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1.
J Neuroimaging ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223766

RESUMEN

BACKGROUND AND PURPOSE: Ischemic strokes due to isolated posterior cerebral artery (PCA) occlusions represent 5% of all strokes but have significant impacts on patients' quality of life, primarily due to visual deficits and thalamic involvement. Current guidelines for acute PCA occlusion management are sparse, and the prognostic value of perfusion imaging parameters remains underexplored. METHODS: We conducted a retrospective analysis of 32 patients with isolated PCA occlusions treated at Johns Hopkins Medical Institutions between January 2017 and March 2023. Patients underwent pretreatment perfusion imaging, with perfusion parameters analyzed using RAPID software. The primary outcome was short-term clinical outcome as measured by the National Institutes of Health Stroke Scale (NIHSS) at discharge. RESULTS: The median age of the cohort was 70 years, with 34% female and 66% male. Significant correlations were found between NIHSS at discharge and various perfusion parameters, including time-to-maximum (Tmax) >6 seconds (ρ = .55, p = .004), Tmax >8 seconds (ρ = .59, p = .002), Tmax >10 seconds (ρ = .6, p = .001), mismatch volume (ρ = .51, p = .008), and cerebral blood volume (CBV) < 34% (ρ = .59, p = .002). CONCLUSIONS: Tmax and CBV volumes significantly correlated with discharge NIHSS with marginal superiority of Tmax >10 seconds and CBV <42% volumes. These findings suggest that CT and MR perfusion imaging can play a crucial role in the acute management of PCA strokes, though larger, standardized studies are needed to validate these results and refine imaging thresholds specific to posterior circulation infarcts.

2.
Genome Biol ; 25(1): 236, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227979

RESUMEN

Missing covariate data is a common problem that has not been addressed in observational studies of gene expression. Here, we present a multiple imputation method that accommodates high dimensional gene expression data by incorporating principal component analysis of the transcriptome into the multiple imputation prediction models to avoid bias. Simulation studies using three datasets show that this method outperforms complete case and single imputation analyses at uncovering true positive differentially expressed genes, limiting false discovery rates, and minimizing bias. This method is easily implemented via an R Bioconductor package, RNAseqCovarImpute that integrates with the limma-voom pipeline for differential expression analysis.


Asunto(s)
Programas Informáticos , Humanos , Perfilación de la Expresión Génica/métodos , Transcriptoma , Análisis de Componente Principal , Análisis de Secuencia de ARN/métodos
3.
Eur J Med Res ; 29(1): 429, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169421

RESUMEN

PURPOSE: The aim of this study was to identify factors that predict favorable functional outcomes in elderly patients with large-vessel occlusion acute ischemic stroke (LVO-AIS) who underwent mechanical thrombectomy (MT). METHODS: We conducted a retrospective observational study using the prospectively maintained Bigdata Observatory for Stroke of China (BOSC) to identify eligible patients who underwent MT for LVO-AIS at four comprehensive stroke centers between August 2019 and February 2022. Inclusion criteria included patients aged 80 years or older with a baseline modified Rankin Scale (mRS) 0-2, baseline National Institutes of Health Stroke Scale (NIHSS) > 6, baseline Alberta Stroke Program Early CT Score (ASPECTS) > 6 who received treatment within 24 h from symptom onset. Pertinent demographic, clinical, and procedural variables were collected. Multivariable regression analyses were performed to identify predictors of favorable long-term functional outcomes, defined as mRS 0-2 at 90 days. RESULTS: A total of 63 patients were included in the study with a mean age of 83 years. Patients with previous diagnosis of atrial fibrillation were more likely to have a favorable functional outcome (OR 2.09, 95% CI 2.09-407.33, p = 0.012), while a higher baseline NIHSS was associated with a less favorable functional outcome (OR 0.64, 95% CI 0.46-0.89, p = 0.007). In addition, there was an observed trend suggesting an association between higher baseline ASPECTS and favorable functional outcomes. This association did not reach statistical significance (OR 2.49, 95% CI 0.94-6.54, p = 0.065). CONCLUSION: In this study, we identified factors that predicted a favorable functional outcome in elderly LVO-AIS patients undergoing MT. A higher baseline NIHSS decreased the odds of mRS 0-2 at 90 days, whereas a history of atrial fibrillation increased the odds of a favorable functional outcome. These results emphasize the complex relationship between clinical factors and functional recovery in this vulnerable population.


Asunto(s)
Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Trombectomía , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/terapia , Anciano de 80 o más Años , Trombectomía/métodos , Procedimientos Endovasculares/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Anciano , Fibrilación Atrial/cirugía , Fibrilación Atrial/fisiopatología
4.
Phys Chem Chem Phys ; 26(33): 22041-22048, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39113537

RESUMEN

Mechanochemistry is drawing attention from the pharmaceutical industry given its potential for sustainable material synthesis and manufacture. Scaling mechanochemical processes to industrial level remains a challenge due to an incomplete understanding of their underlying mechanisms. We here show how time-resolved in situ powder X-ray diffraction data, coupled with analytical kinetic modelling, provides a powerful approach to gain mechanistic insight into mechanochemical reactions. By using the ibuprofen-nicotinamide co-crystal mechanosynthesis as a benchmark system, we investigate the behaviour of the solids involved and identify the factors that promote the reaction. As mechanochemical mechanisms become increasingly clear, it promises to become a breakthrough in the industrial preparation of advanced pharmaceuticals.

5.
bioRxiv ; 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39149398

RESUMEN

Complex behaviors like navigation rely on sequenced motor outputs that combine to generate effective movement. The brain-wide organization of the circuits that integrate sensory signals to select and execute appropriate motor sequences is not well understood. Here, we characterize the architecture of neural circuits that control C. elegans olfactory navigation. We identify error-correcting turns during navigation and use whole-brain calcium imaging and cell-specific perturbations to determine their neural underpinnings. These turns occur as motor sequences accompanied by neural sequences, in which defined neurons activate in a stereotyped order during each turn. Distinct neurons in this sequence respond to sensory cues, anticipate upcoming turn directions, and drive movement, linking key features of this sensorimotor behavior across time. The neuromodulator tyramine coordinates these sequential brain dynamics. Our results illustrate how neuromodulation can act on a defined neural architecture to generate sequential patterns of activity that link sensory cues to motor actions.

6.
Stroke ; 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39185560

RESUMEN

BACKGROUND: Recent large core trials have highlighted the effectiveness of mechanical thrombectomy (MT) in acute ischemic stroke with large vessel occlusion. Variable perfusion-imaging thresholds and poor Alberta Stroke Program Early Computed Tomography Score reliability underline the need for more standardized, quantitative ischemia measures for MT patient selection. We aimed to identify the computed tomography perfusion parameter most strongly associated with poor outcomes in patients with acute ischemic stroke-large vessel occlusion with significant ischemic cores. METHODS: In this study from 2 comprehensive stroke centers from 2 comprehensive stroke centers within the Johns Hopkins Medical Enterprise (Johns Hopkins Hospita-East Baltimore and Bayview Medical Campus) from July 29, 2019 to January 29, 2023 in a continuously maintained database, we included patients with acute ischemic stroke-large vessel occlusion with ischemic core volumes defined as relative cerebral blood flow <30% and ≥50 mL on computed tomography perfusion or Alberta Stroke Program Early Computed Tomography Score <6. We used receiver operating characteristics to find the optimal cutoff for parameters like cerebral blood volume (CBV) <34%, 38%, 42%, and relative cerebral blood flow >20%, 30%, 34%, 38%, and time-to-maximum >4, 6, 8, and 10 seconds. The primary outcome was unfavorable outcomes (90-day modified Rankin Scale score 4-6). Multivariable models were adjusted for age, sex, diabetes, baseline National Institutes of Health Stroke Scale, intravenous thrombolysis, and MT. RESULTS: We identified 59 patients with large ischemic cores. A receiver operating characteristic curve analysis showed that CBV<42% ≥68 mL is associated with unfavorable outcomes (90-day modified Rankin Scale score 4-6) with an area under the curve of 0.90 (95% CI, 0.82-0.99) in the total and MT-only cohorts. Dichotomizing at this CBV threshold, patients in the ≥68 mL group exhibited significantly higher relative cerebral blood flow, time-to-maximum >8 and 10 seconds volumes, higher CBV volumes, higher HIR, and lower CBV index. The multivariable model incorporating CBV<42% ≥68 mL predicted poor outcomes robustly in both cohorts (area under the curve for MT-only subgroup was 0.87 [95% CI, 0.75-1.00]). CONCLUSIONS: CBV<42% ≥68 mL most effectively forecasts poor outcomes in patients with large-core stroke, confirming its value alongside other parameters like time-to-maximum in managing acute ischemic stroke-large vessel occlusion.

7.
Biomed Chromatogr ; : e5993, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39152776

RESUMEN

Colorectal cancer (CRC) is the fourth most common cause of malignant tumor death. The development of novel, more effective drugs is desperately needed to treat CRC. Zingiber officinale is believed to possess anticancer properties due to its flavonoids and phenols. Using Soxhlet (SOXT) and maceration (MACR) techniques, the present study aimed to evaluate the amounts of quercetin, gallic acid, rutin, naringin, and caffeic acid in ginger capsules of Z. officinale. High-performance liquid chromatography (HPLC)/ultraviolet was used for separation and quantitation. In vitro toxicity evaluation of ginger capsules on the CRC cell line HT-29 was also conducted to assess the anticancer activity of the supplement. The cell line HT-29 (HTB-38) colorectal adenocarcinoma was utilized for the antiproliferative effect of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. Ginger herbal supplement extract at dosages of 200 and 100 µg had strong cytotoxic effects (IC50 < 50 µg/mL) on HT-29 CRC cells via MACR. This extract is comparable to the SOXT extract, which has an IC50 of less than 50 µg/mL. The anticancer effect of ginger herbal supplement formulations against CRC lines was investigated, and the results obtained from both the MACR and SOXT extraction procedures were noteworthy. The quercetin content was the highest of all the extracts according to the HPLC data.

8.
Interv Neuroradiol ; : 15910199241271062, 2024 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-39155574

RESUMEN

We describe a case of a 22-year-old man with a traumatic occipital artery pseudoaneurysm revealed by a painful expanding neck hematoma after a penetrating knife injury. A neuroendovascular consultation was requested after a computed tomography angiogram showed active pseudoaneurysm bleeding. Anatomical considerations of the upper cervical region including dangerous anastomosis between the vertebral and internal carotid artery are discussed, illustrating how this impacted our treatment strategy. We also discuss other treatment modalities after a thorough literature review of traumatic occipital artery pseudoaneurysms.

9.
J Neurointerv Surg ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39122256

RESUMEN

BACKGROUND: Venous sinus stenting (VSS) is an increasingly performed procedure for the treatment of idiopathic intracranial hypertension (IIH) refractory to medical treatment. VSS is typically performed under general anesthesia. OBJECTIVE: To present our experience of VSS in patients with IIH performed under conscious sedation. METHODS: Retrospective review of a prospectively maintained database of all patients with IIH who underwent VSS in a single center between September 2019 and January 2024. The sedation protocol consisted of a remifentanil-based target-controlled infusion. Patients' clinical and radiological data, dosage of anesthesia, procedural characteristics, and outcomes were collected. RESULTS: Twenty-six patients with IIH underwent venous manometry (VM) and VSS under awake sedation and were included in our study. Patients were predominantly women (24/26) with a median age (IQR) of 33 (13) years. The median (IQR) body mass index was 34 (10) kg/m2. There was no need for general anesthesia conversion. Technical success was achieved in all patients. Median (IQR) follow-up after stenting was 7 (2) months. All patients reported resolution of the pulsatile tinnitus; headaches regressed in 20/24 (83.3%) patients and papilledema improved in 16/20 (80%). Only one non-neurological complication (retroperitoneal hematoma) occurred, without any permanent morbidity or mortality. CONCLUSION: Our study confirms that performing VM and VSS under conscious sedation is safe and feasible. Conscious sedation is a viable alternative to general anesthesia for managing IIH in these patients.

10.
bioRxiv ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39149264

RESUMEN

Pediatric brain cancer is the leading cause of disease-related mortality in children, and many aggressive tumors still lack effective treatment strategies. Despite extensive studies characterizing these tumor genomes, alternative transcriptional splicing patterns remain underexplored. Here, we systematically characterized aberrant alternative splicing across pediatric brain tumors, identifying pediatric high-grade gliomas (HGGs) among the most heterogeneous. Through integration with UniProt Knowledgebase annotations, we identified 12,145 splice events in 5,424 genes, leading to functional changes in protein activation, folding, and localization. We discovered that the master splicing factor and cell-cycle modulator, CDC-like kinase 1 (CLK1), is aberrantly spliced in HGGs to include exon 4, resulting in a gain of two phosphorylation sites and subsequent activation of CLK1. Inhibition of CLK1 with Cirtuvivint in the pediatric HGG KNS-42 cell line significantly decreased both cell viability and proliferation in a dose-dependent manner. Morpholino-mediated depletion of CLK1 exon 4 splicing reduced RNA expression, protein abundance, and cell viability. Notably, KNS-42 cells treated with the CLK1 exon 4 morpholino demonstrated differential expression 78 genes and differential splicing with loss or gain of a functional site in 193 genes annotated as oncogene or tumor suppressor genes (TSGs). These genes were enriched for cancer-associated pathways, with 20 identified as significant gene dependencies in pediatric HGGs. Our findings highlight a dependency of pediatric HGGs on CLK1 and its roles contributing to tumor splicing heterogeneity through transcriptional dysregulation of splicing factors and transcriptional modulation of oncogenes. Overall, aberrant splicing in HGGs and other pediatric brain tumors represents a potentially targetable oncogenic pathway contributing to tumor growth and maintenance.

11.
J Neurointerv Surg ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164075

RESUMEN

BACKGROUND: The incidence of thrombosis in patients with intracranial atherosclerotic stenosis (ICAS) remains unclear. Optical coherence tomography (OCT) has the potential to explore the vessel wall structure of posterior-circulation ICAS because of its relatively straight anatomical structure compared with that of the anterior cerebral arteries. This study aimed to determine the prevalence and characteristics of thrombosis in the posterior-circulation ICAS using OCT. METHODS: This prospective study was conducted on 135 patients with posterior-circulation arterial stenosis who underwent OCT. All patients were symptomatic and had a severely stenotic lesion (70-99%) in the vetebrobasilar artery. The enrolled patients were classified according to the presence of in situ thrombus as defined by OCT. Clinical data and OCT characteristics were compared. RESULTS: Eighty-two patients diagnosed with posterior-circulation ICAS were enrolled. In situ thrombi were identified in 34 patients. Clinically, patients with in situ thrombus were more prone to cerebral infarctions than transient ischemic attacks. The percentage area of stenosis in the non-thrombus group was significantly lower than that in the thrombus group. The thrombus burden, mean flow area, mean thrombus area, maximum lipid arc, and mean lumen area were significantly different among white, red, and mixed thrombi. CONCLUSIONS: We achieved in vivo vessel wall structural analysis of posterior-circulation ICAS with the largest sample size. We also revealed the true incidence of in situ thrombosis and potential corresponding clinical events of posterior-circulation ICAS for the first time.

12.
J Am Chem Soc ; 146(34): 23831-23841, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39149836

RESUMEN

Chromium and arsenic are two of the most problematic water pollutants due to their high toxicity and prevalence in various water streams. While adsorption and ion-exchange processes have been applied for the efficient removal of numerous toxic contaminants, including heavy metals, from water, these technologies display relatively low overall performances and stabilities for the remediation of chromium and arsenic oxyanions. This work presents the use of polyol-functionalized porous aromatic framework (PAF) adsorbent materials that use chelation, ion-exchange, redox activity, and hydrogen-bonding interactions for the highly selective capture of chromium and arsenic from water. The chromium and arsenic binding mechanisms within these materials are probed using an array of characterization techniques, including X-ray absorption and X-ray photoelectron spectroscopies. Adsorption studies reveal that the functionalized porous aromatic frameworks (PAFs) achieve selective, near-instantaneous (reaching equilibrium capacity within 10 s), and high-capacity (2.5 mmol/g) binding performances owing to their targeted chemistries, high porosities, and high functional group loadings. Cycling tests further demonstrate that the top-performing PAF material can be recycled using mild acid and base washes without any measurable performance loss over at least ten adsorption-desorption cycles. Finally, we establish chemical design principles enabling the selective removal of chromium, arsenic, and boron from water. To achieve this, we show that PAFs appended with analogous binding groups exhibit differences in adsorption behavior, revealing the importance of binding group length and chemical identity.

13.
Proc Natl Acad Sci U S A ; 121(36): e2405210121, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39190360

RESUMEN

In the absence of antiretroviral therapy (ART), a subset of individuals, termed HIV controllers, have levels of plasma viremia that are orders of magnitude lower than non-controllers (NC) who are at higher risk for HIV disease progression. In addition to having fewer infected cells resulting in fewer cells with HIV RNA, it is possible that lower levels of plasma viremia in controllers are due to a lower fraction of the infected cells having HIV-1 unspliced RNA (HIV usRNA) compared with NC. To directly test this possibility, we used sensitive and quantitative single-cell sequencing methods to compare the fraction of infected cells that contain one or more copies of HIV usRNA in peripheral blood mononuclear cells (PBMC) obtained from controllers and NC. The fraction of infected cells containing HIV usRNA did not differ between the two groups. Rather, the levels of viremia were strongly associated with the total number of infected cells that had HIV usRNA, as reported by others, with controllers having 34-fold fewer infected cells per million PBMC. These results reveal that viremic control is not associated with a lower fraction of proviruses expressing HIV usRNA, unlike what is reported for elite controllers, but is only related to having fewer infected cells overall, maybe reflecting greater immune clearance of infected cells. Our findings show that proviral silencing is not a key mechanism for viremic control and will help to refine strategies toward achieving HIV remission without ART.


Asunto(s)
Infecciones por VIH , VIH-1 , Leucocitos Mononucleares , ARN Viral , Viremia , Humanos , VIH-1/genética , VIH-1/fisiología , Infecciones por VIH/virología , Infecciones por VIH/tratamiento farmacológico , ARN Viral/genética , Viremia/virología , Leucocitos Mononucleares/virología , Masculino , Carga Viral , Femenino , Adulto , Persona de Mediana Edad
14.
Life (Basel) ; 14(8)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39202668

RESUMEN

High-grade glioma is the most frequent and lethal primary tumor of the central nervous system. Despite advances in surgical, pharmacological, and cell-directed therapies, there have been no updates to the standard of care in over a decade. This cross-sectional study analyzes patient and trial data from 201 interventional trials completed between 2010 and 2023, encompassing 18,563 participants. Although we found that all trials reported participant age and sex, only 52% of trials reported participant demographics, resulting in 51% of total participant demographics being unreported. The majority of studies did not report ethnicity, with approximately 60% of participants unreported. Additionally, males were significantly underrepresented in trials, comprising 60% of participants despite representing 75% of glioblastoma patients. Improved demographic reporting has been observed since 2011; however, it is inconsistent. Furthermore, we cataloged the geographic diversity of trials across the United States and found significant coverage deserts in relatively rural, but highly affected, areas such as Montana and Maine. We found a wider distribution of trials in both urban and wealthier regions, which indicates extensive coverage gaps and decreased access to participation for patients of a lower socioeconomic status.

15.
Artículo en Inglés | MEDLINE | ID: mdl-39207445

RESUMEN

The sandwich generation faces dual responsibilities of supporting parents and raising children, resulting in heightened levels of stress and negative work-related outcomes. Despite a wealth of research on the sandwich generation, few studies have examined the specific nature of the multigenerational needs of the sandwich generation. Accordingly, we introduce a new concept termed family intergenerational stress (FIS), which refers to the interaction and integration of stresses from elder caregiving, child-rearing, and associated challenges with self-definition. Through the lens of FIS, we collected interview data from 137 sandwich generation employees, secondary network data, and field observation data from 21 employees. We further used grounded theory to explore employees' stress and coping responses to dual family responsibilities. Findings indicate that employees with both elder caregiving and child-rearing responsibilities experience FIS. This, in turn, threatens their identity as an ideal worker and is associated with lower work engagement. Findings further reveal that in coping with FIS, employees adopt different identity-based strategies. Theoretical and practical implications are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

16.
Eur Stroke J ; : 23969873241272542, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39171391

RESUMEN

INTRODUCTION: Thrombectomy complications remain poorly explored. This study aims to characterize periprocedural intracranial vessel perforation including the effect of thrombolysis on patient outcomes. PATIENTS AND METHODS: In this multicenter retrospective cohort study, consecutive patients with vessel perforation during thrombectomy between January 2015 and April 2023 were included. Vessel perforation was defined as active extravasation on digital subtraction angiography. The primary outcome was modified Rankin Scale (mRS) at 90 days. Factors associated with the primary outcome were assessed using proportional odds models. RESULTS: 459 patients with vessel perforation were included (mean age 72.5 ± 13.6 years, 59% female, 41% received thrombolysis). Mortality at 90 days was 51.9% and 16.3% of patients reached mRS 0-2 at 90 days. Thrombolysis was not associated with worse outcome at 90 days. Perforation of a large vessel (LV) as opposed to medium/distal vessel perforation was independently associated with worse outcome at 90 days (aOR 1.709, p = 0.04) and LV perforation was associated with poorer survival probability (HR 1.389, p = 0.021). Patients with active bleeding >20 min had worse survival probability, too (HR 1.797, p = 0.009). Thrombolysis was not associated with longer bleeding duration. Bleeding cessation was achieved faster by permanent vessel occlusion compared to temporary measures (median difference: 4 min, p < 0.001). DISCUSSION AND CONCLUSION: Vessel perforation during thrombectomy is a severe and frequently fatal complication. This study does not suggest that thrombolysis significantly attributes to worse prognosis. Prompt cessation of active bleeding within 20 min is critical, emphasizing the need for interventionalists to be trained in complication management.

18.
Biochim Biophys Acta Gen Subj ; 1868(11): 130690, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39117048

RESUMEN

Increased plasma levels of serum amyloid A (SAA), an acute-phase protein that is secreted in response to inflammation, may lead to the accumulation of amyloid in various organs thereby obstructing their functions. Severe cases can lead to a systemic disorder called AA amyloidosis. Previous studies suggest that the N-terminal helix is the most amyloidogenic region of SAA. Moreover, computational studies implicated a significant role for Arg-1 and the residue-specific interactions formed during the fibrillization process. With a focus on the N-terminal region of helix-1, SAA1-13, mutational analysis was employed to interrogate the roles of the amino acid residues, Arg-1, Ser-5, Glu-9, and Asp-12. The truncated SAA1-13 fragment was systematically modified by substituting the key residues with alanine or uncharged but structurally similar amino acids. We monitored the changes in the amyloidogenic propensities, associated conformational markers, and morphology of the amyloids resulting from the mutation of SAA1-13. Mutating out Arg-1 resulted in much reduced aggregation propensity and a lack of detectable ß-structures alluding to the importance of salt-bridge interactions involving Arg-1. Our data revealed that by systematically mutating the key amino acid residues, we can modulate the amyloidogenic propensity and alter the time-dependent conformational variation of the peptide. When the behaviors of each mutant peptide were analyzed, they provided evidence consistent with the aggregation pathway predicted by MD simulation studies. Here, we detail the important temporal molecular interactions formed by Arg-1 with Ser-5, Glu-9, and Asp-12 and discuss its mechanistic implications on the self-assembly of the helix-1 region of SAA.

19.
Radiology ; 312(2): e233041, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-39105645

RESUMEN

Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.


Asunto(s)
Accidente Cerebrovascular Isquémico , Trombectomía , Terapia Trombolítica , Humanos , Femenino , Masculino , Anciano , Estudios Retrospectivos , Trombectomía/métodos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/terapia , Persona de Mediana Edad , Anciano de 80 o más Años , Terapia Trombolítica/métodos , Terapia Combinada , Resultado del Tratamiento , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Puntaje de Propensión
20.
BMC Oral Health ; 24(1): 930, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127613

RESUMEN

BACKGROUND: The pervasiveness of the Internet in everyday life, especially among young people, has raised concerns about its effects on mental health, education, and, recently, oral health. Previous research has suggested a complex relationship between Problematic Internet Use (PIU), lifestyles, and oral health-related quality of life, highlighting the need to examine these interactions further. This study seeks to explore the PIU as a predictor of oral health-related quality of life and examine the mediating role of lifestyles between both in a sample of Peruvian schoolchildren. METHODS: A cross-sectional study was carried out with 293 Peruvian students aged 12 to 17 years (M = 14.42, SD = 1.5), using structural equations to analyze the relationship between PIU, lifestyles, and quality of life related to oral health. The data collection procedure was through a face-to-face survey. Validated instruments measured PIU, lifestyles, and oral health-related quality of life. The study's theoretical model was analyzed through structural equation modeling with the MLR estimator. The fit assessment was performed using the comparative fit index (CFI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR). RESULTS: They indicated significant correlations between PIU, lifestyles, and oral health-related quality of life. A negative influence of PIU on lifestyles (ß = -0.30, p < .001) and on oral health-related quality of life (ß = -0.35, p < .001) was observed, as well as a positive relationship between PIU and oral health-related quality of life (ß = 0.29, p < .001). The mediation of lifestyles was statistically significant, suggesting that they mediate the relationship between PIU and oral health-related quality of life. CONCLUSIONS: The study confirms that PIU can negatively affect adolescents' oral health-related quality of life, mediated by unhealthy lifestyles. It underlines the importance of promoting balanced Internet use and healthy lifestyles among young people to improve their oral well-being.


Asunto(s)
Estilo de Vida , Salud Bucal , Calidad de Vida , Humanos , Adolescente , Perú , Masculino , Femenino , Estudios Transversales , Niño , Internet , Trastorno de Adicción a Internet/psicología , Encuestas y Cuestionarios
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