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1.
NPJ Precis Oncol ; 8(1): 218, 2024 Oct 02.
Article de Anglais | MEDLINE | ID: mdl-39358389

RÉSUMÉ

As part of the advancement in therapeutic decision-making for brain tumor patients at St. Jude Children's Research Hospital (SJCRH), we developed three robust classifiers, a deep learning neural network (NN), k-nearest neighbor (kNN), and random forest (RF), trained on a reference series DNA-methylation profiles to classify central nervous system (CNS) tumor types. The models' performance was rigorously validated against 2054 samples from two independent cohorts. In addition to classic metrics of model performance, we compared the robustness of the three models to reduced tumor purity, a critical consideration in the clinical utility of such classifiers. Our findings revealed that the NN model exhibited the highest accuracy and maintained a balance between precision and recall. The NN model was the most resistant to drops in performance associated with a reduction in tumor purity, showing good performance until the purity fell below 50%. Through rigorous validation, our study emphasizes the potential of DNA-methylation-based deep learning methods to improve precision medicine for brain tumor classification in the clinical setting.

3.
J Cyst Fibros ; 2024 Sep 13.
Article de Anglais | MEDLINE | ID: mdl-39327190

RÉSUMÉ

BACKGROUND: Rapidly emerging clinical trends offer the opportunity to amend guidance on issues pertaining to CF care delivery. A national survey was conducted to gather perspectives on CF care including potential adaptations to the care model to best meet the needs of this population. METHODS: A survey instrument was developed to capture perspectives on CF care. People with CF (pwCF), including those post lung transplant, caregivers and care teams were surveyed. Descriptive statistics were calculated to characterize respondents and responses. RESULTS: In-person, routine visits with the CF care teams were valued by survey respondents. However, reduced in-person visit frequency from the standard three-month interval was supported for individuals in a stable state of health. This was particularly true for pwCF ages two or older and on a modulator. Lung function, pulmonary exacerbation frequency, and transition periods were noted to influence preference for visit frequency. Integrating telehealth with remote monitoring in between visits was broadly supported. For shared care between CF teams and other medical providers (transplant teams and primary care providers (PCP)), good communication, easily accessible health records, and convenient locations were important. CONCLUSIONS: Survey findings support adapting CF care based on individual needs and life transitions. Themes identified can inform future areas of study and resource development to support successful modification of the CF care model and shared decision-making between patients and their care providers.

4.
J Cyst Fibros ; 2024 Sep 24.
Article de Anglais | MEDLINE | ID: mdl-39327194

RÉSUMÉ

Interdisciplinary teams care for people with cystic fibrosis (pwCF) at specialized treatment centers. These teams have laid the foundation for the cystic fibrosis (CF) care model responsible for gains in health outcomes and quality of life within the CF community. However, the landscape of CF care is transforming, invigorated by new technologies, accessibility of cystic fibrosis transmembrane conductance regulator (CFTR) therapies, and increased utilization of telemedicine. In light of these advances, it is appropriate to re-evaluate the CF care team structure. This position paper offers guidance for the structure of a CF care center designed to meet the evolving needs of the CF community. Fundamental to the proposed center structure is recognition of pwCF and their families as integral members of their care teams, underpinning the necessity for shared decision making, awareness of social determinants of health, and active partnership between all healthcare professionals involved in the care of pwCF.

5.
Int J Mol Sci ; 25(18)2024 Sep 10.
Article de Anglais | MEDLINE | ID: mdl-39337270

RÉSUMÉ

The cytoskeleton mediates fundamental cellular processes by organizing inter-organelle interactions. Pathogenic variants of inverted formin 2 (INF2) CAAX isoform, an actin assembly factor that is predominantly expressed in the endoplasmic reticulum (ER), are linked to focal segmental glomerulosclerosis (FSGS) and Charcot-Marie-Tooth (CMT) neuropathy. To investigate how pathogenic INF2 variants alter ER integrity, we used high-resolution live imaging of HeLa cells. Cells expressing wild-type (WT) INF2 showed a predominant tubular ER with perinuclear clustering. Cells expressing INF2 FSGS variants that cause mild and intermediate disease induced more sheet-like ER, a pattern similar to that seen for cells expressing WT-INF2 that were treated with actin and microtubule (MT) inhibitors. Dual CMT-FSGS INF2 variants led to more severe ER dysmorphism, with a diffuse, fragmented ER and coarse INF2 aggregates. Proper organization of both F-actin and MT was needed to modulate the tubule vs. sheet conformation balance, while MT arrays regulated spatial expansion of tubular ER in the cell periphery. Pathogenic INF2 variants also induced mitochondria fragmentation and dysregulated mitochondria distribution. Such mitochondrial abnormalities were more prominent for cells expressing CMT-FSGS compared to those with FSGS variants, indicating that the severity of the dysfunction is linked to the degree of cytoskeletal disorganization. Our observations suggest that pathogenic INF2 variants disrupt ER continuity by altering interactions between the ER and the cytoskeleton that in turn impairs inter-organelle communication, especially at ER-mitochondria contact sites. ER continuity defects may be a common disease mechanism involved in both peripheral neuropathy and glomerulopathy.


Sujet(s)
Maladie de Charcot-Marie-Tooth , Réticulum endoplasmique , Formines , Mitochondries , Humains , Réticulum endoplasmique/métabolisme , Formines/métabolisme , Formines/génétique , Cellules HeLa , Maladie de Charcot-Marie-Tooth/métabolisme , Maladie de Charcot-Marie-Tooth/génétique , Maladie de Charcot-Marie-Tooth/anatomopathologie , Mitochondries/métabolisme , Glomérulonéphrite segmentaire et focale/métabolisme , Glomérulonéphrite segmentaire et focale/anatomopathologie , Glomérulonéphrite segmentaire et focale/génétique , Actines/métabolisme , Microtubules/métabolisme , Cytosquelette/métabolisme
6.
J Pediatr Surg ; 2024 Jul 18.
Article de Anglais | MEDLINE | ID: mdl-39117538

RÉSUMÉ

BACKGROUND: This study aims to assess the long-term outcomes of a modified pneumatic reduction protocol for intussusception at the Vietnam National Hospital of Pediatrics, an institution with a significant patient load in a lower-middle-income country. PATIENTS AND METHODS: A single center, retrospective cohort observational study was conducted to examine patients who underwent modified fluoroscopic-guided air-enema reduction (FGAR) for intussusception from January 2016 to December 2017. Data on patient demographics, complication rates, and the incidence of long-term recurrence was collected. RESULTS: Between January 2016 and December 2017, a total of 3562 patients underwent modified FGAR at our institution, including 2313 males (64.9%) and 1249 females (35.1%). The median age was 19 months (range: 1-170), and the median FGAR procedure duration was 4 min (range: 2-24). The median hospital stay was 1 day (range: 1-31). Successful reduction was achieved in 98.7% of cases, with 43 unsuccessful cases and 4 cases of perforated bowel requiring surgery. Twenty patients, presenting with severe symptoms due to delayed treatment seeking, were admitted to the pediatric intensive care unit (ICU) post-FGAR. No mortality or severe morbidity was reported. Over a median 6-year follow-up, intussusception recurred in 198 patients, accounting for 5.6% of the cohort, with 97% of recurrences occurring within the first year post-reduction. Infants and children under 12 months of age had the highest complication rates, including failed FGAR, complicated intussusception, ICU admission, or recurrence, compared to other age groups, and this difference was statistically significant (p < 0.05). CONCLUSION: The modified FGAR protocol has been demonstrated to be safe and feasible, with a very high success rate, low complication rate, and low recurrence rate. Although further comparative studies are needed to confirm its reproducibility, it should be considered a promising approach for children in low-to middle-income countries. LEVEL OF EVIDENCE: Level III.

7.
Membranes (Basel) ; 14(6)2024 Jun 03.
Article de Anglais | MEDLINE | ID: mdl-38921495

RÉSUMÉ

This study investigated the use of chicken egg white (CEW) waste immobilized on weak acidic nanofiber membranes for removing the anionic acid orange 7 (AO7) dye in batch and continuous flow modes. Different experiments were conducted to evaluate the effectiveness of CEW-modified nanofiber membranes for AO7 removal, focusing on CEW immobilization conditions, adsorption kinetics, and thermodynamics. The CEW-modified nanofiber membrane (namely NM-COOH-CEW) exhibited a maximum AO7 adsorption capacity of 589.11 mg/g within approximately 30 min. The Freundlich isotherm model best represented the equilibrium adsorption data, while the adsorption kinetics followed a pseudo-second-order rate model. Breakthrough curve analysis using the Thomas model and the bed depth service time (BDST) model showed that the BDST model accurately described the curve, with an error percentage under 5%. To investigate AO7 elution efficiency, different concentrations of organic solvents or salts were tested as eluents. The NM-COOH-CEW nanofiber membrane exhibited promising performance as an effective adsorbent for removing AO7 dye from contaminated water.

8.
J Neuropathol Exp Neurol ; 83(6): 416-424, 2024 May 22.
Article de Anglais | MEDLINE | ID: mdl-38699943

RÉSUMÉ

Ganglioglioma (GG) with anaplasia (anaplastic ganglioglioma) is a rare and controversial diagnosis. When present, anaplasia involves the glial component of the tumor, either at presentation or at recurrence. To date, most published cases lack molecular characterization. We describe the histologic and molecular features of 3 patients presenting with BRAF p. V600E-mutant GG (CNS WHO grade 1) with high-grade glial transformation at recurrence. The tumors occurred in pediatric patients (age 9-16 years) with time to recurrence from 20 months to 7 years. At presentation, each tumor was low-grade, with a BRAFV600E-positive ganglion cell component and a glial component resembling pleomorphic xanthoastrocytoma (PXA) or fibrillary astrocytoma. At recurrence, tumors resembled anaplastic PXA or high-grade astrocytomas without neuronal differentiation. CDKN2A homozygous deletion (HD) was absent in all primary tumors. At recurrence, 2 cases acquired CDKN2A HD; the third case showed loss of p16 and MTAP immunoexpression, but no CDKN2A/B HD or mutation was identified. By DNA methylation profiling, all primary and recurrent tumors either grouped or definitely matched to different methylation classes. Our findings indicate that malignant progression of the glial component can occur in GG and suggest that CDKN2A/B inactivation plays a significant role in this process.


Sujet(s)
Tumeurs du cerveau , Gangliogliome , Humains , Gangliogliome/génétique , Gangliogliome/anatomopathologie , Adolescent , Enfant , Tumeurs du cerveau/génétique , Tumeurs du cerveau/anatomopathologie , Mâle , Femelle , Protéines proto-oncogènes B-raf/génétique , Épigenèse génétique , Récidive tumorale locale/génétique , Récidive tumorale locale/anatomopathologie , Transformation cellulaire néoplasique/génétique , Transformation cellulaire néoplasique/anatomopathologie
9.
Contemp Clin Trials ; 143: 107578, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38789079

RÉSUMÉ

BACKGROUND: Early in the pandemic, extensive attention was cast on limited inclusion of historically underrepresented patient populations in COVID-19 clinical trials. How diverse representation improved following these initial reports remains unclear. METHODS: PubMed, Embase and the Cochrane Library were searched (through April 2024) for US-based COVID-19 trials. Utilizing random-effects, we compared expected proportions of trial participants from racial and ethnic groups and of female sex between trials enrolling primarily in 2020 versus primarily 2021-2022. Meta-regression was performed to assess associations between trial characteristics and group representation. RESULTS: We retrieved 157 studies comprising 198,012 participants. White (2020: 63.1% [95% CI, 60.8%-67.3%]; 2021-2022: 73.8% [95% CI, 71.5%-76.0%]) and female representation (2020: 46.1% [95% CI, 44.7%-47.4%)]; 2021-2022: 51.1% [95% CI, 49.3%-52.8%) increased across enrollment periods. Industry-sponsored trials were associated with higher White (coefficient, 0.10 [95% CI, 0.03-0.18]) and Hispanic or Latinx representation (coefficient, 0.16 [95% CI, 0.08-0.25]) and lower Asian (coefficient, -0.03 [95% CI, -0.06- -0.003]) and female representation (coefficient, -0.03 [95% CI, -0.07- -0.002]). Outpatient trials were associated with higher White (coefficient, 0.20 [95% CI, 0.13-0.26]) and female representation (coefficient, 0.16 [95% CI, 0.13-0.18]), and lower Black representation (coefficient, -0.10 [95% CI, -0.10- -0.08]). CONCLUSIONS: Despite improved female representation in COVID-19 trials over time, there was no clear increase in non-White representation. Trial characteristics such as primary sponsor, clinical setting, and intervention type correlate with representation of specific demographic groups and should be considered in future efforts to improve participant diversity.


Sujet(s)
COVID-19 , Essais cliniques comme sujet , Humains , COVID-19/ethnologie , COVID-19/épidémiologie , Femelle , Essais cliniques comme sujet/statistiques et données numériques , Facteurs sexuels , SARS-CoV-2 , Mâle , Ethnies/statistiques et données numériques , Sélection de patients , 38409 , États-Unis
10.
Sci Total Environ ; 934: 173028, 2024 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-38723963

RÉSUMÉ

Cyanobacteria are oxygen-producing photosynthetic bacteria that convert carbon dioxide into biomass upon exposure to sunlight. However, favorable conditions cause harmful cyanobacterial blooms (HCBs), which are the dense accumulation of biomass at the water surface or subsurface, posing threats to freshwater ecosystems and human health. Understanding the mechanisms underlying cyanobacterial bloom formation is crucial for effective management. In this regard, recent advancements in omics technologies have provided valuable insights into HCBs, which have raised expectations to develop more effective control methods in the near future. This literature review aims to present the genomic architecture, adaptive mechanisms, microbial interactions, and ecological impacts of HCBs through the lens of omics. Genomic analysis indicates that the genome plasticity of cyanobacteria has enabled their resilience and effective adaptation to environmental changes. Transcriptomic investigations have revealed that cyanobacteria use various strategies for adapting to environmental stress. Additionally, metagenomic and metatranscriptomic analyses have emphasized the significant role of the microbial community in regulating HCBs. Finally, we offer perspectives on potential opportunities for further research in this field.


Sujet(s)
Cyanobactéries , Cyanobactéries/métabolisme , Cyanobactéries/génétique , Génomique , Prolifération d'algues nuisibles , Transcriptome , Eutrophisation , Écosystème , Métagénomique
11.
RSC Adv ; 14(19): 13583-13590, 2024 Apr 22.
Article de Anglais | MEDLINE | ID: mdl-38665488

RÉSUMÉ

For undoped SnO2, room temperature ferromagnetism could be seen uniquely in 2-dimensional configurations, particularly in ultra-thin films (whose thickness is ideally below 100 nm). Both bulk samples and nano-powders of pristine SnO2 are diamagnetic, indicating that a 2D surface is a key point in shaping up the magnetic properties in SnO2. As a complement to our experiments, we have performed a series of quantum-mechanical calculations for the bulk rutile-structure SnO2 as well as its (001) and (101) surfaces. The calculations included several atomic configurations with and without vacancies in/under the studied surfaces. The stability of the non-magnetic ground state of rutile SnO2 bulk was cross-checked and confirmed by its phonon spectrum computed within the harmonic approximation. Regarding the surfaces, the bulk-like (001) surface containing Sn vacancies has turned out to be ferromagnetic, while the shift of Sn vacancies under the surface resulted in a more complex ferrimagnetic state. The bulk-like (001) surface without vacancies and that with the O vacancies are predicted to be non-magnetic. Regarding the (101) surfaces, those terminated by a single layer of oxygen atoms and those terminated by tin atoms are non-magnetic, while a surface terminated by two layers of oxygen has turned out to be ferromagnetic.

12.
Brain Pathol ; : e13256, 2024 Mar 24.
Article de Anglais | MEDLINE | ID: mdl-38523251

RÉSUMÉ

Meningeal solitary fibrous tumors (SFT) are rare and have a high frequency of local recurrence and distant metastasis. In a cohort of 126 patients (57 female, 69 male; mean age at surgery 53.0 years) with pathologically confirmed meningeal SFTs with extended clinical follow-up (median 9.9 years; range 15 days-43 years), we performed extensive molecular characterization including genome-wide DNA methylation profiling (n = 80) and targeted TERT promoter mutation testing (n = 98). Associations were examined with NAB2::STAT6 fusion status (n = 101 cases; 51 = ex5-7::ex16-17, 26 = ex4::ex2-3; 12 = ex2-3::exANY/other and 12 = no fusion) and placed in the context of 2021 Central Nervous System (CNS) WHO grade. NAB2::STAT6 fusion breakpoints (fusion type) were significantly associated with metastasis-free survival (MFS) (p = 0.03) and, on multivariate analysis, disease-specific survival (DSS) when adjusting for CNS WHO grade (p = 0.03). DNA methylation profiling revealed three distinct clusters: Cluster 1 (n = 38), Cluster 2 (n = 22), and Cluster 3 (n = 20). Methylation clusters were significantly associated with fusion type (p < 0.001), with Cluster 2 harboring ex4::ex2-3 fusion in 16 (of 20; 80.0%), nearly all TERT promoter mutations (7 of 8; 87.5%), and predominantly an "SFT" histologic phenotype (15 of 22; 68.2%). Clusters 1 and 3 were less distinct, both dominated by tumors having ex5-7::ex16-17 fusion (respectively, 25 of 33; 75.8%, and 12 of 18; 66.7%) and with variable histological phenotypes. Methylation clusters were significantly associated with MFS (p = 0.027), but not overall survival (OS). In summary, NAB2::STAT6 fusion type was significantly associated with MFS and DSS, suggesting that tumors with an ex5::ex16-17 fusion may have inferior patient outcomes. Methylation clusters were significantly associated with fusion type, TERT promoter mutation status, histologic phenotype, and MFS.

14.
Neuro Oncol ; 26(6): 1042-1051, 2024 Jun 03.
Article de Anglais | MEDLINE | ID: mdl-38243818

RÉSUMÉ

BACKGROUND: Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology. The 5th edition of the Central Nervous System World Health Organization (WHO) introduces CDKN2A/B homozygous deletion as a biomarker of grade 4. We sought to investigate the prognostic impact of DNA methylation-derived molecular biomarkers for IDH mutant astrocytoma. METHODS: We analyzed 98 IDH mutant astrocytomas diagnosed at NYU Langone Health between 2014 and 2022. We reviewed DNA methylation subclass, CDKN2A/B homozygous deletion, and ploidy and correlated molecular biomarkers with histological grade, progression free (PFS), and overall (OS) survival. Findings were confirmed using 2 independent validation cohorts. RESULTS: There was no significant difference in OS or PFS when stratified by histologic WHO grade alone, copy number complexity, or extent of resection. OS was significantly different when patients were stratified either by CDKN2A/B homozygous deletion or by DNA methylation subclass (P value = .0286 and .0016, respectively). None of the molecular biomarkers were associated with significantly better PFS, although DNA methylation classification showed a trend (P value = .0534). CONCLUSIONS: The current WHO recognized grading criteria for IDH mutant astrocytomas show limited prognostic value. Stratification based on DNA methylation shows superior prognostic value for OS.


Sujet(s)
Astrocytome , Marqueurs biologiques tumoraux , Tumeurs du cerveau , Inhibiteur p16 de kinase cycline-dépendante , Méthylation de l'ADN , Isocitrate dehydrogenases , Mutation , Humains , Astrocytome/génétique , Astrocytome/anatomopathologie , Astrocytome/mortalité , Isocitrate dehydrogenases/génétique , Mâle , Pronostic , Inhibiteur p16 de kinase cycline-dépendante/génétique , Femelle , Adulte d'âge moyen , Marqueurs biologiques tumoraux/génétique , Tumeurs du cerveau/génétique , Tumeurs du cerveau/anatomopathologie , Tumeurs du cerveau/mortalité , Adulte , Inhibiteur p15 de kinase cycline-dépendante/génétique , Sujet âgé , Taux de survie , Études de suivi , Jeune adulte , Homozygote , Délétion de gène
15.
Inj Prev ; 30(1): 33-38, 2024 Jan 25.
Article de Anglais | MEDLINE | ID: mdl-37863513

RÉSUMÉ

BACKGROUND: The short-term association between increasing temperatures and injury has been described in high-income countries, but less is known for low-income and-middle-income countries, including Vietnam. METHODS: We used emergency injury visits (EIV) data for 2017-2019 from 733 hospitals and clinics in Hanoi, Vietnam to examine the effects of daily temperature on EIV. Time-series analysis with quasi-Poisson models was used to estimate a linear relative risk increase (RRI) for overall populations and ones stratified by age and sex. Exposure-response curves estimated non-linear associations as an RR between daily temperature and injury. Models were adjusted for the day of week, holidays, daily relative humidity, daily particulate matter, and long-term and seasonal trends. RESULTS AND CONCLUSIONS: A total of 39 313 EIV were recorded averaging 36 injuries daily. Injuries more likely occurred in males and those aged 15-44, and aged 44-60. For linear effects, a 5°C increase in same day mean temperature was associated with an overall increased EIV (RRI 4.8; 95% CI 2.3 to 7.3) with males (RRI 5.9; 95% CI 3.0 to 8.9) experiencing a greater effect than females (RRI 3.0; 95% CI -0.5 to 6.5). Non-linear effects showed an increase in EIV at higher temperatures compared with the threshold temperature of 15°C, with the greatest effect at 33°C (RR 1.3; 95% CI 1.2 to 1.6). Further research to investigate temperature-injury among different populations and by the cause of injury is warranted.


Sujet(s)
Température élevée , Matière particulaire , Mâle , Femelle , Humains , Température , Vietnam/épidémiologie , Matière particulaire/analyse , Risque
16.
J Voice ; 2023 Sep 02.
Article de Anglais | MEDLINE | ID: mdl-37666745

RÉSUMÉ

INTRODUCTION: Laryngopharyngeal reflux (LPR) is one of the most common conditions encountered in otolaryngology. Gluten sensitivity may mimic the signs and symptoms of LPR or act as an aggravating cofactor with LPR. Gluten sensitivity and food intolerance also have been implicated as conditions that may be associated specifically with LPR symptoms and signs resistant to traditional medical treatment. Medical management of LPR may be insufficient to control symptoms and laryngeal signs of reflux, constituting resistant LPR. Eliminating gluten from the diet could provide symptomatic relief to patients with gluten sensitivity and LPR that is not controlled adequately by current regimens. The purpose of our study was to investigate the relationship between gluten sensitivity and LPR. We aimed to evaluate reflux finding score (RFS) improvement following elimination of gluten from the diet in patients with resistant LPR who had positive blood tests associated with gluten sensitivity. Symptom improvement was also assessed following dietary gluten elimination. Lastly, we aimed to identify predictors for a positive response to a gluten-free diet. METHODS: Adult patients who underwent gluten sensitivity testing for treatment-resistant LPR symptoms and/or signs were included. Patients with ≥1 positive test were advised to begin a therapeutic trial of a gluten-free diet. Subjects who chose not to trial a gluten-free diet or tested negative for gluten sensitivity markers served as controls. RFS was the primary outcome measure. RESULTS: One hundred ninety-seven patients were included; 81 trialed a gluten-free diet. Subjects who trialed the gluten-free diet were significantly more likely to demonstrate objective improvement in RFS (77.14% vs 43.88%), and report subjective improvement (55.41% vs 25.77%) than those who did not. RFS had decreased significantly from baseline at 1-3, 3-6, 6-12, and >12-month interval follow-up examinations in subjects who trialed a gluten-free diet. Comparison between subjects who trialed the gluten-free diet, tested positive for a gluten sensitivity marker but did not trial the gluten-free diet, and subjects who were negative for all gluten sensitivity markers revealed that a gluten-free diet was associated with a significantly greater percent improvement in RFS compared to controls at 1-3, 6-12, and >12-months. CONCLUSION: Gluten sensitivity can mimic or aggravate LPR. A gluten-free diet should be considered for patients with resistant LPR, especially if blood test abnormalities that suggest gluten sensitivity are identified. The diet should be maintained for a minimum of three months to demonstrate objective improvement using RFS.

18.
Sci Rep ; 13(1): 12003, 2023 07 25.
Article de Anglais | MEDLINE | ID: mdl-37491439

RÉSUMÉ

Focal segmental glomerulosclerosis (FSGS) is a common glomerular injury leading to end-stage renal disease. Monogenic FSGS is primarily ascribed to decreased podocyte integrity. Variants between residues 184 and 245 of INF2, an actin assembly factor, produce the monogenic FSGS phenotype. Meanwhile, variants between residues 57 and 184 cause a dual-faceted disease involving peripheral neurons and podocytes (Charcot-Marie-Tooth CMT/FSGS). To understand the molecular basis for INF2 disorders, we compared structural and cytoskeletal effects of INF2 variants classified into two subgroups: One (G73D, V108D) causes the CMT/FSGS phenotype, and the other (T161N, N202S) produces monogenic FSGS. Molecular dynamics analysis revealed that all INF2 variants show distinct flexibility compared to the wild-type INF2 and could affect stability of an intramolecular interaction between their N- and C-terminal segments. Immunocytochemistry of cells expressing INF2 variants showed fewer actin stress fibers, and disorganization of cytoplasmic microtubule arrays. Notably, CMT/FSGS variants caused more prominent changes in mitochondrial distribution and fragmentation than FSGS variants and these changes correlated with the severity of cytoskeletal disruption. Our results indicate that CMT/FSGS variants are associated with more severe global cellular defects caused by disrupted cytoskeleton-organelle interactions than are FSGS variants. Further study is needed to clarify tissue-specific pathways and/or cellular functions implicated in FSGS and CMT phenotypes.


Sujet(s)
Glomérulonéphrite segmentaire et focale , Podocytes , Humains , Protéines des microfilaments/métabolisme , Glomérulonéphrite segmentaire et focale/complications , Formines/génétique , Actines/génétique , Mutation , Cytosquelette/métabolisme , Podocytes/métabolisme
19.
J Water Health ; 21(3): 372-384, 2023 Mar.
Article de Anglais | MEDLINE | ID: mdl-37338317

RÉSUMÉ

Taiwan's oyster industry produces shell waste in abundant quantities every year. This study explored the feasibility of applying this resource as a simple and low-cost disinfectant to improve the microbial quality of harvested rainwater. Critical parameters affecting the disinfection efficacy of calcined oyster shell particles, i.e., heating temperature and duration, dosage, and contact time of the calcined shell material against Bacillus subtilis endospores in rainwater, were investigated. A central composite design of response surface methodology was employed to study the relative effects. As estimated from R2 coefficients, a quadratic model was identified to predict the response variable satisfactorily. Results indicated that the heating temperature, dosage, and contact time of the calcined material in the rainwater significantly influenced (p < 0.05) the sporicidal effect, consistent with the prior literature on calcined shells of similar nature. However, heating time had a relatively low influence on the sporicidal impact, suggesting that the rate of shell activation, i.e., conversion of the carbonate compound in the shell material to oxide, occurs rapidly at high calcination temperatures. In addition, the sterilization kinetics for heated oyster shell particles in aqueous media under stagnant storage conditions were investigated and found to be in good agreement with Hom's model.


Sujet(s)
Bacillus subtilis , Ostreidae , Animaux , Bacillus subtilis/physiologie , Température élevée , Spores bactériens , Antibactériens/pharmacologie
20.
Open Forum Infect Dis ; 10(5): ofad197, 2023 May.
Article de Anglais | MEDLINE | ID: mdl-37180601

RÉSUMÉ

Background: Clinical trials for coronavirus disease 2019 (COVID-19) have struggled to achieve diverse patient enrollment, despite underrepresented groups bearing the largest burden of the disease and, presumably, being most in need of the treatments under investigation. Methods: To assess the willingness of patients to enroll into inpatient COVID-19 clinical trials when invited, we conducted a cross-sectional analysis of adults hospitalized with COVID-19 who were approached regarding enrollment. Associations between patient and temporal factors and enrollment were assessed by multivariable logistic regression analysis. Results: A total of 926 patients were included in this analysis. Overall, Hispanic/Latinx ethnicity was associated with a nearly half-fold decrease in the likelihood to enroll (adjusted odds ratio [aOR], 0.60 [95% confidence interval {CI}, .41-.88]). Greater baseline disease severity (aOR, 1.09 [95% CI, 1.02-1.17]), age 40-64 years (aOR, 1.83 [95% CI, 1.03-3.25]), and age ≥65 years (aOR, 1.92 [95% CI, 1.08-3.42]) were each independently associated with higher likelihood to enroll. Over the course of the pandemic, patients were less likely to enroll during the summer 2021 wave in COVID-19-related hospitalizations (aOR, 0.14 [95% CI, .10-.19]) compared with patients from the first wave in winter 2020. Conclusions: The decision to enroll into clinical trials is multifactorial. Amid a pandemic disproportionately affecting vulnerable groups, Hispanic/Latinx patients were less likely to participate when invited, whereas older adults were more likely. Future recruitment strategies must consider the nuanced perceptions and needs of diverse patient populations to ensure equitable trial participation that advances the quality of healthcare for all.

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