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1.  Bad Marriage, Broken Heart? Age and Gender Differences in the Link between Marital Quality and Cardiovascular Risks among Older Adults 
Working from a life course perspective, we develop hypotheses about age and gender differences in the link between marital quality and cardiovascular risk and test them using data from the first two waves of the National Social Life, Health, and Aging Project. The analytic sample includes 459 married women and 739 married men (aged 57–85 in the first wave) who were interviewed in both waves. We apply Heckman-type corrections for selection bias due to mortality and marriage. Cardiovascular risk is measured as hypertension, rapid heart rate, C-reactive protein, and general cardiovascular events. Results suggest that changes in marital quality and cardiovascular risk are more closely related for older married people than for their younger counterparts; and that the link between marital quality and cardiovascular risk is more pronounced among women than among men at older ages. These findings fit with the gendered life course perspective and cumulative disadvantage framework.
PMCID: PMC4325990  PMID: 25413802
2.  Influence of Hand Rearing and Bird Age on the Fecal Microbiota of the Critically Endangered Kakapo 
Applied and Environmental Microbiology  2014;80(15):4650-4658.
The critically endangered New Zealand parrot, the kakapo, is subject to an intensive management regime aiming to maintain bird health and boost population size. Newly hatched kakapo chicks are subjected to human intervention and are frequently placed in captivity throughout their formative months. Hand rearing greatly reduces mortality among juveniles, but the potential long-term impact on the kakapo gut microbiota is uncertain. To track development of the kakapo gut microbiota, fecal samples from healthy, prefledged juvenile kakapos, as well as from unrelated adults, were analyzed by using 16S rRNA gene amplicon pyrosequencing. Following the original sampling, juvenile kakapos underwent a period of captivity, so further sampling during and after captivity aimed to elucidate the impact of captivity on the juvenile gut microbiota. Variation in the fecal microbiota over a year was also investigated, with resampling of the original juvenile population. Amplicon pyrosequencing revealed a juvenile fecal microbiota enriched with particular lactic acid bacteria compared to the microbiota of adults, although the overall community structure did not differ significantly among kakapos of different ages. The abundance of key operational taxonomic units (OTUs) was correlated with antibiotic treatment and captivity, although the importance of these factors could not be proven unequivocally within the bounds of this study. Finally, the microbial community structure of juvenile and adult kakapos changed over time, reinforcing the need for continual monitoring of the microbiota as part of regular health screening.
PMCID: PMC4148800  PMID: 24837385
3.  Structural Proteins from Whelk Egg Capsule with Long Range Elasticity Associated with a Solid-state Phase Transition 
Biomacromolecules  2014;15(1):30-42.
The robust, proteinaceous egg capsules of marine prosobranch gastropods (genus Busycotypus) exhibit unique biomechanical properties such as high elastic strain recovery and elastic energy dissipation capability. Capsule material possesses long-range extensibility that is fully recoverable and is the result of a secondary structure phase transition from α-helix to extended β-sheet rather than of entropic (rubber) elasticity. We report here the characterization of the precursor proteins that make up this material. Three different proteins have been purified and analyzed, and complete protein sequences deduced from messenger ribonucleic acid (mRNA) transcripts. Circular dichroism (CD) and Fourier transform infrared (FTIR) spectra indicate that the proteins are strongly α-helical in solution and primary sequence analysis suggests that these proteins have a propensity to form coiled-coils. This is in agreement with previous wide-angle x-ray scattering (WAXS) and solid-state Raman spectroscopic analysis of mature egg capsules.
PMCID: PMC3956310  PMID: 24350603
Egg capsule; elasticity; coiled-coil; α-β transition; shape memory; self-healing
4.  Optimized DPPH assay in a detergent-based buffer system for measuring antioxidant activity of proteins 
MethodsX  2014;1:233-238.
The 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) assay is well established for the in vitro determination of antioxidant activity in food and biological extracts. The standard DPPH assay uses methanol or ethanol as solvents, or buffered alcoholic solutions in a ratio of 40%/60% (buffer/alcohol, v/v) to keep the hydrophobic hydrazyl radical and phenolic test compounds soluble while offering sufficient buffering capacity at different pHs tested. Following this protocol, we were unable to keep proteinaceous antioxidants soluble at different pHs to test for their antioxidant activity. Thus, the assay protocol was modified as follows to improve its utility: Non-ionic detergents were added to keep the DPPH radical soluble and to provide a mild and non-denaturing environment for the antioxidant protein.Maximal concentration of DPPH was limited to 100 μM to stay within the sensitivity range of the detector at the given wavelength (515 nm) and to increase the dynamic range of the assay.0.1 M citrate phosphate buffer was introduced to prevent experimental artifacts due to changing buffer compositions at different pHs
PMCID: PMC4268772  PMID: 25530949
DPPH radical; antioxidant proteins; non-ionic detergent; pH range
5.  Evaluating the efficacy of biological and conventional insecticides with the new ‘MCD bottle’ bioassay 
Malaria Journal  2014;13(1):499.
Control of mosquitoes requires the ability to evaluate new insecticides and to monitor resistance to existing insecticides. Monitoring tools should be flexible and low cost so that they can be deployed in remote, resource poor areas. Ideally, a bioassay should be able to simulate transient contact between mosquitoes and insecticides, and it should allow for excito-repellency and avoidance behaviour in mosquitoes. Presented here is a new bioassay, which has been designed to meet these criteria. This bioassay was developed as part of the Mosquito Contamination Device (MCD) project and, therefore, is referred to as the MCD bottle bioassay.
Presented here are two experiments that serve as a proof-of-concept for the MCD bottle bioassay. The experiments used four insecticide products, ranging from fast-acting, permethrin-treated, long-lasting insecticide nets (LLINs) that are already widely used for malaria vector control, to the slower acting entomopathogenic fungus, Beauveria bassiana, that is currently being evaluated as a prospective biological insecticide. The first experiment used the MCD bottle to test the effect of four different insecticides on Anopheles stephensi with a range of exposure times (1 minute, 3 minutes, 1 hour). The second experiment is a direct comparison of the MCD bottle and World Health Organization (WHO) cone bioassay that tests a subset of the insecticides (a piece of LLIN and a piece of netting coated with B. bassiana spores) and a further reduced exposure time (5 seconds) against both An. stephensi and Anopheles gambiae. Immediate knockdown and mortality after 24 hours were assessed using logistic regression and daily survival was assessed using Cox proportional hazards models.
Across both experiments, fungus performed much more consistently than the chemical insecticides but measuring the effect of fungus required monitoring of mosquito mortality over several days to a week. Qualitatively, the MCD bottle and WHO cone performed comparably, although knockdown and 24 hour mortality tended to be higher in some, but not all, groups of mosquitoes exposed using the WHO cone.
The MCD bottle is feasible as a flexible, low-cost method for testing insecticidal materials. It is promising as a tool for testing transient contact and for capturing the effects of mosquito behavioural responses to insecticides.
PMCID: PMC4300847  PMID: 25515850
Vector control; Olyset; Bendiocarb; Chlorfenapyr; Fungal entomopathogen; Resistance; WHOPES
6.  Perceived barriers and facilitators to increasing physical activity among people with musculoskeletal disorders: a qualitative investigation to inform intervention development 
Musculoskeletal conditions can impair people’s ability to undertake physical activity as they age. The purpose of this qualitative study was to investigate perceived barriers and facilitators to undertaking physical activity reported by patients accessing ambulatory hospital clinics for musculoskeletal disorders.
Patients and methods
A questionnaire with open-ended items was administered to patients (n=217, 73.3% of 296 eligible) from three clinics providing ambulatory services for nonsurgical treatment of musculoskeletal disorders. The survey included questions to capture the clinical and demographic characteristics of the sample. It also comprised two open-ended questions requiring qualitative responses. The first asked the participant to describe factors that made physical activity more difficult, and the second asked which factors made it easier for them to be physically active. Participants’ responses to the two open-ended questions were read, coded, and thematically analyzed independently by two researchers, with a third researcher available to arbitrate any unresolved disagreement.
The mean (standard deviation) age of participants was 53 (15) years; n=113 (52.1%) were male. A total of 112 (51.6%) participants reported having three or more health conditions; n=140 (64.5%) were classified as overweight or obese. Five overarching themes describing perceived barriers for undertaking physical activity were “health conditions”, “time restrictions”, “poor physical condition”, “emotional, social, and psychological barriers”, and “access to exercise opportunities”. Perceived physical activity facilitators were also aligned under five themes, namely “improved health state”, “social, emotional, and behavioral supports”, “access to exercise environment”, “opportunities for physical activities”, and “time availability”.
It was clear from the breadth of the data that meaningful supports and interventions must be multidimensional. They should have the capacity to address a variety of physical, functional, social, psychological, motivational, environmental, lifestyle, and other perceived barriers. It would appear that for such interventions to be effective, they should be flexible enough to address a variety of specific concerns.
PMCID: PMC4264601  PMID: 25584023
exercise; pain; comorbidity; lifestyle; sedentary; behavior
7.  Interference with Ca2+ release activated Ca2+ (CRAC) channel function delays T-cell arrest in vivo 
European journal of immunology  2013;43(12):3343-3354.
Entry of lymphocytes into secondary lymphoid organs (SLOs) involves intravascular arrest and intracellular calcium ion ([Ca2+]i) elevation. TCR activation triggers increased [Ca2+]i and can arrest T-cell motility in vitro. However the requirement for [Ca2+]i elevation in arresting T cells in vivo has not been tested. Here, we have manipulated the Ca2+ release-activated Ca2+ (CRAC) channel pathway required for [Ca2+]i elevation in T cells through genetic deletion of stromal interaction molecule (STIM) 1 or by expression of a dominant negative ORAI1 channel subunit (ORAI1-DN). Interestingly, the absence of CRAC did not interfere with homing of naïve CD4+ T cells to SLOs and only moderately reduced crawling speeds in vivo. T cells expressing ORAI1-DN lacked TCR activation induced [Ca2+]i elevation, yet arrested motility similar to control T cells in vitro. In contrast, antigen specific ORAI1-DN T cells had a two-fold delayed onset of arrest following injection of OVA peptide in vivo. CRAC channel function is not required for homing to SLOs, but enhances spatiotemporal coordination of TCR signaling and motility arrest.
PMCID: PMC3924891  PMID: 23939929
antigen recognition; calcium signaling; intravital microscopy and T-cell activation
8.  An early Phase II randomised controlled trial testing the effect on persecutory delusions of using CBT to reduce negative cognitions about the self: The potential benefits of enhancing self confidence 
Schizophrenia Research  2014;160(1-3):186-192.
Research has shown that paranoia may directly build on negative ideas about the self. Feeling inferior can lead to ideas of vulnerability. The clinical prediction is that decreasing negative self cognitions will reduce paranoia.
Thirty patients with persistent persecutory delusions were randomised to receive brief CBT in addition to standard care or to standard care (ISRCTN06118265). The six session intervention was designed to decrease negative, and increase positive, self cognitions. Assessments at baseline, 8 weeks (posttreatment) and 12 weeks were carried out by a rater blind to allocation. The primary outcomes were posttreatment scores for negative self beliefs and paranoia. Secondary outcomes were psychological well-being, positive beliefs about the self, persecutory delusions, social comparison, self-esteem, anxiety, and depression.
Trial recruitment and retention were feasible and the intervention highly acceptable to the patients. All patients provided follow-up data. Posttreatment there was a small reduction in negative self beliefs (Cohen's d = 0.24) and a moderate reduction in paranoia (d = 0.59), but these were not statistically significant. There were statistically significant improvements in psychological well-being (d = 1.16), positive beliefs about the self (d = 1.00), negative social comparison (d = 0.88), self-esteem (d = 0.62), and depression (d = 0.68). No improvements were maintained. No adverse events were associated with the intervention.
The intervention produced short-term gains consistent with the prediction that improving cognitions about the self will reduce persecutory delusions. The improvement in psychological well-being is important in its own right. We recommend that the different elements of the intervention are tested separately and that the treatment is lengthened.
PMCID: PMC4266450  PMID: 25468186
Paranoia; Delusions; Self-esteem; Well-being; Clinical trial
9.  Versatile tuning of supramolecular hydrogels through metal complexation of oxidation-resistant catechol-inspired ligands 
Soft matter  2013;9(43):10.1039/C3SM51824H.
The mussel byssal cuticle employs DOPA-Fe3+ complexation to provide strong, yet reversible crosslinking. Synthetic constructs employing this design motif based on catechol units are plagued by oxidation-driven degradation of the catechol units and the requirement for highly alkaline pH conditions leading to decreased performance and loss of supramolecular properties. Herein, a platform based on a 4-arm poly(ethylene glycol) hydrogel system is used to explore the utility of DOPA analogues such as the parent catechol and derivatives, 4-nitrocatechol (nCat) and 3-hydroxy-4-pyridinonone (HOPO), as structural crosslinking agents upon complexation with metal ions. HOPO moieties are found to hold particular promise, as robust gelation with Fe3+ occurs at physiological pH and is found to be largely resistant to oxidative degradation. Gelation is also shown to be triggered by other biorelevant metal ions such as Al3+, Ga3+ and Cu2+ which allows for tuning of the release and dissolution profiles with potential application as injectable delivery systems.
PMCID: PMC3838863  PMID: 24285981
10.  Correspondence of biological condition models of California streams at statewide and regional scales 
We used boosted regression trees (BRT) to model stream biological condition as measured by benthic macroinvertebrate taxonomic completeness, the ratio of observed to expected (O/E) taxa. Models were developed with and without exclusion of rare taxa at a site. BRT models are robust, requiring few assumptions compared with traditional modeling techniques such as multiple linear regression. The BRT models were constructed to provide baseline support to stressor delineation by identifying natural physiographic and human land use gradients affecting stream biological condition statewide and for eight ecological regions within the state, as part of the development of numerical biological objectives for California’s wadeable streams. Regions were defined on the basis of ecological, hydrologic, and jurisdictional factors and roughly corresponded with ecoregions. Physiographic and land use variables were derived from geographic information system coverages. The model for the entire state (n = 1,386) identified a composite measure of anthropogenic disturbance (the sum of urban, agricultural, and unmanaged roadside vegetation land cover) within the local watershed as the most important variable, explaining 56 % of the variance in O/E values. Models for individual regions explained between 51 and 84 % of the variance in O/E values. Measures of human disturbance were important in the three coastal regions. In the South Coast and Coastal Chaparral, local watershed measures of urbanization were the most important variables related to biological condition, while in the North Coast the composite measure of human disturbance at the watershed scale was most important. In the two mountain regions, natural gradients were most important, including slope, precipitation, and temperature. The remaining three regions had relatively small sample sizes (n ≤ 75 sites) and had models that gave mixed results. Understanding the spatial scale at which land use and land cover affect taxonomic completeness is imperative for sound management. Our results suggest that invertebrate taxonomic completeness is affected by human disturbance at the statewide and regional levels, with some differences among regions in the importance of natural gradients and types of human disturbance. The construction and application of models similar to the ones presented here could be useful in the planning and prioritization of actions for protection and conservation of biodiversity in California streams.
PMCID: PMC4226928  PMID: 25384371
Bioassessment; Macroinvertebrates; O/E; Monitoring; Boosted regression trees; Planning; Conservation; Spatial scale
11.  Regulation of Synaptic Transmission at the Caenorhabditis elegans M4 Neuromuscular Junction by an Antagonistic Relationship Between Two Calcium Channels 
G3: Genes|Genomes|Genetics  2014;4(12):2535-2543.
In wild-type Caenorhabditis elegans, the synapse from motor neuron M4 to pharyngeal terminal bulb (TB) muscles is silent, and the muscles are instead excited by gap junction connections from adjacent muscles. An eat-5 innexin mutant lacking this electrical connection has few TB contractions and is unable to grow well on certain foods. We showed previously that this defect can be overcome by activation of the M4 → TB synapse. To identify genes that negatively regulate synaptic transmission, we isolated new suppressors of eat-5. To our surprise, these suppressors included null mutations in NPQR-type calcium channel subunit genes unc-2 and unc-36. Our results are consistent with the hypothesis that Ca2+ entry through the NPQR-type channel inhibits synaptic transmission by activating the calcium-activated K+ channel SLO-1, thus antagonizing the EGL-19 L-type calcium channel.
PMCID: PMC4267947  PMID: 25378475
behavior; feeding; synaptic transmission; calcium channels; BK channel
12.  Antioxidant Efficacy and Adhesion Rescue by a Recombinant Mussel Foot Protein-6 
Biotechnology progress  2013;29(6):10.1002/btpr.1810.
Mytilus foot protein type 6 (mfp-6) is crucial for maintaining the reducing conditions needed for optimal wet adhesion in marine mussels. In this report we describe the expression and production of a recombinant Mytilus californianus foot protein type 6 variant 1 (rmfp-6.1) fused with a hexa-histidine affinity tag in Escherichia coli and its purification by affinity chromatography. Recombinant mfp-6 showed high purification yields of 5–6 mg/L cell culture and excellent solubility in low pH buffers that retard oxidation of its many thiol groups. Purified rmfp-6.1 protein showed high DPPH radical scavenging activity as compared to Vitamin C. Using the highly sensitive surface force apparatus (SFA) technique to measure interfacial surface forces in the nanoNewton range we show that rmfp-6.1 is also able to rescue the oxidation-dependent adhesion loss of mussel foot protein 3 (mfp-3) at pH 3. The adhesion rescue is related to a reduction of dopaquinone back to DOPA in mfp-3 which is the reverse reaction observed during the detrimental enzymatic browning process in fruits and vegetables. Broadly viewed, rmfp-6.1 has potential as a versatile antioxidant for applications ranging from personal products to anti-spoilants for perishable foods during processing and storage.
PMCID: PMC3864665  PMID: 24106182
Adhesion rescue; antioxidant; DOPA oxidation; recombinant mussel protein; thiol
13.  Simultaneous Quantification of Active Carbon- and Nitrogen-Fixing Communities and Estimation of Fixation Rates Using Fluorescence In Situ Hybridization and Flow Cytometry 
Applied and Environmental Microbiology  2014;80(21):6750-6759.
Understanding the interconnectivity of oceanic carbon and nitrogen cycles, specifically carbon and nitrogen fixation, is essential in elucidating the fate and distribution of carbon in the ocean. Traditional techniques measure either organism abundance or biochemical rates. As such, measurements are performed on separate samples and on different time scales. Here, we developed a method to simultaneously quantify organisms while estimating rates of fixation across time and space for both carbon and nitrogen. Tyramide signal amplification fluorescence in situ hybridization (TSA-FISH) of mRNA for functionally specific oligonucleotide probes for rbcL (ribulose-1,5-bisphosphate carboxylase/oxygenase; carbon fixation) and nifH (nitrogenase; nitrogen fixation) was combined with flow cytometry to measure abundance and estimate activity. Cultured samples representing a diversity of phytoplankton (cyanobacteria, coccolithophores, chlorophytes, diatoms, and dinoflagellates), as well as environmental samples from the open ocean (Gulf of Mexico, USA, and southeastern Indian Ocean, Australia) and an estuary (Galveston Bay, Texas, USA), were successfully hybridized. Strong correlations between positively tagged community abundance and 14C/15N measurements are presented. We propose that these methods can be used to estimate carbon and nitrogen fixation in environmental communities. The utilization of mRNA TSA-FISH to detect multiple active microbial functions within the same sample will offer increased understanding of important biogeochemical cycles in the ocean.
PMCID: PMC4249028  PMID: 25172848
14.  Boronate Complex Formation with Dopa Containing Mussel Adhesive Protein Retards pH-Induced Oxidation and Enables Adhesion to Mica 
PLoS ONE  2014;9(10):e108869.
The biochemistry of mussel adhesion has inspired the design of surface primers, adhesives, coatings and gels for technological applications. These mussel-inspired systems often focus on incorporating the amino acid 3,4-dihydroxyphenyl-L-alanine (Dopa) or a catecholic analog into a polymer. Unfortunately, effective use of Dopa is compromised by its susceptibility to auto-oxidation at neutral pH. Oxidation can lead to loss of adhesive function and undesired covalent cross-linking. Mussel foot protein 5 (Mfp-5), which contains ∼30 mole % Dopa, is a superb adhesive under reducing conditions but becomes nonadhesive after pH-induced oxidation. Here we report that the bidentate complexation of borate by Dopa to form a catecholato-boronate can be exploited to retard oxidation. Although exposure of Mfp-5 to neutral pH typically oxidizes Dopa, resulting in a>95% decrease in adhesion, inclusion of borate retards oxidation at the same pH. Remarkably, this Dopa-boronate complex dissociates upon contact with mica to allow for a reversible Dopa-mediated adhesion. The borate protection strategy allows for Dopa redox stability and maintained adhesive function in an otherwise oxidizing environment.
PMCID: PMC4193769  PMID: 25303409
15.  Children and adolescents referred for treatment of anxiety disorders: Differences in clinical characteristics 
Journal of Affective Disorders  2014;167(100):326-332.
Reports of the clinical characteristics of children and adolescents with anxiety disorders are typically based on community populations or from clinical samples with exclusion criterion applied. Little is known about the clinical characteristics of children and adolescents routinely referred for treatment for anxiety disorders. Furthermore, children and adolescents are typically treated as one homogeneous group although they may differ in ways that are clinically meaningful.
A consecutive series of children (n=100, aged 6–12 years) and adolescents (n=100, aged 13–18 years), referred to a routine clinical service, were assessed for anxiety and comorbid disorders, school refusal and parental symptoms of psychopathology.
Children with a primary anxiety disorder were significantly more likely to be diagnosed with separation anxiety disorder than adolescents. Adolescents with a primary anxiety disorder had significantly higher self and clinician rated anxiety symptoms and had more frequent primary diagnoses of social anxiety disorder, diagnoses and symptoms of mood disorders, and irregular school attendance.
Childhood and adolescence were considered categorically as distinct, developmental periods; in reality changes would be unlikely to occur in such a discrete manner.
The finding that children and adolescents with anxiety disorders have distinct clinical characteristics has clear implications for treatment. Simply adapting treatments designed for children to make the materials more ‘adolescent-friendly’ is unlikely to sufficiently meet the needs of adolescents.
•Children and adolescents with anxiety disorders have distinct characteristics.•Children have more diagnoses of separation anxiety disorder than adolescents.•Adolescents have more primary diagnoses of social anxiety disorder than children.•Adolescents have more severe symptoms of anxiety than children.•Adolescents have more comorbid mood disorders and school refusal than children.
PMCID: PMC4147961  PMID: 25016489
Anxiety; Childhood; Adolescence; Diagnoses; Comorbidities
16.  Can Palliative Home Care Reduce 30-Day Readmissions? Results of a Propensity Score Matched Cohort Study 
Journal of Palliative Medicine  2013;16(10):1290-1293.
This study examined the impact of palliative home nursing care on rates of hospital 30-day readmissions.
The electronic health record based retrospective cohort study was performed within home care and palliative home care programs. Participants were home care patients discharged from one of three urban teaching hospitals. Outcome measures were propensity score matched rates of hospital readmissions within 30 days of hospital discharge.
Of 406 palliative home care patients, matches were identified for 392 (96%). Of 15,709 home care patients, 890 were used at least once as a match for palliative care patients, for a total final sample of 1282. Using the matched sample we calculated the average treatment effect for treated patients. In this sample, palliative care patients had a 30-day readmission probability of 9.1% compared to a probability of 17.4% in the home care group (mean ATT: 8.3%; 95% confidence interval [CI] 8.0%–8.6%). This effect persisted after adjustment for visit frequency.
Palliative home care may offer benefits to health systems by allowing patients to remain at home and thereby avoiding 30-day rehospitalizations.
PMCID: PMC3791031  PMID: 24007348
17.  Social network properties and self-rated health in later life: comparisons from the Korean social life, health, and aging project and the national social life, health and aging project 
BMC Geriatrics  2014;14:102.
This paper has two objectives. Firstly, it provides an overview of the social network module, data collection procedures, and measurement of ego-centric and complete-network properties in the Korean Social Life, Health, and Aging Project (KSHAP). Secondly, it directly compares the KSHAP structure and results to the ego-centric network structure and results of the National Social Life, Health, and Aging Project (NSHAP), which conducted in-home interviews with 3,005 persons 57 to 85 years of age in the United States.
The structure of the complete social network of 814 KSHAP respondents living in Township K was measured and examined at two levels of networks. Ego-centric network properties include network size, composition, volume of contact with network members, density, and bridging potential. Complete-network properties are degree centrality, closeness centrality, betweenness centrality, and brokerage role.
We found that KSHAP respondents with a smaller number of social network members were more likely to be older and tended to have poorer self-rated health. Compared to the NSHAP, the KSHAP respondents maintained a smaller network size with a greater network density among their members and lower bridging potential. Further analysis of the complete network properties of KSHAP respondents revealed that more brokerage roles inside the same neighborhood (Ri) were significantly associated with better self-rated health. Socially isolated respondents identified by network components had the worst self-rated health.
The findings demonstrate the importance of social network analysis for the study of older adults’ health status in Korea. The study also highlights the importance of complete-network data and its ability to reveal mechanisms beyond ego-centric network data.
PMCID: PMC4236545  PMID: 25217892
Social networks; Density; Centrality; Self-rated health; South Korea; USA
18.  Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin 
Experimental brain research  1999;126(2):270-280.
Changes in brain electrical activity in response to cholinergic agonists, antagonists, or excitotoxic lesions of the basal forebrain may not be reflective entirely of changes in cholinergic tone, in so far as these interventions also involve noncholinergic neurons. We examined electrocortical activity in rats following bilateral intracerebroventricular administration of 192 IgG-saporin (1.8 μg/ventricle), a selective cholinergic immunotoxin directed to the low-affinity nerve growth factor receptor p75. The immunotoxin resulted in extensive loss of choline acetyl transferase (ChAT) activity in neocortex (80%–84%) and hippocampus (93%), with relative sparing of entorhinal-piriform cortex (42%) and amygdala (28%). Electrocortical activity demonstrated modest increases in 1- to 4-Hz power, decreases in 20- to 44-Hz power, and decreases in 4- to 8-Hz intra- and interhemispheric coherence. Rhythmic slow activity (RSA) occurred robustly in toxin-treated animals during voluntary movement and in response to physostigmine, with no significant differences seen in power and peak frequency in comparison with controls. Physostigmine significantly increased intrahemispheric coherence in lesioned and intact animals, with minor increases seen in interhemispheric coherence. Our study suggests that: (1) electrocortical changes in response to selective cholinergic deafferentation are more modest than those previously reported following excitotoxic lesions; (2) changes in cholinergic tone affect primarily brain electrical transmission within, in contrast to between hemispheres; and (3) a substantial cholinergic reserve remains following administration of 192 IgG-saporin, despite dramatic losses of ChAT in cortex and hippocampus. Persistence of a cholinergically modulated RSA suggests that such activity may be mediated through cholinergic neurons which, because they lack the p75 receptor, remain unaffected by the immunotoxin.
PMCID: PMC4134916  PMID: 10369149
Coherence; Entorhinal cortex; Cortex; Hippocampus; Amygdala; 192 IgG-saporin; Rat
19.  Rab14 regulation of claudin-2 trafficking modulates epithelial permeability and lumen morphogenesis 
Molecular Biology of the Cell  2014;25(11):1744-1754.
Epithelial permeability is regulated by targeted insertion and recycling of tight junction proteins. Rab14 regulates the lysosomal targeting of the leaky claudin, claudin-2, and depletion of Rab14 results in increased transepithelial resistance and aberrant morphogenesis in three-dimensional culture.
Regulation of epithelial barrier function requires targeted insertion of tight junction proteins that have distinct selectively permeable characteristics. The insertion of newly synthesized proteins and recycling of internalized tight junction components control both polarity and junction function. Here we show that the small GTPase Rab14 regulates tight junction structure. In Madin–Darby canine kidney (MDCK) II cells, Rab14 colocalizes with junctional proteins, and knockdown of Rab14 results in increased transepithelial resistance. In cells without Rab14, there are small changes in the trafficking of claudin-1 and occludin. In addition, there is substantial depletion of the leaky claudin, claudin-2, but not other tight junction components. The loss of claudin-2 is complemented by inhibition of lysosomal function, suggesting that Rab14 sorts claudin-2 out of the lysosome-directed pathway. MDCK I cells lack claudin-2 endogenously, and knockdown of Rab14 in these cells does not result in a change in transepithelial resistance, suggesting that the effect is specific to claudin-2 trafficking. Furthermore, leaky claudins have been shown to be required for epithelial morphogenesis, and knockdown of Rab14 results in failure to form normal single-lumen cysts in three-dimensional culture. These results implicate Rab14 in specialized trafficking of claudin-2 from the recycling endosome.
PMCID: PMC4038501  PMID: 24694596
20.  Literacy and Learning in Healthcare 
Pediatrics  2009;124(0 3):S275-S281.
The relationship between literacy and health outcomes are well documented in adult medicine, yet specific causal pathways are not entirely clear. Despite an incomplete understanding of the problem, numerous interventions have already been implemented with variable success. Many of the earlier strategies assumed the problem to originate from reading difficulties only. Given the timely need for more effective interventions, it is of increasing importance to reconsider the meaning of health literacy in order to advance our conceptual understanding of the problem and how best to respond. One potentially effective approach might involve recognizing the known associations between a larger set of cognitive and psychosocial abilities with functional literacy skills. We review the current health literacy definition and literature and draw upon relevant research from the fields of education, cognitive science, and psychology. In this framework, a research agenda is proposed that considers an individual's health learning capacity, referring to the broad constellation of cognitive and psychosocial skills patients or family members must draw upon to effectively promote, protect, and manage their own or a child's health. This new, related concept will ideally lead to more effective ways of thinking about health literacy interventions, including the design of health education materials, instructional strategies, and the delivery of healthcare services to support patients and families across the lifespan.
PMCID: PMC4131737  PMID: 19861481
Health literacy; literacy; learning; cognition; education
21.  Computational Fluid Dynamic Analysis of the Posterior Airway Space After Maxillomandibular Advancement For Obstructive Sleep Apnea Syndrome 
Evaluate the soft tissue change of the upper airway after maxillomandibular advancement (MMA) by computational fluid dynamics (CFD).
Materials and Methods
Eight OSAS patients who required MMA were recruited into this study. All participants had pre- and post-operative computed tomography (CT) and underwent MMA by a single oral and maxillofacial surgeon. Upper airway CT data sets for these 8 participants were created with high-fidelity 3-D numerical models for computational fluid dynamics (CFD). The 3-D models were simulated and analyzed to study how changes in airway anatomy affects pressure effort required for normal breathing. Airway dimensions, skeletal changes, Apnea-Hypopnea Index (AHI), and pressure efforts of pre- and post-operative 3-D models were compared and correlations interpreted.
After MMA, laminar and turbulent air flow was significantly decreased at every level of the airway. The cross-sectional areas at the soft palate and tongue base were significantly increased.
This study shows that MMA increases airway dimensions by the increasing the occipital base (Base) - pogonion (Pg) distance. An increase of the Base-Pg distance showed a significant correlation with an AHI improvement and a decreased pressure effort of the upper airway. Decreasing the pressure effort will decrease the breathing workload. This improves the condition of OSAS.
PMCID: PMC3720766  PMID: 23642544
obstructive sleep apnea syndrome (OSAS); sleep apnea; computational fluid dynamics (CFD); mesh generation; maxillomandibular advancement (MMA); image processing; hybrid meshes; computed tomography (CT)
22.  Layer-by-layer polyelectrolyte deposition: a mechanism for forming biocomposite materials 
Biomacromolecules  2013;14(6):1715-1726.
Complex coacervates prepared from poly-Aspartic acid (polyAsp) and poly-L-Histidine (polyHis) were investigated as models of the metastable protein phases used in the formation of biological structures such as squid beak. When mixed, polyHis and polyAsp form coacervates whereas poly-L-Glutamic acid (polyGlu) forms precipitates with polyHis. Layer-by-layer (LbL) structures of polyHis-polyAsp on gold substrates were compared with those of precipitate-forming polyHis-polyGlu by monitoring with iSPR and QCM-D. PolyHis-polyAsp LbL was found to be stiffer than polyHis-polyGlu LbL with most water evicted from the structure but with sufficient interfacial water remaining for molecular rearrangement to occur. This thin layer is believed to be fluid and like preformed coacervate films, capable of spreading over both hydrophilic ethylene glycol as well as hydrophobic monolayers. These results suggest that coacervate-forming polyelectrolytes deserve consideration for potential LbL applications and point to LbL as an important process by which biological materials form.
PMCID: PMC4104756  PMID: 23600626
Complex coacervates; biomaterials; iSPR; QCM; polyelectrolytes; Layer-by-layer
23.  Identification and independent validation of a stable yield and thousand grain weight QTL on chromosome 6A of hexaploid wheat (Triticum aestivum L.) 
BMC Plant Biology  2014;14:191.
Grain yield in wheat is a polygenic trait that is influenced by environmental and genetic interactions at all stages of the plant’s growth. Yield is usually broken down into three components; number of spikes per area, grain number per spike, and grain weight (TGW). In polyploid wheat, studies have identified quantitative trait loci (QTL) which affect TGW, yet few have been validated and fine-mapped using independent germplasm, thereby having limited impact in breeding.
In this study we identified a major QTL for TGW, yield and green canopy duration on wheat chromosome 6A of the Spark x Rialto population, across 12 North European environments. Using independent germplasm in the form of BC2 and BC4 near isogenic lines (NILs), we validated the three QTL effects across environments. In four of the five experiments the Rialto 6A introgression gave significant improvements in yield (5.5%) and TGW (5.1%), with morphometric measurements showing that the increased grain weight was a result of wider grains. The extended green canopy duration associated with the high yielding/TGW Rialto allele was comprised of two independent effects; earlier flowering and delayed final maturity, and was expressed stably across the five environments. The wheat homologue (TaGW2) of a rice gene associated with increased TGW and grain width was mapped within the QTL interval. However, no polymorphisms were identified in the coding sequence between the parents.
The discovery and validation through near-isogenic lines of robust QTL which affect yield, green canopy duration, thousand grain weight, and grain width on chromosome 6A of hexaploid wheat provide an important first step to advance our understanding of the genetic mechanisms regulating the complex processes governing grain size and yield in polyploid wheat.
PMCID: PMC4105860  PMID: 25034643
Wheat; Yield; Grain size; Grain shape; Green canopy duration; QTL; NILs
24.  Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions 
Medical hypotheses  2008;72(1):14-22.
While it is well established that the principal ascending pathways for pain originate in the dorsal horn of the spinal cord and in the medulla, the control and sensitivity to pain may reside in additional neurological loci, especially in the mesolimbic system of the brain (i.e., a reward center), and a number of genes and associated polymorphisms may indeed impact pain tolerance and or sensitivity. It is hypothesized that these polymorphisms associate with a predisposition to intolerance or tolerance to pain. It is further hypothesized that identification of certain gene polymorphisms provides a unique therapeutic target to assist in the treatment of pain. It is hereby proposed that pharmacogenetic testing of certain candidate genes (i.e., mu receptors, PENK etc.) will result in pharmacogenomic solutions personalized to the individual patient, with potential improvement in clinical outcomes.
PMCID: PMC4098664  PMID: 18951726
25.  Carbon Monoxide Poisoning and Flooding: Changes in Risk Before, During and After Flooding Require Appropriate Public Health Interventions 
PLoS Currents  2014;6:ecurrents.dis.2b2eb9e15f9b982784938803584487f1.
Introduction While many of the acute risks posed by flooding and other disasters are well characterised, the burden of carbon monoxide (CO) poisoning and the wide range of ways in which this avoidable poisoning can occur around flooding episodes is poorly understood, particularly in Europe. The risk to health from CO may continue over extended periods of time after flooding and different stages of disaster impact and recovery are associated with different hazards. Methods A review of the literature was undertaken to describe the changing risk of CO poisoning throughout flooding/disaster situations. The key objectives were to identify published reports of flood-related carbon monoxide incidents that have resulted in a public health impact and to categorise these according to Noji’s Framework of Disaster Phases (Noji 1997); to summarise and review carbon monoxide incidents in Europe associated with flooding in order to understand the burden of CO poisoning associated with flooding and power outages; and to summarise those strategies in Europe which aim to prevent CO poisoning that have been published and/or evaluated. The review identified 23 papers which met its criteria. The team also reviewed and discussed relevant government and non-government guidance documents. This paper presents a summary of the outcomes and recommendations from this review of the literature. Results Papers describing poisonings can be considered in terms of the appliance/source of CO or the circumstances leading to poisoning.The specific circumstances identified which lead to CO poisoning during flooding and other disasters vary according to disaster phase. Three key situations were identified in which flooding can lead to CO poisoning; pre-disaster, emergency/recovery phase and post-recovery/delayed phase. These circumstances are described in detail with case studies. This classification of situations is important as different public health messages are more appropriate at different phases of a disaster. The burden of disease from poisoning caused by each potential source and at each phase of a disaster is different. CO poisoning is not compulsory and deaths associated with a flood but delayed for a period of months, for example due to a damaged boiler, may never be attributed to the flood as surveillance often ends once the floodwaters recede. The problem of under–reporting is crucial to our understanding of flooding-related poisoning. The indoor use of portable generators, cooking and heating appliances designed for use outdoors during periods of loss of mains power or gas is a particular problem. In the recovery phase, equipment for pumping, dehumidifying and drying out of properties poses a new risk. In the long term, mortality and morbidity associated with the renewed use of boilers which may have suffered covert damage in flooding is recognised but very difficult to quantify. Papers evaluating interventions were not found and where literature exists on prevention of CO poisoning in disaster situations, it is from the USA. Conclusions This paper for the first time describes the different risks of CO poisoning posed by the different phases of a disaster. There is a specific need to recognise that any room in a building can harbour a CO emitting appliance in flooding; wood burners and rarely used chimney flues may become particularly problematic following a flood. Recommendations 1) Public health workers and policy makers should consider establishing toolkits using the CDC toolkit approach; the acceptability of any intervention must be evaluated further to guide informed policy. 2) CO poisoning must form part of syndromic and event based surveillance systems for flooding and should be included in measures of the health impact of flooding. 3) CO monitors in the domestic environment should be sited not only in proximity to known CO emitters but also in locations where mobile or short term CO emitting appliances may be placed, including woodburners and infrequently used fireplaces.
PMCID: PMC4096798  PMID: 25045587

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