Multifunctional stimuli responsive polymer-gated iron and gold-embedded silica nano golf balls:Nanoshuttles for targeted on-demand theranostics

Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis, efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles （NP）-embedded silica nanoshuttles （MGNSs） with nanopores on their surface. Fluorescently labeled Doxombicin （DOX）, a cancer drug, was loaded in the MGNSs as a payload. DOX loaded MGNSs were encapsulated in heat and pH sensitive polymer P（NIPAM-co- MAA） to enable controlled release of the payload. Magnetically-guided transport of MGNSs was examined in： （a） a glass capillary tube to simulate their delivery via blood vessels; and （b） porous hydrogels to simulate their transport in composite human tissues, including bone, cartilage, tendon, muscles and blood-brain barrier {BBB）. The viscoelastic properties of hydrogels were examined by atomic force microscopy （AFM）. Cellular uptake of DOX- loaded MGNSs and the subsequent pH and temperature-mediated release were demonstrated in differentiated human neurons derived from induced pluripotent stem cells （iPSCs） as well as epithelial HeLa cells. The presence of embedded iron and gold NPs in silica shells and polymer-coating are supported by SEM and TEM. Fluorescence spectroscopy and microscopy documented DOX loading in the MGNSs. Time-dependent transport of MGNSs guided by an external magnetic field was observed in both glass capillary tubes and in the porous hydrogel. AFM results affirmed that the stiffness of the hydrogels model the rigidity range from soft tissues to bone. pH and temperature-dependent drug release analysis showed stimuli responsive and gradual drug release. Cells＇ viability MTT assays showed that MGNSs are non-toxic. The cell death from on-demand DOX release was observed in both neurons and epithelial cells even though the drug release efficiency was higher in neurons. Therefore, development of smart nanoshuttles have significant translational potential for controlled delivery of theranostics＇ payloads and precisely guided transport in specified tissues and organs （for example, bone, cartilage, tendon, bone marrow, heart, lung, liver, kidney, and brain） for highly efficient personalized medicine applications.

Peritraumatic Behavior Questionnaire- Observer Rated: Validation of the objective version of a measure for combatrelated peritraumatic stress

AIM: To validate the first third-person-rated measure assessing combat-related peritraumatic stress symptoms and evaluate its psychometric properties and war-zone applicability.METHODS: The valid assessment of peritraumatic symptoms in the theater of military operations represents a significant challenge in combat-related, mental health research, which mainly relies on retrospective, subjective self-report ratings. This longitudinal observational study used data from actively deployed troops to correlate third-person observer ratings of deployment peritraumatic behaviors [Peritraumatic Behavior Questionnaire- Observer Rated(PBQ-OR)] collected on a bimonthly basis with post-deployment(1-wk follow-up) ratings of the previously validated PBQ self-rate version(PBQ-SR), and(3-mo follow-up) clinician assessed and self-report posttraumatic stress disorder(PTSD) symptoms(Clinician Administered PTSD Scale, PTSD Checklist). Cronbach's alpha(α) and correlation coefficients were calculated to assess internal reliability and concurrent validity respectively. RESULTS: Eight hundred and sixty male Marines were included in this study after signing informed consents at pre-deployment(mean age 23.2 ± 2.6 years). Although our findings were limited by an overall sparse return rate of PBQ-OR ratings, the main results indicate satisfactory psychometric properties with good internal consistency for the PBQ-OR(α = 0.88) and high convergent and concurrent validity with 1-wk post-deployment PBQSR ratings and 3-mo posttraumatic stress symptoms. Overall, later PBQ-OR report date was associated with higher correlation between PBQ-OR and postdeployment measures. Kappa analysis between PBQOR and PBQ-SR single items, showed best agreement in questions relating of mortal peril, desire for revenge, and experience of intense physical reactions. Logistic regression demonstrated satisfactory predictive validity of PBQ-OR total score with respect to PTSD caseness(OR = 1.0513; 95%CI: 1.011-1.093; P = 0.02).CONCLUSION: Since no comparable tools have been developed, PBQ-OR could be valuable as real-time screening tool for earlier detection of Service Members at risk.

Contained colonic perforation due to cecal retroflexion

Complications of cecal retroflexion performed during colonoscopy have not previously been reported to occur. We report a case of contained colonic perforation secondary to using cecal retroflexion technique to examine the colon, and review available published reports of complications associated with this technique. We conclude that complications may rarely occur with use of cecal retroflexion, and that the clinical benefit of this technique is uncertain.

Does Positive Airway Pressure Therapy Result in Improved Sleep Quality?

Introduction: Positive airway pressure (PAP) therapy is the gold-standard for obstructive sleep apnea (OSA) management. While it is known that PAP is efficacious for controlling breathing events during sleep when it is worn at the right pressure for the amount of time prescribed, there is less clear data on how well it improves sleep quality. There are few studies that have examined the effectiveness of PAP therapy on sleep quality. Methods: OSA participants (n = 241) from a larger trial examining a PAP adherence were included. Participants were provided with PAP instruction and followed at 2 months and 4 months. PAP adherence was measured as the number of hours per night at prescribed pressure, an objective measure of treatment adherence. The Pittsburgh Sleep Quality Index (PSQI) was used as the primary measure of sleep quality. Results: The PSQI was significantly correlated with PAP adherence at both the 2-month and 4-month time points, such that lower sleep quality was associated with lower PAP use. This finding held for the sleep disturbance subscale of the PSQI. Over 55% of those using PAP therapy at the 4-month time point continued to report significantly disturbed sleep. Discussion: This study shows that PAP therapy does not appear to improve sleep quality to a degree that would be expected. Over half of those patients using PAP therapy still experienced disturbed sleep. Whether the disturbed sleep is directly attributable to the PAP device itself or to disturbed sleep secondary to uncontrolled OSA when PAP is not worn is worthy of further investigation.

急诊科心力衰竭患者中的“灰色带”BNP水平:来自多中心研究REDHOT(快速的急诊科心力衰竭门诊患者试验)的结果

目的:本研究在已确诊的充血性心力衰竭(CHF)患者中就相关临床因素、查知严重程度和预后方面,评价B型利钠肽(BNP)水平“灰色带”(100～500ng/L)。背景:“灰色带”BNP水平可能诊断界定模糊,其在已确诊的CHF患者中的意义尚未明确。方法:REDHOT是一项全国性、前瞻性研究。

Alginate hydrogel cross-linked by Ca^(2+)to promote spinal cord neural stem/progenitor cell differentiation and functional recovery after a spinal cord injuryhh

Alginate capillary hydrogels seeded with differentiated cells can fill the lesion cavity and promote axonal regeneration after grafting into the injured spinal cord.Neural stem/progenitor cells(NSPCs)can potentially repair the spinal cord;however,effects of alginate hydrogels(AHs)on NSPCs remain unknown.In this study,we fabricated AHs cross-linked by Ca^(2+)and seeded hydrogels with rat embryonic day 14 NSPCs.Immunocytochemistry and electron microscopy show that NSPCs survive,proliferate and differentiate into neurons in vitro within the capillaries.After transplantation into an acute T8 complete spinal cord transection site in adult rats,approximately one-third(38.3%)of grafted cells survive and differentiate into neurons(40.7%),astrocytes(26.6%)and oligodendrocytes(28.4%)at 8weeks post-grafting.NSPCs promote the growth of host axons within the capillaries in a time-dependent manner.Host axons make synapse-like contacts with NSPC-derived neurons within the hydrogel channels,and graft-derived axons extend into the host white and gray matter making putative synapses.This is paralleled by improved electrophysiological conductivity across the lesion and partial hindlimb locomotor recovery.