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1.  Awareness and Use of Non-conventional Tobacco Products Among U.S. Students, 2012 
American journal of preventive medicine  2014;47(2 0 1):S36-S52.
Background
Increasing diversity of the tobacco product landscape, including electronic cigarettes (e-cigarettes), hookah, snus, and dissolvable tobacco products (dissolvables), raises concerns about the public health impact of these non-conventional tobacco products among youth.
Purpose
This study assessed awareness, ever use, and current use of non-conventional tobacco products among U.S. students in 2012, overall and by demographic and tobacco use characteristics.
Methods
Data from the 2012 National Youth Tobacco Survey, a nationally representative survey of U.S. middle and high school students, were analyzed in 2013. Prevalence of awareness, ever use, and current use of e-cigarettes, hookah, snus, and dissolvables were calculated overall and by sex, school level, race/ethnicity, and conventional tobacco product use, including cigarettes, cigars, or smokeless tobacco (chewing tobacco, snuff, or dip).
Results
Overall, 50.3% of students were aware of e-cigarettes; prevalence of ever and current use of e-cigarettes was 6.8% and 2.1%, respectively. Awareness of hookah was 41.2% among all students, and that of ever and current use were 8.9% and 3.6%, respectively. Overall awareness; ever; and current use of snus (32%, 5.3%, 1.7%, respectively) and dissolvables (19.3%, 2.0%, 0.7%, respectively) were generally lower than those of e-cigarettes or hookah. Conventional tobacco product users were more likely to be aware of and to use non-conventional tobacco products.
Conclusions
Many U.S. students are aware of and use non-conventional tobacco products. Evidence-based interventions should be implemented to prevent and reduce all tobacco use among youth.
doi:10.1016/j.amepre.2014.05.003
PMCID: PMC4519346  PMID: 25044194
2.  A Case-Only Study of Vulnerability to Heat Wave–Related Mortality in New York City (2000–2011) 
Environmental Health Perspectives  2015;123(7):672-678.
Background
As a result of climate change, the frequency of extreme temperature events is expected to increase, and such events are associated with increased morbidity and mortality. Vulnerability patterns, and corresponding adaptation strategies, are most usefully conceptualized at a local level.
Methods
We used a case-only analysis to examine subject and neighborhood characteristics that modified the association between heat waves and mortality. All deaths of New York City residents from 2000 through 2011 were included in this analysis. Meteorological data were obtained from the National Climatic Data Center. Modifying characteristics were obtained from the death record and geographic data sets.
Results
A total of 234,042 adult deaths occurred during the warm season of our study period. Compared with other warm-season days, deaths during heat waves were more likely to occur in black (non-Hispanic) individuals than other race/ethnicities [odds ratio (OR) = 1.08; 95% CI: 1.03, 1.12], more likely to occur at home than in institutions and hospital settings (OR = 1.11; 95% CI: 1.06, 1.16), and more likely among those living in census tracts that received greater public assistance (OR = 1.05; 95% CI: 1.01, 1.09). Finally, deaths during heat waves were more likely among residents in areas of the city with higher relative daytime summer surface temperature and less likely among residents living in areas with more green space.
Conclusion
Mortality during heat waves varies widely within a city. Understanding which individuals and neighborhoods are most vulnerable can help guide local preparedness efforts.
Citation
Madrigano J, Ito K, Johnson S, Kinney PL, Matte T. 2015. A case-only study of vulnerability to heat wave–related mortality in New York City (2000–2011). Environ Health Perspect 123:672–678; http://dx.doi.org/10.1289/ehp.1408178
doi:10.1289/ehp.1408178
PMCID: PMC4492264  PMID: 25782056
3.  Strategies to improve quantitative assessment of immunohistochemical and immunofluorescent labelling 
Scientific Reports  2015;5:10607.
Binary image thresholding is the most commonly used technique to quantitatively examine changes in immunolabelled material. In this article we demonstrate that if implicit assumptions predicating this technique are not met then the resulting analysis and data interpretation can be incorrect. We then propose a transparent approach to image quantification that is straightforward to execute using currently available software and therefore can be readily and cost-effectively implemented.
doi:10.1038/srep10607
PMCID: PMC4464180  PMID: 26066532
4.  Disruption of Parenting Behaviors in California Mice, a Monogamous Rodent Species, by Endocrine Disrupting Chemicals 
PLoS ONE  2015;10(6):e0126284.
The nature and extent of care received by an infant can affect social, emotional and cognitive development, features that endure into adulthood. Here we employed the monogamous, California mouse (Peromyscus californicus), a species, like the human, where both parents invest in offspring care, to determine whether early exposure to endocrine disrupting chemicals (EDC: bisphenol A, BPA; ethinyl estradiol, EE) of one or both parents altered their behaviors towards their pups. Females exposed to either compound spent less time nursing, grooming and being associated with their pups than controls, although there was little consequence on their weight gain. Care of pups by males was less affected by exposure to BPA and EE, but control, non-exposed females appeared able to “sense” a male partner previously exposed to either compound and, as a consequence, reduced their own parental investment in offspring from such pairings. The data emphasize the potential vulnerability of pups born to parents that had been exposed during their own early development to EDC, and that effects on the male, although subtle, also have consequences on overall parental care due to lack of full acceptance of the male by the female partner.
doi:10.1371/journal.pone.0126284
PMCID: PMC4454565  PMID: 26039462
5.  Spatial Variation in Environmental Noise and Air Pollution in New York City 
Exposure to environmental noise from traffic is common in urban areas and has been linked to increased risks of adverse health effects including cardiovascular disease. Because traffic sources also produce air pollutants that increase the risk of cardiovascular morbidity, associations between traffic exposures and health outcomes may involve confounding and/or synergisms between air pollution and noise. While prior studies have characterized intraurban spatial variation in air pollution in New York City (NYC), limited data exists on the levels and spatial variation in noise levels. We measured 1-week equivalent continuous sound pressure levels (Leq) at 56 sites during the fall of 2012 across NYC locations with varying traffic intensity and building density that are routinely monitored for combustion-related air pollutants. We evaluated correlations among several noise metrics used to characterize noise exposures, including Leq during different time periods (night, day, weekday, weekend), Ldn (day-night noise), and measures of intermittent noise defined as the ratio of peak levels to median and background levels. We also examined correlations between sound pressure levels and co-located simultaneous measures of nitric oxide (NO), nitrogen dioxide (NO2), fine particulate matter (PM2.5), and black carbon (BC) as well as estimates of traffic and building density around the monitoring sites. Noise levels varied widely across the 56 monitoring sites; 1-week Leq varied by 21.6 dBA (range 59.1–80.7 dBA) with the highest levels observed during the weekday, daytime hours. Indices of average noise were well correlated with each other (r > 0.83), while indices of intermittent noise were not well correlated with average noise levels (r < 0.41). One-week Leq correlated well with NO, NO2, and EC levels (r = 0.61 to 0.68) and less so with PM2.5 levels (r = 0.45). We observed associations between 1-week noise levels and traffic intensity within 100 m of the monitoring sites (r = 0.58). The high levels of noise observed in NYC often exceed recommended guidelines for outdoor and personal exposures, suggesting unhealthy levels in many locations. Associations between noise, traffic, and combustion air pollutants suggest the possibility for confounding and/or synergism in intraurban epidemiological studies of traffic-related health effects. The different spatial pattern of intermittent noise compared to average noise level may suggest different sources.
doi:10.1007/s11524-013-9857-0
PMCID: PMC4074330  PMID: 24488652
Noise; Air pollution; Traffic; Noise metrics; Environmental noise; Air monitoring
6.  The use of molecular-based risk stratification and pharmacogenomics for outcome prediction and personalized therapeutic management of multiple myeloma 
Despite improvement in therapeutic efficacy, multiple myeloma (MM) remains incurable with a median survival of approximately 10 years. Gene-expression profiling (GEP) can be used to elucidate the molecular basis for resistance to chemotherapy through global assessment of molecular alterations that exist at diagnosis, after therapeutic treatment and that evolve during tumor progression. Unique GEP signatures associated with recurrent chromosomal translocations and ploidy changes have defined molecular classes with differing clinical features and outcomes. When compared to other stratification systems the GEP70 test remained a significant predictor of outcome, reduced the number of patients classified with a poor prognosis, and identified patients at increased risk of relapse despite their standard clinico-pathologic and genetic findings. GEP studies of serial samples showed that risk increases over time, with relapsed disease showing GEP shifts toward a signature of poor outcomes. GEP signatures of myeloma cells after therapy were prognostic for event-free and overall survival and thus may be used to identify novel strategies for overcoming drug resistance. This brief review will focus on the use of GEP of MM to define high-risk myeloma, and elucidate underlying mechanisms that are beginning to change clinical decision-making and inform drug design.
doi:10.1007/s12185-011-0948-y
PMCID: PMC4433024  PMID: 22002477
Gene-expression profiling; Fluorescence in situ hybridization; Cytogenetics; Multiple myeloma; Classification; Prognosis; High risk; Therapeutic management
7.  Adenovirus Small E1A Employs the Lysine Acetylases p300/CBP and Tumor Suppressor Rb to Repress Select Host Genes and Promote Productive Virus Infection 
Cell host & microbe  2014;16(5):663-676.
SUMMARY
Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with the host lysine acetylases p300/CBP and the tumor suppressor RB. How these interactions influence cellular gene expression remains unclear. We find that e1a displaces RBs from E2F transcription factors and promotes p300 acetylation of RB1 K873/K874 to lock it into a repressing conformation that interacts with repressive chromatin-modifying enzymes. These repressing p300-e1a-RB1 complexes specifically interact with host genes that have unusually high p300 association within the gene body. The TGFβ-, TNF-, and interleukin-signaling pathway components are enriched among such p300-targeted genes. The p300-e1a-RB1 complex condenses chromatin in a manner dependent on HDAC activity, p300 lysine acetylase activity, the p300 bromodomain, and RB K873/K874 and e1a K239 acetylation to repress host genes that would otherwise inhibit productive virus infection. Thus, adenovirus employs e1a to repress host genes that interfere with viral replication.
doi:10.1016/j.chom.2014.10.004
PMCID: PMC4418520  PMID: 25525796
8.  Insights from the Metagenome of an Acid Salt Lake: The Role of Biology in an Extreme Depositional Environment 
PLoS ONE  2015;10(4):e0122869.
The extremely acidic brine lakes of the Yilgarn Craton of Western Australia are home to some of the most biologically challenging waters on Earth. In this study, we employed metagenomic shotgun sequencing to generate a microbial profile of the depositional environment associated with the sulfur-rich sediments of one such lake. Of the 1.5 M high-quality reads generated, 0.25 M were mapped to protein features, which in turn provide new insights into the metabolic function of this community. In particular, 45 diverse genes associated with sulfur metabolism were identified, the majority of which were linked to either the conversion of sulfate to adenylylsulfate and the subsequent production of sulfide from sulfite or the oxidation of sulfide, elemental sulfur, and thiosulfate via the sulfur oxidation (Sox) system. This is the first metagenomic study of an acidic, hypersaline depositional environment, and we present evidence for a surprisingly high level of microbial diversity. Our findings also illuminate the possibility that we may be meaningfully underestimating the effects of biology on the chemistry of these sulfur-rich sediments, thereby influencing our understanding of past geobiological conditions that may have been present on Earth as well as early Mars.
doi:10.1371/journal.pone.0122869
PMCID: PMC4414474  PMID: 25923206
9.  Patients’ preferred mode of travel to the orthopaedic theatre 
World Journal of Orthopedics  2015;6(3):360-362.
AIM: To determine the preferred mode of travel to the operating theatre for elective orthopaedic patients.
METHODS: Data was collected prospectively over a 2-wk period at an elective Orthopaedic Treatment Centre. Patients were asked to complete a patient satisfaction questionnaire following their surgery on their experience and subsequent preferred mode of transport to theatre. The data was then recorded in a tabulated format and analysed with percentages. Fisher’s exact test was used to determine if there was any statistical association between patients’ preference to walk and various groups; in-patient or day case procedures, and whether patients were < 60 years or > 60 years of age.
RESULTS: Seventy patients (40 females and 30 males) fully completed the questionnaire. In total there were 33 d-cases and 37 in-patients. The spectrum of orthopaedic sub-specialties included was knee (41%), hip (17%), foot and ankle (24%), spine (13%) and upper limb (4%). Patient satisfaction for overall experience of travelling to theatre was either excellent (77%) or good (23%). Following their experience of travelling to theatre, 87% (95%CI: 79%-95%) of the total cohort would have preferred to walk to the operating theatre. There was a statistically significant association (P = 0.003) between patients’ preference to walk and whether they were day-case or in-patients. Similarly, there was a statistically significance association (P = 0.028) between patients’ preference to walk and whether they were < 60 years or > 60 years of age.
CONCLUSION: This study confirms the majority of Orthopaedic elective patients would prefer to walk to theatre, when given the choice and if practically possible.
doi:10.5312/wjo.v6.i3.360
PMCID: PMC4390898  PMID: 25893179
Patient satisfaction; Orthopaedic theatre; Patient autonomy
10.  Genomic Rearrangements Define Lineage Relationships between Adjacent Lepidic and Invasive Components in Lung Adenocarcinoma 
Cancer research  2014;74(11):3157-3167.
The development of adenocarcinoma of the lung is believed to proceed from in situ disease (adenocarcinoma in situ, AIS) to minimally invasive disease with prominent lepidic growth (minimally invasive adenocarcinoma, MIA), then to fully invasive adenocarcinoma (AD), but direct evidence for this model has been lacking. Because some lung adenocarcinomas show prominent lepidic growth (AD-L), we designed a study to address the lineage relationship between the lepidic (noninvasive) component (L) and the adjacent nonlepidic growth component representing invasive disease within individual tumors. Lineage relationships were evaluated by next-generation DNA sequencing to define large genomic rearrangements in microdissected tissue specimens collected by laser capture. We found a strong lineage relationship between the majority of adjacent lepidic and invasive components, supporting a putative AIS–AD transition. Notably, many rearrangements were detected in the less aggressive lepidic component, although the invasive component exhibited an overall higher rate of genomic rearrangement. Furthermore, a significant number of genomic rearrangements were present in histologically normal lung adjacent to tumor, but not in host germline DNA, suggesting field defects restricted to zonal regions near a tumor. Our results offer a perspective on the genetic pathogenesis underlying adenocarcinoma development and its clinical management.
doi:10.1158/0008-5472.CAN-13-1727
PMCID: PMC4399556  PMID: 24879567
11.  Multimodal imaging enables early detection and characterization of changes in tumor permeability of brain metastases 
Our goal was to develop strategies to quantify the accumulation of model therapeutics in small brain metastases using multimodal imaging, in order to enhance the potential for successful treatment. Human melanoma cells were injected into the left cardiac ventricle of immunodeficient mice. Bioluminescent, MR and PET imaging were applied to evaluate the limits of detection and potential for contrast agent extravasation in small brain metastases. A pharmacokinetic model was applied to estimate vascular permeability. Bioluminescent imaging after injecting D-Luciferin (molecular weight (MW) 320D) suggested tumor cell extravasation had already occurred at week 1, which was confirmed by histology. 7T T1w MRI at week 4 was able to detect non-leaky 100 μm sized lesions and leaky tumors with diameters down to 200 μm after contrast injection at week 5. PET imaging showed that 18F-FLT (MW 244D) accumulated in the brain at week 4. Gadolinium-based MRI tracers (MW 559D and 2.066kD) extravasated after 5 weeks (tumor diameter 600 μm), and the lower MW agent cleared more rapidly from the tumor (mean apparent permeabilities 2.27×10-5 cm/s versus 1.12×10-5 cm/s). PET imaging further demonstrated tumor permeability to 64Cu-BSA (MW 65.55kD) at week 6 (tumor diameter 700 μm). In conclusion, high field T1w MRI without contrast may improve the detection limit of small brain metastases, allowing for earlier diagnosis of patients, although the smallest lesions detected with T1w MRI were permeable only to D-Luciferin and the amphipathic small molecule 18F-FLT. Different-sized MR and PET contrast agents demonstrated the gradual increase in leakiness of the blood tumor barrier during metastatic progression, which could guide clinicians in choosing tailored treatment strategies.
doi:10.1016/j.jconrel.2013.10.019
PMCID: PMC3922207  PMID: 24161382
Brain metastasis; MRI; PET; bioluminescence imaging; contrast agents
12.  CD8+ T-cell Cytotoxic Capacity Associated with Human Immunodeficiency Virus-1 Control Can Be Mediated through Various Epitopes and Human Leukocyte Antigen Types 
EBioMedicine  2014;2(1):46-58.
Understanding natural immunologic control over Human Immunodeficiency Virus (HIV)-1 replication, as occurs in rare long-term nonprogressors/elite controllers (LTNP/EC), should inform the design of efficacious HIV vaccines and immunotherapies. Durable control in LTNP/EC is likely mediated by highly functional virus-specific CD8+ T-cells. Protective Human Leukocyte Antigen (HLA) class I alleles, like B*27 and B*57, are present in most, but not all LTNP/EC, providing an opportunity to investigate features shared by their HIV-specific immune responses. To better understand the contribution of epitope targeting and conservation to immune control, we compared the CD8+ T-cell specificity and function of B*27/57neg LTNP/EC (n = 23), B*27/57pos LTNP/EC (n = 23) and B*27/57neg progressors (n = 13). Fine mapping revealed 11 previously unreported immunodominant responses. Although B*27/57neg LTNP/EC did not target more highly conserved epitopes, their CD8+ T-cell cytotoxic capacity was significantly higher than progressors. Similar to B*27/57pos LTNP/EC, this superior cytotoxicity was mediated by preferential expansion of immunodominant responses and lysis through the predicted HLA. These findings suggest that increased CD8+ T-cell cytotoxic capacity is a common mechanism of control in most LTNP/EC regardless of HLA type. They also suggest that potent cytotoxicity can be mediated through various epitopes and HLA molecules and could, in theory, be induced in most people.
Highlights
•HIV-specific cytotoxicity associated with control can be mediated across a wide variety of epitopes and HLA types.•Targeting of conserved epitopes does not differentiate patients with immunologic control of HIV-1.•High level cytotoxic capacity is a feature shared among LTNP/EC across HLA types.
doi:10.1016/j.ebiom.2014.12.009
PMCID: PMC4485486  PMID: 26137533
Long-term nonprogressors/elite controllers; Immune control; CD8+ T cells; Cytotoxic capacity; Epitope specificity
13.  Quantitative assessment of microglial morphology and density reveals remarkable consistency in the distribution and morphology of cells within the healthy prefrontal cortex of the rat 
Background
Microglial morphology within the healthy brain has been the subject of a number of observational studies. These have suggested that microglia may consist of separate classes, which possess substantially different morphological features. Critically, there have been no systematic quantitative studies of microglial morphology within the healthy brain.
Methods
We examined microglial cells within the adult rat prefrontal cortex. At high magnification, digital reconstructions of cells labelled with the microglial-specific marker ionized calcium-binding adapter molecule-1 (Iba-1) were made in each of the cortical layers. These reconstructions were subsequently analyzed to determine the convex hull area of the cells, their somal perimeter, the length of processes, the number of processes, the extent of process branching and the volume of processes. We additionally examined whether cells’ morphological features were associated with cell size or numerical density.
Results
Our analysis indicated that while there was substantial variability in the size of cells within the prefrontal cortex, cellular morphology was extremely consistent within each of the cortical layers.
Conclusions
Our results provide quantitative confirmation that microglia are largely homogenous in the uninjured rodent prefrontal cortex.
doi:10.1186/s12974-014-0182-7
PMCID: PMC4213482  PMID: 25343964
Iba-1; Microglia; Morphology; Prefrontal cortex
14.  Effects of Obesity on Bone Mass and Quality in Ovariectomized Female Zucker Rats 
Journal of Obesity  2014;2014:690123.
Obesity and osteoporosis are two chronic conditions that have been increasing in prevalence. Despite prior data supporting the positive relationship between body weight and bone mineral density (BMD), recent findings show excess body weight to be detrimental to bone mass, strength, and quality. To evaluate whether obesity would further exacerbate the effects of ovariectomy on bone, we examined the tibiae and fourth lumbar (L4) vertebrae from leptin receptor-deficient female (Leprfa/fa) Zucker rats and their heterozygous lean controls (Leprfa/+) that were either sham-operated or ovariectomized (Ovx). BMD of L4 vertebra was measured using dual-energy X-ray absorptiometry, and microcomputed tomography was used to assess the microstructural properties of the tibiae. Ovariectomy significantly (P < 0.001) decreased the BMD of L4 vertebrae in lean and obese Zucker rats. Lower trabecular number and greater trabecular separation (P < 0.001) were also observed in the tibiae of lean- and obese-Ovx rats when compared to sham rats. However, only the obese-Ovx rats had lower trabecular thickness (Tb.Th) (P < 0.005) than the other groups. These findings demonstrated that ovarian hormone deficiency adversely affected bone mass and quality in lean and obese rats while obesity only affected Tb.Th in Ovx-female Zucker rats.
doi:10.1155/2014/690123
PMCID: PMC4189520  PMID: 25309751
15.  The effect of expectancy and personality on cortical excitability in Parkinson’s disease 
Background
Our previous studies in PD have shown that both levodopa and expectancy of receiving levodopa reduce cortical excitability. We designed this study to evaluate how degree of expectancy and other individual factors modulate placebo response in Parkinson’s patients.
Methods
Twenty-six Parkinson’s patients were randomized to one of three groups: 0%, 50% and 100% expectancy of receiving levodopa. All subjects received placebo regardless of expectancy group. Subjects completed the NEO-Five Factor Inventory, General Perceived Self-Efficacy Scale, and Perceived Stress Scale. Cortical excitability was measured by the amplitude of motor evoked potential (MEP) evoked by transcranial magnetic stimulation. Objective physical fatigue of Extensor carpi radialis before and after placebo levodopa was also measured. Responders were defined as subjects who responded to the placebo levodopa with a decrease in MEP.
Results
Degree of expectancy had a significant effect on MEP response (p<0.05). Subjects in the 50% and 100% expectancy groups responded with a decrease in MEP, while those in the 0% expectancy group responded with an increase in MEP (p<0.05). Responders tended to be more open to experience than non-responders. There were no significant changes in objective physical fatigue between the expectancy groups, or between responders and non-responders.
Conclusions
Expectancy is associated with changes in cortical excitability. Further studies are needed to examine the relationship between personality and placebo effect in Parkinson’s patients.
doi:10.1002/mds.25471
PMCID: PMC3735617  PMID: 23630185
Parkinson’s disease; Levodopa; Expectancy; Cortical Excitability; Transcranial Magnetic Stimulation (TMS)
16.  Artesunate overcomes drug resistance in multiple myeloma by inducing mitochondrial stress and non-caspase apoptosis 
Oncotarget  2014;5(12):4118-4128.
Although novel drugs have contributed immensely to improving outcomes of patients with multiple myeloma (MM), many patients develop drug resistance and ultimately succumb to MM. Here, we show that artesunate, an anti-malarial drug, reliably induces cell death in vitro in naïve as well as drug-resistant MM cells at concentrations shown to be safe in humans. Artesunate induced apoptosis predominantly through the non-caspase mediated pathway by primarily targeting mitochondria and causing outer mitochondrial membrane permeabilization that led to cytosolic and subsequent nuclear translocation of mitochondrial proteins apoptosis inducing factor (AIF) and endonuclease G (EndoG). Nuclear translocation of AIF and EndoG was accompanied by low levels of reactive oxygen species (ROS) and increased mitochondrial production of superoxide. These effects were present before apoptosis was evident and were related to intracellular levels of bivalent iron (Fe+2). Artesunate's unique mechanism probably was at least partially responsible for, its ability to act synergistically with multiple anti-myeloma agents. Our findings suggest that artesunate acts through iron to affect the mitochondria and induce low ROS and non-caspase–mediated apoptosis. Its potency, toxicity profile, and synergism with other drugs make it an intriguing new candidate for MM treatment.
PMCID: PMC4147310  PMID: 24948357
artesunate; apoptosis; caspases; myeloma; ROS
17.  Hippocampal Shape Abnormalities of Patients With Childhood-Onset Schizophrenia and Their Unaffected Siblings 
Objective
The hippocampus has been implicated in the pathogenesis of schizophrenia, and hippocampal volume deficits have been a consistently reported abnormality, but the subregional specificity of the deficits remains unknown. The authors explored the nature and developmental trajectory of subregional shape abnormalities of the hippocampus in patients with childhood-onset schizophrenia (COS), their healthy siblings, and healthy volunteers.
Method
Two hundred twenty-five anatomic brain magnetic resonance images were obtained from 103 patients with COS, 169 from their 79 healthy siblings, and 255 from 101 age- and sex-matched healthy volunteers (age range = 9–29 years). The hippocampus was segmented using Free-Surfer automated image analysis software, and hippocampal shape was evaluated by comparing subjects at more than 6,000 vertices on the left and right hippocampal surfaces. Longitudinal data were examined using mixed model regression analysis.
Results
Patients with COS showed significant bilateral inward deformation in the anterior hippocampus. Healthy siblings also showed a trend for anterior inward deformation. However, the trajectory of shape change did not differ significantly between the groups. Inward deformations in the anterior hippocampus were positively related to positive symptom severity, whereas outward surface displacement was positively related to overall functioning.
Conclusion
This is the first and largest longitudinal three-way analysis of subregional hippocampal shape abnormalities in patients with COS and their healthy siblings compared with healthy controls. The anterior hippocampal abnormalities in COS suggest the pathophysiologic importance of this subregion in schizophrenia. The trend level and overlapping shape abnormalities in the healthy siblings suggest a more subtle, subregionally specific neuroanatomic endophenotype.
doi:10.1016/j.jaac.2013.02.003
PMCID: PMC3812431  PMID: 23622854
hippocampus; longitudinal; magnetic resonance imaging; neurodevelopment; schizophrenia
18.  Study to find the best extraction solvent for use with guava leaves (Psidium guajava L.) for high antioxidant efficacy 
Food Science & Nutrition  2014;2(2):174-180.
The effects of guava leaves extracted using solvents of water, ethanol, methanol, and different concentrations of hydroethanolic solvents on phenolic compounds and flavonoids, and antioxidant properties have been investigated. The antioxidant capability was assessed based on 2,2-diphenyl-1-picrylhydrazyl radical and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging abilities, reducing power, and nitric oxide-and nitrate-scavenging activities. The results demonstrated that the antioxidant ability of guava leaf extracts has a strong relationship with phenolic compound content rather than flavonoid content. Phenolic compound content of water extracted guava leaves was higher compared to pure ethanol and methanol extracts. However, phenolic compound content extracted using hydroethanolic solvent was higher than water, whereas 50% hydroethanolic was observed to be the most effective solvent showing high antioxidant ability.
doi:10.1002/fsn3.91
PMCID: PMC3959964  PMID: 24804076
Antioxidant; flavonoid; guava; hydroethanolic solvent; phenolic compound
19.  Absence of anatomic corpus callosal abnormalities in childhood onset schizophrenia patients and healthy siblings 
Psychiatry research  2012;211(1):11-16.
The corpus callosum (CC) has been implicated in the pathogenesis of schizophrenia, and CC deficits have been reported in adults with schizophrenia. We explored the developmental trajectory of the corpus callosum in Childhood-onset schizophrenia (COS) patients, their healthy siblings and healthy volunteers. We obtained 235 anatomic brain MRI scans from 98 COS patients, 153 scans from 71 of their healthy siblings, and 253 scans from 100 age and gender matched healthy volunteers, across ages 9–30 years. The volumes of 5 sub-regions of the CC were calculated using FreeSurfer, and summed to give the total volume. Longitudinal data were examined using mixed model regression analysis. There were no significant differences for the total or sub-regional CC volumes between the three groups. There were also no significant differences between the groups for developmental trajectory (slope) of the CC. This is the largest longitudinal study of CC development in schizophrenia and the first COS study of the CC to include healthy siblings. Overall, CC volume and growth trajectory did not differ between COS patients, healthy siblings, or healthy volunteers. These results suggest that CC development, at least at a macroscopic level, may not be a salient feature of schizophrenia.
doi:10.1016/j.pscychresns.2012.09.013
PMCID: PMC3557544  PMID: 23154096
Corpus Callosum; MRI; Neuroimaging; Development
20.  DNA Damage Enhancement from Gold Nanoparticles for Clinical MV Photon Beams 
Radiation research  2012;178(6):604-608.
In this study, we quantify the relative damage enhancement due to the presence of gold nanoparticles (GNP) in vitro in a clinical 6 MV beam for various delivery parameters and depths. It is expected that depths and delivery modes that produce a larger proportions of low-energy photons will have a larger effect on the cell samples containing GNP. HeLa cells with and without 50 nm GNP were irradiated at depths of 1.5, 5, 10, 15 and 20 cm. Conventional beams with square aperture sizes 5, 10 and 15 cm at isocenter, and flattening filter free (FFF) beams were used. Relative DNA damage enhancement with GNP was evaluated by γ-H2AX staining. Statistically significant increases in DNA damage with GNP, compared to the absence of GNP, were observed for all depths and delivery modes. Relative to the shallowest depth, damage enhancement was observed to increase as a function of increasing depth for all deliveries. For the conventional (open field) delivery, DNA damage enhancement with GNP was seen to increase as a function of field size. For FFF delivery, a substantial increase in enhancement was found relative to the conventional field delivery. The measured relative DNA damage enhancement validates the theoretically predicted trends as a function of depth and delivery mode for clinical MV photon beams. The results of this study open new possibilities for the clinical development of gold nanoparticle-aided radiation therapy.
doi:10.1667/RR3001.1
PMCID: PMC3525114  PMID: 23148509
21.  Interactions between Parents and Parents and Pups in the Monogamous California Mouse (Peromyscus californicus) 
PLoS ONE  2013;8(9):e75725.
The California mouse (Peromyscuscalifornicus) may be a valuable animal model to study parenting as it is one of the few monogamous and biparental rodent species. By using automated infra-red imaging and video documentation of established pairs spanning two days prior to birth of the litter until d 5 of post natal development (PND), it was possible to follow interactions between parents and between parents and pups. The paired males were attentive to their partners in the form of grooming and sniffing throughout the time period studied. Both these and other activities of the partners, such as eating and drinking, peaked during late light/ mid-dark period. Beginning the day before birth, and most significantly on PND 0, the female made aggressive attempts to exclude the male from nest-attending, acts that were not reciprocated by the male, although he made repeated attempts to mate his partner during that period. By PND 1, males were permitted to return to the nest, where they initiated grooming, licking, and huddling over the litter, although time spent by the male on parental care was still less than that of the female. Male and female pups were of similar size and grew at the same rate. Pups, which are believed to be exothermic for at least the first two weeks post-natally, maintained a body temperature higher than that of their parents until PND 16. Data are consistent with the inference that the male California mouse parent is important in helping retain pup body heat and permit dams increased time to procure food to accommodate her increased energy needs for lactation. These assessments provide indices that may be used to assess the effects of extrinsic factors, such as endocrine disrupting chemicals, on biparental behaviors and offspring development.
doi:10.1371/journal.pone.0075725
PMCID: PMC3777941  PMID: 24069441
22.  Effects of Vitamin E on Bone Biomechanical and Histomorphometric Parameters in Ovariectomized Rats 
Journal of Osteoporosis  2013;2013:825985.
The present study examined the dose-dependent effect of vitamin E in reversing bone loss in ovariectomized (Ovx) rats. Sprague-Dawley rats were either Sham-operated (Sham) or Ovx and fed control diet for 120 days to lose bone. Subsequently, rats were divided into 5 groups (n = 12/group): Sham, Ovx-control, low dose (Ovx + 300 mg/kg diet; LD), medium dose (Ovx + 525 mg/kg diet; MD), and high dose (Ovx + 750 mg/kg diet; HD) of vitamin E and sacrificed after 100 days. Animals receiving MD and HD of vitamin E had increased serum alkaline phosphatase compared to the Ovx-control group. Bone histomorphometry analysis indicated a decrease in bone resorption as well as increased bone formation and mineralization in the Ovx groups supplemented with MD and HD of vitamin E. Microcomputed tomography findings indicated no effects of vitamin E on trabecular bone of fifth lumbar vertebrae. Animals receiving HD of vitamin E had enhanced fourth lumbar vertebra quality as evidenced by improved ultimate and yield load and stress when compared to Ovx-control group. These findings demonstrate that vitamin E improves bone quality, attenuates bone resorption, and enhances the rate of bone formation while being unable to restore bone density and trabecular bone structure.
doi:10.1155/2013/825985
PMCID: PMC3780659  PMID: 24089643
23.  Characterization of a Mouse-Adapted Staphylococcus aureus Strain 
PLoS ONE  2013;8(9):e71142.
More effective antibiotics and a protective vaccine are desperately needed to combat the ‘superbug’ Staphylococcus aureus. While in vivo pathogenicity studies routinely involve infection of mice with human S. aureus isolates, recent genetic studies have demonstrated that S. aureus lineages are largely host-specific. The use of such animal-adapted S. aureus strains may therefore be a promising approach for developing more clinically relevant animal infection models. We have isolated a mouse-adapted S. aureus strain (JSNZ) which caused a severe outbreak of preputial gland abscesses among male C57BL/6J mice. We aimed to extensively characterize this strain on a genomic level and determine its virulence potential in murine colonization and infection models. JSNZ belongs to the MLST type ST88, rare among human isolates, and lacks an hlb-converting phage encoding human-specific immune evasion factors. Naive mice were found to be more susceptible to nasal and gastrointestinal colonization with JSNZ than with the human-derived Newman strain. Furthermore, naïve mice required antibiotic pre-treatment to become colonized with Newman. In contrast, JSNZ was able to colonize mice in the absence of antibiotic treatment suggesting that this strain can compete with the natural flora for space and nutrients. In a renal abscess model, JSNZ caused more severe disease than Newman with greater weight loss and bacterial burden. In contrast to most other clinical isolates, JSNZ can also be readily genetically modified by phage transduction and electroporation. In conclusion, the mouse-adapted strain JSNZ may represent a valuable tool for studying aspects of mucosal colonization and for screening novel vaccines and therapies directed at preventing colonization.
doi:10.1371/journal.pone.0071142
PMCID: PMC3759423  PMID: 24023720
24.  Examining Racial and Ethnic Minority Differences among YMSM during Recruitment for an Online HIV Prevention Intervention Study 
AIDS and Behavior  2012;16(6):1430-1435.
HIV disproportionately affects racial and ethnic minority young men who have sex with men (YMSM). HIV prevention research does not include these YMSM commensurate to their HIV burden. We examined racial and ethnic differences during a unique three-step recruitment process for an online, YMSM HIV prevention intervention study (N=660). Step one was completed in-person; steps two and three online. Fewer Black and Latino YMSM completed step two – initiating online participation – than White YMSM. Internet use frequency accounted for the Latino vs. White difference in initiating online participation, but not the Black vs. White difference. Future online HIV prevention interventions recruiting diverse YMSM should focus on initiating online engagement among Black participants.
doi:10.1007/s10461-011-0058-0
PMCID: PMC3288566  PMID: 21986869
YMSM; HIV prevention; online intervention; research engagement; Keep it Up!
25.  Spatial and temporal estimation of air pollutants in New York City: exposure assignment for use in a birth outcomes study 
Environmental Health  2013;12:51.
Background
Recent epidemiological studies have examined the associations between air pollution and birth outcomes. Regulatory air quality monitors often used in these studies, however, were spatially sparse and unable to capture relevant within-city variation in exposure during pregnancy.
Methods
This study developed two-week average exposure estimates for fine particles (PM2.5) and nitrogen dioxide (NO2) during pregnancy for 274,996 New York City births in 2008–2010. The two-week average exposures were constructed by first developing land use regression (LUR) models of spatial variation in annual average PM2.5 and NO2 data from 150 locations in the New York City Community Air Survey and emissions source data near monitors. The annual average concentrations from the spatial models were adjusted to account for city-wide temporal trends using time series derived from regulatory monitors. Models were developed using Year 1 data and validated using Year 2 data. Two-week average exposures were then estimated for three buffers of maternal address and were averaged into the last six weeks, the trimesters, and the entire period of gestation. We characterized temporal variation of exposure estimates, correlation between PM2.5 and NO2, and correlation of exposures across trimesters.
Results
The LUR models of average annual concentrations explained a substantial amount of the spatial variation (R2 = 0.79 for PM2.5 and 0.80 for NO2). In the validation, predictions of Year 2 two-week average concentrations showed strong agreement with measured concentrations (R2 = 0.83 for PM2.5 and 0.79 for NO2). PM2.5 exhibited greater temporal variation than NO2. The relative contribution of temporal vs. spatial variation in the estimated exposures varied by time window. The differing seasonal cycle of these pollutants (bi-annual for PM2.5 and annual for NO2) resulted in different patterns of correlations in the estimated exposures across trimesters. The three levels of spatial buffer did not make a substantive difference in estimated exposures.
Conclusions
The combination of spatially resolved monitoring data, LUR models and temporal adjustment using regulatory monitoring data yielded exposure estimates for PM2.5 and NO2 that performed well in validation tests. The interaction between seasonality of air pollution and exposure intervals during pregnancy needs to be considered in future studies.
doi:10.1186/1476-069X-12-51
PMCID: PMC3704849  PMID: 23802774
Air pollution; Birth outcomes; Particulate matter; Nitrogen dioxide; Land use regression; NYCCAS; Temporal adjustment

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