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1.  An excitatory ventral hippocampus to lateral septum circuit that suppresses feeding 
Nature Communications  2015;6:10188.
Previous research has focused on feeding circuits residing in the hindbrain and midbrain that govern homeostatic or hedonic control of food intake. However, the feeding circuits controlling emotional or cognitive aspects of food intake are largely unknown. Here we use chemical genetics and optogenetic techniques to dissect appetite control circuits originating from ventral hippocampus (vHPC), a brain region implicated in emotion and cognition. We find that the vHPC projects functional glutamatergic synaptic inputs to the lateral septum (LS) and optogenetic activation of vHPC projections in LS reduces food intake. Consistently, food intake is suppressed by chemogenetic activation of glutamatergic neurons in the vHPC that project to the LS and inactivation of LS neurons blunts vHPC-induced suppression of feeding. Collectively, our results identify an anorexigenic neural circuit originating from vHPC to LS in the brain, revealing a potential therapeutic target for the treatment of anorexia or other appetite disorders.
The ventral hippocampus connects to the hypothalamus and has been implicated in feeding behaviours. Here, the authors use a combination of optogenetics and DREADD strategies to dissect the underlying circuit, showing that projections from the vHC to the lateral septum work to regulate feeding suppression.
PMCID: PMC4682174  PMID: 26666960
Neuro-Oncology  2014;16(Suppl 5):v189.
BACKGROUND: The therapeutic benefit of targeting T2/FLAIR in addition to contrast-enhancing (CE) tumor during re-irradiation for recurrent glioma can be attenuated by augmented toxicity. Given its steep dose fall-off and narrow penumbrae, PT minimizes volume of brain parenchyma outside target volume, potentially permitting a less toxic delivery of large-volume re-irradiation. METHODS: From 2/2011 to 12/2013, 19 consecutive adult patients with recurrent glioma treated with PT re-irradiation at a single institution were retrospectively analyzed. Planning target volume (PTV) included T2/FLAIR and CE abnormalities. Covariates assessed were age, gender, KPS at time of PT, number of salvage treatments, grade at initial diagnosis, interval between prior radiotherapy and PT, PT dose, PT PTV, bevacizumab failure, concurrent use of temozolomide and/or bevacizumab, and post-PT radiation necrosis. OS time from PT start was estimated with Kaplan-Meier analysis; comparisons used log-rank statistic. Multivariate analysis used the Cox proportional hazards model. RESULTS: Median age was 42 and median KPS was 90. Median salvage treatments was 2 (range 1-9). Median interval between prior radiotherapy and PT was 36.1 months (mos) (range 6.9-162.9). 12 patients (63%) were bevacizumab-refractory. Median PT dose was 50.4 CGE and median PTV was 224.2 cc. 5 patients (26%) remain alive. Median OS was 9.4 mos overall, 6.6 mos amongst bevacizumab-refractory patients, and 12.3 mos amongst bevacizumab-naive patients. Prior bevacizumab failure (hazard ratio (HR) 3.79; P = 0.047), shorter interval since prior radiotherapy (HR 1.04; P = 0.02), and Grade 4 disease (HR 4.17; P = 0.03) were prognostic of inferior OS. One patient had grade 3 radiation necrosis in the setting of PT re-irradiation for progressive brainstem glioma. One patient had grade 2 radiation necrosis, and another had grade 2 stroke. No other grade ≥3 toxicities were observed. CONCLUSION: Large-volume PT re-irradiation for recurrent glioma is safe and associated with promising OS outcomes, particularly in the setting of bevacizumab-refractory tumors.
PMCID: PMC4218549
3.  Digitization workflows for flat sheets and packets of plants, algae, and fungi1 
Applications in Plant Sciences  2015;3(9):apps.1500065.
Effective workflows are essential components in the digitization of biodiversity specimen collections. To date, no comprehensive, community-vetted workflows have been published for digitizing flat sheets and packets of plants, algae, and fungi, even though latest estimates suggest that only 33% of herbarium specimens have been digitally transcribed, 54% of herbaria use a specimen database, and 24% are imaging specimens. In 2012, iDigBio, the U.S. National Science Foundation’s (NSF) coordinating center and national resource for the digitization of public, nonfederal U.S. collections, launched several working groups to address this deficiency. Here, we report the development of 14 workflow modules with 7–36 tasks each. These workflows represent the combined work of approximately 35 curators, directors, and collections managers representing more than 30 herbaria, including 15 NSF-supported plant-related Thematic Collections Networks and collaboratives. The workflows are provided for download as Portable Document Format (PDF) and Microsoft Word files. Customization of these workflows for specific institutional implementation is encouraged.
PMCID: PMC4578381  PMID: 26421256
citizen science; digital imaging; digitization; herbarium; specimen database; workflow
4.  A Preventive Intervention for Pregnant Women on Public Assistance at Risk for Postpartum Depression 
The American journal of psychiatry  2006;163(8):1443-1445.
Promising results were obtained in an earlier pilot study of a preventive intervention based on the principles of interpersonal psychotherapy to reduce the risk of postpartum major depressive disorder. In this study, the authors examined whether the intervention would reduce the risk of postpartum major depressive disorder in a larger sample of pregnant women.
Ninety-nine pregnant women on public assistance who were assessed to be at risk for postpartum depression were randomly assigned to receive standard antenatal care plus the intervention or standard antenatal care only. Diagnostic interviews were administered 3 months after delivery to assess for major depressive disorder.
Within 3 months after delivery, eight (20%) of the women in the standard antenatal care condition had developed postpartum major depressive disorder, compared with two (4%) in the intervention condition.
This study provides further evidence for the efficacy of a brief intervention to reduce the occurrence of major depressive disorder among financially disadvantaged women during a postpartum period of 3 months.
PMCID: PMC4387544  PMID: 16877662
5.  Tobacco Cessation Among Low-Income Smokers: Motivational Enhancement and Nicotine Patch Treatment 
Nicotine & Tobacco Research  2013;16(4):413-422.
Despite decades of tobacco use decline among the general population in the United States, tobacco use among low-income populations continues to be a major public health concern. Smoking rates are higher among individuals with less than a high school education, those with no health insurance, and among individuals living below the federal poverty level. Despite these disparities, smoking cessation treatments for low-income populations have not been extensively tested. In the current study, the efficacy of 2 adjunctive smoking cessation interventions was evaluated among low-income smokers who were seen in a primary care setting.
A total of 846 participants were randomly assigned either to motivational enhancement treatment plus brief physician advice and 8 weeks of nicotine replacement therapy (NRT) or to standard care, which consisted of brief physician advice and 8 weeks of NRT. Tobacco smoking abstinence was at 1, 2, 6, and 12 months following baseline.
The use of the nicotine patch, telephone counseling, and positive decisional balance were predictive of increased abstinence rates, and elevated stress levels and temptation to smoke in both social/habit and negative affect situations decreased abstinence rates across time. Analyses showed intervention effects on smoking temptations, length of patch use, and number of telephone contacts. Direct intervention effects on abstinence rates were not significant, after adjusting for model predictors and selection bias due to perirandomization attrition.
Integrating therapeutic approaches that promote use of and adherence to medications for quitting smoking and that target stress management and reducing negative affect may enhance smoking cessation among low-income smokers.
PMCID: PMC3954421  PMID: 24174612
6.  Peroxiredoxin 3 levels regulate a mitochondrial redox setpoint in malignant mesothelioma cells 
Redox Biology  2014;3:79-87.
Peroxiredoxin 3 (PRX3), a typical 2-Cys peroxiredoxin located exclusively in the mitochondrial matrix, is the principal peroxidase responsible for metabolizing mitochondrial hydrogen peroxide, a byproduct of cellular respiration originating from the mitochondrial electron transport chain. Mitochondrial oxidants are produced in excess in cancer cells due to oncogenic transformation and metabolic reorganization, and signals through FOXM1 and other redox-responsive factors to support a hyper-proliferative state. Over-expression of PRX3 in cancer cells has been shown to counteract oncogene-induced senescence and support tumor cell growth and survival making PRX3 a credible therapeutic target. Using malignant mesothelioma (MM) cells stably expressing shRNAs to PRX3 we show that decreased expression of PRX3 alters mitochondrial structure, function and cell cycle kinetics. As compared to control cells, knockdown of PRX3 expression increased mitochondrial membrane potential, basal ATP production, oxygen consumption and extracellular acidification rates. shPRX3 MM cells failed to progress through the cell cycle compared to wild type controls, with increased numbers of cells in G2/M phase. Diminished PRX3 expression also induced mitochondrial hyperfusion similar to the DRP1 inhibitor mdivi-1. Cell cycle progression and changes in mitochondrial networking were rescued by transient expression of either catalase or mitochondrial-targeted catalase, indicating high levels of hydrogen peroxide contribute to perturbations in mitochondrial structure and function in shPRX3 MM cells. Our results indicate that PRX3 levels establish a redox set point that permits MM cells to thrive in response to increased levels of mROS, and that perturbing the redox status governed by PRX3 impairs proliferation by altering cell cycle-dependent dynamics between mitochondrial networking and energy metabolism.
Graphical abstract
•Knockdown of PRX3 in malignant mesothelioma cells increases mitochondrial oxidants.•Knockdown of PRX3 induces mitochondrial fusion and an increase in G2/M cells.•Overexpression of catalase or mito-catalase rescues G2/M cell cycle block and mitochondrial defects.
PMCID: PMC4297934  PMID: 25462069
Peroxiredoxin 3; Mitochondrial structure; Cell cycle; Oxidative stress
7.  Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies 
Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical trials include the inability of animal models to recapitulate the human disease, variations in breeding and colony maintenance, lack of standards in design, conduct and analysis of animal trials, and publication bias due to under-reporting of negative results in the scientific literature. The quality of animal model research on novel therapeutics can be improved by bringing the rigor of human clinical trials to animal studies. Research communities in several disease areas have developed recommendations for the conduct and reporting of preclinical studies in order to increase their validity, reproducibility, and predictive value. To address these issues in the AD community, the Alzheimer's Drug Discovery Foundation partnered with Charles River Discovery Services (Morrisville, NC, USA) and Cerebricon Ltd. (Kuopio, Finland) to convene an expert advisory panel of academic, industry, and government scientists to make recommendations on best practices for animal studies testing investigational AD therapies. The panel produced recommendations regarding the measurement, analysis, and reporting of relevant AD targets, th choice of animal model, quality control measures for breeding and colony maintenance, and preclinical animal study design. Major considerations to incorporate into preclinical study design include a priori hypotheses, pharmacokinetics-pharmacodynamics studies prior to proof-of-concept testing, biomarker measurements, sample size determination, and power analysis. The panel also recommended distinguishing between pilot 'exploratory' animal studies and more extensive 'therapeutic' studies to guide interpretation. Finally, the panel proposed infrastructure and resource development, such as the establishment of a public data repository in which both positive animal studies and negative ones could be reported. By promoting best practices, these recommendations can improve the methodological quality and predictive value of AD animal studies and make the translation to human clinical trials more efficient and reliable.
PMCID: PMC3218805  PMID: 21943025
8.  Intravenous piperacillin/tazobactam plus fluoroquinolone prophylaxis prior to prostate ultrasound biopsy reduces serious infectious complications and is cost effective 
Infectious complications related to prostate ultrasound and biopsy have increased in the past decade with the emergence of increasing fluoroquinolone bacterial resistance. We investigated the addition of intravenous (iv) piperacillin/tazobactam immediately prior to prostate ultrasound and biopsy with standard fluoroquinolone prophylaxis to determine if it would decrease the incidence of serious infectious complications after prostate ultrasound and biopsy. Group 1 patients were a historic control of 197 patients who underwent prostate ultrasound and biopsy with standard fluoroquinolone prophylaxis. Group 2 patients, 104 patients, received standard fluoroquinolone prophylaxis and the addition of a single dose of iv piperacillin/tazobactam 30 minutes prior to prostate ultrasound and biopsy. There were ten serious bacterial infectious complications in group 1 patients. No patients in group 2 developed serious bacterial infections after prostate ultrasound and biopsy. There was approximately a 5% incidence of serious bacterial infection in group 1 patients. Subgroup analysis revealed an almost 2.5 times increased risk of infection in diabetes patients undergoing prostate ultrasound and biopsy. There was a 10% risk of serious bacterial infection in diabetics compared with a 3.8% risk group 1 nondiabetes patients. The addition of a single dose of iv piperacillin/tazobactam along with standard fluoroquinolone prophylaxis substantially reduces the risk of serious bacterial infection after prostate ultrasound and biopsy (P < 0.02).
PMCID: PMC3818943  PMID: 24198647
piperacillin/tazobactam; fluoroquinolone; prostate biopsy; infectious complications
10.  A Case of Infantile Cortical Hyperostosis 
Postgraduate Medical Journal  1958;34(397):598-600.
PMCID: PMC2501595  PMID: 13591075
11.  A Case of Megaoesophagus due to Cardiospasm 
Postgraduate Medical Journal  1957;33(375):27-28.
PMCID: PMC2501121  PMID: 13389033
12.  Farmer's Lung 
The Ulster Medical Journal  1952;21(2):150-154.
PMCID: PMC2479998  PMID: 13029294
13.  Chronic Hypoplastic Anaemia arising in Infancy 
Archives of Disease in Childhood  1948;23(116):294-296.
PMCID: PMC1988175  PMID: 18108437
14.  Differential Diagnosis of Coma 
Postgraduate Medical Journal  1948;24(278):637-642.
PMCID: PMC2529918  PMID: 18105130

Results 1-14 (14)