Organization and repair of the trigeminal system in the lamprey using fluorescent double labeling [abstract]

Abstract only availableFaculty Mentor: Andrew McClellan, Biological ScienceIn the CNS, many sensory and motor systems are topologically organized relative to various body structures.  For example, in humans, sensory inputs from the lower, middle, and upper parts of the body are received by the anterior, middle, and posterior somatosensory cortex, respectively.  Following injury in the CNS of higher vertebrates, such as birds and mammals, there is very little regeneration and recovery of function.  In contrast, in lower vertebrates, including lamprey, fish, and certain amphibians, substantial axonal regeneration occurs following CNS injuries, and there is virtually complete recovery of functions.  However, it is not known whether axonal regeneration restores the topological organization that may have existed prior to injury.  The trigeminal system is responsible for transmitting sensory and motor information from the head via axons in the trigeminal cranial nerve.  In the lamprey following injury of the trigeminal nerve, sensory and motor axons regenerate.  The purpose of the present study was to determine whether the trigeminal system of normal lamprey is topologically organized and whether regeneration of axons in injured trigeminal nerve restores this organization.  In normal larval lamprey, Alexa 488 dextran amine (Alexa) and Texas red dextran amine (TRDA), two different anatomical fluorescent tracers, were applied to the medial and lateral parts of the head, respectively.  This resulted in clear labeling of the medial and lateral parts of the trigeminal system in the brain with Alexa and TRDA, respectively.  Thus, in normal lamprey, the trigeminal system appears to be topologically organized.  If following injury of the trigeminal nerve, axonal regeneration restores this topological organization, this will indicate that regeneration in the lamprey is relatively precise and possibly controlled by specific guidance factors.  Identification of these guidance factors would greatly improve our understanding of the mechanisms that regulate axonal regeneration following CNS injury in vertebrate animals, including humans.

Associations between child maltreatment and adolescents’ health-related quality of life and emotional and social problems in low-income families, and the moderating role of social support

This study aimed to examine the associations between different types of child maltreatment and health-related quality of life (HRQoL) and emotional and social problems in adolescents, and to examine the moderating effect of social support on those associations. A cross-sectional survey was conducted between January and June 2016 in Hong Kong. The sample comprised 351 parent and adolescent dyads from low-income families. The parents reported on child maltreatment (physical abuse, psychological aggression, and neglect), and the adolescents reported on their HRQoL, emotional problems, and social problems. The adolescents’ perceived social support was included as a potential moderator. Results of the study show that child physical abuse was strongly associated with emotional and social problems (B = 0.91-1.45, p < .05). Lower overall HRQoL was associated with psychological aggression (B = −3.96, p < .05) and neglect (B = −4.14, p < .05). Physical functioning was affected by psychological aggression (B = −3.16, p < .05), and emotional functioning was affected by neglect (B = −4.82, p < .05). Social functioning was impacted by all three types of maltreatment (B = −9.16 to −5.26, p < .05). This study extends previous literature by showing the varying effects of different types of child maltreatment on children’s health in the context of low-income families. The findings of this study also support that peer social support may buffer the effects of child physical abuse on adolescents’ emotional and social problems

Associations between child maltreatment and adolescents’ health-related quality of life and emotional and social problems in low-income families, and the moderating role of social support

This study aimed to examine the associations between different types of child maltreatment and health-related quality of life (HRQoL) and emotional and social problems in adolescents, and to examine the moderating effect of social support on those associations. A cross-sectional survey was conducted between January and June 2016 in Hong Kong. The sample comprised 351 parent and adolescent dyads from low-income families. The parents reported on child maltreatment (physical abuse, psychological aggression, and neglect), and the adolescents reported on their HRQoL, emotional problems, and social problems. The adolescents’ perceived social support was included as a potential moderator. Results of the study show that child physical abuse was strongly associated with emotional and social problems (B = 0.91-1.45, p < .05). Lower overall HRQoL was associated with psychological aggression (B = −3.96, p < .05) and neglect (B = −4.14, p < .05). Physical functioning was affected by psychological aggression (B = −3.16, p < .05), and emotional functioning was affected by neglect (B = −4.82, p < .05). Social functioning was impacted by all three types of maltreatment (B = −9.16 to −5.26, p < .05). This study extends previous literature by showing the varying effects of different types of child maltreatment on children’s health in the context of low-income families. The findings of this study also support that peer social support may buffer the effects of child physical abuse on adolescents’ emotional and social problems

Concomitant Hepatorenal Dysfunction and Malnutrition in Valvular Heart Surgery:Long-Term Prognostic Implications for Death and Heart Failure

BACKGROUND: Strategies to improve long-term prediction of heart failure and death in valvular surgery are urgently needed because of an increasing number of procedures globally. This study sought to report the prevalence, changes, and prognostic implications of concomitant hepatorenal dysfunction and malnutrition in valvular surgery. METHODS AND RESULTS: In 909 patients undergoing valvular surgery, 3 groups were defined based on hepatorenal function (the modified model for end-stage liver disease excluding international normalized ratio score) and nutritional status (Controlling Nutritional Status score): normal hepatorenal function and nutrition (normal), hepatorenal dysfunction or malnutrition alone (mild), and concomitant hepatorenal dysfunction and malnutrition (severe). Overall, 32%, 46%, and 19% of patients were classified into normal, mild, and severe groups, respectively. Over a 4.1-year median follow-up, mild and severe groups in-curred a higher risk of mortality (hazard ratio [HR], 3.17 [95% CI, 1.40–7.17] and HR, 9.30 [95% CI, 4.09– 21.16], respectively), cardiovascular death (subdistribution HR, 3.29 [95% CI, 1.14– 9.52] and subdistribution HR, 9.29 [95% CI, 3.09– 27.99]), heart failure hospitalization (subdistribution HR, 2.11 [95% CI, 1.25– 3.55] and subdistribution HR, 3.55 [95% CI, 2.04– 6.16]), and adverse outcomes (HR, 2.11 [95% CI, 1.25– 3.55] and HR, 3.55 [95% CI, 2.04– 6.16]). Modified model for end-stage liver disease excluding international normalized ratio and controlling nutritional status scores improved the predictive ability of European System for Cardiac Operative Risk Evaluation (area under the curve: 0.80 versus 0.73, P<0.001) and Society of Thoracic Surgeons score (area under the curve: 0.79 versus 0.72, P=0.004) for all-cause mortality. One year following surgery (n=707), patients with persistent concomitant hepatorenal dysfunction and malnutrition (severe) experienced worse outcomes than those without.  CONCLUSIONS: Concomitant hepatorenal dysfunction and malnutrition was frequent and strongly linked to heart failure and mortality in valvular surgery

Embryonic Lethality in Mice Lacking the Nuclear Factor of Activated T Cells 5 Protein Due to Impaired Cardiac Development and Function

Nuclear factor of activated T cells 5 protein (NFAT5) is thought to be important for cellular adaptation to osmotic stress by regulating the transcription of genes responsible for the synthesis or transport of organic osmolytes. It is also thought to play a role in immune function, myogenesis and cancer invasion. To better understand the function of NFAT5, we developed NFAT5 gene knockout mice. Homozygous NFAT5 null (NFAT5−/−) mouse embryos failed to develop normally and died after 14.5 days of embryonic development (E14.5). The embryos showed peripheral edema, and abnormal heart development as indicated by thinner ventricular wall and reduced cell density at the compact and trabecular areas of myocardium. This is associated with reduced level of proliferating cell nuclear antigen and increased caspase-3 in these tissues. Cardiomyocytes from E14.5 NFAT5−/− embryos showed a significant reduction of beating rate and abnormal Ca2+ signaling profile as a consequence of reduced sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and ryanodine receptor (RyR) expressions. Expression of NFAT5 target genes, such as HSP 70 and SMIT were reduced in NFAT5−/− cardiomyocytes. Our findings demonstrated an essential role of NFAT5 in cardiac development and Ca2+ signaling. Cardiac failure is most likely responsible for the peripheral edema and death of NFAT5−/− embryos at E14.5 days

TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells

TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4+CD8+ double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in an uncontrolled expansion that was dependent on the nonclassical major histocompatibility complex (MHC) protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR)

Receptor-targeted liposome-peptide-siRNA nanoparticles represent a novel and efficient therapeutic approach to prevent conjunctival fibrosis.

There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye

A multicomponent intervention for the management of chronic pain in older adults: study protocol for a randomized controlled trial

Background: Studies have shown that physical interventions and psychological methods based on the cognitive behavioral approach are efficacious in alleviating pain and that combining both tends to yield more benefits than either intervention alone. In view of the aging population with chronic pain and the lack of evidence-based pain management programs locally, we developed a multicomponent intervention incorporating physical exercise and cognitive behavioral techniques and examined its long-term effects against treatment as usual (i.e., pain education) in older adults with chronic musculoskeletal pain in Hong Kong. Methods/design: We are conducting a double-blind, cluster-randomized controlled trial. A sample of 160 participants aged ≥ 60 years will be recruited from social centers or outpatient clinics and will be randomized on the basis of center/clinic to either the multicomponent intervention or the pain education program. Both interventions consist of ten weekly sessions of 90 minutes each. The primary outcome is pain intensity, and the secondary outcomes include pain interference, pain persistence, pain self-efficacy, pain coping, pain catastrophizing cognitions, health-related quality of life, depressive symptoms, and hip and knee muscle strength. All outcome measures will be collected at baseline, postintervention, and at 3 and 6 months follow-up. Intention-to-treat analysis will be performed using mixed-effects regression to see whether the multicomponent intervention alleviates pain intensity and associated outcomes over and above the effects of pain education (i.e., a treatment × time intervention effect). Discussion: Because the activities included in the multicomponent intervention were carefully selected for ready implementation by allied health professionals in general, the results of this study, if positive, will make available an efficacious, nonpharmacological pain management program that can be widely adopted in clinical and social service settings and will hence improve older people’s access to pain management services

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO