Holmeshan5681

While a growing body of evidence points to potentially modifiable individual risk factors for dementia, the built and social environments in which people develop and navigate cognitive decline are largely overlooked. This paper proposes a new theoretical concept, Cognability, to conceptualize how supportive an area is to cognitive health among aging residents. Cognability incorporates a constellation of both positive and negative neighborhood features related to physical activity, social interaction and cognitive stimulation in later life. Darapladib price We analyzed data from the REasons for Geographic And Racial Differences in Stroke Study, a national sample of older Black and white adults in the United States (n = 21,151; mean age at assessment = 67; data collected 2006-2017). Generalized additive multilevel models examined how cognitive function varied by neighborhood features. Access to civic and social organizations, recreation centers, fast-food and coffee establishments, arts centers, museums, and highways were significantly associated with cognitive function. Race-, gender-, and education-specific models did not yield substantial improvements to the full-model. Our results suggest that the unequal distribution of amenities and hazards across neighborhoods may help account for considerable inequities observed in cognitive health among older adults. Cognability advances ecological theories of aging through an innovative "whole neighborhood" approach. It aims to identify which specific neighborhood features are most protective of cognitive health among aging adults to inform upstream public health initiatives, community interventions, and policy.Electroconvulsive therapy (ECT) has been demonstrated to be effective in treating depressed patients. Previous neuroimaging studies have focused mainly on alterations in static brain activity and connectivity to study the effects of ECT in depressed patients. However, it remains unclear whether the temporal dynamics of brain activity are associated with mechanisms of ECT in depressed patients. We measured the dynamics of spontaneous brain activity using dynamic amplitude of low-frequency fluctuation (dALFF) in healthy controls (n = 40) and patients diagnosed with unipolar depression (UD, n = 36) or bipolar disorder (BD, n = 9) before and after ECT. Furthermore, the temporal variability of intrinsic brain activity (iBA) was quantified as the variance of dALFF across sliding window. In addition, correlation analysis was performed to investigate the relationships among dALFF, depressive symptoms, and cognitive function in depressed patients. We lack second resting-state functional magnetic resonance imaging (rs-fMRI) data for healthy controls. After ECT, patients showed decreased brain dynamics (less temporal variability) in the right dorsal anterior cingulate cortex (dACC) and the right precuneus, whereas they showed increased brain dynamics in the bilateral superior medial frontal cortex (mSFC). No significant correlation was found between the dALFF and clinical variables in depressed patients. Our findings suggest that right dACC, right precuneus, and bilateral mSFC play an important role in response to ECT depressed patients from the perspective of dynamic local brain activity, indicating that the dALFF variability may be useful in further understanding the mechanisms of ECT's antidepressant effects.Cognitive deficit is one of the core features of schizophrenia and is associated with poor functional outcomes. There is a lack of validated criteria to screen and monitor cognitive deficits in schizophrenia. This study aimed to evaluate the concurrent validity and sensitivity of MoCA (Montreal Cognitive Assessment) and DSST (Digit Symbol Substitution Test) in identifying cognitive deficits in Schizophrenia comparing with a comprehensive MCCB [MATRICS (Measurement And Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery] equivalent battery. We did clinical and cognitive assessments on 30 patients with schizophrenia and 30 age and gender-matched healthy controls. The Cronbach's Alpha of MoCA was 0.839, and on adding the DSST, it increased to 0.859. In stepwise binary logistic regression, adding DSST to MoCA improved the prediction of cognitive impairment as defined by a comprehensive battery with 86.7% classification accuracy. Receiver operating characteristic curve analysis suggested a score of 25 of MoCA and 59 of DSST as an optimal cut-off in identifying severe cognitive deficits with an additional MoCA cut-off of 27 for identifying mild cognitive deficits. Combined MoCA and DSST is a sensitive and quick method to screen for neurocognitive deficits in schizophrenia.Nanodynamic therapy (NDT) based on reactive oxygen species (ROS) generation has been envisioned as a distinct modality for efficient cancer treatment. However, insufficient ROS generation and partial ROS consumption frequently limit the theraputic effect and outcome of NDT owing to the low oxygen (O2) tension and high glutathione (GSH) level in tumor microenvironment (TME). To circumvent these critical issues, we herein proposed and engineered the biodegradable GSH-depletion Mn(III)-riched manganese oxide nanospikes (MnOx NSs) with the photosynthetic bacterial cyanobacteria (Cyan) as a high-efficient and synergistic platform to reshape TME by simultaneously increasing oxygen content and decreasing GSH level. Specifically, under the trigger of acidity, MnOx NSs reacted with photosynthetic oxygen can generate toxic singlet oxygen (1O2). Moreover, MnOx NSs significantly reduced intracellular GSH, resulting in decreased GPX4 activity, which induced tumor cell non-apoptotic ferroptosis. Consequently, this combined strategy based on coadministration with Cyan and MnOx NSs demonstrated the superior antitumor efficacy via amplification of oxidative stress in 4T1 tumor-bearing mice for the synergetic oxygen-augmented nanodynamic/ferroptosis therapy. This work highlights a facile synergistic micro-/nano-system with the specific capability of reshaping TME to augment the sensitivity and therapeutic efficacy of NDT in solid hypoxic tumor therapy.Renal ischemia-reperfusion (IR) injury (RIRI) is the leading cause of acute kidney injury (AKI), a common disease with high morbidity and mortality. However, due to the lack of effective diagnostic and therapeutic tools, patients have to resort to conservative treatment. To address this issue, we have developed a novel prophylactic strategy that involves the pre-treatment use of ceria nanoparticles (CNPs) before surgery. Based on our careful study of the three different sizes of CNPs that we synthesized, 46 nm (NP46), 81 nm (NP81), and 118 nm (NP118), we have found that NP118 can be used as effective prophylactic agents against RIRI and subsequent renal fibrosis. In our experiments, the CNPs exhibited excellent antioxidant and anti-inflammatory activities in vitro and effectively protected the kidney against RIRI and renal fibrosis in vivo, as proved by the decreases in renal lesions, serum creatinine, blood urea nitrogen, apoptotic cell, KIM-1 expression, and fibrotic area in CNPs treated samples relative to RIRI group. Mechanistically, not only did the CNPs reduce oxidative stress by regulating the Nrf2 pathway, but they also attenuated RIRI induced inflammatory response by decreasing macrophage infiltration and polarization to M1 phenotype, and reducing pro-inflammatory cytokine and chemokine production. In vitro results further confirmed that CNPs pre-treatment not only dramatically decreased intracellular ROS production in renal tubular epithelial cells and vascular endothelial cells, but also effectively attenuated lipopolysaccharide-induced inflammation in RAW264.7 cells. In addition, we found that one fourth of the NP118 persisted for more than 21 days in IR kidneys, and that out of the three sizes of CNPs, NP118 achieved the best results in all our experiments. Our study provides new insights into the usage and majorization of CNPs as a potential therapy to treat or prevent RIRI and renal fibrosis.

To investigate if the presence of metallic markers (markers) influences the diagnostic accuracy of preoperative breast MRI for the prediction of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients.

In this single-center, retrospective, observational study approved by the IRB of our institution, we included all consecutive patients that underwent preoperative breast MRI after completion of NAC (Mean 4,4 days ± 15,9). The presence or absence of markers, the type of markers, the size and type of artefact on each MRI sequence were recorded. Two radiologists blinded to histopathological results and to each other's findings evaluated all MRI examinations for presence or absence of complete response. Pathology was the standard of reference. Diagnostic performance of MRI for prediction of pCR in the presence or absence of markers and also between two most represented markers brands (O'Twist and UltraClip) were compared using Chi-squared tests or equivalents.

Ninety-three patients (mean age 48 ± 11years) were included in this study. Nineteen of them had no markers and 74 had 108 markers. Sensitivity and specificity of MRI for the prediction of pCR were 0.73 and 0,81 for patients with and 0.67 and 0.90 for patients without markers (p<0.05).There was no statistical difference in the performance of MRI for the two different types of markers studied.

Diagnostic performance of pre-operative MRI after NAC for the prediction of pCR did not differ statistically in the presence or absence of metallic markers nor between the two markers' brands studied.

Diagnostic performance of pre-operative MRI after NAC for the prediction of pCR did not differ statistically in the presence or absence of metallic markers nor between the two markers' brands studied.

This prospective study aimed to compare the diagnostic accuracy of shear wave elastography (SWE) with that of shear wave dispersion (SWD) in evaluation of hepatic fibrosis in patients with hepatocellular carcinoma before resection.

A total of 210 consecutive patients with hepatocellular carcinoma (HCC) who were scheduled to undergo hepatectomy were prospectively enrolled, pre-operative SWE and SWD examinations were performed. Fibrosis staging and necroinflammatory activity were determined histopathologically according to the Scheuer standard. Multivariate linear regression analysis was used to identify factors associated with SWE and SWD values. The performance of SWE and SWD were determined by receiver operating characteristic (ROC) analysis.

Both SWE and SWD values of liver were highly correlated with liver fibrosis stage and necroinflammatory activity (p<0.05). Both SWE and SWD values were significantly different among the patients with different stages of liver fibrosis (p<0.001). ROC analysis revealed that SWE that predicted substantial fibrosis (S≥2), severe fibrosis (S≥3) and cirrhosis (S=4) were 0.895, 0.877 and 0.854, the SWD that predicted substantial fibrosis (S≥2), severe fibrosis (S≥3) and cirrhosis (S=4) were 0.857, 0.815 and 0.791. SWE had better diagnostic performance than SWD in predicting severe fibrosis (S≥3) and cirrhosis (S=4).

Both SWE and SWD are useful, accurate and non-invasive methods for evaluating hepatic fibrosis in patients with hepatocellular carcinoma adapted to hepatectomy, SWE is a more accurate imaging modality than SWD in predicting severe fibrosis (S≥3) and cirrhosis (S=4).

Both SWE and SWD are useful, accurate and non-invasive methods for evaluating hepatic fibrosis in patients with hepatocellular carcinoma adapted to hepatectomy, SWE is a more accurate imaging modality than SWD in predicting severe fibrosis (S ≥ 3) and cirrhosis (S = 4).