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Background: We evaluated the feasibility of asking pregnant women to self-collect and ship respiratory specimens., Methods: In a preliminary laboratory study, we compared the RT-PCR cycle threshold (CT) values of influenza A and B viruses incubated at 4 storage temperatures (from 4 to 35°C) for 6 time periods (8, 24, 48, 72, and 168 hours and 30 days), resulting in 24 conditions that were compared to an aliquot tested after standard freezing (-20°C) (baseline condition). In a subsequent pilot study, during January-February, 2014, we delivered respiratory specimen collection kits to 53 pregnant women with a medically attended acute respiratory illness using three delivery methods., Results: CT values were stable after storage at temperatures <27°C for up to 72 hours for influenza A viruses and 48 hours for influenza B viruses. Of 53 women who received kits during the pilot, 89% collected and shipped nasal swabs as requested. However, 30% (14/47) of the women took over 2 days to collect and ship their specimen. The human control gene, ribonuclease P (RNase P), was detected in 100% of nasal swab specimens. However, the mean CT values for RNase P (26.5, 95% confidence interval [CI] = 26.0-27.1) and for the 8 influenza A virus positives in our pilot (32.2, 95% CI = 28.9-35.5) were significantly higher than the CTs observed in our 2010-2012 study using staff-collected nasal pharyngeal swabs (P-values < 0.01)., Discussion: Self-collection of respiratory specimens is a promising research method, but further research is needed to quantify the sensitivity and specificity of the approach., (© 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Circadian gene disruptions are associated with the development of psychiatric disorders, including addiction. However, the mechanisms by which circadian genes regulate reward remain poorly understood., Methods: We used mice with a mutation in Npas2 and adeno-associated virus-short hairpin RNA mediated knockdown of Npas2 and Clock in the nucleus accumbens (NAc). We performed conditioned place preference assays. We utilized cell sorting quantitative real-time polymerase chain reaction, and chromatin immunoprecipitation followed by deep sequencing., Results: Npas2 mutants exhibit decreased sensitivity to cocaine reward, which is recapitulated with a knockdown of neuronal PAS domain protein 2 (NPAS2) specifically in the NAc, demonstrating the importance of NPAS2 in this region. Interestingly, reducing circadian locomotor output cycles kaput (CLOCK) (a homologue of NPAS2) in the NAc had no effect, suggesting an important distinction in NPAS2 and CLOCK function. Furthermore, we found that NPAS2 expression is restricted to Drd1 expressing neurons while CLOCK is ubiquitous. Moreover, NPAS2 and CLOCK have distinct temporal patterns of DNA binding, and we identified novel and unique binding sites for each protein. We identified the Drd3 dopamine receptor as a direct transcriptional target of NPAS2 and found that NPAS2 knockdown in the NAc disrupts its diurnal rhythm in expression. Chronic cocaine treatment likewise disrupts the normal rhythm in Npas2 and Drd3 expression in the NAc, which may underlie behavioral plasticity in response to cocaine., Conclusions: Together, these findings identify an important role for the circadian protein, NPAS2, in the NAc in the regulation of dopamine receptor expression and drug reward., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background.  Most inactivated influenza vaccines contain purified and standardized hemagglutinin (HA) and residual neuraminidase (NA) antigens. Vaccine-associated HA antibody responses (hemagglutination inhibition [HAI]) are well described, but less is known about the immune response to the NA. Methods.  Serum of 1349 healthcare personnel (HCP) electing or declining the 2010-2011 trivalent-inactivated influenza vaccine ([IIV3], containing A/California/7/2009 p(H1N1), A/Perth/16/2009 [H3N2], B/Brisbane/60/2008 strains) were tested for NA-inhibiting (NAI) antibody by a modified lectin-based assay using pseudotyped N1 and N2 influenza A viruses with an irrelevant (H5) HA. Neuraminidase-inhibiting and HAI antibody titers were evaluated approximately 30 days after vaccination and end-of-season for those with polymerase chain reaction (PCR)-confirmed influenza infection. Results.  In 916 HCP (68%) receiving IIV3, a 2-fold increase in N1 and N2 NAI antibody occurred in 63.7% and 47.3%, respectively. Smaller responses occurred in HCP age >50 years and those without prior 2009-2010 IIV3 nor monovalent A(H1N1)pdm09 influenza vaccinations. Forty-four PCR-confirmed influenza infections were observed, primarily affecting those with lower pre-exposure HAI and NAI antibodies. Higher pre-NAI titers correlated with shorter duration of illness for A(H1N1)pdm09 virus infections. Conclusions.  Trivalent-inactivated influenza vaccine is modestly immunogenic for N1 and N2 antigens in HCP. Vaccines eliciting robust NA immune responses may improve efficacy and reduce influenza-associated morbidity.

Objective: Internet sex-seeking is common among young men who have sex with men (MSM). However, research examining its association with risky sexual behaviour has produced mixed findings, possibly due to various operational definitions of internet sex-seeking which fail to account for its multi-dimensionality. This study purposed to: (1) examine if the way internet sex-seeking behaviour is operationalised influences its association with risky sexual behaviour (unprotected anal intercourse (UAI) and casual sex) and (2) determine the association of each operational definition with sexual risk., Methods: We recruited 263 sexually-experienced young MSM (18-29 years) and operationalised internet sex-seeking behaviour in four ways: (i) ever used the internet to meet other men, (ii) currently own a profile on a website dedicated to meeting other men, (iii) ever physically met a man you initially met online and (iv) ever had sex with a man you met online. Using binomial regression, we examined the association of each operationalisation with UAI and casual sex., Results: Only MSM who reported physically meeting a man they met online and those who ever had sex with a man they met online were more likely to report a history of UAI (p<0.05), while MSM who engaged in all forms of internet sex-seeking were more likely to engage in casual sex (p<0.05). However, the strength of these associations varied according to the mode of operationalisation., Conclusions: The way internet sex-seeking is operationalised in research is differentially associated with sexual risk. Against this backdrop, the utility of these operational definitions in future research and inferences drawn from such research must be interpreted with caution. Findings have important implications for sexual health research and methodology, survey development, sexual health prevention interventions, and evaluating sexual risk among young MSM., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background and Objective: There is no accepted nutrition approach for wound healing in children. Our aims were to determine optimal nutrition support for pediatric wound healing. Methods: We applied local methods to create evidence- and consensus-based recommendations, supported by implementation tools, including algorithms, clinical decision supports, and measures. We applied these recommendations to the care of 49 patients from December 5, 2011, to December 5, 2012. Results: Six articles were found that addressed our clinical questions, and we formulated 5 clinical recommendations. Evidence supported evaluating patients for vitamin C, zinc, and protein deficiency. Of the patients where laboratory values were checked, 9 patients were zinc deficient (33%) and 12 patients were vitamin C deficient (48%). Discussion and Practical Application: The implementation of our recommendations has led to increased identification of micronutrient deficiencies and closer monitoring of nutrition status and intake. Online clinical decision supports can accelerate the adoption of clinical recommendations and reduce provider practice variation., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Mice with a mutation in the Clock gene (ClockΔ19) have been identified as a model of mania; however, the mechanisms that underlie this phenotype, and the changes in the brain that are necessary for lithium's effectiveness on these mice remain unclear. Here, we find that cholecystokinin (Cck) is a direct transcriptional target of CLOCK and levels of Cck are reduced in the ventral tegmental area (VTA) of ClockΔ19 mice. Selective knockdown of Cck expression via RNA interference in the VTA of wild-type mice produces a manic-like phenotype. Moreover, chronic treatment with lithium restores Cck expression to near wild-type and this increase is necessary for the therapeutic actions of lithium. The decrease in Cck expression in the ClockΔ19 mice appears to be due to a lack of interaction with the histone methyltransferase, MLL1, resulting in decreased histone H3K4me3 and gene transcription, an effect reversed by lithium. Human postmortem tissue from bipolar subjects reveals a similar increase in Cck expression in the VTA with mood stabilizer treatment. These studies identify a key role for Cck in the development and treatment of mania, and describe some of the molecular mechanisms by which lithium may act as an effective antimanic agent.

Background: Each year, the US Influenza Vaccine Effectiveness Network examines the effectiveness of influenza vaccines in preventing medically attended acute respiratory illnesses caused by influenza., Methods: Patients with acute respiratory illnesses of ≤ 7 days' duration were enrolled at ambulatory care facilities in 5 communities. Specimens were collected and tested for influenza by real-time reverse-transcriptase polymerase chain reaction. Receipt of influenza vaccine was defined based on documented evidence of vaccination in medical records or immunization registries. Vaccine effectiveness was estimated in adjusted logistic regression models by comparing the vaccination coverage in those who tested positive for influenza with those who tested negative., Results: The 2011-2012 season was mild and peaked late, with circulation of both type A viruses and both lineages of type B. Overall adjusted vaccine effectiveness was 47% (95% confidence interval [CI], 36-56) in preventing medically attended influenza; vaccine effectiveness was 65% (95% CI, 44-79) against type A (H1N1) pdm09 but only 39% (95% CI, 23-52) against type A (H3N2). Estimates of vaccine effectiveness against both type B lineages were similar (overall, 58%; 95% CI, 35-73). An apparent negative effect of prior year vaccination on current year effectiveness estimates was noted, particularly for A (H3N2) outcomes., Conclusions: Vaccine effectiveness in the 2011-2012 season was modest overall, with lower effectiveness against the predominant A (H3N2) virus. This may be related to antigenic drift, but past history of vaccination might also play a role.

Background: Concerns about influenza vaccine effectiveness in older adults and the role of influenza strains encountered earlier in life led to this study., Methods: Antibody responses against antigens in the 2011-2012 influenza vaccine at 21 days post vaccination were analyzed in 264 individuals aged 50-80 years. At Days 0 and 21, sera were tested for hemagglutination-inhibition titers against these vaccine strains and at Day 0 against a panel of 15 historical seasonal strains.:, Results: The proportions of participants with seroprotective titers ≥1:40 to the vaccine strains at Days 0 and 21, respectively, were 37% and 66% for A(H1N1) and 28% and 63% for A(H3N2). An increasing number of responses ≥1:40 against historical strains was associated with seroprotective responses after vaccination among participants with a titer<1:40 at Day 0 for A(H1N1) and A(H3N2) vaccine strains (P<0.01). In multivariable regression analyses among those with Day 0 titer<1:40, after controlling for age, sex, race, site and diabetes, Day 21 titers ≥ 1:40 for the vaccine A strains were significantly more likely as the number of seroprotective responses against historical strains increased (A(H1N1) odds ratio [OR] = 1.41, 95% confidence interval [CI] = 1.09-1.82 and A(H3N2) OR = 1.32, 95% CI = 1.07-1.62). The likelihood of seroconversion was significantly higher with an increasing number of responses to historical strains for A(H3N2) only (OR = 1.24, 95% CI = 1.01-1.52). Seroconversion was significantly less likely as Day 0 vaccine strain titers increased., Conclusions: Seroprotective titers after influenza vaccination increased as the number of responses to historical strains increased.

Caregiving can have a profound effect on the health of the caregiver, yet research on caregiving among American Indians is limited. The purpose of this study was to examine the influence of caregiving on the health-related quality of life (HRQoL) of American Indians enrolled in the Education And Research Towards Health (EARTH) study. Participants in the EARTH study represented three different tribes in the Northern Plains and Southwestern regions of the United States who completed self-administered, computer-assisted questionnaires between 2003 and 2006. Participants were classified as caregivers if at least one adult relied on them for personal care or as non-caregivers (n = 3,736). Caregivers were further classified according to type; those caring for an adult with unspecified needs (CAU, n = 482) and those caring for an adult with mental or physical difficulties (CAD, n = 295). HRQoL was measured using the mental and physical health component scores of the Medical Outcomes Study 12-item Short-Form Health Survey. Regional differences emerged with regard to caregiver type. Across both regions, non-caregivers reported significantly better mental and physical health than CAD, and the health of participants classified as CAU did not differ from that of non-caregivers. The health of American Indian caregivers depends on the kind of care provided, but detailed measures of caregiving are necessary to understand how caregiving influences health. This has implications for the design of effective interventions in tribal communities., (© 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.)

The primary aim of this study was to examine the contributions of individual characteristics and strategic processing to the prediction of decision quality. Data were provided by 176 adults, ages 18 to 93 years, who completed computerized decision-making vignettes and a battery of demographic and cognitive measures. We examined the relations among age, domain-specific experience, working memory, and three measures of strategic information search to the prediction of solution quality using a 4-step hierarchical linear regression analysis. Working memory and two measures of strategic processing uniquely contributed to the variance explained. Results are discussed in terms of potential advances to both theory and intervention efforts.

Purpose: Self-perceptions of health vary depending on one's social and cultural context. Rural residents have been characterized as having a distinct culture, and health differences by residence have been well documented. While there is evidence of poor health among rural older adults, little research has examined how they perceive and define health. Qualitative methods may help capture these lay meanings of health. The purpose of our study was to use a qualitative approach to examine what perceptions community-dwelling rural older adults have regarding their health., Methods: The study involved thirteen 90-minute focus groups and short self-administered surveys with community-dwelling persons aged 60 years or older residing in 6 rural West Virginia communities. A total of 101 participants were asked questions about their personal definitions of health. With professional transcribed tapes from the focus group discussions, we used a systematic text analysis approach., Findings: Discussions included 4 themes on the meaning of health: (1) health as a value, (2) dimensions of life, (3) holistic nature of health, and (4) health care use and adherence., Conclusion: Our results expand on previous studies and demonstrate that health is a subjective, multidimensional construct deeply embedded in the everyday experience of rural older adults. We found that older adults' perceptions about health contain components which most medical professionals would not take into account. Health care providers may consider supplementing traditional medical approaches with a more contextually sensitive recognition of rural elders' desired health goals and outcomes., (© 2010 National Rural Health Association.)

Purpose: With a sample of American Indian adults, we estimated the prevalence of adult caregiving, assessed the demographic and cultural profile of caregivers, and examined the association between cultural factors and being a caregiver. This is the first such study conducted with American Indians., Design and Methods: Data came from a cross-sectional study of 5,207 American Indian adults residing on 2 closely related Lakota Sioux reservations in the Northern Plains and one American Indian community in the Southwest. Cultural factors included measures of cultural identity and traditional healing practices., Results: Seventeen percent of our sample reported being caregivers. In both the Northern Plains and Southwest, caregiving was positively correlated with younger age, being a woman, larger household size, attending and participating in Native events, and endorsement of traditional healing practices. In both regions, attendance and participation in Native events and engagement in traditional healing practices were associated with increased odds of caregiving after adjusting for covariates. Only in the Northern Plains did we find that speaking some Native language at home was associated with increased odds of being a caregiver. Examination of interaction terms indicated some sex differences in the association between cultural factors and caregiving in the Northern Plains but not in the Southwest., Implications: Our findings indicate that greater cultural identity and engagement in traditional healing practices are related to caregiving in American Indian populations. Caregiving research, intervention efforts, and caregiving programs and services in Native communities should pay special attention to the dynamics of culture and caregiving.

Background: The health pessimism hypothesis suggests that Black elders are more pessimistic about health than Whites and therefore tend to report lower self-rated health (SRH) at comparable health status. The current analysis examined the factors associated with SRH and tested the health pessimism hypothesis among older adults at similar levels of physical functioning., Methods: The study example included 2,729 Health, Aging, and Body Composition study participants aged 70-79 years. We used hierarchical logistic regression to examine the association between race and SRH while adjusting for demographic, physical health, and psychosocial factors. The analyses were repeated for participants at similar levels of objective functioning to test the health pessimism hypothesis., Results: The association between race and SRH remained independent of physical and psychosocial health variables, with Whites being 3.7 times more likely than Black elders to report favorable SRH. This association was significant at each level of physical functioning and greater at the higher (odds ratio [OR] = 5.5) versus lower (OR = 2.2) levels of functioning., Conclusions: The results suggest greater health pessimism among Black elders and expand previous work by including objective functioning in multidimensional models to deconstruct race variations in the SRH of older adults.

It is unclear whether older adults of different race or ethnicity vary in the ways they perceive functional limitations. Variation in such self-reports may be relevant clinically, because many diagnoses (and subsequent care) depend on self-reported disability. To examine this question, self-reported hand function was compared with performance-based assessment of strength (hand dynamometer) and dexterity (Moberg Pick-Up Test) in white (n=102), African-American (n=67), and Hispanic (n=196) elderly people. Participants were Medicare beneficiaries from northern Manhattan, New York City, aged 70 and older. In adjusted analyses, self-reported hand function was associated with weaker grip strength in African-American and Hispanic participants but not in white participants. Self-reported difficulty with hand function was associated with poorer dexterity in all three groups. Similar results were observed in the subsample of participants with arthritis. These results suggest that culture or socioenvironmental differences associated with culture may influence reports of functional limitation.

Ethnic differences in mental health have been established using large between-group research designs. Across ethnicity, studies have found that caregivers are at increased risk for depression, but little is known about within-group variability in depressive symptomatology. African American caregivers and noncaregivers were compared on different factors of depressive symptoms as measured by the Center for Epidemiologic Studies Depression subscales. Caregivers reported significantly less positive affect than noncaregivers. Rates were similar for negative affect, somatic complaints, and interpersonal relations. Depression may present itself in different ways among African Americans in the caregiving context, and results suggest information may be lost when global measures of depression are used.

Research has suggested that race, gender, and menthol cigarette use influence tobacco-smoke exposure measures and smoking-related disease risk. For example, a high proportion of Black smokers prefer menthol cigarettes and, despite smoking fewer cigarettes per day (CPD) than do Whites, tend to have higher cotinine levels. Additionally, Black males are more at risk for smoking-related lung cancer. High cotinine levels and smoking menthol cigarettes may lead to higher toxin intake, which contributes to increased disease risk. We explored the relationship between tobacco exposure variables (i.e., cotinine, CPD, carbon monoxide [CO], nicotine content, and nicotine dependence) with respect to race, gender, and menthol content in a sample of 307 smokers recruited from the greater Boston area to participate in a smoking cessation treatment trial. The pattern of correlations between tobacco exposure measures and cotinine showed a consistently positive correlation between cotinine and CO in all smokers and a correlation between cotinine and CPD in those who smoked nonmenthol cigarettes. Cotinine and CPD correlations varied by gender and race among menthol cigarette smokers. Consistently, we found a significant gender x race x menthol interaction on salivary cotinine level as well as cotinine/CPD ratio. These findings suggest that the relationship between number of cigarettes consumed and salivary cotinine is more complex than previously believed. It is not sufficient to look at race alone; researchers and clinicians need to look at race and gender concurrently, as well as type of cigarette consumed.

Background: There is a paucity of research on health behaviors, health status, and overall health-related quality of life among Appalachian elderly. Identifying factors among older adults that place them at risk for low health-related quality of life is important for targeting unmet health needs and guiding community efforts to help improve population health., Methods: For this study, we examined the relationship between obesity and health-related quality of life among Appalachians aged 65 years or older using the 2000 Behavioral Risk Factor Surveillance Survey data., Results: Our results showed that obese elderly Appalachians report poorer self-rated health and more days of poor physical health compared with their nonobese counterparts., Conclusion: The goals put forward in Healthy People 2010 include the reduction of obesity and enhancement of quality of life. If such health disparities are to be eliminated and quality of life enhanced, a sustained effort to identify their determinants among Appalachian elderly is needed.

Studies of high-risk offspring (HR) of schizophrenic patients have found abnormalities in attention, working memory and executive functions, suggesting impaired integrity of the prefrontal cortex and related brain regions. The authors conducted a preliminary high-field (3 T) functional magnetic resonance imaging (fMRI) study to assess performance and activation during a memory-guided saccade (MGS) task, which measures spatial working memory. HR subjects showed significant decreases in fMRI-measured activation in the dorsolateral prefrontal cortex (Brodmann's areas 8 and 9/46) and the inferior parietal cortex (Brodmann's area 40) compared to age- and sex-matched healthy controls (HC). Abnormal functional integrity of prefrontal and parietal regions of the heteromodal association cortical (HAC) regions in subjects at genetic risk for schizophrenia is consistent with findings observed in adults with the illness [Callicott et al., Cereb. Cortex 10 (2000) 1078; Manoach et al., Biol. Psychiatry 48 (2000) 99.]. These abnormalities need to be prospectively investigated in nonpsychotic individuals at risk for schizophrenia in order to determine their predictive value for eventual emergence of schizophrenia or related disorders.

Structure-function studies with mammalian reoviruses have been limited by the lack of a reverse-genetic system for engineering mutations into the viral genome. To circumvent this limitation in a partial way for the major outer-capsid protein sigma3, we obtained in vitro assembly of large numbers of virion-like particles by binding baculovirus-expressed sigma3 protein to infectious subvirion particles (ISVPs) that lack sigma3. A level of sigma3 binding approaching 100% of that in native virions was routinely achieved. The sigma3 coat in these recoated ISVPs (rcISVPs) appeared very similar to that in virions by electron microscopy and three-dimensional image reconstruction. rcISVPs retained full infectivity in murine L cells, allowing their use to study sigma3 functions in virus entry. Upon infection, rcISVPs behaved identically to virions in showing an extended lag phase prior to exponential growth and in being inhibited from entering cells by either the weak base NH4Cl or the cysteine proteinase inhibitor E-64. rcISVPs also mimicked virions in being incapable of in vitro activation to mediate lysis of erythrocytes and transcription of the viral mRNAs. Last, rcISVPs behaved like virions in showing minor loss of infectivity at 52 degrees C. Since rcISVPs contain virion-like levels of sigma3 but contain outer-capsid protein mu1/mu1C mostly cleaved at the delta-phi junction as in ISVPs, the fact that rcISVPs behaved like virions (and not ISVPs) in all of the assays that we performed suggests that sigma3, and not the delta-phi cleavage of mu1/mu1C, determines the observed differences in behavior between virions and ISVPs. To demonstrate the applicability of rcISVPs for genetic studies of protein functions in reovirus entry (an approach that we call recoating genetics), we used chimeric sigma3 proteins to localize the primary determinants of a strain-dependent difference in sigma3 cleavage rate to a carboxy-terminal region of the ISVP-bound protein.

Much work on psychosocial sequelae of breast cancer has been guided by the assumption that body image and partner reaction issues are focal. In a tri-ethnic sample of 223 women treated for early-stage breast cancer within the prior year, the authors assessed a wider range of concerns and relations to well-being. Strongest concerns were recurrence, pain, death, harm from adjuvant treatment, and bills. Body-image concerns were moderate; concern about rejection was minimal. Younger women had stronger sexual and partner-related concerns than older women. Hispanic women had many stronger concerns and more disruption than other women. Life and pain concerns and sexuality concerns contributed uniquely to predicting emotional and psychosexual disruption; life and pain concerns and rejection concerns contributed to predicting social disruption. In sum, adaptation to breast cancer is a process bearing on several aspects of the patient's life space.

Structures of biological macromolecules determined by transmission cryoelectron microscopy (cryo-TEM) and three-dimensional image reconstruction are often displayed as surface-shaded representations with depth cueing along the viewed direction (Z cueing). Depth cueing to indicate distance from the center of virus particles (radial-depth cueing, or R cueing) has also been used. We have found that a style of R cueing in which color is applied in smooth or discontinuous gradients using the IRIS Explorer software is an informative technique for displaying the structures of virus particles solved by cryo-TEM and image reconstruction. To develop and test these methods, we used existing cryo-TEM reconstructions of mammalian reovirus particles. The newly applied visualization techniques allowed us to discern several new structural features, including sites in the inner capsid through which the viral mRNAs may be extruded after they are synthesized by the reovirus transcriptase complexes. To demonstrate the broad utility of the methods, we also applied them to cryo-TEM reconstructions of human rhinovirus, native and swollen forms of cowpea chlorotic mottle virus, truncated core of pyruvate dehydrogenase complex from Saccharomyces cerevisiae, and flagellar filament of Salmonella typhimurium. We conclude that R cueing with color gradients is a useful tool for displaying virus particles and other macromolecules analyzed by cryo-TEM and image reconstruction.