Self-Exfoliating and Reactive Polymer (SERP) as A Protection Against Chemical Warfare Agents (CWAs)

According to the US army report, there are still significant numbers of stockpiles of chemical warfare agents (CWAs) produced during the Second World War. CWAs production and stockpiling were officially outlawed by the Chemical Weapons Convention of 1993. Nevertheless, some fanatics around the world use CWA as a weapon of mass destruction, such as the Sarin gas attack in Syria in 2013. Since the discovery that toxic pentavalent organophosphorus (OP) compounds has facilitated the development of CWAs as well as insecticides, research on developing protective materials against those toxins have become a priority. Simply, those poisonous molecules are referred to as a “nerve agent” because it prevents nervous system from transferring messages by forming a covalent bond with nerve enzyme, referred to as acetylcholinesterase. As a result of this chemical interference, organs are tightly constricted and muscles cannot relax displying noticeable physical symptoms: contraction of the pupils, excessive mucus, tears and sweat, nausea, vomiting, chest tightness, loss of bowel control like urinating and defecating, and eventually coma or death. Remarkably, even trivial amount of toxins (LD50: ~10 µg/kg) is enough to cause those severe results. Those OP-based compounds can be facilely hydrolyzed by strong base, such as sodium hydroxide and converted to non-toxic compounds. However, this chemical reaction is highly vigorous, generating excess heat. Therefore, it is important to develop a mild catalyst, which can be employed in fabrics or mask for protective garment applications. This can be achieved by selecting organo-based, nucleophiles such as amines, or pyridine-aldoxime. With these organo-based nucleophilic materials, it may be possible to fabricate personal protective equipment to prepare for sudden CWA attacks. The ultimate goal of this project is the fabrication of a protective polymer which can be easily coated on fabric, essentially creating a “second skin”. Protection can be achieved by blocking permeation of toxins through layer and simultaneously detoxifying molecules through chemical modification Furthermore, we challenge ourselves to regenerate fresh reactive layers by physically destructing contaminated area, referred to as a self-exfoliation. Chapter 1 briefly describes the concept of self-exfoliating and reactive polymer (SERP) layer as a protection against CWAs and how to experimentally accomplish and evaluate. Chapter 2 introduces a stimuli-responsive, self-exfoliating polymer with promising acid-sensitive, acetal/ketal-based crosslinkers that exhibit self-exfoliation at room temperature. Synthesis of acid-sensitive crosslinker and their acid-hydrolysis kinetics were studied. Chapter 3 focuses on developing a nucleophilic polymer as a CWA reactant to decontaminate organophosphate-based nerve agents. Chapter 4 evaluates a reactive polymer layer by investigating moisture-vapor transmission rate (MVTR), permeation of nerve agents through polymer films by using Surface-Enhanced Raman Spectroscopy (SERS). Chapter 5 describes conclusions and future work

Characterization of Vitamin B12 Supplementation and Correlation with Clinical Outcomes in a Large Longitudinal Study of Early Parkinson's Disease.

ObjectiveIn Parkinson's disease (PD), vitamin B12 levels are lower, and comorbid B12 deficiency has been associated with the development of neuropathy and early gait instability. Because little is known about B12 supplement use in PD, we sought to evaluate its use in a large PD cohort and, as an exploratory analysis, to determine whether baseline characteristics or disease progression differed according to B12 supplementation.MethodsWe utilized data collected as part of the National Institutes of Health Exploratory Trials in PD (NET-PD) Long-term Study (LS-1), a longitudinal study of 1,741 participants. We stratified subjects into 4 groups according to daily supplement use: no B12, multivitamin (MVI) containing < 100 μg B12, B12 ≥ 100 μg, and MVI + B12 ≥ 100 μg. Clinical outcomes were assessed at 3 years for each group using the Unified Parkinson's Disease Rating Scale (UPDRS), its subscores, and selected individual questions.ResultsOf the 1,147 participants who completed the 3-year visit, 41% took an MVI, 2% took B12, 3% took MVI + B12, and 54% reported taking no supplements. At 3 years, no significant differences in clinical outcomes were observed. However, there was a trend toward lower hazard ratios for developing sensory symptoms (UPDRS Item 17) in the MVI (p = 0.08) and B12 + MVI (p = 0.08) groups compared to that in the no supplement group.ConclusionThese results show that supplementation with vitamin B12 ≥ 100 μg is uncommon in early PD. The finding of a trend toward a lower hazard ratio for the development of sensory symptoms in those taking an MVI or B12 + MVI warrants further study

A cognitive-behavioral group intervention for parents of youth with chronic pain: Development, feasibility, and preliminary effectiveness.

Background: Caregiving for a youth with chronic pain is associated with unique stressors. Parents can play important roles for youth coping and functional outcomes, although parents often report uncertainty about how to support their youth and may benefit from learning evidence-based strategies. However, few parent-targeted interventions for pediatric chronic pain exist, particularly delivered within a group format. Objectives: The aims of this study were to describe the development of a parent-targeted group intervention within an outpatient interdisciplinary pediatric chronic pain clinic and to assess preliminary feasibility and effectiveness. Method: The development and content of the intervention are described in detail. Feasibility was assessed via enrollment, attendance, and attrition. Effectiveness was assessed via parent self-reported responses to pain and psychological flexibility (PF) before and after treatment. Results: Seventy parents consented and participated in the 5-week group intervention (2 hr/session). Preliminary results demonstrated adequate feasibility, with attendance rates at 61.4% and attrition rates at 24.3%. After treatment, there were significant moderate- to large-sized decreases in 3 of 4 parent behaviors assessed (protectiveness, monitoring, minimizing) and large-sized increases in PF. Conclusions: This group intervention for parents can produce positive changes in self-reported parent behavior and PF and may be a feasible way to intervene within an outpatient interdisciplinary setting. (PsycInfo Database Record (c) 2021 APA, all rights reserved

Characterization of vitamin D supplementation and clinical outcomes in a large cohort of early Parkinson's disease.

BackgroundVitamin D (VitD) deficiency is common in Parkinson's disease (PD) and has been raised as a possible PD risk factor. In the past decade, VitD supplementation for potential prevention of age related conditions has become more common. In this study, we sought to characterize VitD supplementation in early PD and determine as an exploratory analysis whether baseline characteristics or disease progression differed according to reported VitD use.MethodsWe analyzed data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD) Long-term study (LS-1), a longitudinal study of 1741 participants. Subjects were divided into following supplement groups according to subject exposure (6 months prior to baseline and during the study): no VitD supplement, multivitamin (MVI), VitD ≥400 IU/day, and VitD + multivitamin (VitD+MVI). Clinical status was followed using the Unified Parkinson's Disease Rating Scale, Symbol Digit Modalities Test, total daily levodopa equivalent dose, and Parkinson's Disease Questionnaire.ResultsAbout 5% of subjects took VitD alone, 7% took VitD+MVI, 34% took MVI alone, while 54% took no supplement. Clinical outcomes at 3 years were similar across all groups.ConclusionThis study shows VitD supplementation ≥400 IU/day was not common in early PD and that its use was similar to that seen in the US population. At 3 years, there was no difference in disease progression according to vitamin D supplement use

Effect of Exercise Intervention on Flow-Mediated Dilation in Overweight and Obese Adults: Meta-Analysis

The objective of this meta-analysis is to summarize the effect of exercise intervention on flow-mediated dilatation (FMD) in overweight and obese adults. We searched four electronic databases (PubMed/Medline, Scopus, and CINAHL) through June 2016 for relevant studies pertaining to the effectiveness of exercise intervention on FMD. Seventeen of the 91 studies identified met the inclusion criteria. Comprehensive Meta-Analysis software (version 3) was used to compute the standardized mean difference effect size (ES) and 95% CI using a random effects model. We calculated 34 ESs. We found that exercise intervention had medium and positive effects on FMD, with an overall ES of 0.522 (95% CI = 0.257, 0.786). Heterogeneity of ESs was observed ( = 239, ≤ 0.001, 2 = 86.19), and the effect was moderated by comorbidity ( = 6.39, df = 1, = 0.011). A large ES for the combination exercise, low intensity exercise, and comorbidity subgroups (ES = 0.82∼1.24) was found. We conclude that while exercise intervention significantly improves FMD in overweight and obese adults, the effect may depend on the different characteristics of exercise intervention and on participants’ demographics

Quality of Life in Youth with Chronic Pain: An Examination of Youth and Parent Resilience and Risk Factors

Objectives: Pediatric chronic pain has often been examined from a risk perspective, and relatively less is known about the individual and family-level resilience factors that help youth with chronic pain maintain their quality of life. This cross-sectional study: (a) examined the relations among purported youth and parent resilience (youth pain acceptance and pain self-efficacy, parent psychological flexibility) and risk (youth pain intensity, parent protectiveness) factors with youth quality of life, and (b) tested exploratory statistical mechanisms that may explain relations between parent and youth variables. Methods: Participants included 122 youth (10 to 17 years; M=14.26, SD=2.19) seen in an interdisciplinary pediatric chronic pain program and a parent. Youth completed measures of their average pain, quality of life, pain acceptance, and pain self-efficacy. Parents completed measures of their pain-related psychological flexibility and behavioral responses to pain (i.e., protectiveness, distraction, monitoring, minimizing). Results: Youth pain acceptance, pain self-efficacy, and parent psychological flexibility were highly positively correlated with each other, and with overall youth quality of life. Evidence for a buffering effect of pain acceptance and pain self-efficacy on the association between pain intensity and quality of life was not found. Protectiveness was found to be a significant mediator of the relation between parental psychological flexibility and youth quality of life. Discussion: The results are discussed in the context of the resilience-risk framework and current understandings of the role of parental factors for pediatric chronic pain

KHAN: Knowledge-Aware Hierarchical Attention Networks for Accurate Political Stance Prediction

The political stance prediction for news articles has been widely studied to mitigate the echo chamber effect -- people fall into their thoughts and reinforce their pre-existing beliefs. The previous works for the political stance problem focus on (1) identifying political factors that could reflect the political stance of a news article and (2) capturing those factors effectively. Despite their empirical successes, they are not sufficiently justified in terms of how effective their identified factors are in the political stance prediction. Motivated by this, in this work, we conduct a user study to investigate important factors in political stance prediction, and observe that the context and tone of a news article (implicit) and external knowledge for real-world entities appearing in the article (explicit) are important in determining its political stance. Based on this observation, we propose a novel knowledge-aware approach to political stance prediction (KHAN), employing (1) hierarchical attention networks (HAN) to learn the relationships among words and sentences in three different levels and (2) knowledge encoding (KE) to incorporate external knowledge for real-world entities into the process of political stance prediction. Also, to take into account the subtle and important difference between opposite political stances, we build two independent political knowledge graphs (KG) (i.e., KG-lib and KG-con) by ourselves and learn to fuse the different political knowledge. Through extensive evaluations on three real-world datasets, we demonstrate the superiority of DASH in terms of (1) accuracy, (2) efficiency, and (3) effectiveness.Comment: 12 pages, 5 figures, 10 tables, the Web Conference 2023 (WWW

Hypoxia-inducible factor-1 alpha regulates microglial functions affecting neuronal survival in the acute phase of ischemic stroke in mice

Cells universally adapt to ischemic conditions by turning on a transcription factor hypoxia-inducible factor (HIF), in which its role is known to differ widely across many different types of cells. Given that microglia have been reported as an essential mediator of neuroinflammation in many brain diseases, we examined the role of HIF in microglia in the progression of an acute phase of ischemic stroke by challenging our novel strains of myeloid-specific Hif-1 alpha or Hif-2 alpha knockout (KO) mice created by Cre-loxP system via middle cerebral artery occlusion (MCAO). We observed that Hif-1 alpha but not Hif-2 alpha KO mice exhibited an improved recovery compared to wild-type (WT) mice determined by behavioral tests. Immunostaining analyses revealed that there were increased numbers of both mature and immature neurons while microglia and apoptotic cells were significantly decreased in the dentate gyrus of Hif-1 alpha KO mice following MCAO. By isolating microglia with fluorescence-activated cell sorter, we found that HIF-1 alpha-deficient microglia were impaired in phagocytosis, reactive oxygen species (ROS) production, and tumor necrosis factor-alpha (TNF-alpha) secretion. We further observed a significant decrease in the expression of Cd36 and milk fat globule-epidermal growth factor 8 (Mfg-e8) genes, both of which contain hypoxia-responsive element (HRE). Knocking down either of these genes in BV2 microglial cells was sufficient to abrogate HIF-mediated increase in phagocytosis, production of intracellular ROS, or TNF-alpha secretion. Our results therefore suggest that HIF-1 alpha in microglia is a novel therapeutic target to protect neuronal survival following an acute phase of ischemic stroke.113Ysciescopu

Development of severe junctional bradycardia after dexmedetomidine infusion in a polypharmacy patient: a case report and literature review

The authors report a case of newly manifested severe junctional bradycardia following dexmedetomidine administration during spinal anesthesia in a polypharmacy patient. A 77-year-old woman receiving multiple medications, including a beta-blocker and a calcium channel blocker, underwent right total knee arthroplasty. After spinal anesthesia, intravenous dexmedetomidine was initiated as a sedative; her heart rate decreased, followed by junctional bradycardia (heart rate, 37–41 beats/min). Dexmedetomidine was discontinued, and a dopamine infusion was initiated. Seven hours after surgery, junctional bradycardia persisted; a temporary transvenous pacemaker was inserted, and the beta-blocker and calcium channel blocker were discontinued. The patient was discharged on postoperative day 11 without any sequelae. Anesthesiologists should be aware of dexmedetomidine’s inhibitory effects on the cardiac conduction system, especially in geriatric patients taking medications with negative chronotropic effects and in combination with neuraxial anesthesia