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1.  Validation of the Patient Health Questionnaire-9 (PHQ-9) For Depression Screening in Adults with Epilepsy 
Epilepsy & behavior : E&B  2014;37:215-220.
Assess accuracy and operating characteristics of the Patient Health Questionnaire-9 (PHQ-9) for depression-screening in adults with epilepsy.
Tertiary epilepsy center patients served as the study population with 237 agreeing to structured interview using the Mini-International Neuropsychiatric Interview (MINI), a “gold standard” instrument developed for rapid diagnosis of neuropsychiatric disorders, including major depressive disorder (MDD); 172 also completed the PHQ-9, and 127 completed both the PHQ-9 and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) within two days of the MINI. Sensitivity, specificity, positive & negative predictive values & areas under the ROC curves for each instrument were determined. Cut-points of 10 for the PHQ-9 and 15 for the NDDI-E were used and ratings at or above the cut-points were considered screen-positive. The PHQ-9 was divided into cognitive/affective (PHQ-9/CA) and somatic (PHQ-9/S) subscales to determine comparative depression-screening accuracy.
The calculated areas under the ROC curves for the PHQ-9 (n=172) and the PHQ-9/CA and PHQ-9/S sub-scales were 0.914, 0.924, and 0.846, respectively, with the PHQ-9 more accurate than the PHQ-9/S (p=0.002) but no different than the PHQ-9/CA (p=0.378). At cut-points of 10 and 15, respectively, the PHQ-9 had higher sensitivity (0.92 vs 0.87), but lower specificity (0.74 vs 0.89) than the NDDI-E. The areas under the ROC curves of the PHQ-9 and the NDDI-E showed similar accuracy (n=127; 0.930 vs 0.934; p=0.864).
The PHQ-9 is an efficient & non-proprietary depression screening instrument with excellent accuracy validated for use in adult epilepsy patients as well as multiple other medical populations.
PMCID: PMC4427235  PMID: 25064739
Epilepsy/Seizures; Depression; PHQ-9; NDDI-E; Screening
2.  Delay in reperfusion with transradial percutaneous coronary intervention for ST-elevation myocardial infarction: Might some delays be acceptable? 
American heart journal  2014;168(1):103-109.
Randomized clinical trials (RCTs) suggest benefits for the transradial approach to percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). However, transradial PCI may delay reperfusion, leading to its avoidance. We sought to quantify the delay in reperfusion from transradial PCI (“transradial delay”) that would need to be introduced to offset the potential mortality benefit of transradial PCI, compared with transfemoral, observed in RCTs.
We developed a decision-analytic model to compare transfemoral and transradial PCI in STEMI. 30-day mortality rates were estimated by pooling STEMI patients from two RCTs comparing transfemoral and transradial PCI. We projected the impact of transradial delay using estimates of the increase in mortality associated with door-to-balloon time delays. Sensitivity analyses were performed to understand the impact of uncertainty in assumptions.
In the base case, a transradial delay of 83.0 minutes was needed to offset the mortality benefit of transradial PCI. When the mortality benefit of transradial PCI was one-quarter that observed in RCTs, the delay associated with equivalent mortality was 20.9 minutes. In probabilistic sensitivity analyses, transradial PCI was preferred over transfemoral PCI in 97.5% of simulations when transradial delay was 30 minutes and 79.0% of simulations when delay was 60 minutes.
A substantial transradial delay is required to eliminate even a fraction of the mortality benefit observed with transradial PCI in RCTs. Results were robust to changing multiple assumptions and have implications for operators reluctant to transition to transradial PCI in STEMI due to concern for delaying reperfusion.
PMCID: PMC4067602  PMID: 24952866
transradial; percutaneous coronary intervention; ST-segment elevation myocardial infarction; door-to-balloon time; decision analysis
3.  In vitro propagation of female Ephedra foliata Boiss. & Kotschy ex Boiss.: an endemic and threatened Gymnosperm of the Thar Desert 
Ephedra foliata Boiss. & Kotschy ex Boiss., (family – Ephedraceae), is an ecologically and economically important threatened Gymnosperm of the Indian Thar Desert. A method for micropropagation of E. foliata using nodal explant of mature female plant has been developed. Maximum bud-break (90 %) of the explant was obtained on MS medium supplemented with 1.5 mg l−1 of benzyl adenine (BA) + additives. Explant produces 5.3 ± 0.40 shoots from single node with 3.25 ± 0.29 cm length. The multiplication of shoots in culture was affected by salt composition of media, types and concentrations of plant growth regulators (PGR’s) and their interactions, time of transfer of the cultures. Maximum number of shoots (26.3 ± 0.82 per culture vessel) were regenerated on MS medium modified by reducing the concentration of nitrates to half supplemented with 200 mg l−1 ammonium sulphate {(NH4) 2SO4} (MMS3) + BA (0.25 mg l−1), Kinetin (Kin; 0.25 mg l−1), Indole-3-acetic acid (IAA; 0.1 mg l−1) and additives. The in vitro produced shoots rooted under ex vitro on soilrite moistened with one-fourth strength of MS macro salts in screw cap bottles by treating the shoot base (s) with 500 mg l−1 of Indole-3-butyric acid (IBA) for 5 min. The micropropagated plants were hardened in the green house. The described protocol can be applicable for (i) large scale plant production (ii) establishment of plants in natural habitat and (iii) germplasm conservation of this endemic Gymnosperm of arid regions.
PMCID: PMC4101145  PMID: 25049465
Ephedra foliata; Fleshy fruit bract; In vitro propagation; Modified MS medium; Ex vitro rooting
5.  Neurilemmoma of Retromolar Region in the Oral Cavity 
Case Reports in Dentistry  2015;2015:320830.
Neurilemmoma also known as schwannoma is benign nerve sheath tumor rarely occurring in the oral cavity. Only 1% of all extracranial schwannomas show that intraoral occurrence with tongue is the commonest site and retromolar region is the least common site. It presents as encapsulated, slow growing, solitary, smooth-surfaced, usually asymptomatic tumor. We report a case of 70-year-old male with well-defined mass on left retromolar region which was painless and slow growing. Diagnosis is made by histological examination and immunohistochemistry analysis to confirm the neural tissue origin of the lesion. The treatment is complete surgical excision of the lesion without recurrence.
PMCID: PMC4499617  PMID: 26221545
6.  Exploring the attitudes of medical faculty members and students in Pakistan towards plagiarism: a cross sectional survey 
PeerJ  2015;3:e1031.
Objective. The objective of this survey was to explore the attitudes towards plagiarism of faculty members and medical students in Pakistan.
Methods. The Attitudes Toward Plagiarism questionnaire (ATP) was modified and distributed among 550 medical students and 130 faculty members in 7 medical colleges of Lahore and Rawalpindi. Data was entered in the SPSS v.20 and descriptive statistics were analyzed. The questionnaire was validated by principal axis factoring analysis.
Results. Response rate was 93% and 73%, respectively. Principal axis factoring analysis confirmed one factor structure of ATP in the present sample. It had an acceptable Cronbach’s alpha value of 0.73. There were 421 medical students (218 (52%) female, 46% 3rd year MBBS students, mean age of 20.93 ± 1.4 years) and 95 faculty members (54.7% female, mean age 34.5 ± 8.9 years). One fifth of the students (19.7%) trained in medical writing (19.7%), research ethics (25.2%) or were currently involved in medical writing (17.6%). Most of the faculty members were demonstrators (66) or assistant professors (20) with work experience between 1 and 10 years. Most of them had trained in medical writing (68), research ethics (64) and were currently involved in medical writing (64). Medical students and faculty members had a mean score of 43.21 (7.1) and 48.4 (5.9) respectively on ATP. Most of the respondents did not consider that they worked in a plagiarism free environment and reported that self-plagiarism should not be punishable in the same way as plagiarism. Opinion regarding leniency in punishment of younger researchers who were just learning medical writing was divided.
Conclusions. The general attitudes of Pakistani medical faculty members and medical students as assessed by ATP were positive. We propose training in medical writing and research ethics as part of the under and post graduate medical curriculum.
PMCID: PMC4476128  PMID: 26157615
Medical education; Plagiarism; Medical writing; Scientific writing; Ethics; Attitudes; Pakistan
7.  A Randomised Controlled Trial to Compare Intravenous Iron Sucrose and Oral Iron in Treatment of Iron Deficiency Anemia in Pregnancy 
The aim of this study was to compare the efficacy and safety of intravenous iron sucrose with oral iron therapy in pregnant patients with anemia. The primary outcome of the study was increase in haemoglobin on day 7, 14 & 28 and rise of serum ferritin over 28 days. The study population consisted of 100 patients with singleton pregnancy between 24 and 34 weeks, hemoglobin levels between 7.0–9.0 gm/dL and serum ferritin levels less than 15 ng/mL. The participants in the oral group were given daily 180 mg elemental iron in three divided oral doses for 4 weeks. Total calculated dose of iron sucrose with a target hemoglobin of 11 gm %, was given in 200 mg dose on alternate days. Mean haemoglobin rise was 0.58 gm/dL in the IV group as compared to 0.23 gm/dL in the oral group on day 14 and 1.9 gm/dL in the IV group & 1.3 gm/dL in the oral group on day 28, (p <0.05). In the IV group, 76% of the subjects achieved haemoglobin levels of ≥11 gm% at the time of delivery, as compared to only 54% of the subjects in the oral group who achieved these levels. Serum ferritin value was significantly higher in the IV group, 37.45 ± 5.73 ng/mL as compared to 13.96 ± 1.88 ng/mL in the oral group at 4th week (p <0.001). There was no major side effect in the IV group. 36% subjects in the oral group developed gastrointestinal side effects & 10% of the subjects were non compliant. The rate of hemoglobin rise is faster with intravenous iron sucrose therapy as compared to oral iron therapy which can be beneficial in pregnant women presenting with anemia at a later period of gestation. Intravenous iron sucrose is very well tolerated during pregnancy.
PMCID: PMC4022911  PMID: 24839366
Iron deficiency; Pregnancy; Hemoglobin rise; Iron sucrose; Cord blood hemoglobin
8.  A rare mutation in UNC5C predisposes to Alzheimer’s disease and increases neuronal cell death 
Nature medicine  2014;20(12):1452-1457.
We have identified a rare coding mutation, T835M (rs137875858), in the Netrin receptor UNC5C that segregated with disease in an autosomal dominant pattern in two families enriched for late-onset Alzheimer’s disease (LOAD), and was associated with disease across four large case/control cohorts (OR = 2.15, Pmeta= 0.0095). T835M alters a conserved residue in the hinge region of UNC5C, and in vitro studies demonstrate that this mutation leads to increased cell death in several cell types, including neurons. Furthermore, neurons expressing T835M UNC5C are more susceptible to multiple neurodegenerative stimuli, including β-Amyloid (Aβ). Based on these data and the enriched hippocampal expression of UNC5C in the adult nervous system, we propose one possible mechanism in which T835M UNC5C contributes to the risk of Alzheimer’s disease is by increasing susceptibility to neuronal cell death, particularly in vulnerable regions of the Alzheimer’s brain.
PMCID: PMC4301587  PMID: 25419706
9.  Effect of divalent Ba cation substitution with Sr on coupled ‘multiglass’ state in the magnetoelectric multiferroic compound Ba3NbFe3Si2O14 
Scientific Reports  2015;5:9751.
(Ba/Sr)3NbFe3Si2O14 is a magneto-electric multiferroic with an incommensurate antiferromagnetic spiral magnetic structure which induces electric polarization at 26 K. Structural studies show that both the compounds have similar crystal structure down to 6 K. They exhibit a transition, TN at 26 K and 25 K respectively, as indicated by heat capacity and magnetization, into an antiferromagnetic state. Although Ba and Sr are isovalent, they exhibit very different static and dynamic magnetic behaviors. The Ba-compound exhibits a glassy behavior with critical slowing dynamics with a freezing temperature of ~35 K and a critical exponent of 3.9, a value close to the 3-D Ising model above TN, in addition to the invariant transition into an antiferromagnetic state. The Sr-compound however does not exhibit any dispersive behavior except for the invariant transition at TN. The dielectric constant reflects magnetic behavior of the two compounds: the Ba-compound has two distinct dispersive peaks while the Sr-compound has a single dispersive peak. Thus the compounds exhibit coupled ‘multiglass’ behavior. The difference in magnetic properties between the two compounds is found to be due to modifications to super exchange path angle and length as well as anti-site defects which stabilize either ferromagnetic or antiferromagnetic interactions.
PMCID: PMC4437043  PMID: 25988657
10.  Synthesis and Antimicrobial Activities of His(2-aryl)-Arg and Trp-His(2-aryl) Classes of Dipeptidomimetics 
MedChemComm  2014;5(5):671-676.
In this communication, we report the design, synthesis and in vitro antimicrobial activity of ultra short peptidomimetics. Besides producing promising antibacterial activities against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), the dipeptidomimetics exhibited high antifungal activity against C. neoformans with IC50 values in the range of 0.16-19 μg/mL. The most potent analogs exhibited 4-fold higher activity than the currently used drug amphotericin B, with no apparent cytotoxicity in a panel of mammalian cell lines.
PMCID: PMC4066839  PMID: 24976942
11.  A critical review of pharmacological significance of Hydrogen Sulfide in hypertension 
Indian Journal of Pharmacology  2015;47(3):243-247.
In the family of gas transmitters, hydrogen sulfide (H2S) is yet not adequately researched. Known for its rotten egg smell and adverse effects on the brain, lungs, and kidneys for more than 300 years, the vasorelaxant effects of H2S on blood vessel was first observed in 1997. Since then, research continued to explore the possible therapeutic effects of H2S in hypertension, inflammation, pancreatitis, different types of shock, diabetes, and heart failure. However, a considerable amount of efforts are yet needed to elucidate the mechanisms involved in the therapeutic effects of H2S, such as nitric oxide-dependent or independent vasodilation in hypertension and regression of left ventricular hypertrophy. More than a decade of good repute among researchers, H2S research has certain results that need to be clarified or reevaluated. H2S produces its response by multiple modes of action, such as opening the ATP-sensitive potassium channel, angiotensin-converting enzyme inhibition, and calcium channel blockade. H2S is endogenously produced from two sulfur-containing amino acids L-cysteine and L-methionine by the two enzymes cystathionine γ lyase and cystathionine β synthase. Recently, the third enzyme, 3-mercaptopyruvate sulfur transferase, along with cysteine aminotransferase, which is similar to aspartate aminotransferase, has been found to produce H2S in the brain. The H2S has interested researchers, and a great deal of information is being generated every year. This review aims to provide an update on the developments in the research of H2S in hypertension amid the ambiguity in defining the exact role of H2S in hypertension because of insufficient number of research results on this area. This critical review on the role of H2S in hypertension will clarify the gray areas and highlight its future prospects.
PMCID: PMC4450547  PMID: 26069359
3-3-mercaptopyruvate sulfur transferase; cystathionine γ lyase; cystathionine β synthase; cysteine aminotransferase; hydrogen sulfide; hypertension
12.  The AVRDC – The World Vegetable Center mungbean (Vigna radiata) core and mini core collections 
BMC Genomics  2015;16(1):344.
Large ex situ germplasm collections generally harbor a wide range of crop diversity. AVRDC – The World Vegetable Center is holding in trust the world’s second largest mungbean (Vigna radiata) germplasm collection with more than 6,700 accessions. Screening large collections for traits of interest is laborious and expensive. To enhance the access of breeders to the diversity of the crop, mungbean core and mini core collections have been established.
The core collection of 1,481 entries has been built by random selection of 20% of the accessions after geographical stratification and subsequent cluster analysis of eight phenotypic descriptors in the whole collection. Summary statistics, especially the low differences of means, equal variance of the traits in both the whole and core collection and the visual inspection of quantile-quantile plots comparing the variation of phenotypic traits present in both collections indicated that the core collection well represented the pattern of diversity of the whole collection. The core collection was genotyped with 20 simple sequence repeat markers and a mini core set of 289 accessions was selected, which depicted the allele and genotype diversity of the core collection.
The mungbean core and mini core collections plus their phenotypic and genotypic data are available for distribution to breeders. It is expected that these collections will enhance the access to biodiverse mungbean germplasm for breeding.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1556-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4422537  PMID: 25925106
Mungbean; Genetic diversity; Germplasm collection; Core and mini core collection; Breeding
13.  Injection practice in Kaski district, Western Nepal: a community perspective 
BMC Public Health  2015;15:435.
Previous studies have shown that unsafe injection practice is a major public health problem in Nepal but did not quantify the problem. The present community-based study was planned to: 1) quantify injection usage, 2) identify injection providers, 3) explore differences, if any, in injection usage and injection providers, and 4) study and compare people’s knowledge and perception about injections between the urban and rural areas of Kaski district.
A descriptive, cross-sectional mixed-methods study was conducted from July to November 2012, using a questionnaire based survey and focus group discussions (FGDs). A semi-structured questionnaire advocated by the World Health Organization was modified and administered to household heads and injection receivers in selected households and the FGDs were conducted using a topic guide. The district was divided into urban and rural areas and 300 households from each area were selected. Twenty FGDs were held.
In 218 households (36.33%) [99 in urban and 119 in rural] one or more members received at least one injection. During the three month recall period, 258 subjects (10.44%) reported receiving injection(s) with a median of two injections. The average number of injections per person per year was calculated to be 2.37. Health care workers (34.8%), staff of medical dispensaries (37.7%), physicians (25.2%), and traditional healers (2.3%) were consulted by the respondents for their basic health care needs and for injections. Compared to urban respondents, more rural respondents preferred injections for fever (p < 0.001). People preferred injections due to injections being perceived by them as being powerful, fast-acting, and longer lasting than oral pills. More than 82% of respondents were aware of, and named, at least one disease transmitted by using unsterile syringes during injection administration or when syringes are shared between people.
Less preference for injections and high awareness about the association between injections and injection-borne infections among the general population is encouraging for safe injection practice. However, respondents were not aware of the importance of having qualified injection providers for safe injections and were receiving injections from unqualified personnel.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-015-1775-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4425888  PMID: 25928311
Community; Injection practice; Knowledge; Needle-stick injury; Nepal
14.  Underweight Full-Term Indian Neonates Show Differences in Umbilical Cord Blood Leukocyte Phenotype: A Cross-Sectional Study 
PLoS ONE  2015;10(4):e0123589.
While infections are a major cause of neonatal mortality in India even in full-term neonates, this is an especial problem in the large proportion (~20%) of neonates born underweight (or small-for-gestational-age; SGA). One potential contributory factor for this susceptibility is the possibility that immune system maturation may be affected along with intrauterine growth retardation.
In order to examine the possibility that differences in immune status may underlie the susceptibility of SGA neonates to infections, we enumerated the frequencies and concentrations of 22 leukocyte subset populations as well as IgM and IgA levels in umbilical cord blood from full-term SGA neonates and compared them with values from normal-weight (or appropriate-for-gestational-age; AGA) full-term neonates. We eliminated most SGA-associated risk factors in the exclusion criteria so as to ensure that AGA-SGA differences, if any, would be more likely to be associated with the underweight status itself.
An analysis of 502 such samples, including 50 from SGA neonates, showed that SGA neonates have significantly fewer plasmacytoid dendritic cells (pDCs), a higher myeloid DC (mDC) to pDC ratio, more natural killer (NK) cells, and higher IgM levels in cord blood in comparison with AGA neonates. Other differences were also observed such as tendencies to lower CD4:CD8 ratios and greater prominence of inflammatory monocytes, mDCs and neutrophils, but while some of them had substantial differences, they did not quite reach the standard level of statistical significance.
These differences in cellular lineages of the immune system possibly reflect stress responses in utero associated with growth restriction. Increased susceptibility to infections may thus be linked to complex immune system dysregulation rather than simply retarded immune system maturation.
PMCID: PMC4405369  PMID: 25898362
15.  Oral manifestations of vitamin D resistant rickets in orthopantomogram 
BMJ Case Reports  2013;2013:bcr2012008318.
PMCID: PMC3618756  PMID: 23486344
16.  Hemicrania continua with contralateral cranial autonomic features: a case report 
Hemicrania continua is characterized by continuous strictly unilateral head pain with episodic exacerbations. Episodic exacerbations are associated with ipsilateral cranial autonomic features.
Case description
We report a 24-year female with a 2-year history of continuous right-sided headache with superimposed exacerbations. Episodic exacerbations were associated with marked agitation and contralateral cranial autonomic features. The patient showed a complete response to indomethacin within 8 hours.
The dichotomy of pain and autonomic features is in accordance with the concept about the possibility of two separate pathways for pain and autonomic features in trigeminal autonomic cephalalgias.
PMCID: PMC4385230  PMID: 25902939
Hemicrania continua; Cluster headache; Paroxysmal hemicrania; Trigeminal autonomic cephalagias; Indomethacin
17.  Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution 
Leung, Wilson | Shaffer, Christopher D. | Reed, Laura K. | Smith, Sheryl T. | Barshop, William | Dirkes, William | Dothager, Matthew | Lee, Paul | Wong, Jeannette | Xiong, David | Yuan, Han | Bedard, James E. J. | Machone, Joshua F. | Patterson, Seantay D. | Price, Amber L. | Turner, Bryce A. | Robic, Srebrenka | Luippold, Erin K. | McCartha, Shannon R. | Walji, Tezin A. | Walker, Chelsea A. | Saville, Kenneth | Abrams, Marita K. | Armstrong, Andrew R. | Armstrong, William | Bailey, Robert J. | Barberi, Chelsea R. | Beck, Lauren R. | Blaker, Amanda L. | Blunden, Christopher E. | Brand, Jordan P. | Brock, Ethan J. | Brooks, Dana W. | Brown, Marie | Butzler, Sarah C. | Clark, Eric M. | Clark, Nicole B. | Collins, Ashley A. | Cotteleer, Rebecca J. | Cullimore, Peterson R. | Dawson, Seth G. | Docking, Carter T. | Dorsett, Sasha L. | Dougherty, Grace A. | Downey, Kaitlyn A. | Drake, Andrew P. | Earl, Erica K. | Floyd, Trevor G. | Forsyth, Joshua D. | Foust, Jonathan D. | Franchi, Spencer L. | Geary, James F. | Hanson, Cynthia K. | Harding, Taylor S. | Harris, Cameron B. | Heckman, Jonathan M. | Holderness, Heather L. | Howey, Nicole A. | Jacobs, Dontae A. | Jewell, Elizabeth S. | Kaisler, Maria | Karaska, Elizabeth A. | Kehoe, James L. | Koaches, Hannah C. | Koehler, Jessica | Koenig, Dana | Kujawski, Alexander J. | Kus, Jordan E. | Lammers, Jennifer A. | Leads, Rachel R. | Leatherman, Emily C. | Lippert, Rachel N. | Messenger, Gregory S. | Morrow, Adam T. | Newcomb, Victoria | Plasman, Haley J. | Potocny, Stephanie J. | Powers, Michelle K. | Reem, Rachel M. | Rennhack, Jonathan P. | Reynolds, Katherine R. | Reynolds, Lyndsey A. | Rhee, Dong K. | Rivard, Allyson B. | Ronk, Adam J. | Rooney, Meghan B. | Rubin, Lainey S. | Salbert, Luke R. | Saluja, Rasleen K. | Schauder, Taylor | Schneiter, Allison R. | Schulz, Robert W. | Smith, Karl E. | Spencer, Sarah | Swanson, Bryant R. | Tache, Melissa A. | Tewilliager, Ashley A. | Tilot, Amanda K. | VanEck, Eve | Villerot, Matthew M. | Vylonis, Megan B. | Watson, David T. | Wurzler, Juliana A. | Wysocki, Lauren M. | Yalamanchili, Monica | Zaborowicz, Matthew A. | Emerson, Julia A. | Ortiz, Carlos | Deuschle, Frederic J. | DiLorenzo, Lauren A. | Goeller, Katie L. | Macchi, Christopher R. | Muller, Sarah E. | Pasierb, Brittany D. | Sable, Joseph E. | Tucci, Jessica M. | Tynon, Marykathryn | Dunbar, David A. | Beken, Levent H. | Conturso, Alaina C. | Danner, Benjamin L. | DeMichele, Gabriella A. | Gonzales, Justin A. | Hammond, Maureen S. | Kelley, Colleen V. | Kelly, Elisabeth A. | Kulich, Danielle | Mageeney, Catherine M. | McCabe, Nikie L. | Newman, Alyssa M. | Spaeder, Lindsay A. | Tumminello, Richard A. | Revie, Dennis | Benson, Jonathon M. | Cristostomo, Michael C. | DaSilva, Paolo A. | Harker, Katherine S. | Jarrell, Jenifer N. | Jimenez, Luis A. | Katz, Brandon M. | Kennedy, William R. | Kolibas, Kimberly S. | LeBlanc, Mark T. | Nguyen, Trung T. | Nicolas, Daniel S. | Patao, Melissa D. | Patao, Shane M. | Rupley, Bryan J. | Sessions, Bridget J. | Weaver, Jennifer A. | Goodman, Anya L. | Alvendia, Erica L. | Baldassari, Shana M. | Brown, Ashley S. | Chase, Ian O. | Chen, Maida | Chiang, Scott | Cromwell, Avery B. | Custer, Ashley F. | DiTommaso, Tia M. | El-Adaimi, Jad | Goscinski, Nora C. | Grove, Ryan A. | Gutierrez, Nestor | Harnoto, Raechel S. | Hedeen, Heather | Hong, Emily L. | Hopkins, Barbara L. | Huerta, Vilma F. | Khoshabian, Colin | LaForge, Kristin M. | Lee, Cassidy T. | Lewis, Benjamin M. | Lydon, Anniken M. | Maniaci, Brian J. | Mitchell, Ryan D. | Morlock, Elaine V. | Morris, William M. | Naik, Priyanka | Olson, Nicole C. | Osterloh, Jeannette M. | Perez, Marcos A. | Presley, Jonathan D. | Randazzo, Matt J. | Regan, Melanie K. | Rossi, Franca G. | Smith, Melanie A. | Soliterman, Eugenia A. | Sparks, Ciani J. | Tran, Danny L. | Wan, Tiffany | Welker, Anne A. | Wong, Jeremy N. | Sreenivasan, Aparna | Youngblom, Jim | Adams, Andrew | Alldredge, Justin | Bryant, Ashley | Carranza, David | Cifelli, Alyssa | Coulson, Kevin | Debow, Calise | Delacruz, Noelle | Emerson, Charlene | Farrar, Cassandra | Foret, Don | Garibay, Edgar | Gooch, John | Heslop, Michelle | Kaur, Sukhjit | Khan, Ambreen | Kim, Van | Lamb, Travis | Lindbeck, Peter | Lucas, Gabi | Macias, Elizabeth | Martiniuc, Daniela | Mayorga, Lissett | Medina, Joseph | Membreno, Nelson | Messiah, Shady | Neufeld, Lacey | Nguyen, San Francisco | Nichols, Zachary | Odisho, George | Peterson, Daymon | Rodela, Laura | Rodriguez, Priscilla | Rodriguez, Vanessa | Ruiz, Jorge | Sherrill, Will | Silva, Valeria | Sparks, Jeri | Statton, Geeta | Townsend, Ashley | Valdez, Isabel | Waters, Mary | Westphal, Kyle | Winkler, Stacey | Zumkehr, Joannee | DeJong, Randall J. | Hoogewerf, Arlene J. | Ackerman, Cheri M. | Armistead, Isaac O. | Baatenburg, Lara | Borr, Matthew J. | Brouwer, Lindsay K. | Burkhart, Brandon J. | Bushhouse, Kelsey T. | Cesko, Lejla | Choi, Tiffany Y. 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Devin | Stemler, Kristina M. | Throm, Allison A. | Van Camp, Matt | Weihbrecht, Katie | Wiles, T. Aaron | Williams, Mallory A. | Williams, Matthew | Zoll, Kyle | Bailey, Cheryl | Zhou, Leming | Balthaser, Darla M. | Bashiri, Azita | Bower, Mindy E. | Florian, Kayla A. | Ghavam, Nazanin | Greiner-Sosanko, Elizabeth S. | Karim, Helmet | Mullen, Victor W. | Pelchen, Carly E. | Yenerall, Paul M. | Zhang, Jiayu | Rubin, Michael R. | Arias-Mejias, Suzette M. | Bermudez-Capo, Armando G. | Bernal-Vega, Gabriela V. | Colon-Vazquez, Mariela | Flores-Vazquez, Arelys | Gines-Rosario, Mariela | Llavona-Cartagena, Ivan G. | Martinez-Rodriguez, Javier O. | Ortiz-Fuentes, Lionel | Perez-Colomba, Eliezer O. | Perez-Otero, Joseph | Rivera, Elisandra | Rodriguez-Giron, Luke J. | Santiago-Sanabria, Arnaldo J. | Senquiz-Gonzalez, Andrea M. | delValle, Frank R. Soto | Vargas-Franco, Dorianmarie | Velázquez-Soto, Karla I. | Zambrana-Burgos, Joan D. | Martinez-Cruzado, Juan Carlos | Asencio-Zayas, Lillyann | Babilonia-Figueroa, Kevin | Beauchamp-Pérez, Francis D. | Belén-Rodríguez, Juliana | Bracero-Quiñones, Luciann | Burgos-Bula, Andrea P. | Collado-Méndez, Xavier A. | Colón-Cruz, Luis R. | Correa-Muller, Ana I. | Crooke-Rosado, Jonathan L. | Cruz-García, José M. | Defendini-Ávila, Marianna | Delgado-Peraza, Francheska M. | Feliciano-Cancela, Alex J. | Gónzalez-Pérez, Valerie M. | Guiblet, Wilfried | Heredia-Negrón, Aldo | Hernández-Muñiz, Jennifer | Irizarry-González, Lourdes N. | Laboy-Corales, Ángel L. | Llaurador-Caraballo, Gabriela A. | Marín-Maldonado, Frances | Marrero-Llerena, Ulises | Martell-Martínez, Héctor A. | Martínez-Traverso, Idaliz M. | Medina-Ortega, Kiara N. | Méndez-Castellanos, Sonya G. | Menéndez-Serrano, Krizia C. | Morales-Caraballo, Carol I. | Ortiz-DeChoudens, Saryleine | Ortiz-Ortiz, Patricia | Pagán-Torres, Hendrick | Pérez-Afanador, Diana | Quintana-Torres, Enid M. | Ramírez-Aponte, Edwin G. | Riascos-Cuero, Carolina | Rivera-Llovet, Michelle S. | Rivera-Pagán, Ingrid T. | Rivera-Vicéns, Ramón E. | Robles-Juarbe, Fabiola | Rodríguez-Bonilla, Lorraine | Rodríguez-Echevarría, Brian O. | Rodríguez-García, Priscila M. | Rodríguez-Laboy, Abneris E. | Rodríguez-Santiago, Susana | Rojas-Vargas, Michael L. | Rubio-Marrero, Eva N. | Santiago-Colón, Albeliz | Santiago-Ortiz, Jorge L. | Santos-Ramos, Carlos E. | Serrano-González, Joseline | Tamayo-Figueroa, Alina M. | Tascón-Peñaranda, Edna P. | Torres-Castillo, José L. | Valentín-Feliciano, Nelson A. | Valentín-Feliciano, Yashira M. | Vargas-Barreto, Nadyan M. | Vélez-Vázquez, Miguel | Vilanova-Vélez, Luis R. | Zambrana-Echevarría, Cristina | MacKinnon, Christy | Chung, Hui-Min | Kay, Chris | Pinto, Anthony | Kopp, Olga R. | Burkhardt, Joshua | Harward, Chris | Allen, Robert | Bhat, Pavan | Chang, Jimmy Hsiang-Chun | Chen, York | Chesley, Christopher | Cohn, Dara | DuPuis, David | Fasano, Michael | Fazzio, Nicholas | Gavinski, Katherine | Gebreyesus, Heran | Giarla, Thomas | Gostelow, Marcus | Greenstein, Rachel | Gunasinghe, Hashini | Hanson, Casey | Hay, Amanda | He, Tao Jian | Homa, Katie | Howe, Ruth | Howenstein, Jeff | Huang, Henry | Khatri, Aaditya | Kim, Young Lu | Knowles, Olivia | Kong, Sarah | Krock, Rebecca | Kroll, Matt | Kuhn, Julia | Kwong, Matthew | Lee, Brandon | Lee, Ryan | Levine, Kevin | Li, Yedda | Liu, Bo | Liu, Lucy | Liu, Max | Lousararian, Adam | Ma, Jimmy | Mallya, Allyson | Manchee, Charlie | Marcus, Joseph | McDaniel, Stephen | Miller, Michelle L. | Molleston, Jerome M. | Diez, Cristina Montero | Ng, Patrick | Ngai, Natalie | Nguyen, Hien | Nylander, Andrew | Pollack, Jason | Rastogi, Suchita | Reddy, Himabindu | Regenold, Nathaniel | Sarezky, Jon | Schultz, Michael | Shim, Jien | Skorupa, Tara | Smith, Kenneth | Spencer, Sarah J. | Srikanth, Priya | Stancu, Gabriel | Stein, Andrew P. | Strother, Marshall | Sudmeier, Lisa | Sun, Mengyang | Sundaram, Varun | Tazudeen, Noor | Tseng, Alan | Tzeng, Albert | Venkat, Rohit | Venkataram, Sandeep | Waldman, Leah | Wang, Tracy | Yang, Hao | Yu, Jack Y. | Zheng, Yin | Preuss, Mary L. | Garcia, Angelica | Juergens, Matt | Morris, Robert W. | Nagengast, Alexis A. | Azarewicz, Julie | Carr, Thomas J. | Chichearo, Nicole | Colgan, Mike | Donegan, Megan | Gardner, Bob | Kolba, Nik | Krumm, Janice L. | Lytle, Stacey | MacMillian, Laurell | Miller, Mary | Montgomery, Andrew | Moretti, Alysha | Offenbacker, Brittney | Polen, Mike | Toth, John | Woytanowski, John | Kadlec, Lisa | Crawford, Justin | Spratt, Mary L. | Adams, Ashley L. | Barnard, Brianna K. | Cheramie, Martin N. | Eime, Anne M. | Golden, Kathryn L. | Hawkins, Allyson P. | Hill, Jessica E. | Kampmeier, Jessica A. | Kern, Cody D. | Magnuson, Emily E. | Miller, Ashley R. | Morrow, Cody M. | Peairs, Julia C. | Pickett, Gentry L. | Popelka, Sarah A. | Scott, Alexis J. | Teepe, Emily J. | TerMeer, Katie A. | Watchinski, Carmen A. | Watson, Lucas A. | Weber, Rachel E. | Woodard, Kate A. | Barnard, Daron C. | Appiah, Isaac | Giddens, Michelle M. | McNeil, Gerard P. | Adebayo, Adeola | Bagaeva, Kate
G3: Genes|Genomes|Genetics  2015;5(5):719-740.
The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.
PMCID: PMC4426361  PMID: 25740935
codon bias; evolution of heterochromatin; gene size; melting characteristics; transposons
18.  Primary Anetoderma in a Young Male Involving Palms, Soles and the Scalp: Rarest of the Rare 
Primary anetoderma is a rare idiopathic disease of the skin, characterized by circumscribed areas of loose skin, and loss of elastic fibers upon histopathologic examination. Two forms are traditionally distinguished, primary and secondary. Primary anetoderma occurs when there is no underlying associated skin disease, whereas the latter refers to an abnormal repair mechanism of preexisting skin lesions. We are reporting a case of primary anetoderma with lesions present all over the body, including the scalp, palms and soles, the sites that are not known to be involved in this condition.
PMCID: PMC4372953  PMID: 25814749
Elastolysis and elastorrhexis; palms; soles and scalp; primary anetoderma
19.  Acute kidney injury in patients with human immunodeficiency virus infection 
Indian Journal of Nephrology  2015;25(2):86-90.
Acute kidney injury (AKI) is an important cause of hospitalization and morbidity in human immunodeficiency virus (HIV)-positive patients. However, the data on AKI in such patients is limited. The aim of the present study was to analyze the incidence, causes and outcome of AKI in HIV-positive patients from our antiretroviral therapy centre. All HIV-positive patients were evaluated for evidence of clinical AKI. AKI was noted in 138/3540 (3.9%) patients. Of 138 AKI patients, 96 (69.6%) had acquired immuno deficiency syndrome and 42 (30.4%) were HIV seropositive. Majority of AKI patients belonged to AKI network (AKIN) Stage II (42%) or III (48.5%) at presentation. Prerenal, intrinsic and postrenal AKI were noted in 53.6%, 44.2% and 2.2% of cases, respectively. Hypovolemia (44.2%) and sepsis (14.5%) contributed to AKI in vast majority of cases. AKI was multifactorial (volume depletion, sepsis and drugs) in 39% of patients. Acute tubular necrosis (ATN) was the most common intrinsic lesion. Acute interstitial nephritis and diffuse endocapillary proliferative glomerulonephritis were noted in five and two cases, respectively. In-hospital mortality was 24.64%. Lower CD4 count, decreased serum albumin level and Stage 4 WHO disease were associated with higher mortality. At 3 months or more follow-up complete recovery of renal function, chronic kidney disease Stage 3-5 and progression to end stage renal disease were noted in 58.69%, 14.5% and 2.2% of cases, respectively. Thus, prerenal factors and ischemic ATN were the most common cause of AKI in HIV-infected patients. Recovery of renal function was seen in 59% of cases, but AKI had high in-hospital mortality.
PMCID: PMC4379631  PMID: 25838645
Acute glomerulonephritis; acute kidney injury; acute tubular necrosis; human immunodeficiency virus; sepsis
20.  Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients 
Prostate Cancer  2015;2015:285193.
Background. New nontoxic targeted approaches are needed for patients with castrate resistant prostate cancer (CRPC). Our preclinical studies show that activated T cells (ATC) armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi) kill prostate cancer cells lines, induce a Th1 cytokine pattern upon engagement of tumor cells, prevent the development of prostate tumors, and retard tumor growth in immunodeficient mice. These studies provided strong rationale for our phase I dose-escalation pilot study to test ATC armed with Her2Bi (aATC) for safety in men with CRPC. Methods. Seven of 8 men with CRPC were evaluable after receiving two infusions per week for 4 weeks. The men received 2.5, 5 or 10 × 109 aATC per infusion with low dose interleukin-2 and granulocyte-macrophage colony stimulating factor. Results. There were no dose limiting toxicities, and there was 1 partial responder and 3 of 7 patients had significant decreases in their PSA levels and pain scores. Immune evaluations of peripheral blood mononuclear cells in 2 patients before and after immunotherapy showed increases in IFN-γ EliSpot responses and Th1 serum cytokines. Conclusions. These results provide a strong rationale for developing phase II trials to determine whether aATC are effective for treating CRPC.
PMCID: PMC4352947  PMID: 25802762
21.  Acute and Chronic Mu Opioids Differentially Regulate Thrombospondins 1 and 2 Isoforms in Astrocytes 
ACS Chemical Neuroscience  2013;5(2):106-114.
Chronic opioids induce synaptic plasticity, a major neuronal adaptation. Astrocyte activation in synaptogenesis may play a critical role in opioid tolerance, withdrawal, and dependence. Thrombospondins 1 and 2 (TSP1/2) are astrocyte-secreted matricellular glycoproteins that promote neurite outgrowth as well as dendritic spine and synapse formation, all of which are inhibited by chronic μ opioids. In prior studies, we discovered that the mechanism of TSP1 regulation by μ opioids in astrocytes involves crosstalk between three different classes of receptors, μ opioid receptor, EGFR and TGFβR. Moreover, TGFβ1 stimulated TSP1 expression via EGFR and ERK/MAPK activation, indicating that EGFR is a signaling hub for opioid and TGFβ1 actions. Using various selective antagonists, and inhibitors, here we compared the mechanisms of chronic opioid regulation of TSP1/2 isoform expression in vivo and in immortalized rat cortical astrocytes. TSP1/2 release from astrocytes was also monitored. Acute and chronic μ opioids, morphine, and the prototypic μ ligand, DAMGO, modulated TSP2 protein levels. TSP2 but not TSP1 protein content was up-regulated by acute (3 h) morphine or DAMGO by an ERK/MAPK dependent mechanism. Paradoxically, TSP2 protein levels were altered neither by TGFβ1 nor by astrocytic neurotrophic factors, EGF, CNTF, and BMP4. TSP1/2 immunofluorescence was increased in astrocytes subjected to scratch-wounding, suggesting TSPs may be useful markers for the “reactive” state of these cells and potentially for different types of injury. Previously, we determined that chronic morphine attenuated both neurite outgrowth and synapse formation in cocultures of primary astrocytes and neurons under similar temporal conditions that μ opioids reduced TSP1 protein levels in astrocytes. Here we found that, after the same 8 day treatment, morphine or DAMGO diminished TSP2 protein levels in astrocytes. Therefore, μ opioids may deter synaptogenesis via both TSP1/2 isoforms, but by distinct mechanisms.
PMCID: PMC3930990  PMID: 24304333
Opioids; morphine; opioid receptors; astrocytes; ERK/MAPK; growth factors
22.  The extent of grain yield and plant growth enhancement by plant growth-promoting broad-spectrum Streptomyces sp. in chickpea 
SpringerPlus  2015;4:31.
The physiological and molecular responses of five strains of Streptomyces sp. (CAI-17, CAI-68, CAI-78, KAI-26 and KAI-27), with their proven potential for charcoal rot disease control in sorghum and plant growth-promotion (PGP) in sorghum and rice, were studied to understand the mechanisms causing the beneficial effects. In this investigation, those five strains were evaluated for their PGP capabilities in chickpea in the 2012–13 and 2013–14 post-rainy seasons. All of the Streptomyces sp. strains exhibited enhanced nodule number, nodule weight, root weight and shoot weight at 30 days after sowing (DAS) and pod number, pod weight, leaf area, leaf weight and stem weight at 60 DAS in both seasons over the un-inoculated control. At crop maturity, the Streptomyces strains had enhanced stover yield, grain yield, total dry matter and seed number plant−1 in both seasons over the un-inoculated control. In the rhizosphere, the Streptomyces sp. also significantly enhanced microbial biomass carbon, dehydrogenase activity, total nitrogen, available phosphorous and organic carbon in both seasons over the un-inoculated control. Of the five strains of Streptomyces sp., CAI-17, CAI-68 and CAI-78 were superior to KAI-26 and KAI-27 in terms of their effects on root and shoot development, nodule formation and crop productivity. Scanning electron microscopy (SEM) micrographs had revealed the success in colonization of the chickpea roots by all five strains. Quantitative real-time PCR (qRT-PCR) analysis of selected PGP genes of actinomycetes revealed the selective up-regulation of indole-3-acetic acid (IAA)-related and siderophore-related genes by CAI-68 and of β-1,3-glucanase genes by KAI-26.
PMCID: PMC4310830  PMID: 25646153
Field evaluation; Plant growth-promotion (PGP); qRT-PCR analysis; Scanning electron microscopy; Streptomyces sp.
23.  Nephrocutaneous fistula as the initial manifestation of asymptomatic nephrolithiasis: A call for radical management 
Urology Annals  2015;7(1):94-96.
Renal stones are a common affliction presenting in an acute setting. We report a case of asymptomatic renal stone in an elderly gentleman presenting initially as a discharging lumbar sinus managed by subcapsular nephrectomy and radical excision of the fistula tract. Nephrocutaneous fistula is most commonly associated with tuberculosis, xanthogranulomatous pyelonephritis, and rarely with complicated calyceal stones, and its occurrence with asymptomatic pelvic stones is rare. We present the points in favor of radical open surgery in the management of such patients.
PMCID: PMC4310129  PMID: 25657555
Chronic pyelonephritis; nephrocutaneous fistula; nephrolithiasis; nephrectomy
24.  Genomics-assisted breeding for boosting crop improvement in pigeonpea (Cajanus cajan) 
Pigeonpea is an important pulse crop grown predominantly in the tropical and sub-tropical regions of the world. Although pigeonpea growing area has considerably increased, yield has remained stagnant for the last six decades mainly due to the exposure of the crop to various biotic and abiotic constraints. In addition, low level of genetic variability and limited genomic resources have been serious impediments to pigeonpea crop improvement through modern breeding approaches. In recent years, however, due to the availability of next generation sequencing and high-throughput genotyping technologies, the scenario has changed tremendously. The reduced sequencing costs resulting in the decoding of the pigeonpea genome has led to the development of various genomic resources including molecular markers, transcript sequences and comprehensive genetic maps. Mapping of some important traits including resistance to Fusarium wilt and sterility mosaic disease, fertility restoration, determinacy with other agronomically important traits have paved the way for applying genomics-assisted breeding (GAB) through marker assisted selection as well as genomic selection (GS). This would accelerate the development and improvement of both varieties and hybrids in pigeonpea. Particularly for hybrid breeding programme, mitochondrial genomes of cytoplasmic male sterile (CMS) lines, maintainers and hybrids have been sequenced to identify genes responsible for cytoplasmic male sterility. Furthermore, several diagnostic molecular markers have been developed to assess the purity of commercial hybrids. In summary, pigeonpea has become a genomic resources-rich crop and efforts have already been initiated to integrate these resources in pigeonpea breeding.
PMCID: PMC4330709  PMID: 25741349
pigeonpea; genetic variability; genomic resources; genomics-assisted breeding; marker assisted selection; genomic selection
25.  Serum homocysteine level in vegetarians in District Tharparker, Sindh 
The aim of present study was to investigate serum homocysteine levels in apparently healthy vegetarians and ominvores in Mithi, district Tharparker, Sindh, Pakistan.
This study was conducted in the Department of Biochemistry, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Center (JPMC), Karachi and blood samples were collected from Mithi, district Tharparker, Sindh, Pakistan, in 2012. One hundred vegetarian and one hundred omnivores (age ranging from 20-40 years) were enrolled for this study. Serum homocysteine levels were measured by the chemiluminescence enzyme immunoassay method.
Serum homocysteine (Hcy) level was considerably higher (p<0.001) in vegetarian group compared to omnivores. We further grouped and analyzed our study subjects according to their gender and according to Hcy level (greater than or lower than 15µmol/L). A considerable number of vegetarian subjects 30% were having Hcy >15µmol/L compared to omnivores 6%, (p<0.001). Gender-wise comparison showed that 27.02% male and 38.46% females had >15µmol/L serum Hcy level in vegetarian group and 6.9% male and 3.5% females had >15µmol/L serum Hcy level in omnivores group, but the difference was not significant in any group.
Vegetarians are more prone to develop hyperhomocysteinemia, so they are at high risk to develop cardiovascular disease.
PMCID: PMC4386171  PMID: 25878628
Homocysteine; Vegetarians; Omnivores

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