Recent Stanford Publications in PubMed
- Thermal niche predicts tolerance to habitat conversion in tropical amphibians and reptiles.Frishkoff LO, Hadly EA, Daily GCGlob Chang Biol
- 99mTc-phytate as a diagnostic probe for assessing inflammatory reaction in malignant tumors.Fernandes RS, Mota LG, Kalbasi A, Moghbel M, Werner TJ, Alavi A, Rubello D, Cardoso VN, de Barros ALNucl Med Commun
- Spatially resolved ultrafast magnetic dynamics initiated at a complex oxide heterointerface.Först M, Caviglia AD, Scherwitzl R, Mankowsky R, Zubko P, Khanna V, Bromberger H, Wilkins SB, Chuang YD, Lee WS, Schlotter WF, Turner JJ, Dakovski GL, Minitti MP, Robinson J, Clark SR, Jaksch D, Triscone JM, Hill JP, Dhesi SS, Cavalleri ANat Mater
- β2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis.Smith LK, He Y, Park JS, Bieri G, Snethlage CE, Lin K, Gontier G, Wabl R, Plambeck KE, Udeochu J, Wheatley EG, Bouchard J, Eggel A, Narasimha R, Grant JL, Luo J, Wyss-Coray T, Villeda SANat Med
- Risks of Epilepsy During Pregnancy: How Much Do We Really Know?French JA, Meador KJAMA Neurol
- Physiologically normal 5% O2 supports neuronal differentiation and resistance to inflammatory injury in neural stem cell cultures.Sun X, Voloboueva LA, Stary CM, Giffard RGJ Neurosci Res
- Predictors Associated With Changes of Weight and Total Cholesterol Among Two Occupational Cohorts Over 10 Years.Ott U, Stanford JB, Murtaugh MA, Greenwood JL, Gren LH, Hegmann KT, Thiese MSJ Occup Environ Med
- Epstein-Barr Virus Modulates Host Cell MicroRNA-194 to Promote IL-10 Production and B Lymphoma Cell Survival.Harris-Arnold A, Arnold CP, Schaffert S, Hatton O, Krams SM, Esquivel CO, Martinez OMAm J Transplant
- Therapeutic Potential of Differentiated Mesenchymal Stem Cells for Treatment of Osteoarthritis.Ham O, Lee CY, Kim R, Lee J, Oh S, Lee MY, Kim J, Hwang KC, Maeng LS, Chang WInt J Mol Sci
- Heparin Kinetics: The "Holy Grail" of Periprocedural Anticoagulation for ablation of atrial fibrillation.Briceno DF, Natale A, Biase LDPacing Clin Electrophysiol
- Atomic layer deposition in nanostructured photovoltaics: tuning optical, electronic and surface properties.Palmstrom AF, Santra PK, Bent SFNanoscale
- Preventive Genomic Sequencing and Care of the Individual Patient.Char DAm J Bioeth
- Preventive Genomic Sequencing in the General Population: Do PGS Fly?Cho MKAm J Bioeth
- A User-Centered Design Approach to Information Sharing for Older Patients and Their Families.Nath PA, Sharp CDJAMA Intern Med
- Increases in multiple psychiatric disorders in parents and grandparents of patients with bipolar disorder from the USA compared with The Netherlands and Germany.Post RM, Leverich GS, Kupka R, Keck PE, McElroy SL, Altshuler LL, Frye MA, Rowe M, Grunze H, Suppes T, Nolen WAPsychiatr Genet
- Escherichia coli heme oxygenase modulates host innate immune responses.Maharshak N, Ryu HS, Fan TJ, Onyiah JC, Schulz S, Otterbein SL, Wong R, Hansen J, Otterbein L, Carroll I, Plevy SEMicrobiol Immunol
- Subcutaneous panniculitis-like T-cell lymphoma: Pediatric case series demonstrating heterogeneous presentation and option for watchful waiting.Johnston EE, LeBlanc RE, Kim J, Chung J, Balagtas J, Kim YH, Link MPPediatr Blood Cancer
- Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning.Rezvani AR, Kanate AS, Efron B, Chhabra S, Kohrt HE, Shizuru JA, Laport GG, Miklos DB, Benjamin JE, Johnston LJ, Arai S, Weng WK, Negrin RS, Strober S, Lowsky RBone Marrow Transplant
- Howard Holtzer -- developmental and cell biologist 1922-2014.Stockdale FE, Sanger JW, Emerson CPDev Biol
- Catalytic Efficiency Is a Function of How Rhodium(I) (5 + 2) Catalysts Accommodate a Conserved Substrate Transition State Geometry: Induced Fit Model for Explaining Transition Metal Catalysis.Mustard TJ, Wender PA, Cheong PHACS Catal
- Tuning the Reactivity of Mononuclear Nonheme Manganese(IV)-Oxo Complexes by Triflic Acid.Chen J, Yoon H, Lee YM, Seo MS, Sarangi R, Fukuzumi S, Nam WChem Sci
- Pattern-Based Detection of Anion Pollutants in Water with DNA Polyfluorophores.Kwon H, Jiang W, Kool ETChem Sci
- Sex differences in cortical volume and gyrification in autism.Schaer M, Kochalka J, Padmanabhan A, Supekar K, Menon VMol Autism
- OpenMM: A Hardware Independent Framework for Molecular Simulations.Eastman P, Pande VSComput Sci Eng
- Adaptive Immunity and Antigen-Specific Activation in Obesity-Associated Insulin Resistance.Chng MH, Alonso MN, Barnes SE, Nguyen KD, Engleman EGMediators Inflamm
- RASA: Robust Alternative Splicing Analysis for Human Transcriptome Arrays.Seok J, Xu W, Davis RW, Xiao WSci Rep
- Child Feeding Perceptions among Mothers with Eating Disorders.Sadeh-Sharvit S, Levy-Shiff R, Feldman T, Ram A, Gur E, Zubery E, Steiner E, Latzer Y, Lock JAppetite
- Facelift combined with simultaneous fractional laser resurfacing: Outcomes and complications.Wright EJ, Struck SKJ Plast Reconstr Aesthet Surg
- Comparison of Bevacizumab Alone or with Chemotherapy in Recurrent Ovarian Cancer Patients.Fuh KC, Secord AA, Bevis KS, Huh W, ElNaggar A, Blansit K, Previs R, Tillmanns T, Kapp DS, Chan JKGynecol Oncol
- Inadequacies of Physical Examination as a Cause of Medical Errors and Adverse Events--A Collection of Vignettes.Verghese A, Charlton B, Kassirer JP, Ramsey M, Ioannidis JPAm J Med
- Sensory hair cell development and regeneration: similarities and differences.Atkinson PJ, Huarcaya Najarro E, Sayyid ZN, Cheng AGDevelopment
- Genetic conflict reflected in tissue-specific maps of genomic imprinting in human and mouse.Babak T, DeVeale B, Tsang EK, Zhou Y, Li X, Smith KS, Kukurba KR, Zhang R, Li JB, van der Kooy D, Montgomery SB, Fraser HBNat Genet
- Fixed-dose combination of sofosbuvir and ledipasvir for the treatment of chronic hepatitis C genotype 1.Kumari R, Nguyen MHExpert Opin Pharmacother
- Whole-genome sequencing of the world's oldest people.Gierman HJ, Fortney K, Roach JC, Coles NS, Li H, Glusman G, Markov GJ, Smith JD, Hood L, Coles LS, Kim SKPLoS One
- The molecular machinery of neurotransmitter release (Nobel lecture).Südhof TCAngew Chem Int Ed Engl
- Transcription factors bind negatively selected sites within human mtDNA genes.Blumberg A, Sri Sailaja B, Kundaje A, Levin L, Dadon S, Shmorak S, Shaulian E, Meshorer E, Mishmar DGenome Biol Evol
- Electroencephalographic features of moyamoya in adults.Frechette ES, Bell-Stephens TE, Steinberg GK, Fisher RSClin Neurophysiol
- Optimal management of a multispecies shorebird flyway under sea-level rise.Iwamura T, Fuller RA, Possingham HPConserv Biol
- The importance of keeping cool: Reply regarding the Wilderness Medical Society practice guidelines for the prevention and treatment of heat-related illness.Lipman GS, Eifling KP, Ellis MA, Gaudio FG, Otten EM, Grissom CKWilderness Environ Med
- Survival of a patient with tetanus in Bhutan using a magnesium infusion managed only by clinical signs.Wangmo KP, Teng M, Henker R, Kinnear S, Tshering J, Wang NEWilderness Environ Med
- Keeping a broad perspective: Reply regarding the Wilderness Medical Society practice guidelines for the prevention and treatment of heat-related illness.Lipman GS, Eifling KP, Ellis MA, Gaudio FG, Otten EM, Grissom CKWilderness Environ Med
- Poly-L-arginine topical lotion tested in a mouse model for frostbite injury.Auerbach LJ, DeClerk BK, Fathman CG, Gurtner GC, Auerbach PSWilderness Environ Med
Thermal niche predicts tolerance to habitat conversion in tropical amphibians and reptiles.
Glob Chang Biol. 2015 Jul 3;
Authors: Frishkoff LO, Hadly EA, Daily GC
Habitat conversion is a major driver of the biodiversity crisis, yet why some species undergo local extinction while others thrive under novel conditions remains unclear. We suggest that focusing on species' niches, rather than traits, may provide the predictive power needed to forecast biodiversity change. We first examine two Neotropical frog congeners with drastically different affinities to deforestation, and document how thermal niche explains deforestation tolerance. The more deforestation-tolerant species is associated with warmer macroclimates across Costa Rica, and warmer microclimates within landscapes. Further, in laboratory experiments the more deforestation-tolerant species has critical thermal limits, and a jumping performance optimum, shifted ~2 °C warmer than those of the more forest-affiliated species, corresponding to the ~3 °C difference in daytime maximum temperature that these species experience between habitats. Crucially neither species strictly specializes on either habitat-instead habitat use is governed by regional environmental temperature. Both species track temperature along an elevational gradient, and shift their habitat use from cooler forest at lower elevations, to warmer deforested pastures upslope. To generalize these conclusions, we expand our analysis to the entire mid-elevational herpetological community of southern Costa Rica. We assess the climatological affinities of 33 amphibian and reptile species, showing that across both taxonomic classes thermal niche predicts presence in deforested habitat as well as or better than many commonly used traits. These data suggest that warm-adapted species carry a significant survival advantage amidst the synergistic impacts of land-use conversion and climate change. This article is protected by copyright. All rights reserved.
PMID: 26148337 [PubMed - as supplied by publisher]
99mTc-phytate as a diagnostic probe for assessing inflammatory reaction in malignant tumors.
Nucl Med Commun. 2015 Jul 1;
Authors: Fernandes RS, Mota LG, Kalbasi A, Moghbel M, Werner TJ, Alavi A, Rubello D, Cardoso VN, de Barros AL
OBJECTIVE: Once administered intravenously, technetium-99m (Tc)-labeled phytate binds to calcium in the serum and behaves as a nanoparticle. On the basis of the high permeability of the tumor vasculature, Tc-phytate is expected to leak and accumulate specifically in inflammatory cells. The aim of this study was to evaluate the potential of Tc-phytate in assessing the degree of inflammation in Ehrlich solid tumors in mice.
MATERIALS AND METHODS: Tc-phytate was prepared by adding pertechnetate to a solution containing phytic acid and stannous chloride. The blood half-life of this particle following intravenous injection was determined using blood samples from healthy animals, whereas its size was measured by photon correlation spectroscopy. Scintigraphic imaging and biodistribution studies were carried out in tumor-bearing mice at 30 min and 2 h after injection.
RESULTS: The average size of the particles was in the range of 200 nm, suggesting that they are capable of passively passing through fenestrations in tumor vessels, which are 200-2000 nm in size. The blood half-life for Tc-phytate was found to be 2.1 min, a result that is in agreement with previous studies. Data from tumor-bearing mice showed high tumor uptake at 2 h after Tc-phytate administration. As a result, a high tumor-to-muscle ratio was achieved (T/M=25.9±7.54).
CONCLUSION: These findings indicate that Tc-sodium phytate has promising properties for identifying the type of tumor. This approach will have significant implications for characterizing tumor biology and treatment of malignant lesions.
PMID: 26147941 [PubMed - as supplied by publisher]
Spatially resolved ultrafast magnetic dynamics initiated at a complex oxide heterointerface.
Nat Mater. 2015 Jul 6;
Authors: Först M, Caviglia AD, Scherwitzl R, Mankowsky R, Zubko P, Khanna V, Bromberger H, Wilkins SB, Chuang YD, Lee WS, Schlotter WF, Turner JJ, Dakovski GL, Minitti MP, Robinson J, Clark SR, Jaksch D, Triscone JM, Hill JP, Dhesi SS, Cavalleri A
Static strain in complex oxide heterostructures has been extensively used to engineer electronic and magnetic properties at equilibrium. In the same spirit, deformations of the crystal lattice with light may be used to achieve functional control across heterointerfaces dynamically. Here, by exciting large-amplitude infrared-active vibrations in a LaAlO3 substrate we induce magnetic order melting in a NdNiO3 film across a heterointerface. Femtosecond resonant soft X-ray diffraction is used to determine the spatiotemporal evolution of the magnetic disordering. We observe a magnetic melt front that propagates from the substrate interface into the film, at a speed that suggests electronically driven motion. Light control and ultrafast phase front propagation at heterointerfaces may lead to new opportunities in optomagnetism, for example by driving domain wall motion to transport information across suitably designed devices.
PMID: 26147844 [PubMed - as supplied by publisher]
β2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis.
Nat Med. 2015 Jul 6;
Authors: Smith LK, He Y, Park JS, Bieri G, Snethlage CE, Lin K, Gontier G, Wabl R, Plambeck KE, Udeochu J, Wheatley EG, Bouchard J, Eggel A, Narasimha R, Grant JL, Luo J, Wyss-Coray T, Villeda SA
Aging drives cognitive and regenerative impairments in the adult brain, increasing susceptibility to neurodegenerative disorders in healthy individuals. Experiments using heterochronic parabiosis, in which the circulatory systems of young and old animals are joined, indicate that circulating pro-aging factors in old blood drive aging phenotypes in the brain. Here we identify β2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. B2M is elevated in the blood of aging humans and mice, and it is increased within the hippocampus of aged mice and young heterochronic parabionts. Exogenous B2M injected systemically, or locally in the hippocampus, impairs hippocampal-dependent cognitive function and neurogenesis in young mice. The negative effects of B2M and heterochronic parabiosis are, in part, mitigated in the hippocampus of young transporter associated with antigen processing 1 (Tap1)-deficient mice with reduced cell surface expression of MHC I. The absence of endogenous B2M expression abrogates age-related cognitive decline and enhances neurogenesis in aged mice. Our data indicate that systemic B2M accumulation in aging blood promotes age-related cognitive dysfunction and impairs neurogenesis, in part via MHC I, suggesting that B2M may be targeted therapeutically in old age.
PMID: 26147761 [PubMed - as supplied by publisher]
Risks of Epilepsy During Pregnancy: How Much Do We Really Know?
JAMA Neurol. 2015 Jul 6;
Authors: French JA, Meador K
PMID: 26147713 [PubMed - as supplied by publisher]
Physiologically normal 5% O2 supports neuronal differentiation and resistance to inflammatory injury in neural stem cell cultures.
J Neurosci Res. 2015 Jul 3;
Authors: Sun X, Voloboueva LA, Stary CM, Giffard RG
Recent studies have demonstrated that neural stem cell (NSC) culture at physiologically normoxic conditions (2-5% O2 ) is advantageous in terms of neuronal differentiation and survival. Neuronal differentiation is accompanied by a remarkable shift to mitochondrial oxidative metabolism compared with preferentially glycolytic metabolism of proliferating cells. However, metabolic changes induced by growth in a normoxic (5%) O2 culture environment in NSCs have been minimally explored. This study demonstrates that culturing under 5% O2 conditions results in higher levels of mitochondrial oxidative metabolism, decreased glycolysis, and reduced levels of reactive oxygen species in NSC cultures. Inflammation is one of the major environmental factors limiting postinjury NSC neuronal differentiation and survival. Our results show that NSCs differentiated under 5% O2 conditions possess better resistance to in vitro inflammatory injury compared with those exposed to 20% O2 . The present work demonstrates that lower, more physiologically normal O2 levels support metabolic changes induced during NSC neuronal differentiation and provide increased resistance to inflammatory injury, thus highlighting O2 tension as an important determinant of cell fate and survival in various stem cell therapies. © 2015 Wiley Periodicals, Inc.
PMID: 26147710 [PubMed - as supplied by publisher]
Predictors Associated With Changes of Weight and Total Cholesterol Among Two Occupational Cohorts Over 10 Years.
J Occup Environ Med. 2015 Jul;57(7):743-750
Authors: Ott U, Stanford JB, Murtaugh MA, Greenwood JL, Gren LH, Hegmann KT, Thiese MS
OBJECTIVE: To ascertain worker health characteristics and psychosocial factors associated with changes in body weight and total cholesterol (TC) among two production operation populations.
METHODS: We performed descriptive and predictive analysis of questionnaire data and biomedical measurements from two prospective cohort studies. Our key outcomes were changes in weight, and TC over 5 to 10 years between baseline and exit assessments.
RESULTS: A total of 146 subjects were analyzed. Increases in weight were associated with belief in being overweight and baseline overweight and obesity. Increases in TC levels were associated with female sex, belief that TC levels were "not good," and feeling depressed.
CONCLUSIONS: Most of the reported associations with increases in weight and TC levels are amenable to interventions and may be a target for workplace intervention programs.
PMID: 26147542 [PubMed - as supplied by publisher]
Epstein-Barr Virus Modulates Host Cell MicroRNA-194 to Promote IL-10 Production and B Lymphoma Cell Survival.
Am J Transplant. 2015 Jul 3;
Authors: Harris-Arnold A, Arnold CP, Schaffert S, Hatton O, Krams SM, Esquivel CO, Martinez OM
Epstein-Barr virus (EBV) is a γ-herpesvirus that is linked to the development of posttransplant lymphoproliferative disorder (PTLD) in solid organ recipients. We previously demonstrated that EBV(+) B cell lymphoma cell lines isolated from patients with PTLD produce human IL-10 as an autocrine growth factor. However, little is known regarding IL-10 regulation in B cells. Here we show that EBV infection markedly alters the expression of host B cell microRNA, a class of small noncoding RNA that is an important regulator of transcriptional and posttranscriptional gene expression. Gene arrays reveal unique microRNA profiles in EBV(+) B cell lymphoma lines from patients with PTLD, compared to normal B cells or in vitro generated EBV(+) lymphoblastoid cell lines. We show that microRNA-194 expression is uniquely suppressed in EBV(+) B cell lines from PTLD patients and that the 3'untranslated region of IL-10 is targeted by microRNA-194. Overexpression of microRNA-194 attenuates IL-10 production and increases apoptosis of EBV(+) B cell lymphoma lines. Together, these data indicate that EBV co-opts the host B cell microRNA network and specifically suppresses microRNA-194 to override control of IL-10 expression. Thus, modulation of microRNA-194 may constitute a novel approach to inhibiting proliferation of EBV(+) B cell lymphomas in PTLD.
PMID: 26147452 [PubMed - as supplied by publisher]
Therapeutic Potential of Differentiated Mesenchymal Stem Cells for Treatment of Osteoarthritis.
Int J Mol Sci. 2015;16(7):14961-14978
Authors: Ham O, Lee CY, Kim R, Lee J, Oh S, Lee MY, Kim J, Hwang KC, Maeng LS, Chang W
Osteoarthritis (OA) is a chronic, progressive, and irreversible degenerative joint disease. Conventional OA treatments often result in complications such as pain and limited activity. However, transplantation of mesenchymal stem cells (MSCs) has several beneficial effects such as paracrine effects, anti-inflammatory activity, and immunomodulatory capacity. In addition, MSCs can be differentiated into several cell types, including chondrocytes, osteocytes, endothelia, and adipocytes. Thus, transplantation of MSCs is a suggested therapeutic tool for treatment of OA. However, transplanted naïve MSCs can cause problems such as heterogeneous populations including differentiated MSCs and undifferentiated cells. To overcome this problem, new strategies for inducing differentiation of MSCs are needed. One possibility is the application of microRNA (miRNA) and small molecules, which regulate multiple molecular pathways and cellular processes such as differentiation. Here, we provide insight into possible strategies for cartilage regeneration by transplantation of differentiated MSCs to treat OA patients.
PMID: 26147426 [PubMed - as supplied by publisher]
Heparin Kinetics: The "Holy Grail" of Periprocedural Anticoagulation for ablation of atrial fibrillation.
Pacing Clin Electrophysiol. 2015 Jul 3;
Authors: Briceno DF, Natale A, Biase LD
Catheter ablation of atrial fibrillation (AF) is the standard of care to achieve rhythm control in selected patients who have failed medical therapy. Despite advances in ablation strategies and technology, thromboembolism and bleeding are still important complications of catheter ablation of AF occurring in up to 5% of cases. This article is protected by copyright. All rights reserved.
PMID: 26147363 [PubMed - as supplied by publisher]
Atomic layer deposition in nanostructured photovoltaics: tuning optical, electronic and surface properties.
Nanoscale. 2015 Jul 6;
Authors: Palmstrom AF, Santra PK, Bent SF
Nanostructured materials offer key advantages for third-generation photovoltaics, such as the ability to achieve high optical absorption together with enhanced charge carrier collection using low cost components. However, the extensive interfacial areas in nanostructured photovoltaic devices can cause high recombination rates and a high density of surface electronic states. In this feature article, we provide a brief review of some nanostructured photovoltaic technologies including dye-sensitized, quantum dot sensitized and colloidal quantum dot solar cells. We then introduce the technique of atomic layer deposition (ALD), which is a vapor phase deposition method using a sequence of self-limiting surface reaction steps to grow thin, uniform and conformal films. We discuss how ALD has established itself as a promising tool for addressing different aspects of nanostructured photovoltaics. Examples include the use of ALD to synthesize absorber materials for both quantum dot and plasmonic solar cells, to grow barrier layers for dye and quantum dot sensitized solar cells, and to infiltrate coatings into colloidal quantum dot solar cell to improve charge carrier mobilities as well as stability. We also provide an example of monolayer surface modification in which adsorbed ligand molecules on quantum dots are used to tune the band structure of colloidal quantum dot solar cells for improved charge collection. Finally, we comment on the present challenges and future outlook of the use of ALD for nanostructured photovoltaics.
PMID: 26147328 [PubMed - as supplied by publisher]
Preventive Genomic Sequencing and Care of the Individual Patient.
Am J Bioeth. 2015 Jul;15(7):32-33
Authors: Char D
PMID: 26147263 [PubMed - as supplied by publisher]
Preventive Genomic Sequencing in the General Population: Do PGS Fly?
Am J Bioeth. 2015 Jul;15(7):1-2
Authors: Cho MK
PMID: 26147253 [PubMed - as supplied by publisher]
A User-Centered Design Approach to Information Sharing for Older Patients and Their Families.
JAMA Intern Med. 2015 Jul 6;
Authors: Nath PA, Sharp CD
PMID: 26147128 [PubMed - as supplied by publisher]
Increases in multiple psychiatric disorders in parents and grandparents of patients with bipolar disorder from the USA compared with The Netherlands and Germany.
Psychiatr Genet. 2015 Jul 2;
Authors: Post RM, Leverich GS, Kupka R, Keck PE, McElroy SL, Altshuler LL, Frye MA, Rowe M, Grunze H, Suppes T, Nolen WA
OBJECTIVE: We previously found that compared with Europe more parents of the USA patients were positive for a mood disorder, and that this was associated with early onset bipolar disorder. Here we examine family history of psychiatric illness in more detail across several generations.
METHODS: A total of 968 outpatients (average age 41) with bipolar disorder from four sites in the USA and three in the Netherlands and Germany (abbreviated as Europe) gave informed consent and provided detailed demographic and family history information on a patient questionnaire. Family history of psychiatric illness (bipolar disorder, unipolar depression, suicide attempt, alcohol abuse, substance abuse, and other illness) was collected for each parent, four grandparents, siblings, and children.
RESULTS: Parents of the probands with bipolar disorder from the USA compared with Europe had a significantly higher incidence of both unipolar and bipolar mood disorders, as well as each of the other psychiatric conditions listed above. With a few exceptions, this burden of psychiatric disorders was also significantly greater in the grandparents, siblings, and children of the USA versus European patients.
CONCLUSION: The increased complexity of psychiatric illness and its occurrence over several generations in the families of patients with bipolar disorder from the USA versus Europe could be contributing to the higher incidence of childhood onsets and greater virulence of illness in the USA compared with Europe. These data are convergent with others suggesting increased both genetic and environmental risk in the USA, but require replication in epidemiologically-derived populations with data based on interviews of the family members.
PMID: 26146875 [PubMed - as supplied by publisher]
Escherichia coli heme oxygenase modulates host innate immune responses.
Microbiol Immunol. 2015 Jul 3;
Authors: Maharshak N, Ryu HS, Fan TJ, Onyiah JC, Schulz S, Otterbein SL, Wong R, Hansen J, Otterbein L, Carroll I, Plevy SE
Induction of mammalian heme oxygenase-1 and exposure of animals to carbon monoxide ameliorates experimental colitis. When enteric bacteria, including Escherichia coli, are exposed to low iron conditions, they express an heme oxygenase-like enzyme, chuS, and metabolize heme into iron, biliverdin and carbon monoxide. Given the abundance of enteric bacteria residing in the intestinal lumen, we hypothesized that commensal intestinal bacteria may be a significant source of carbon monoxide, with the consequence that enteric bacteria expressing chuS and other heme oxygenase -like molecules suppress inflammatory immune responses through release of carbon monoxide. Carbon monoxide exposed mice have altered enteric bacterial composition and increased E. coli 16S and chuS DNA by real-time PCR. Moreover, severity of experimental colitis correlates with increased E. coli chuS expression in IL-10 deficient mice. To explore functional roles, E. coli were genetically modified to overexpress chuS or the chuS gene was deleted. Co-culture of chuS-overexpressing E. coli with bone marrow derived macrophages results in decreased IL-12 p40 and increased IL-10 secretion compared to wild-type or chuS-deficient E. coli. Mice infected with chuS-overexpressing E. coli have increased levels of hepatic carbon monoxide and decreased serum IL-12 p40 compared to mice infected with chuS-deficient E. coli. Thus, carbon monoxide alters the composition of the commensal intestinal microbiota and expands E. coli populations harboring the chuS gene. These bacteria are capable of attenuating innate immune responses through expression of chuS. Bacterial heme oxygenase -like molecules and bacterial-derived carbon monoxide may represent novel targets for therapeutic intervention in inflammatory conditions.
PMID: 26146866 [PubMed - as supplied by publisher]
Subcutaneous panniculitis-like T-cell lymphoma: Pediatric case series demonstrating heterogeneous presentation and option for watchful waiting.
Pediatr Blood Cancer. 2015 Jul 6;
Authors: Johnston EE, LeBlanc RE, Kim J, Chung J, Balagtas J, Kim YH, Link MP
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and primary cutaneous gamma delta T-cell lymphoma (PCGD-TCL) were initially both classified as subcutaneous panniculitis-like T-cell lymphoma. In 2008, SPTCL with alpha-beta T-cell receptor subtype was separated from primary cutaneous gamma delta T-cell lymphomas (PCGD-TCL). We report four pediatric cases that demonstrate the heterogeneity of each disease and show that PCGD-TCL in children can have an indolent course, whereas SPTCL can behave aggressively. Three patients had spontaneous, durable remissions without treatment, whereas the one patient with disease progression was treated successfully. Watchful waiting may thus be appropriate for initial management of children. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.
PMID: 26146844 [PubMed - as supplied by publisher]
Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning.
Bone Marrow Transplant. 2015 Jul 6;
Authors: Rezvani AR, Kanate AS, Efron B, Chhabra S, Kohrt HE, Shizuru JA, Laport GG, Miklos DB, Benjamin JE, Johnston LJ, Arai S, Weng WK, Negrin RS, Strober S, Lowsky R
We describe 47 patients with lymphoma and failed prior autologous hematopoietic cell transplantation (HCT) who received TLI-ATG (anti-thymocyte globulin) conditioning followed by allogeneic HCT. Thirty-two patients had non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma (n=19), T-cell NHL (n=6), mantle cell lymphoma (n=4) or other B-cell subtypes (n=3)), and 15 had Hodgkin lymphoma. The median follow-up was 4.9 (range, 2.1-11.9) years. The cumulative incidence of grade II-IV acute GvHD at day +100 was 12%, and the cumulative incidence of extensive chronic GvHD at 1 year was 36%. The 3-year cumulative incidences of overall survival (OS), PFS and non-relapse mortality (NRM) were 81%, 44% and 7%, respectively. Fifteen patients died (relapse, n=10; NRM, n=5). Among the 25 patients with relapse after allogeneic HCT, 11 (44%) achieved durable (>1 year) CRs following donor lymphocyte infusion or chemoradiotherapy. The majority of surviving patients (75%; n=24) were able to discontinue all immunosuppression. For patients with relapsed lymphoma after autologous HCT, allogeneic HCT using TLI-ATG conditioning is a well-tolerated, predominantly outpatient therapy with low NRM (7% at 3 years), a low incidence of GvHD, durable disease control and excellent OS (81% at 3 years).Bone Marrow Transplantation advance online publication, 6 July 2015; doi:10.1038/bmt.2015.149.
PMID: 26146806 [PubMed - as supplied by publisher]
Howard Holtzer -- developmental and cell biologist 1922-2014.
Dev Biol. 2015 May 15;401(2):185-7
Authors: Stockdale FE, Sanger JW, Emerson CP
PMID: 26146752 [PubMed - in process]
Catalytic Efficiency Is a Function of How Rhodium(I) (5 + 2) Catalysts Accommodate a Conserved Substrate Transition State Geometry: Induced Fit Model for Explaining Transition Metal Catalysis.
ACS Catal. 2015 Mar 6;5(3):1758-1763
Authors: Mustard TJ, Wender PA, Cheong PH
The origins of differential catalytic reactivities of four Rh(I) catalysts and their derivatives in the (5 + 2) cycloaddition reaction were elucidated using density functional theory. Computed free energy spans are in excellent agreement with known experimental rates. For every catalyst, the substrate geometries in the transition state remained constant (<0.1 Å RMSD for atoms involved in bond-making and -breaking processes). Catalytic efficiency is shown to be a function of how well the catalyst accommodates the substrate transition state geometry and electronics. This shows that the induced fit model for explaining biological catalysis may be relevant to transition metal catalysis. This could serve as a general model for understanding the origins of efficiencies of catalytic reactions.
PMID: 26146588 [PubMed - as supplied by publisher]
Tuning the Reactivity of Mononuclear Nonheme Manganese(IV)-Oxo Complexes by Triflic Acid.
Chem Sci. 2015 Jun 1;6(6):3624-3632
Authors: Chen J, Yoon H, Lee YM, Seo MS, Sarangi R, Fukuzumi S, Nam W
Triflic acid (HOTf)-bound nonheme Mn(IV)-oxo complexes, [(L)Mn(IV)(O)](2+)-(HOTf)2 (L = N4Py and Bn-TPEN; N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) and Bn-TPEN = N-benzyl-N,N',N'-tris(2-pyridylmethyl)ethane-1,2-diamine), were synthesized by adding HOTf to the solutions of the [(L)Mn(IV)(O)](2+) complexes and were characterized by various spectroscopies. The one-electron reduction potentials of the Mn(IV)(O) complexes exhibited a significant positive shift upon binding of HOTf. The driving force dependence of electron transfer (ET) from electron donors to the Mn(IV)(O) and Mn(IV)(O)-(HOTf)2 complexes were examined and evaluated in light of the Marcus theory of ET to determine the reorganization energies of ET. The smaller reorganization energies and much more positive reduction potentials of the [(L)Mn(IV)(O)](2+)-(HOTf)2 complexes resulted in much enhanced oxidation capacity towards one-electron reductants and para-X-substituted-thioanisoles. The reactivities of the Mn(IV)-oxo complexes were markedly enhanced by binding of HOTf, such as a 6.4 × 10(5)-fold increase in the oxygen atom transfer (OAT) reaction (i.e., sulfoxidation). Such a remarkable acceleration in the OAT reaction results from the enhancement of ET from para-X-substituted-thioanisoles to the Mn(IV)(O) complexes as revealed by the unified ET driving force dependence of the rate constants of OAT and ET reactions of [(L)Mn(IV)(O)](2+)-(HOTf)2. In contrast, deceleration was observed in the rate of H-atom transfer (HAT) reaction of [(L)Mn(IV)(O)](2+)-(HOTf)2 complexes with 1,4-cyclohexadiene as compared with those of the [(L)Mn(IV)(O)](2+) complexes. Thus, the binding of two HOTf molecules to the Mn(IV)(O) moiety resulted in remarkable acceleration of the ET rate when the ET is thermodynamically feasible. When the ET reaction is highly endergonic, the rate of the HAT reaction is decelerated due to the steric effect of the counter anion of HOTf.
PMID: 26146538 [PubMed - as supplied by publisher]
Pattern-Based Detection of Anion Pollutants in Water with DNA Polyfluorophores.
Chem Sci. 2015 Apr 1;6(4):2575-2583
Authors: Kwon H, Jiang W, Kool ET
Many existing irrigation, industrial and chemical storage sites are currently introducing hazardous anions into groundwater, making the monitoring of such sites a high priority. Detecting and quantifying anions in water samples typically requires complex instrumentation, adding cost and delaying analysis. Here we address these challenges by development of an optical molecular method to detect and discriminate a broad range of anionic contaminants with DNA-based fluorescent sensors. A library of 1296 tetrameric-length oligodeoxyfluorosides (ODFs) composed of metal ligand and fluorescence modulating monomers was constructed with a DNA synthesizer on PEG-polystyrene microbeads. These oligomers on beads were incubated with Y(III) or Zn(II) ions to provide affinity and responsiveness to anions. Seventeen anions were screened with the library under an epifluorescence microscope, ultimately yielding eight chemosensors that could discriminate 250 μM solutions of all 17 anions in buffered water using their patterns of response. This sensor set was able to identify two unknown anion samples from ten closely-responding anions and could also function quantitatively, determining unknown concentrations of anions such as cyanide (as low as 1 mM) and selenate (as low as 50 μM). Further studies with calibration curves established detection limits of selected anions including thiocyanate (detection limit ~300 μM) and arsenate (~800 μM). The results demonstrate DNA-like fluorescent chemosensors as versatile tools for optically analyzing environmentally hazardous anions in aqueous environments.
PMID: 26146537 [PubMed - as supplied by publisher]
Sex differences in cortical volume and gyrification in autism.
Mol Autism. 2015;6:42
Authors: Schaer M, Kochalka J, Padmanabhan A, Supekar K, Menon V
BACKGROUND: Male predominance is a prominent feature of autism spectrum disorders (ASD), with a reported male to female ratio of 4:1. Because of the overwhelming focus on males, little is known about the neuroanatomical basis of sex differences in ASD. Investigations of sex differences with adequate sample sizes are critical for improving our understanding of the biological mechanisms underlying ASD in females.
METHODS: We leveraged the open-access autism brain imaging data exchange (ABIDE) dataset to obtain structural brain imaging data from 53 females with ASD, who were matched with equivalent samples of males with ASD, and their typically developing (TD) male and female peers. Brain images were processed with FreeSurfer to assess three key features of local cortical morphometry: volume, thickness, and gyrification. A whole-brain approach was used to identify significant effects of sex, diagnosis, and sex-by-diagnosis interaction, using a stringent threshold of p < 0.01 to control for false positives. Stability and power analyses were conducted to guide future research on sex differences in ASD.
RESULTS: We detected a main effect of sex in the bilateral superior temporal cortex, driven by greater cortical volume in females compared to males in both the ASD and TD groups. Sex-by-diagnosis interaction was detected in the gyrification of the ventromedial/orbitofrontal prefrontal cortex (vmPFC/OFC). Post-hoc analyses revealed that sex-by-diagnosis interaction was driven by reduced vmPFC/OFC gyrification in males with ASD, compared to females with ASD as well as TD males and females. Finally, stability analyses demonstrated a dramatic drop in the likelihood of observing significant clusters as the sample size decreased, suggesting that previous studies have been largely underpowered. For instance, with a sample of 30 females with ASD (total n = 120), a significant sex-by-diagnosis interaction was only detected in 50 % of the simulated subsamples.
CONCLUSIONS: Our results demonstrate that some features of typical sex differences are preserved in the brain of individuals with ASD, while others are not. Sex differences in ASD are associated with cortical regions involved in language and social function, two domains of deficits in the disorder. Stability analyses provide novel quantitative insights into why smaller samples may have previously failed to detect sex differences.
PMID: 26146534 [PubMed]
OpenMM: A Hardware Independent Framework for Molecular Simulations.
Comput Sci Eng. 2015 Jul 1;12(4):34-39
Authors: Eastman P, Pande VS
The wide diversity of computer architectures today requires a new approach to software development. OpenMM is a framework for molecular mechanics simulations, allowing a single program to run efficiently on a variety of hardware platforms.
PMID: 26146490 [PubMed - as supplied by publisher]
Adaptive Immunity and Antigen-Specific Activation in Obesity-Associated Insulin Resistance.
Mediators Inflamm. 2015;2015:593075
Authors: Chng MH, Alonso MN, Barnes SE, Nguyen KD, Engleman EG
Type 2 diabetes mellitus (T2D) is a metabolic disease that is strongly tied to obesity and often preceded by insulin resistance (IR). It has been established that chronic inflammation of hypertrophic adipose tissue depots in obese individuals leads to obesity-associated IR and is mediated by cells of the innate immune system, particularly macrophages. More recently, cells of the adaptive immune system, B and T lymphocytes, have also emerged as important regulators of glucose homeostasis, raising the intriguing possibility that antigen-driven immune responses play a role in disease. In this review, we critically evaluate the roles that various B and T cell subsets play in IR, and then we examine the data suggesting that antigen-driven mechanisms, such as antigen presentation and costimulation, may drive the activity of these lymphocytes.
PMID: 26146464 [PubMed - as supplied by publisher]
RASA: Robust Alternative Splicing Analysis for Human Transcriptome Arrays.
Sci Rep. 2015;5:11917
Authors: Seok J, Xu W, Davis RW, Xiao W
Human transcriptome arrays (HTA) have recently been developed for high-throughput alternative splicing analysis by measuring signals not only from exons but also from exon-exon junctions. Effective use of these rich signals requires the development of computational methods for better gene and alternative splicing analyses. In this work, we introduce a computational method, Robust Alternative Splicing Analysis (RASA), for the analysis of the new transcriptome arrays by effective integration of the exon and junction signals. To increase robustness, RASA calculates the expression of each gene by selecting exons classified as not alternatively spliced. It then identifies alternatively spliced exons that are supported by both exon and junction signals to reduce the false positives. Finally, it detects additional alternative splicing candidates that are supported by only exon signals because the signals from the corresponding junctions are not well detected. RASA was demonstrated with Affymetrix HTAs and its performance was evaluated with mRNA-Seq and RT-PCR. The validation rate is 52.4%, which is a 60% increase when compared with previous methods that do not use selected exons for gene expression calculation and junction signals for splicing detection. These results suggest that RASA significantly improves alternative splicing analyses on HTA platforms.
PMID: 26145443 [PubMed - as supplied by publisher]
Child Feeding Perceptions among Mothers with Eating Disorders.
Appetite. 2015 Jul 2;
Authors: Sadeh-Sharvit S, Levy-Shiff R, Feldman T, Ram A, Gur E, Zubery E, Steiner E, Latzer Y, Lock J
Feeding and eating difficulties are documented among the offspring of mothers with eating disorders. Understanding the perspective of mothers with eating disorders is likely essential to develop parent-based early prevention programs for children of these mothers. In the present study, twenty-nine mothers who were diagnosed with an eating disorder prior to becoming mothers and who currently had toddler age children participated in a semi-structured interview examining maternal functioning and child feeding. The maternal perceptions that emerged from the interviews were sorted into central themes and subcategories using interpretive phenomenological analysis. Data indicate that mothers with eating disorders express preoccupation with their child's eating, shape and weight, and many dilemmas about child feeding. They also reported rarity of family meals and their toddlers' preliminary awareness of maternal symptoms. Maternal concerns regarding child nutrition, feeding and weight were reported as more intense in regards to daughters. These maternal perceptions illuminate the maternal psychological processes that underlie the feeding and eating problems of the children of mothers with lifetime eating disorders. Findings should be addressed in the evaluation, treatment, and research of adult and childhood eating disorders.
PMID: 26145278 [PubMed - as supplied by publisher]
Facelift combined with simultaneous fractional laser resurfacing: Outcomes and complications.
J Plast Reconstr Aesthet Surg. 2015 Jun 19;
Authors: Wright EJ, Struck SK
BACKGROUND: The combination of simultaneous surgical rhytidectomy with ablative resurfacing has been a controversial procedure due to the concern of postoperative wound healing. Traditional ablative resurfacing lasers are believed to have higher rates of complications, leading to delayed healing and skin flap loss when combined with face rhytidectomy surgeries. With the development of fractionated ablative laser therapy, there has been increased interest in combining these two procedures. The objective of this study is to evaluate the clinical outcomes of patients undergoing simultaneous full-face rhytidectomy in combination with fractionated ablative skin resurfacing.
METHODS: A retrospective chart analysis was performed for all patients who had a combined procedure of facelift and ablative fractional laser resurfacing from 2008 to 2013 by the senior author (SKS). Postoperative recovery and complications were recorded. The surgical technique used for performing the facelift was an extended supraplatysmal dissection with SMAS plication. Fraxel Re:Pair 10,600-nm fractional carbon dioxide laser was used to perform an ablative resurfacing including the elevated skin flaps.
RESULTS: A total of 86 patients were included. Average age was 60.01 years (range of 45-78 years). Longest follow up was five years. The average size of the elevated skin flaps was 100 cm(2). Average skin type was a Fitzpatrick type 2. All patients had complete re-epithelialization by one week after their procedure. Four patients (4.6%) experienced acne outbreaks. Four patients (4.6%) had facial erythema that persisted greater than two weeks. Of these four patients, all resolved by five weeks postoperatively. There was no delayed wound healing or skin flap loss observed.
CONCLUSION: Our results indicate that simultaneous rhytidectomy with fractionated ablative laser resurfacing does not cause an increase in wound healing or skin loss. Due to improved patient outcomes with combining these procedures, we believe that this can be increasingly offered as a safe combination.
PMID: 26144639 [PubMed - as supplied by publisher]
Comparison of Bevacizumab Alone or with Chemotherapy in Recurrent Ovarian Cancer Patients.
Gynecol Oncol. 2015 Jul 2;
Authors: Fuh KC, Secord AA, Bevis KS, Huh W, ElNaggar A, Blansit K, Previs R, Tillmanns T, Kapp DS, Chan JK
BACKGROUND: To compare the efficacy of chemotherapy (C) combined with bevacizumab (Bev) versus Bev alone in recurrent, heavily pretreated epithelial ovarian cancer (EOC).
METHODS: A multicenter analysis of patients treated from 2004 to 2011 was performed. Demographic, treatment, response, and adverse event information were obtained. Progression-free (PFS) and overall survival (OS) were analyzed.
RESULTS: Of 277 patients (median age: 58years), the majority had Stage III and IV (86%) disease, and 72% had serous histology. 244 (88%) were treated with C+Bev and 33 (12%) with Bev. Corresponding median progression-free survival (PFS) was 8.7 and 6.7months, and median overall survival (OS) was 14.3 and 10.5months, respectively. The chemotherapeutic agents combined with Bev and the median OS include: pegylated liposomal doxorubicin (n=19, OS of 20.4months), taxanes (n=55, OS of 20.2months), gemcitabine (n=106, OS of 14.1months), topotecan (n=43, OS of 13months), and cyclophosphamide (n=21, OS of 13months). There was no significant difference in toxicities between the C+Bev vs. Bev alone group.
CONCLUSION: This retrospective analysis supports that combination chemotherapy and bevacizumab prolongs PFS and OS compared with bevacizumab alone.
PMID: 26144600 [PubMed - as supplied by publisher]
Inadequacies of Physical Examination as a Cause of Medical Errors and Adverse Events--A Collection of Vignettes.
Am J Med. 2015 Jul 2;
Authors: Verghese A, Charlton B, Kassirer JP, Ramsey M, Ioannidis JP
PURPOSE/BACKGROUND: Oversights in the physical exam are a type of medical error not easily studied by chart review. They may be a major contributor to missed or delayed diagnosis, unnecessary exposure to contrast and radiation, incorrect treatment and other adverse consequences. Our purpose was to collect vignettes of physical exam oversights and to capture the diversity of their characteristics and consequences.
METHODS: A cross-sectional study using an 11-question qualitative survey for physicians and distributed electronically, with data collected from February to June of 2011. The participants were all physicians responding to email or social media invitations to complete survey. There were no limitations on geography, specialty, or practice setting.
RESULTS: Of the 208 reported vignettes that met inclusion criteria, the oversight was caused by a failure to perform the physical exam in 63%; 14% reported that the correct physical exam sign was elicited but misinterpreted while 11% reported that the relevant sign was missed or not sought. Consequence of the physical exam inadequacy included missed or delayed diagnosis in 76% of cases, incorrect diagnosis in 27%, unnecessary treatment in 18%, no or delayed treatment in 42%, unnecessary diagnostic cost in 25%, unnecessary exposure to radiation or contrast in 17%, and complications caused by treatments in 4%. The mode of the number of physicians missing the finding was 2 but many oversights were missed by many physicians. Most oversights took up to 5 days to identify, but 66 took longer. Special attention and skill in examining the skin and its appendages as well as the abdomen, groin and genito-urinary area could reduce the reported oversights by half.
CONCLUSIONS: Physical examination inadequacies are a preventable source of medical error and adverse events caused mostly by failure to perform the relevant exam.
PMID: 26144103 [PubMed - as supplied by publisher]
Sensory hair cell development and regeneration: similarities and differences.
Development. 2015 May 1;142(9):1561-71
Authors: Atkinson PJ, Huarcaya Najarro E, Sayyid ZN, Cheng AG
Sensory hair cells are mechanoreceptors of the auditory and vestibular systems and are crucial for hearing and balance. In adult mammals, auditory hair cells are unable to regenerate, and damage to these cells results in permanent hearing loss. By contrast, hair cells in the chick cochlea and the zebrafish lateral line are able to regenerate, prompting studies into the signaling pathways, morphogen gradients and transcription factors that regulate hair cell development and regeneration in various species. Here, we review these findings and discuss how various signaling pathways and factors function to modulate sensory hair cell development and regeneration. By comparing and contrasting development and regeneration, we also highlight the utility and limitations of using defined developmental cues to drive mammalian hair cell regeneration.
PMID: 25922522 [PubMed - indexed for MEDLINE]
Genetic conflict reflected in tissue-specific maps of genomic imprinting in human and mouse.
Nat Genet. 2015 May;47(5):544-9
Authors: Babak T, DeVeale B, Tsang EK, Zhou Y, Li X, Smith KS, Kukurba KR, Zhang R, Li JB, van der Kooy D, Montgomery SB, Fraser HB
Genomic imprinting is an epigenetic process that restricts gene expression to either the maternally or paternally inherited allele. Many theories have been proposed to explain its evolutionary origin, but understanding has been limited by a paucity of data mapping the breadth and dynamics of imprinting within any organism. We generated an atlas of imprinting spanning 33 mouse and 45 human developmental stages and tissues. Nearly all imprinted genes were imprinted in early development and either retained their parent-of-origin expression in adults or lost it completely. Consistent with an evolutionary signature of parental conflict, imprinted genes were enriched for coexpressed pairs of maternally and paternally expressed genes, showed accelerated expression divergence between human and mouse, and were more highly expressed than their non-imprinted orthologs in other species. Our approach demonstrates a general framework for the discovery of imprinting in any species and sheds light on the causes and consequences of genomic imprinting in mammals.
PMID: 25848752 [PubMed - indexed for MEDLINE]
Fixed-dose combination of sofosbuvir and ledipasvir for the treatment of chronic hepatitis C genotype 1.
Expert Opin Pharmacother. 2015 Apr;16(5):739-48
Authors: Kumari R, Nguyen MH
INTRODUCTION: The recent October 2014 approval of the fixed dose combination (FDC) of the NS5B polymerase inhibitor sofosbuvir (SOF) and the NS5A inhibitor ledipasvir (LDV) for the treatment of treatment-naive and -experienced HCV genotype 1a/1b (HCV-1) has marked a new era of IFN and ribavirin free treatment for chronic hepatitis C. SOF/LDV combination is approved for 12 weeks in treatment-naive patients with and without cirrhosis. For treatment-experienced patients, it is approved for 12 weeks in patients without cirrhosis but for 24 weeks in patients with cirrhosis. A shorter 8-week course of treatment can be considered for treatment-naive patients who have pretreatment HCV RNA of < 6 million IU/ml and do not have cirrhosis.
AREAS COVERED: The purpose of this synopsis is to review the pharmacotherapy and results of pivotal clinical trials for SOF/LDV as the current standard-of-care for HCV-1 patients. We also briefly discuss emerging data with SOF/LDV for certain special populations. Preliminary data is also emerging for HCV genotypes non-1, but their discussion is beyond the scope of this synopsis. The review was done based on data from Phase I, II and III published studies as well as data presented at major national and international meetings.
EXPERT OPINION: The FDC of LDV (90 mg) and SOF (400 mg) has a sustained virologic response of approximately 96% when given as a once-a-day pill for 3 months to both treatment-naive and -experienced HCV-1 patients with the exception of prior null responders with cirrhosis. The latter group of patients also achieves high sustained virologic response of 95% but with therapy for 24 weeks. In addition, emerging data suggest that this FDC regimen may be effective in the treatment of HCV-1 co-infected patients with HIV, HCV-1 and -4, patients with cirrhosis and hepatic decompensation and those with post-liver transplant HCV recurrence.
PMID: 25676581 [PubMed - indexed for MEDLINE]
Whole-genome sequencing of the world's oldest people.
PLoS One. 2014;9(11):e112430
Authors: Gierman HJ, Fortney K, Roach JC, Coles NS, Li H, Glusman G, Markov GJ, Smith JD, Hood L, Coles LS, Kim SK
Supercentenarians (110 years or older) are the world's oldest people. Seventy four are alive worldwide, with twenty two in the United States. We performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme human longevity. We found no significant evidence of enrichment for a single rare protein-altering variant or for a gene harboring different rare protein altering variants in supercentenarian compared to control genomes. We followed up on the gene most enriched for rare protein-altering variants in our cohort of supercentenarians, TSHZ3, by sequencing it in a second cohort of 99 long-lived individuals but did not find a significant enrichment. The genome of one supercentenarian had a pathogenic mutation in DSC2, known to predispose to arrhythmogenic right ventricular cardiomyopathy, which is recommended to be reported to this individual as an incidental finding according to a recent position statement by the American College of Medical Genetics and Genomics. Even with this pathogenic mutation, the proband lived to over 110 years. The entire list of rare protein-altering variants and DNA sequence of all 17 supercentenarian genomes is available as a resource to assist the discovery of the genetic basis of extreme longevity in future studies.
PMID: 25390934 [PubMed - indexed for MEDLINE]
The molecular machinery of neurotransmitter release (Nobel lecture).
Angew Chem Int Ed Engl. 2014 Nov 17;53(47):12696-717
Authors: Südhof TC
The most important property of synaptic transmission is its speed, which is crucial for the overall workings of the brain. In his Nobel Lecture, T. C. Südhof explains how the synaptic vesicle and the plasma membrane undergo rapid fusion during neurotransmitter release and how this process is spatially organized, such that opening of Ca(2+) -channels allows rapid translation of the entering Ca(2+) signal into a fusion event.
PMID: 25339369 [PubMed - indexed for MEDLINE]
Transcription factors bind negatively selected sites within human mtDNA genes.
Genome Biol Evol. 2014 Oct;6(10):2634-46
Authors: Blumberg A, Sri Sailaja B, Kundaje A, Levin L, Dadon S, Shmorak S, Shaulian E, Meshorer E, Mishmar D
Transcription of mitochondrial DNA (mtDNA)-encoded genes is thought to be regulated by a handful of dedicated transcription factors (TFs), suggesting that mtDNA genes are separately regulated from the nucleus. However, several TFs, with known nuclear activities, were found to bind mtDNA and regulate mitochondrial transcription. Additionally, mtDNA transcriptional regulatory elements, which were proved important in vitro, were harbored by a deletion that normally segregated among healthy individuals. Hence, mtDNA transcriptional regulation is more complex than once thought. Here, by analyzing ENCODE chromatin immunoprecipitation sequencing (ChIP-seq) data, we identified strong binding sites of three bona fide nuclear TFs (c-Jun, Jun-D, and CEBPb) within human mtDNA protein-coding genes. We validated the binding of two TFs by ChIP-quantitative polymerase chain reaction (c-Jun and Jun-D) and showed their mitochondrial localization by electron microscopy and subcellular fractionation. As a step toward investigating the functionality of these TF-binding sites (TFBS), we assessed signatures of selection. By analyzing 9,868 human mtDNA sequences encompassing all major global populations, we recorded genetic variants in tips and nodes of mtDNA phylogeny within the TFBS. We next calculated the effects of variants on binding motif prediction scores. Finally, the mtDNA variation pattern in predicted TFBS, occurring within ChIP-seq negative-binding sites, was compared with ChIP-seq positive-TFBS (CPR). Motifs within CPRs of c-Jun, Jun-D, and CEBPb harbored either only tip variants or their nodal variants retained high motif prediction scores. This reflects negative selection within mtDNA CPRs, thus supporting their functionality. Hence, human mtDNA-coding sequences may have dual roles, namely coding for genes yet possibly also possessing regulatory potential.
PMID: 25245407 [PubMed - indexed for MEDLINE]
Electroencephalographic features of moyamoya in adults.
Clin Neurophysiol. 2015 Mar;126(3):481-5
Authors: Frechette ES, Bell-Stephens TE, Steinberg GK, Fisher RS
OBJECTIVE: Electroencephalography is useful for evaluating transient neurological events in the setting of moyamoya disease.
METHODS: EEG findings of adults with moyamoya seen at a large moyamoya referral center are summarized. Patients were identified by retrospective chart review.
RESULTS: EEGs were ordered after cerebral revascularization for altered mental status, aphasia, limb shaking, or facial twitching. Among the study population of 103 patients having EEGs, 24% of adults with moyamoya had a history of clinical seizures. Ischemic or hemorrhagic strokes were associated with a twofold relative risk of seizures. Overall, 90% of EEGs were abnormal, most commonly focally (78%), or diffusely slow (68%). Epileptiform EEG discharges were seen in 24%. Whereas hemispheres with an ischemic stroke had a 19% risk of epileptiform discharges and an 8% risk of seizures on EEG, hemispheres with hemorrhagic stroke had a 35% risk of epileptiform discharges and 19% risk of seizures on EEG. Focal amplitude attenuation was seen in 19%, breach rhythm in 15%, rhythmic delta in 14%, and electrographic seizures in 12%.
CONCLUSIONS: Seizures and epileptiform EEG changes are common in patients with moyamoya disease.
SIGNIFICANCE: Transient events in patients with moyamoya can result from seizures as well as ischemia.
PMID: 25065300 [PubMed - indexed for MEDLINE]
Optimal management of a multispecies shorebird flyway under sea-level rise.
Conserv Biol. 2014 Dec;28(6):1710-20
Authors: Iwamura T, Fuller RA, Possingham HP
Every year, millions of migratory shorebirds fly through the East Asian-Australasian Flyway between their arctic breeding grounds and Australasia. This flyway includes numerous coastal wetlands in Asia and the Pacific that are used as stopover sites where birds rest and feed. Loss of a few important stopover sites through sea-level rise (SLR) could cause sudden population declines. We formulated and solved mathematically the problem of how to identify the most important stopover sites to minimize losses of bird populations across flyways by conserving land that facilitates upshore shifts of tidal flats in response to SLR. To guide conservation investment that minimizes losses of migratory bird populations during migration, we developed a spatially explicit flyway model coupled with a maximum flow algorithm. Migratory routes of 10 shorebird taxa were modeled in a graph theoretic framework by representing clusters of important wetlands as nodes and the number of birds flying between 2 nodes as edges. We also evaluated several resource allocation algorithms that required only partial information on flyway connectivity (node strategy, based on the impacts of SLR at nodes; habitat strategy, based on habitat change at sites; population strategy, based on population change at sites; and random investment). The resource allocation algorithms based on flyway information performed on average 15% better than simpler allocations based on patterns of habitat loss or local bird counts. The Yellow Sea region stood out as the most important priority for effective conservation of migratory shorebirds, but investment in this area alone will not ensure the persistence of species across the flyway. The spatial distribution of conservation investments differed enormously according to the severity of SLR and whether information about flyway connectivity was used to guide the prioritizations. With the rapid ongoing loss of coastal wetlands globally, our method provides insight into efficient conservation planning for migratory species.
PMID: 24975747 [PubMed - indexed for MEDLINE]
The importance of keeping cool: Reply regarding the Wilderness Medical Society practice guidelines for the prevention and treatment of heat-related illness.
Wilderness Environ Med. 2014 Jun;25(2):247-9
Authors: Lipman GS, Eifling KP, Ellis MA, Gaudio FG, Otten EM, Grissom CK
PMID: 24864070 [PubMed - indexed for MEDLINE]
Survival of a patient with tetanus in Bhutan using a magnesium infusion managed only by clinical signs.
Wilderness Environ Med. 2014 Jun;25(2):194-7
Authors: Wangmo KP, Teng M, Henker R, Kinnear S, Tshering J, Wang NE
Tetanus is a life-threatening disease that continues to have a high prevalence in developing countries. Severe muscle spasms often require patients to receive tracheostomy, high-dose sedatives, and sometimes prolonged neuromuscular blockade. Magnesium sulfate (MgSO4) infusion has great promise as an adjunct treatment for severe tetanus, as it may allow clinicians to decrease the dose of other sedative medications. Although the mechanism of action of MgSO4 is not well understood, it appears to attenuate both the muscle spasms and autonomic instability associated with severe tetanus infections. However, MgSO4 infusions are often managed based on serial measurements of serum magnesium levels and other laboratory tests such as arterial blood gases, which can be difficult to obtain in resource-poor settings. We describe a case of severe tetanus in Bhutan managed through the use of magnesium infusion titrated solely to physical examination findings.
PMID: 24792133 [PubMed - indexed for MEDLINE]
Keeping a broad perspective: Reply regarding the Wilderness Medical Society practice guidelines for the prevention and treatment of heat-related illness.
Wilderness Environ Med. 2014 Jun;25(2):251-2
Authors: Lipman GS, Eifling KP, Ellis MA, Gaudio FG, Otten EM, Grissom CK
PMID: 24656907 [PubMed - indexed for MEDLINE]
Poly-L-arginine topical lotion tested in a mouse model for frostbite injury.
Wilderness Environ Med. 2014 Jun;25(2):160-5
Authors: Auerbach LJ, DeClerk BK, Fathman CG, Gurtner GC, Auerbach PS
BACKGROUND: Frostbite injury occurs when exposure to cold results in frozen tissue. We recently reported a novel mouse model for frostbite injury to be used in screening potentially therapeutic drugs and other modalities.
OBJECTIVE: We used the mouse skin frostbite model to evaluate the effect of poly-l-arginine contained in lotion (PAL) applied topically to involved skin.
METHODS: Sixty mice were studied in a randomized, double-blind method. Standardized 2.9-cm-diameter circles were tattooed on the mouse dorsum. Magnets snap frozen in dry ice (-78.5°C) were used to create a frostbite injury on skin within the circle as a continuous 5-minute freeze. Mice were treated with prefreeze placebo, postthaw placebo, combined prefreeze and postthaw placebo, prefreeze with PAL, postthaw with PAL, or combined prefreeze and postthaw with PAL. Appearance, healing rate, tissue loss, and histology were recorded until the wounds were healed.
RESULTS: Application of PAL before inducing frostbite injury resulted in decreased tissue loss as compared with other treatment conditions.
CONCLUSIONS: Applying PAL topically to frostbitten mouse skin caused decreased tissue loss. Poly-l-arginine should be studied further to determine whether it is a beneficial therapeutic modality for frostbite injury.
PMID: 24631228 [PubMed - indexed for MEDLINE]
Access restricted to Stanford community
Can't find it?
Look if we have it in print:
- All Biomedical Resources
- Specialty Portals
- Obstetrics & Gynecology
- Biomedical Ethics
- Palliative Care
- Comparative Medicine
- Consumer Health
- Emergency Medicine
- Global Health
- Physical & Rehabilitation Med
- Infectious Diseases
- Internal Medicine
- LPCH Heart Center Nursing
- Reference Desk
- Medical Education
- Spiritual Care
- Multicultural Health
- Student IL Materials
- Classes & Tutorials
- Using the Library
- About Lane
- How To