ( = 0.032) and NYHA functional class ( = 0.01), had lower baseline oxygen saturation ( = 0.0001), and more frequently had a history of atrial arrhythmia ( < 0.0001), previous hospitalization for heart failure ( < 0.0007), and were more likely hospitalized for COVID-19 ( < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; < 0.0001) were independently associated with increased risk of TE/bleeding complications.
CONCLUSIONS
ACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants.
PubMed: 38938489
DOI: 10.1016/j.jacadv.2023.100701 -
Health status and quality of life before critical illness: Northern Finland Birth Cohort 1966 study.Acta Anaesthesiologica Scandinavica Jun 2024Previous findings support the claim intensive care unit (ICU) patients have a higher rate of comorbidities and reduction of health- and functional status compared with...
BACKGROUND
Previous findings support the claim intensive care unit (ICU) patients have a higher rate of comorbidities and reduction of health- and functional status compared with the normal population.
AIM
In this prospective observational study, our aim was to determine those health-related factors at the age of 31 years which were associated with a later critical illness among previously un-hospitalized individuals by exploring data obtained from the Northern Finland Birth Cohort 1966 (NFBC1966).
METHODS
NFBC1966 is a Finnish birth cohort, which includes 12,058 live births with expected dates of delivery during 1966. The study was conducted among cohort participants who had not been hospitalized for any reason before the cohort follow-up visit at the age of 31. The study group included NFBC1966 participants who were admitted to the ICU of the Oulu University Hospital. The control group included participants who were treated for any reason in regular hospital wards. The data considering the participants' health status and behavior at the age of 31 were collected from the NFBC1966 database. The gathering of ICU and hospitalization data was concluded on December 31, 2016.
RESULTS
849 NFBC1966 participants met the inclusion criteria: 69 were treated in the ICU (study group) and 780 on regular hospital wards (controls). In the study group, the rate of neurological diseases (26% vs. 16%, 95% CI: -21.8%, -0.2%), malignancy (3% vs. 0.7%, 95% CI: -9.7%, 0.0%), alcohol abuse (4.5% vs. 1%, 95% CI: -11.5%, -0.3%) and smoking (77% vs. 65%, 95% CI: -21.6%, -0.3%) were higher compared with the control group. The patients in the ICU group were also more prone to violent injuries, (17% vs. 7%, 95% CI: -20.2%, -1.9%), practiced less hard physical activity (65% vs. 78%, 95% CI: 2.1%, 25.3%) and had lower maximal muscle strength according to the hand grip test (30 vs. 34 kg, 95% CI: -8.2, 8.6 kg).
CONCLUSIONS
In this study examining previously un-hospitalized patients, the main factors associated with future critical illness were neurological comorbidities, malignancy, alcohol misuse, smoking, low maximum muscle strength, and less frequent physical exercise compared with those with hospitalization not requiring ICU admission.
PubMed: 38938220
DOI: 10.1111/aas.14490 -
Journal of Burn Care & Research :... Jun 2024This study examines a rare case of frostbite on the hands caused by liquid nitrogen, focusing on the scar maturation process. Frostbite is typically less prone to...
This study examines a rare case of frostbite on the hands caused by liquid nitrogen, focusing on the scar maturation process. Frostbite is typically less prone to abnormal scarring compared to burns, and this report contrasts the differences in scar maturation between the two. A 31-year-old male hospital employee sustained first- to second-degree frostbite on his gloved hands from a 20-second exposure to liquid nitrogen while changing a cylinder. Conservative treatment was applied, and the patient was monitored for 9 months. The deeply affected area took 50 days to epithelialize but healed without hypertrophic scarring. A mild extension contracture was noted in the distal interphalangeal joint of the right index finger, but the skin remained supple and soft. Incidents of liquid nitrogen-induced frostbite are uncommon, with only 14 cases reported in PubMed® previously. In frostbite, the wound healing involves a slow replacement of damaged connective tissue, which acts as an internal splint, reducing wound contraction. This contrasts with burns, where rapid connective tissue replacement occurs, often leading to significant wound contraction due to the presence of myofibroblasts in granulation tissue. In the presented case, the slow healing process and minimal wound contraction led to mature scarring without abnormalities, underlining a distinctive healing trajectory in frostbite injuries compared to burns.
PubMed: 38938100
DOI: 10.1093/jbcr/irae127 -
Pediatric Research Jun 2024The COVID-19 pandemic has prompted investigations into the association between this novel virus and allergic diseases, particularly asthma in children. However, the...
BACKGROUND
The COVID-19 pandemic has prompted investigations into the association between this novel virus and allergic diseases, particularly asthma in children. However, the nature of this relationship remains poorly established.
OBJECTIVE
This study aims to determine the clinical characteristics of children with allergic diseases who have contracted COVID-19.
METHODS
A retrospective study was conducted at the Children's Hospital Affiliated to the Capital Institute of Pediatrics from January to March 2023. A total of 568 children aged 0-17 years diagnosed with asthma and COVID-19 infection were included. A comparative analysis of clinical characteristics was conducted between asthma and non-asthma groups.
RESULTS
Asthmatic children with COVID-19 infection showed significantly higher frequencies of cough, wheezing, expectoration, and long-term symptoms compared to those without asthma (P < 0.05). Subgroups with poor therapy compliance exhibited elevated proportions of cough, chest tightness, and wheezing compared to good therapy compliance (P < 0.05). Multivariate logistic regression identified poor therapy compliance as a risk factor for long COVID in asthmatic children.
CONCLUSION
Children with asthma secondary to COVID-19 infection were more prone to developing coughs, expectoration, and wheezing. Poor therapy compliance emerged as a significant risk factor for long COVID-19 in these individuals.
IMPACT
Asthmatic children with COVID-19 infection showed significantly higher frequencies of cough, wheezing, expectoration. Poor therapy compliance was the risk factor for long COVID in asthmatic children. This article supplements the effects of different therapeutic drugs on the condition of children with asthma after infection with COVID-19 as well as the possible risk factors for the long COVID. The results of our study have important implications for public health policy makers and healthcare professionals. To understand the impact of COVID-19 on children with asthma will help guide appropriate management strategies and ensure access to necessary healthcare resources.
PubMed: 38937639
DOI: 10.1038/s41390-024-03365-3 -
Leukemia Jun 2024Germline heterozygous mutations in DDX41 predispose individuals to hematologic malignancies in adulthood. Most of these DDX41 mutations result in a truncated protein,...
Germline heterozygous mutations in DDX41 predispose individuals to hematologic malignancies in adulthood. Most of these DDX41 mutations result in a truncated protein, leading to loss of protein function. To investigate the impact of these mutations on hematopoiesis, we generated mice with hematopoietic-specific knockout of one Ddx41 allele. Under normal steady-state conditions, there was minimal effect on lifelong hematopoiesis, resulting in a mild yet persistent reduction in red blood cell counts. However, stress induced by transplantation of the Ddx41 BM resulted in hematopoietic stem/progenitor cell (HSPC) defects and onset of hematopoietic failure upon aging. Transcriptomic analysis of HSPC subsets from the transplanted BM revealed activation of cellular stress responses, including upregulation of p53 target genes in erythroid progenitors. To understand how the loss of p53 affects the phenotype of Ddx41 HSPCs, we generated mice with combined Ddx41 and Trp53 heterozygous deletions. The reduction in p53 expression rescued the fitness defects in HSPC caused by Ddx41 heterozygosity. However, the combined Ddx41 and Trp53 mutant mice were prone to developing hematologic malignancies that resemble human myelodysplastic syndrome and acute myeloid leukemia. In conclusion, DDX41 heterozygosity causes dysregulation of the response to hematopoietic stress, which increases the risk of transformation with a p53 mutation.
PubMed: 38937548
DOI: 10.1038/s41375-024-02304-9