Strausswilcox2977

To utilize noninvasive collection of amniotic fluid in the setting of preterm premature rupture of membranes (PPROMs) to report the time concentration profile of azithromycin in amniotic fluid over 7 days from a single dose, and evaluate the correlation between azithromycin concentration and inflammatory markers in amniotic fluid. Prospective cohort study of five pregnant patients admitted with PPROMs and treated with a single 1 g oral azithromycin dose. Amniotic fluid was collected from pads and used to quantify azithromycin concentration as well as TNFa, IL-1a, IL-1b, IL-6, IL-8, and IL-10 concentrations. Primary outcome was time/concentration profile of azithromycin in amniotic fluid. Secondary outcome included correlation between azithromycin concentration and cytokine concentrations. Five patients were enrolled. Mean gestational age on admission with PPROM was 27.5 ± 2.3 weeks with a median latency of 7 days (interquartile range [IQR] = 4-13). A median of two samples/day (IQR = 1-3) were collected per participant. Azithromycin was quantified in duplicate; intra-assay coefficient of variation was 17%. Azithromycin concentration was less than 60 ng/ml after day 3. Azithromycin concentration was positively correlated with IL-8 (r = 0.38, p = 0.03), IL1a (r = 0.39, p = 0.03), and IL-1b (r = 0.36, p = 0.04) in amniotic fluid. Azithromycin is detectable in amniotic fluid over 7 days from a single 1 g maternal dose, however, it is not sustained over the range of minimum inhibitory concentration for common genitourinary flora. Based on correlation with specific cytokines, azithromycin penetration in amniotic fluid may relate to maternal monocyte concentration in amniotic fluid in the setting of PPROM.3D bioprinting is an emerging additive manufacturing technique to fabricate constructs for human disease modeling. However, current cell-laden bioinks lack sufficient biocompatibility, printability, and structural stability needed to translate this technology to preclinical and clinical trials. Here, a new class of nanoengineered hydrogel-based cell-laden bioinks is introduced, that can be printed into 3D, anatomically accurate, multicellular blood vessels to recapitulate both the physical and chemical microenvironments of native human vasculature. Navitoclax cell line A remarkably unique characteristic of this bioink is that regardless of cell density, it demonstrates a high printability and ability to protect encapsulated cells against high shear forces in the bioprinting process. 3D bioprinted cells maintain a healthy phenotype and remain viable for nearly one-month post-fabrication. Leveraging these properties, the nanoengineered bioink is printed into 3D cylindrical blood vessels, consisting of living co-culture of endothelial cells and vascular smooth muscle cells, providing the opportunity to model vascular function and pathophysiology. Upon cytokine stimulation and blood perfusion, this 3D bioprinted vessel is able to recapitulate thromboinflammatory responses observed only in advanced in vitro preclinical models or in vivo. Therefore, this 3D bioprinted vessel provides a potential tool to understand vascular disease pathophysiology and assess therapeutics, toxins, or other chemicals.The aim of this meta-analysis was to review systematically and to identify the relationship between the severity and location of white matter hyperintensities (WMHs) and the degree of cognitive decline in patients with Parkinson's disease (PD). We searched the PubMed, EMBASE, Web of Science, Ovid, and Cochrane Library databases for clinical trials of the severity and location of WMHs on the degree of cognitive impairment in PD through October 2020. We conducted the survey to compare the association of WMH burden in patients with PD with mild cognitive impairment (PD-MCI) versus those with normal cognition (PD-NC) and in patients with PD with dementia (PDD) versus those with PD without dementia (PD-ND). Nine studies with PD-MCI versus PD-NC and 10 studies with PDD versus PD-ND comparisons were included. The WMH burden in PD-MCI patients was significantly different compared to that in PD-NC patients (standard mean difference, SMD = 0.39, 95% CI 0.12 to 0.66, p = 0.005), while there was no correlation shown in the age-matched subgroup of the comparison. In addition, PDD patients had a significantly higher burden of WMHs (SMD = 0.8, 95% CI 0.44 to 1.71, p less then 0.0001), especially deep white matter hyperintensities (SMD = 0.54, 95% CI 0.36 to 0.73, p less then 0.00001) and periventricular hyperintensities (SMD = 0.70, 95% CI 0.36 to 1.04, p less then 0.0001), than PD-NC patients, regardless of the adjustment of age. WMHs might be imaging markers for cognitive impairment in PDD but not in PD-MCI, regardless of age, vascular risk factors, or race. Further prospective studies are needed to validate the conclusions.

Chronic obstructive pulmonary disease (COPD) increases susceptibility to sleep disturbances. This study aimed to evaluate the association between COPD severity criteria with sleep quality.

One hundred fifty-eight patients in Rasul Akram Hospital of Iran University of Medical Sciences, Tehran, Iran, from April 2019 to March 2021 diagnosed with COPD were examined using the Pittsburgh Sleep Quality Index (PSQI), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnoea scale, spirometry and pulse oximetry.

Of 158 subjects, 125 patients were male (79%), and 33 were female (21%). The mean subject's age and FEV1/FVC ratio were 62.6± 11.5 and 65.6± 14.9%, respectively. The mean CAT scoring and Spo2 saturation reported 16.2±7 and 91.5±10.8%, respectively. The mean PSQI score was 8.2±3.8. The association between PSQI score with FEV1 and FEV1/FVC ratio was not statistically significant (p=0.64 and 0.58, respectively), whereas the association between PSQI scores with CAT score (p˂0.0001, r

=0.51) and dyspnoea severity (p˂0.0001, r

=0.29) were statistically significant. The patients with higher CAT score demonstrated poor sleep quality, particularly in longer sleep latency (p=0.001, r

=0.056), bad subjective sleep quality (p˂0.0001, r

=0.286), lower sleep efficiency (p=0.002, r

=0.077), higher sleep disturbance (p˂0.0001, r

=0.225), daytime dysfunction (p˂0.0001, r

=0.259) and sleep medication intake times a week (p=0.01, r

=0.069). Dyspnoea severity was attributed to bad subjective sleep quality (p˂0.0001, r

=0.069), higher sleep disturbances (p=0.005, r

=0.08), and daytime dysfunction (p˂0.0001, r

=0.108).

The PSQI has a significant association with the CAT and mMRC for COPD patients and is linked to the disease's severity.

The PSQI has a significant association with the CAT and mMRC for COPD patients and is linked to the disease's severity.Lactate, as the most abundant component with concentrations of 4-40 mm in tumors, contributes to the regulation of metabolic pathways, angiogenesis, and immunosuppression, exhibiting remarkable potential in cancer treatment. Therefore, a codelivery strategy that combined the cascaded enzymes Lactate oxidase/Catalase (LOx/CAT) and vascular endothelial growth factor (VEGF) siRNA (siVEGF) to suppress tumor proliferation and angiogenesis synergistically is creatively proposed. In brief, the cationic liposomes (LIP) encapsulated with LOx/CAT and siVEGF via hydrophilic interaction and electrostatic adsorption followed by coating with PEGylated phenylboronic acid (PP) is established (PPL@[LOX+CAT]). Moreover, a simple 3-aminophenylboronic acid (PBA)-shielded strategy via fructose (Fru) is applied to further enhance the targeting efficiency in the tumor site. The obtained co-encapsulated nanoparticles (NPs) can simultaneous intracellular release of LOx/CAT and siVEGF, and the collaborative use of LOx and CAT can promote lactate consumption even under a hypoxic tumor microenvironment (TME) without producing systemic toxicity. The combined application of lactate depletion and VEGF silencing demonstrated the efficient migration suppression of 4T1 cells in vitro and superior antitumor and antimetastatic properties in vivo. This work offers a promising tumor treatment strategy via integrating cascaded enzymes and gene therapy, and explores a promising therapy regimen for 4T1 triple-negative breast cancer.A wound dressing is a sterile pad or compress that is used in direct contact with a wound to help it heal and prevent further issues or complications. Though wound healing is an intricate dynamic process that involves multiple biomolecular species, conventional wound dressings have a limited ability to provide timely information of abnormal conditions, missing the best time for early treatment. The current perspective presents and discusses the design and development of smart wound dressings that are integrated with multifunctional materials, wearable sensors and drug delivery systems as well as their application ranging from wound monitoring to timely application of therapeutics. The perspective also discusses the ongoing challenges and exciting opportunities associated with the development of wearable sensor-based smart wound dressing and provide critical insights into wound healing monitoring and management.Highly evolved substrate channels in natural enzymes facilitate the rapid capture of substrates and direct transfer of intermediates between cascaded catalytic units, thus rationalizing their efficient catalysis. In this study, a nanoscale ordered mesoporous Ce-based metal-organic framework (OMUiO-66(Ce)) is designed as an artificial substrate channel, where MnO2 is coupled to Ce-O clusters as a super-active catalase (CAT). An in situ soft template reduction strategy is developed to deposit well-dispersed and exposed MnO2 in the mesochannels of OMUiO-66(Ce). Several synthesis parameters are optimized to minimize the particle size to ≈150 nm for efficient intracellular endocytosis. The mesochannels provide interaction guidance that not only rapidly drove H2 O2 substrates to CAT-like catalytic centers, but also seamlessly transfer H2 O2 intermediates between superoxide dismutase-like and CAT-like biocatalytic cascades. As a result, the biomimetic system exhibits high efficiency, low dosage, and long-lasting intracellular antioxidant function. Under disease-related oxidative stress, the artificial substrate channels promote the rate of the reactions catalyzed by MnO2 , which exceeds that of the reactions catalyzed by natural CAT. Based on this observation, a set of design rules for substrate channels are proposed to guide the rational design of super-active biomimetic systems.Mitogen-activated protein kinase (MAPK) signaling plays a significant role in reactive oxygen species (ROS) production. The authors have previously shown that Brahma-related gene 1 (BRG1), a chromatin remodeling protein, contributes to hepatic ROS accumulation in multiple animal and cellular models of liver injury. Here it is reported that DNA damage-induced transcript 4 (DDIT4) is identified as a direct transcriptional target for BRG1. DDIT4 overexpression overcomes BRG1 deficiency to restore ROS production whereas DDIT4 knockdown phenocopies BRG1 deficiency in suppressing ROS production in vitro and in vivo. Mechanistically, DDIT4 coordinates the assembly of the p38-MAPK signaling complex to drive ROS production in an S-nitrosylation dependent manner. Molecular docking identifies several bioactive DDIT4-inteacting compounds including imatinib, nilotinib, and nateglinide, all of which are confirmed to attenuate hepatic ROS production, dampen p38-MAPK signaling, and ameliorate liver injury by influencing DDIT4 S-nitrosylation.