• Infection in Renal Transplant Recipients

      Fishman, Jay A.; Ramos, Emilio (Elsevier, 2005-12-01)
    • Microorganisms Responsible for Neonatal Diarrhea

      O'Ryan, Miguel L.; Nataro, James P.; Cleary, Thomas G. (Elsevier, 2006-12-01)
    • Infection in renal transplant recipients

      Kotton, Camille Nelson; Ramos, Emilio (Elsevier, 2010-10-22)
    • HIV/AIDS: Patient Preferences

      Alexander, Carla S. (Elsevier, 2011-04-27)
    • Quantification of Plasma miRNAs by Digital PCR for Cancer Diagnosis.

      Ma, Jie; Li, Ning; Guarnera, Maria; Jiang, Feng (SAGE Publications Inc., 2013-11-14)
      otential approach for cancer diagnosis. However, absolutely quantifying low abundant plasma miRNAs is challenging with qPCR. Digital PCR offers a unique means for assessment of nucleic acids presenting at low levels in plasma. This study aimed to evaluate the efficacy of digital PCR for quantification of plasma miRNAs and the potential utility of this technique for cancer diagnosis. We used digital PCR to quantify the copy number of plasma microRNA-21-5p (miR-21–5p) and microRNA-335–3p (miR-335–3p) in 36 lung cancer patients and 38 controls. Digital PCR showed a high degree of linearity and quantitative correlation with miRNAs in a dynamic range from 1 to 10,000 copies/μL of input, with high reproducibility. qPCR exhibited a dynamic range from 100 to 1X107 copies/μL of input. Digital PCR had a higher sensitivity to detect copy number of the miRNAs compared with qPCR. In plasma, digital PCR could detect copy number of both miR-21–5p and miR-335–3p, whereas qPCR was only able to assess miR-21–5p. Quantification of the plasma miRNAs by digital PCR provided 71.8% sensitivity and 80.6% specificity in distinguishing lung cancer patients from cancer-free subjects.
    • Evaluation of mouse urinary bladder smooth muscle for diurnal differences in contractile properties

      White, Rachel S; Zemen, Betsir G; Khan, Zulqarnain; Montgomery, Jenna R; Herrera, Gerald M; Meredith, Andrea L (Frontiers Media S.A., 2015-01-09)
      Most physiological systems show daily variations in functional output, entrained to the day–night cycle. Humans exhibit a daily rhythm in urinary voiding (micturition), and disruption of this rhythm (nocturia) has significant clinical impact. However, the underlying mechanisms are not well-understood. Recently, a circadian rhythm in micturition was demonstrated in rodents, correlated with functional changes in urodynamics, providing the opportunity to address this issue in an animal model. Smooth muscle cells from mouse bladder have been proposed to express a functional and autonomous circadian clock at the molecular level. In this study, we addressed whether a semi-intact preparation of mouse urinary bladder smooth muscle (UBSM) exhibited measurable differences in contractility between day and night. UBSM tissue strips were harvested at four time points over the diurnal cycle, and spontaneous (phasic) and nerve-evoked contractions were assessed using isometric tension recordings. During the active period (ZT12-24) when micturition frequency is higher in rodents, UBSM strips had no significant differences in maximal- (high K+) or nerve-evoked contractions compared to strips harvested from the resting period (ZT0-12). However, a diurnal rhythm in phasic contraction was observed, with higher amplitudes at ZT10. Consistent with the enhanced phasic amplitudes, expression of the BK K+ channel, a key suppressor of UBSM excitability, was lower at ZT8. Higher expression of BK at ZT20 was correlated with an enhanced effect of the BK antagonist paxilline (PAX) on phasic amplitude, but PAX had no significant time-of-day dependent effect on phasic frequency or nerve-evoked contractions. Overall, these results identify a diurnal difference for one contractile parameter of bladder muscle. Taken together, the results suggest that autonomous clocks in UBSM make only a limited contribution to the integrated control of diurnal micturition patterns. Copyright © 2015 White, Zemen, Khan, Montgomery, Herrera and Meredith.
    • Vγ2Vδ2 T-cell co-stimulation increases natural killer cell killing of monocyte-derived dendritic cells

      Cairo, Cristiana; Surendran, Naveen; Harris, Kristina M.; Mazan-Mamczarz, Krystyna; Sakoda, Yukimi; Diaz-Mendez, Felisa; Tamada, Koji; Gartenhaus, Ronald B.; Mann, Dean L.; Pauza, C. David (2015-03-01)
      Interactions between natural killer (NK) cells and dendritic cells (DC) affect maturation and function of both cell populations, including NK cell killing of DC (editing), which is important for controlling the quality of immune responses. We also know that antigen-stimulated Vγ2Vδ2 T cells co-stimulate NK cells via 4-1BB to enhance the killing of tumour cell lines but we do not know what regulates 4-1BB expression or whether other NK effector functions including DC killing, might also be influenced by NK–γδ T-cell cross-talk. Here we show that antigen-stimulated γδ T cells co-stimulate NK cells through inducible T-cell co-stimulator (ICOS)– ICOS ligand (ICOSL) and this signal increases NK cell killing of autologous DC. Effects of NK–γδ T-cell co-culture, which could be repro-duced with soluble ICOS-Fc fusion protein, included increased CD69 and 4-1BB expression, interferon-γ, tumour necrosis factor-α, macrophage inflammatory protein-1β, I-309, RANTES and sFas ligand production, as well as elevated mRNA levels for co-stimulatory receptors OX40 (TNFRSF4) and GITR (TNFRSF18). Hence, ICOS–ICOSL co-stimulation of NK by Vγ2Vδ2 T cells had broad effects on NK phenotype and effector functions. The NK–γδ T-cell cross-talk links innate and antigen-specific lymphocyte responses in the control of cytotoxic effector function and DC killing. © 2014 John Wiley & Sons Ltd, Immunology.
    • Is there a Regional Difference in Morphology Interpretation of A3/A4 Fractures among Different Cultures?

      Schroeder, Gregory; Kepler, Christopher; Dvorak, Marcel; Chapman, Jens; Fehlings, Michael; Aarabi, Bizhan; Rajasekaran, Shanmuganathan; Kandziora, Frank; Schnake, Klaus; Bellabarba, Carlo; et al. (Sage, 2015-05-01)
      Introduction. The AOSpine Thoracolumbar Spine Injury Classification System was recently published, but before establishing a treatment algorithm to accompany the classification, further investigation on the cause of current regional treatment variations is required. The objective of this study is to determine if the ability of a surgeon to correctly classify A3 (burst fractures with a single endplate involved) and A4 (burst fractures with both end plates involved) fractures were affected by either the region or the experience of the surgeon. Material and Methods. A survey was sent to 100 AOSpine members from all six AO regions of the world (North America, South America, Europe, Africa, Asia, and the Middle East) that had no prior knowledge of the new AOSpine Thoracolumbar Spine Injury Classification System. Respondents were asked to classify 25 cases, including 6 thoracolumbar burst fractures (A3 or A4). The current analysis focuses on the effect of region and experience on surgeons' ability to properly classify these controversial fractures. Results. All 100 surveyed surgeons completed the survey, and no significant regional variability in the ability to correctly classify burst fractures was identified (p > 0.50). Further analysis demonstrated that no region predisposed surgeons increasing the severity of burst fractures. Similarly, experience did not affect surgeons' ability to correctly classify burst fracture (p > 0.21). Conclusion. Regional variation in the treatment of thoracolumbar burst fractures (A3 and A4) is not because of the differing radiographic interpretation of the fractures.
    • Concomitant Pituitary Apoplexy and Acute Fatty Liver of Pregnancy Complicated With Disseminated Intravascular Coagulation

      Barvalia, Umang; Eliades, Myrto; Melhem, Lina (Elsevier, 2015-09-01)
      Objective: Pituitary complications during delivery are relatively rare in developed countries. In this case report we describe a case of panhypopituitarism during pregnancy with concomitant acute liver failure. Methods: We present the case of a pregnant female with acute fatty liver of pregnancy (AFLP) complicated by panhypopituitarism. We also review the current literature on cases of anterior pituitary hormone deficiencies with AFLP, including presentation, management, and outcomes. Results: A 29 year-old female at 25-weeks gestation presented with subacute onset of headache accompanied by nausea and vomiting. She was diagnosed with acute liver failure and coagulopathy secondary to disseminated intravascular coagulation (DIC). Further workup revealed deficiencies of all anterior pituitary hormones, and magnetic resonance imaging (MRI) of the brain was compatible with pituitary hemorrhage/apoplexy from probable infarction. Conclusion: AFLP, especially in association with DIC, can lead to pituitary apoplexy and panhypopituitarism related to underlying coagulopathy. Given the high mortality rates associated with pituitary apoplexy, clinical awareness and a high index of suspicion are important for diagnosing this condition. Prompt initiation of hormone replacement therapy is essential to reduce morbidity and mortality risk. Abbreviations: AFLP acute fatty liver of pregnancy DIC disseminated intravascular coagulation MRI magnetic resonance imaging
    • Third-Trimester Intraplacental Choriocarcinoma Presenting With Respiratory Failure and Hyperthyroidism

      Subang, Maria Laarni L.; Konig, Manige; Staats, Paul N.; Lamos, Elizabeth M.; Munir, Kashif M.; Malek, Rana (Elsevier, 2016-06-01)
      Objective: Choriocarcinoma is an aggressive disease typically identified after a molar pregnancy. Diagnosis with a co-existing pregnancy is extremely rare. Only 35 cases have been reported from 1907 to 1995. We report a case of choriocarcinoma diagnosed during the third trimester of an intra-uterine pregnancy presenting with respiratory failure and biochemical hyperthyroidism. Methods: This is a case report of an intraplacental choriocarcinoma during the third trimester of pregnancy. We included a review of literature highlighting the rarity of this disease, diagnostic challenges, and treatment options. Results: A 34-year-old woman, 31 weeks pregnant, presented with dyspnea and hemoptysis for 2 weeks. Imaging showed bilateral pulmonary infiltrates, suggestive of pneumonia. Thyroid function tests checked due to tachycardia revealed hyperthyroidism, with thyroid-stimulating hormone of 0.02 μIU/mL (normal range, 0.5 to 4.5 μIU/mL) and free thyroxine of 4.8 ng/dL (normal range, 0.7 to 1.8 ng/dL). Serum human chorionic gonadotropin was elevated, at 1,433,740 mIU/mL. Respiratory failure ensued, requiring ventilatory support. Emergent cesarean section was done due to worsening clinical status. Histopathologic findings of the placenta were diagnostic of intraplacental choriocarcinoma. Chemotherapy was given; however, the patient developed acute cerebral hemorrhage and she eventually expired. Conclusion: Diagnosis of choriocarcinoma co-existing with intra-uterine pregnancy can be difficult, as initial symptoms can be mistaken for other diseases, such as pneumonia in this case. Biochemical hyperthyroidism during the third trimester in a patient with no history of thyroid disease is rare, and choriocarcinoma should be considered. A timely diagnosis is imperative, as early intervention with chemotherapy can be curative and potentially life-saving. Abbreviations: FIGO = International Federation of Gynecology and Obstetrics GTN = gestational throphoblastic neoplasia hCG = human chorionic gonadotropin T4 = free thyroxine TSH = thyroid-stimulating hormone WHO = World Health Organization
    • Early Kidney Allograft Dysfunction (Threatened Allograft): Comparative Effectiveness of Continuing Versus Discontinuation of Tacrolimus and Use of Sirolimus to Prevent Graft Failure: A Retrospective Patient-Centered Outcome Study.

      Wali, Ravinder K; Prentice, Heather A; Reddivari, Venkata; Baffoe-Bonnie, Geroge; Drachenberg, Cinthia I; Pappadimitriou, John C; Ramos, Emilio; Cooper, Matthew; Jonsson, Johann; Bartlett, Stephen; et al. (Wolters Kluwer Health, 2016-08-11)
      Weighted odds for death-censored graft failure (odds ratio [OR], 1.20; 95% confidence interval [95% CI], 0.66-2.19, P = 0.555) was similar in the 2 groups, but a trend for increased risk of greater than 50% loss in estimated glomerular filtration rate from baseline in sirolimus group (OR, 1.90; 95% CI, 0.96-3.76; P = 0.067) compared with tacrolimus group. Sirloimus group compared with tacrolimus group had increased risk for death with functioning graft (OR, 2.01; 95% CI, 1.29-3.14; P = 0.002) as well as increased risk of late death (death after graft failure while on dialysis) (OR, 2.39; 95% CI, 1.59-3.59; P < 0.001). Analysis of subgroups based on the absence or presence of T cell-mediated rejection or tubulointerstitial inflammation in the index biopsy, or the use of different types of induction agents, and all subgroups had increased risk of death with functioning graft and late death if exposed to sirolimus-based therapy.
    • Pediatric anti-N-methyl-d-aspartate receptor encephalitis: A review with pooled analysis and critical care emphasis

      Remy, K.E.; Custer, J.W.; Cappell, J. (Frontiers Media S.A., 2017)
      Purpose: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is being recognized with increasing frequency among children. Given the paucity of evidence to guide the critical care management of these complex patients, we provide a comprehensive review of the literature with pooled analysis of published case reports and case series. Methods: We performed a comprehensive literature search using PubMed, Scopus, EMBASE, and Web of Science for relevant published studies. The literature search was conducted using the terms NMDA, anti-NMDA, Anti-N-methyl-d-aspartate, pediatric encephalitis, and anti-NMDAR and included articles published between 2005 and May 1, 2016. Results: Forty-eight references met inclusion criteria accounting for 373 cases. For first-line treatments, 335 (89.8%) received high-dose corticosteroids, 296 received intravenous immunoglobulin (79.3%), and 116 (31%) received therapeutic plasma exchange. In these, 187 children (50.1%) had a full recovery with only minor deficits, 174 patients (46.7%) had partial recovery with major deficits, and 12 children died. In addition, 14 patients were reported to require mechanical ventilation. Conclusion: Anti-NMDA encephalitis is a formidable disease with great variation in clinical presentation and response to treatment. With early recognition of this second most common cause of pediatric encephalitis, a multidisciplinary approach by physicians may provide earlier access to first- and second-line therapies. Future studies are needed to examine the efficacy of these current therapeutic strategies on long-term morbidity. Copyright 2017 Remy, Custer, Cappell, Foster, Garber, Walker, Simon and Bagdure.
    • Promoter architecture and transcriptional regulation of musculoskeletal embryonic nuclear protein 1b (mustn1b) gene in zebrafish

      Suarez-Bregua, P.; Chien, C.-J.; Megias, M. (John Wiley and Sons Inc., 2017)
      Background: Mustn1 is a specific musculoskeletal protein that plays a critical role in myogenesis and chondrogenesis in vertebrates. Whole-mount in situ hybridization revealed that mustn1b mRNAs are specifically expressed in skeletal and cardiac muscles in Zebrafish embryos. However, the precise function and the regulatory elements required for its muscle-specific expression are largely unknown. Results: The purpose of this study was to explore and uncover the target genomic regions that regulate mustn1b gene expression by in vivo functional characterization of the mustn1b promoter. We report here stable expression analyses of eGFP from fluorescent transgenic reporter Zebrafish line containing a 0.8kb_mustn1b-Tol2-eGFP construct. eGFP expression was specifically found in the skeletal and cardiac muscle tissues. We show that reporter Zebrafish lines generated replicate the endogenous mustn1b expression pattern in early Zebrafish embryos. Specific site directed-mutagenesis analysis revealed that promoter activity resides in two annotated genomic regulatory regions, each one corresponding to a specific functional transcription factor binding site. Conclusions: Our data indicate that mustn1b is specifically expressed in skeletal and cardiac muscle tissues and its muscle specificity is controlled by the 0.2-kb promoter and flanking sequences and in vivo regulated by the action of two sequence-specific families of transcription factors. Developmental Dynamics 246:992-1000, 2017.
    • Evaluation of the Potential for Drug Interactions with Patiromer in Healthy Volunteers

      Lesko, L.J.; Offman, E.; Brew, C.T. (SAGE Publications Ltd, 2017)
      Introduction: Patiromer is a potassium-binding polymer that is not systemically absorbed; however, it may bind coadministered oral drugs in the gastrointestinal tract, potentially reducing their absorption. Methods: Twelve randomized, open-label, 3-period, 3-sequence crossover studies were conducted in healthy volunteers to evaluate the effect of patiromer (perpetrator drug) on absorption and single-dose pharmacokinetics (PK) of drugs (victims) that might be commonly used with patiromer. Subjects received victim drug alone, victim drug administered together with patiromer 25.2 g (highest approved dose), and victim drug administered 3 hours before patiromer 25.2 g. The primary PK endpoints were area under the curve (AUC), extrapolated to infinity (AUC0-∞), and maximum concentration (Cmax). Results were reported as 90% confidence intervals (CIs) about the geometric mean AUC0-∞ and Cmax ratios with prespecified equivalence limits of 80% to 125%. Results: Overall, 370 subjects were enrolled, with 365 receiving ≥1 dose of patiromer; 351 subjects completed the studies and all required treatments. When coadministered with patiromer, the 90% CIs for AUC0-∞ remained within 80% to 125% for 9 drugs (amlodipine, cinacalcet, clopidogrel, furosemide, lithium, metoprolol, trimethoprim, verapamil, and warfarin). The AUC0-∞ point estimate ratios for levothyroxine and metformin with patiromer coadministration were ≥80%, with the lower bounds of the 90% CIs at 76.8% and 72.8%, respectively. For ciprofloxacin, the point estimate for AUC0-∞ was 71.5% (90% CI: 65.3-78.4). For 8 of 12 drugs, point estimates for Cmax were ≥80% with patiromer coadministration; for ciprofloxacin, clopidogrel, metformin, and metoprolol, the point estimates were <80%. When patiromer was administered 3 hours after each victim drug, the 90% CIs for AUC0-∞ and Cmax for each drug were within the prespecified 80% to 125% limits. Conclusion: For 9 of the 12 drugs coadministered with patiromer, there were no clinically significant drug–drug interactions. For 3 drugs (ciprofloxacin, levothyroxine, and metformin), a 3-hour separation between patiromer and their administration resulted in no clinically significant drug–drug interactions. Copyright 2017 Author(s).
    • Review of reviews on exposures to synthetic organic chemicals and children's neurodevelopment: Methodological and interpretation challenges

      LaKind, J.S.; Anthony, L.G.; Goodman, M. (Taylor and Francis Inc., 2017)
      Environmental epidemiology data are becoming increasingly important in public health decision making, which commonly incorporates a systematic review of multiple studies. This review addresses two fundamental questions: What is the quality of available reviews on associations between exposure to synthetic organic chemicals and neurodevelopmental outcomes? What is the value (e.g., quality and consistency) of the underlying literature? Published reviews on associations between synthetic organic environmental chemical exposures and neurodevelopmental outcomes in children were systematically evaluated. Seventy-four relevant reviews were identified, and these were evaluated with respect to four methodological characteristics: (1) systematic inclusion/exclusion criteria and reproducible methods for search and retrieval of studies; (2) structured evaluation of underlying data quality; (3) systematic assessment of consistency across specific exposure-outcome associations; and (4) evaluation of reporting/publication bias. None of the 74 reviews fully met the criteria for all four methodological characteristics. Only four reviews met two criteria, and six reviews fulfilled only one criterion. Perhaps more importantly, the higher quality reviews were not able to meet all of the criteria owing to the shortcomings of underlying studies, which lacked comparability in terms of specific research question of interest, overall design, exposure assessment, outcome ascertainment, and analytic methods. Thus, even the most thoughtful and rigorous review may be of limited value if the underlying literature includes investigations that address different hypotheses and are beset by methodological inconsistencies and limitations. Issues identified in this review of reviews illustrate considerable challenges that are facing assessments of epidemiological evidence. Copyright 2017 The Author(s).
    • Identification of conserved proteins from diverse shell matrix proteome in Crassostrea gigas: Characterization of genetic bases regulating shell formation

      Feng, D.; Li, Q.; Yu, H. (Nature Publishing Group, 2017)
      The calcifying shell is an excellent model for studying biomineralization and evolution. However, the molecular mechanisms of shell formation are only beginning to be elucidated in Mollusca. It is known that shell matrix proteins (SMPs) play important roles in shell formation. With increasing data of shell matrix proteomes from various species, we carried out a BLASTp bioinformatics analysis using the shell matrix proteome from Crassostrea gigas against 443 SMPs from nine other species. The highly conserved tyrosinase and chitin related proteins were identified in bivalve. In addition, the relatively conserved proteins containing domains of carbonic anhydrase, Sushi, Von Willebrand factor type A, and chitin binding, were identified from all the ten species. Moreover, 25 genes encoding SMPs were annotated and characterized that are involved in CaCO 3 crystallization and represent chitin related or ECM related proteins. Together, data from these analyses provide new knowledge underlying the molecular mechanism of shell formation in C.gigas, supporting a refined shell formation model including chitin and ECM-related proteins. Copyright 2017 The Author(s).
    • Draft genome sequence of the Wolbachia endosymbiont of Wuchereria bancrofti wWb

      Chung, M.; Small, S.T.; Serre, D. (Oxford University Press, 2017)
      The draft genome assembly of the Wolbachia endosymbiont of Wuchereria bancrofti (wWb) consists of 1060 850 bp in 100 contigs and contains 961 ORFs, with a single copy of the 5S rRNA, 16S rRNA and 23S rRNA and each of the 34 tRNA genes. Phylogenetic core genome analyses show wWb to cluster with other strains in supergroup D of the Wolbachia phylogeny, while being most closely related to the Wolbachia endosymbiont of Brugia malayi strain TRS (wBm). The wWb and wBm genomes share 779 orthologous clusters with wWb having 101 unclustered genes and wBm having 23 unclustered genes. The higher number of unclustered genes in the wWb genome likely reflects the fragmentation of the draft genome.
    • Ambiguous interactions between diastolic and SR Ca2+ in the regulation of cardiac Ca2+ release

      Sobie, E.A.; Williams, G.S.B.; Lederer, W.J. (Rockefeller University Press, 2017)
    • Uterine cancer, mutational phenotype, and the era of immune checkpoint blockade

      Roque, D.M.; Santin, A.D. (Taylor and Francis Ltd, 2017)