Recent Stanford Publications in PubMedSubscribe to Recent Stanford Publications in PubMed
- The Medical Liability Climate and Prospects for Reform.Mello MM, Studdert DM, Kachalia AJAMA
- Real-time observation of signal recognition particle binding to actively translating ribosomes.Noriega TR, Chen J, Walter P, Puglisi JDElife
- Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein.Al Olaby RR, Cocquerel L, Zemla A, Saas L, Dubuisson J, Vielmetter J, Marcotrigiano J, Khan AG, Catalan FV, Perryman AL, Freundlich JS, Forli S, Levy S, Balhorn R, Azzazy HMPLoS One
- Substrate Selection for Fundamental Studies of Electrocatalysts and Photoelectrodes: Inert Potential Windows in Acidic, Neutral, and Basic Electrolyte.Benck JD, Pinaud BA, Gorlin Y, Jaramillo TFPLoS One
- Reply: Tension Shielding with the embrace Device: Does It Really Improve Scars?Gurtner GC, Longaker MTPlast Reconstr Surg
- Surgical Interventions and Medical Treatments in Treatment-Naïve Patients With Acromegaly: Systematic Review and Meta-Analysis.Abu Dabrh AM, Mohammed K, Asi N, Farah WH, Wang Z, Farah MH, Prokop LJ, Katznelson L, Murad MHJ Clin Endocrinol Metab
- Acromegaly: An Endocrine Society Clinical Practice Guideline.Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A, Wass JAJ Clin Endocrinol Metab
- Mycobacterium tuberculosis Lipoprotein LprG Binds Lipoarabinomannan and Determines Its Cell Envelope Localization to Control Phagolysosomal Fusion.Shukla S, Richardson ET, Athman JJ, Shi L, Wearsch PA, McDonald D, Banaei N, Boom WH, Jackson M, Harding CVPLoS Pathog
- 3D spheroid model of mIMCD3 cells for studying ciliopathies and renal epithelial disorders.Giles RH, Ajzenberg H, Jackson PKNat Protoc
- The great beyond: radiofrequency ablation for hemostasis.Triadafilopoulos GEndoscopy
- The contractile ring coordinates curvature dependent septum assembly during fission yeast cytokinesis.Zhou Z, Munteanu EL, He J, Ursell T, Bathe M, Huang KC, Chang FMol Biol Cell
- CD28-CD80 Interactions Control Regulatory T Cell Motility and Immunological Synapse Formation.Thauland TJ, Koguchi Y, Dustin ML, Parker DCJ Immunol
- Primary progressive narcolepsy type 1: The other side of the coin.Pizza F, Vandi S, Liguori R, Parchi P, Avoni P, Mignot E, Plazzi GNeurology
- Endoscopic molecular imaging of human bladder cancer using a CD47 antibody.Pan Y, Volkmer JP, Mach KE, Rouse RV, Liu JJ, Sahoo D, Chang TC, Metzner TJ, Kang L, van de Rijn M, Skinner EC, Gambhir SS, Weissman IL, Liao JCSci Transl Med
- Graphene Nanoribbons Under Mechanical Strain.Chen C, Wu JZ, Lam KT, Hong G, Gong M, Zhang B, Lu Y, Antaris AL, Diao S, Guo J, Dai HAdv Mater
- Bibliometrics: Is your most cited work your best?Ioannidis JP, Boyack KW, Small H, Sorensen AA, Klavans RNature
- Developing sustainable global health technologies: Insight from an initiative to address neonatal hypothermia.Gupta R, Patel R, Murty N, Panicker R, Chen JJ Public Health Policy
- Unique Function of Kinesin Kif5A in Localization of Mitochondria in Axons.Campbell PD, Shen K, Sapio MR, Glenn TD, Talbot WS, Marlow FLJ Neurosci
- Dissociable Roles of Right Inferior Frontal Cortex and Anterior Insula in Inhibitory Control: Evidence from Intrinsic and Task-Related Functional Parcellation, Connectivity, and Response Profile Analyses across Multiple Datasets.Cai W, Ryali S, Chen T, Li CS, Menon VJ Neurosci
- Oxytocin treatment for amphetamine-induced social impairments.Carson DSJ Neurosci
- Supracricoid Partial Laryngectomy with Cricohyoidoepiglottopexy: Surgical Technique Illustrated in the Anatomy Lab.Holsinger FC, Tomeh C, Moore MW, Yan W, Chen C, Laccourreye OHead Neck
- A Protocol for Eliciting Nonmaterial Values Through a Cultural Ecosystem Services Frame.Gould RK, Klain SC, Ardoin NM, Satterfield T, Woodside U, Hannahs N, Daily GC, Chan KMConserv Biol
- Book Review: "Regenerative Medicine Applications in Organ Transplantation"Gurtner GCTissue Eng Part A
- Government health insurance for people below poverty line in India: quasi-experimental evaluation of insurance and health outcomes.Sood N, Bendavid E, Mukherji A, Wagner Z, Nagpal S, Mullen PBMJ
- Transcriptome sequencing of a large human family identifies the impact of rare noncoding variants.Li X, Battle A, Karczewski KJ, Zappala Z, Knowles DA, Smith KS, Kukurba KR, Wu E, Simon N, Montgomery SBAm J Hum Genet
- Uncertainty of oil field GHG emissions resulting from information gaps: a Monte Carlo approach.Vafi K, Brandt AREnviron Sci Technol
- The consequences of chronic kidney disease mislabeling in living kidney donors.Lenihan CR, Tan JCMayo Clin Proc
- The role of radiosurgery for infratentorial arteriovenous malformations.Iyer A, Chang SDWorld Neurosurg
- Three-dimensional, distendable bladder phantom for optical coherence tomography and white light cystoscopy.Lurie KL, Smith GT, Khan SA, Liao JC, Ellerbee AKJ Biomed Opt
- Acute lung injury in patients with subarachnoid hemorrhage: a nationwide inpatient sample study.Veeravagu A, Chen YR, Ludwig C, Rincon F, Maltenfort M, Jallo J, Choudhri O, Steinberg GK, Ratliff JKWorld Neurosurg
- Global clinical response in Cushing's syndrome patients treated with mifepristone.Katznelson L, Loriaux DL, Feldman D, Braunstein GD, Schteingart DE, Gross CClin Endocrinol (Oxf)
- Temporary artery occlusion in ruptured aneurysms.Mukerji N, Cook DJ, Steinberg GKWorld Neurosurg
The Medical Liability Climate and Prospects for Reform.
JAMA. 2014 Oct 30;
Authors: Mello MM, Studdert DM, Kachalia A
For many physicians, the prospect of being sued for medical malpractice is a singularly disturbing aspect of modern clinical practice. State legislatures have enacted tort reforms, such as caps on damages, in an effort to reduce the volume and costs of malpractice litigation. Attempts to introduce similar traditional reform measures at the federal level have so far failed. Much less prominent, but potentially more important, are proposed alternative approaches for resolving medical injuries; a number of these efforts are currently being tested in federally sponsored demonstration projects. These nontraditional reforms have considerable promise for addressing some of the system's most challenging issues, including high costs and barriers to accessing compensation. In this Special Communication, we review recent national trends in medical liability claims and costs, which indicate a sharp reduction in the rate of paid claims and flat or declining levels in compensation payments and liability insurance costs over the last 7 to 10 years. We discuss a number of nontraditional reform approaches-communication-and-resolution programs, presuit notification and apology laws, safe harbor legislation, judge-directed negotiation, and administrative compensation systems-and we conclude by describing several forces likely to shape change in the medical liability environment over the next decade.
PMID: 25358122 [PubMed - as supplied by publisher]
Real-time observation of signal recognition particle binding to actively translating ribosomes.
Authors: Noriega TR, Chen J, Walter P, Puglisi JD
The signal recognition particle (SRP) directs translating ribosome-nascent chain complexes (RNCs) that display a signal sequence to protein translocation channels in target membranes. All previous work on the initial step of the targeting reaction, when SRP binds to RNCs, used stalled and non-translating RNCs. This meant that an important dimension of the co-translational process remained unstudied. We apply single-molecule fluorescence measurements to observe directly and in real-time E. coli SRP binding to actively translating RNCs. We show at physiologically relevant SRP concentrations that SRP-RNC association and dissociation rates depend on nascent chain length and the exposure of a functional signal sequence outside the ribosome. Our results resolve a long-standing question: how can a limited, sub-stoichiometric pool of cellular SRP effectively distinguish RNCs displaying a signal sequence from those that are not? The answer is strikingly simple: as originally proposed, SRP only stably engages translating RNCs exposing a functional signal sequence.
PMID: 25358118 [PubMed - as supplied by publisher]
Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein.
PLoS One. 2014;9(10):e111333
Authors: Al Olaby RR, Cocquerel L, Zemla A, Saas L, Dubuisson J, Vielmetter J, Marcotrigiano J, Khan AG, Catalan FV, Perryman AL, Freundlich JS, Forli S, Levy S, Balhorn R, Azzazy HM
Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2's interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421-645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. Surface plasmon resonance detection was used to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50's ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment.
PMID: 25357246 [PubMed - as supplied by publisher]
Substrate Selection for Fundamental Studies of Electrocatalysts and Photoelectrodes: Inert Potential Windows in Acidic, Neutral, and Basic Electrolyte.
PLoS One. 2014;9(10):e107942
Authors: Benck JD, Pinaud BA, Gorlin Y, Jaramillo TF
The selection of an appropriate substrate is an important initial step for many studies of electrochemically active materials. In order to help researchers with the substrate selection process, we employ a consistent experimental methodology to evaluate the electrochemical reactivity and stability of seven potential substrate materials for electrocatalyst and photoelectrode evaluation. Using cyclic voltammetry with a progressively increased scan range, we characterize three transparent conducting oxides (indium tin oxide, fluorine-doped tin oxide, and aluminum-doped zinc oxide) and four opaque conductors (gold, stainless steel 304, glassy carbon, and highly oriented pyrolytic graphite) in three different electrolytes (sulfuric acid, sodium acetate, and sodium hydroxide). We determine the inert potential window for each substrate/electrolyte combination and make recommendations about which materials may be most suitable for application under different experimental conditions. Furthermore, the testing methodology provides a framework for other researchers to evaluate and report the baseline activity of other substrates of interest to the broader community.
PMID: 25357131 [PubMed - as supplied by publisher]
Reply: Tension Shielding with the embrace Device: Does It Really Improve Scars?
Plast Reconstr Surg. 2014 Oct;134(4):664e-666e
Authors: Gurtner GC, Longaker MT
PMID: 25357068 [PubMed - as supplied by publisher]
Surgical Interventions and Medical Treatments in Treatment-Naïve Patients With Acromegaly: Systematic Review and Meta-Analysis.
J Clin Endocrinol Metab. 2014 Oct 30;:jc20142900
Authors: Abu Dabrh AM, Mohammed K, Asi N, Farah WH, Wang Z, Farah MH, Prokop LJ, Katznelson L, Murad MH
Context: Acromegaly is usually treated with surgery as a first-line treatment, although medical therapy has also been used as an alternative primary treatment. Objective: We conducted a systematic review and meta-analysis to synthesize the existing evidence comparing these two approaches in treatment-naÏve patients with acromegaly. Data Sources: This study performed a comprehensive search in multiple databases, including Medline, EMBASE, and Scopus from early inception through April 2014. Study Selection: The study used original controlled and uncontrolled studies that enrolled patients with acromegaly to receive either surgical treatment or medical treatment as their first-line treatment. Data Extraction: Reviewers extracted data independently and in duplicates. Because of the noncomparative nature of the available studies, we modified the Newcastle-Ottawa Scale to assess the quality of included studies. Outcomes evaluated were biochemical remission and change in IGF-1 or GH levels. We pooled outcomes using the random-effects model. Data Synthesis: The final search yielded 35 studies enrolling 2629 patients. Studies were noncomparative series with a follow-up range of 6-360 months. Compared with medical therapy, surgery was associated with a higher remission rate (67% vs 45%; P = .02). Surgery had higher remission rates at longer follow-up periods (≥24 mo) (66% vs 44%; P = .04) but not the shorter follow-up periods (≤6 mo) (53% vs 26%; P = .02). Surgery had higher remission rates in the follow-up levels of GH (65% vs 46%; P = .05). In one study, the IGF-1 level was reduced more with surgery compared with medical treatment (-731 μg/L vs -251 μg/L; P = .04). Studies in which surgery was performed by a single operator reported a higher remission rate than those with multiple operators (71% vs 47%; P = .002). Conclusions: Surgery may be associated with higher remission rate; however, the confidence in such evidence is very low due to the noncomparative nature of the studies, high heterogeneity, and imprecision.
PMID: 25356809 [PubMed - as supplied by publisher]
Acromegaly: An Endocrine Society Clinical Practice Guideline.
J Clin Endocrinol Metab. 2014 Oct 30;:jc20142700
Authors: Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA
Objective: The aim was to formulate clinical practice guidelines for acromegaly. Participants: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. Conclusions: Using an evidence-based approach, this acromegaly guideline addresses important clinical issues regarding the evaluation and management of acromegaly, including the appropriate biochemical assessment, a therapeutic algorithm, including use of medical monotherapy or combination therapy, and management during pregnancy.
PMID: 25356808 [PubMed - as supplied by publisher]
Mycobacterium tuberculosis Lipoprotein LprG Binds Lipoarabinomannan and Determines Its Cell Envelope Localization to Control Phagolysosomal Fusion.
PLoS Pathog. 2014 Oct;10(10):e1004471
Authors: Shukla S, Richardson ET, Athman JJ, Shi L, Wearsch PA, McDonald D, Banaei N, Boom WH, Jackson M, Harding CV
Mycobacterium tuberculosis (Mtb) virulence is decreased by genetic deletion of the lipoprotein LprG, but the function of LprG remains unclear. We report that LprG expressed in Mtb binds to lipoglycans, such as lipoarabinomannan (LAM), that mediate Mtb immune evasion. Lipoglycan binding to LprG was dependent on both insertion of lipoglycan acyl chains into a hydrophobic pocket on LprG and a novel contribution of lipoglycan polysaccharide components outside of this pocket. An lprG null mutant (Mtb ΔlprG) had lower levels of surface-exposed LAM, revealing a novel role for LprG in determining the distribution of components in the Mtb cell envelope. Furthermore, this mutant failed to inhibit phagosome-lysosome fusion, an immune evasion strategy mediated by LAM. We propose that LprG binding to LAM facilitates its transfer from the plasma membrane into the cell envelope, increasing surface-exposed LAM, enhancing cell envelope integrity, allowing inhibition of phagosome-lysosome fusion and enhancing Mtb survival in macrophages.
PMID: 25356793 [PubMed - as supplied by publisher]
3D spheroid model of mIMCD3 cells for studying ciliopathies and renal epithelial disorders.
Nat Protoc. 2014 Dec;9(12):2725-2731
Authors: Giles RH, Ajzenberg H, Jackson PK
We have developed a novel 3D cell culture model that uses mouse inner-medullary collecting duct (mIMCD3) cells to generate epithelial spheroids. This model is amenable to efficient siRNA knockdown and subsequent rescue with human patient-derived alleles. Spheroids develop apicobasal polarity and complete lumens, and they are consequently an ideal model for polarity defects seen in renal ciliopathies such as nephronophthisis. Briefly, mIMCD3 cells are transfected and subsequently passaged to a Matrigel mixture, which is seeded in chamber slides and covered in growth medium. Once the spheroids are formed, Matrigel is dissolved and immunocytochemistry is performed in the chamber slides. The technique is amenable to semiautomatic imaging analysis, and it can test multiple genes simultaneously, gene-dosing effects and a variety of therapeutic interventions. The spheroid technique is a unique and simple 6-d in vitro method of interrogating ex vivo tissue organization.
PMID: 25356583 [PubMed - as supplied by publisher]
The great beyond: radiofrequency ablation for hemostasis.
Endoscopy. 2014 Oct;46(11):925-926
Authors: Triadafilopoulos G
PMID: 25356511 [PubMed - as supplied by publisher]
The contractile ring coordinates curvature dependent septum assembly during fission yeast cytokinesis.
Mol Biol Cell. 2014 Oct 29;
Authors: Zhou Z, Munteanu EL, He J, Ursell T, Bathe M, Huang KC, Chang F
The functions of the actin-myosin-based contractile ring in cytokinesis remain to be elucidated. Recent findings show that in the fission yeast Schizosaccharomyces pombe, cleavage furrow ingression is driven by polymerization of cell wall fibers outside the plasma membrane, not by the contractile ring. Here, we show that one function of the ring is to spatially coordinate septum assembly. We develop an improved method for live-cell imaging of the division apparatus by orienting the rod-shaped cells vertically using microfabricated wells. We observe that the septum hole and ring are circular and centered in wild-type cells, and that in the absence of a functional ring, the septum continues to ingress but in a disorganized and asymmetric manner. By manipulating the cleavage furrow into different shapes, we show that the ring promotes local septum growth in a curvature-dependent manner, allowing even a misshapen septum to grow into a more regular shape. This curvature-dependent growth suggests a model in which contractile forces of the ring shape the septum cell wall by stimulating the cell wall machinery in a mechanosensitive manner. Mechanical regulation of the cell wall assembly may have general relevance to the morphogenesis of walled cells.
PMID: 25355954 [PubMed - as supplied by publisher]
CD28-CD80 Interactions Control Regulatory T Cell Motility and Immunological Synapse Formation.
J Immunol. 2014 Oct 29;
Authors: Thauland TJ, Koguchi Y, Dustin ML, Parker DC
Regulatory T cells (Tregs) are essential for tolerance to self and environmental Ags, acting in part by downmodulating costimulatory molecules on the surface of dendritic cells (DCs) and altering naive CD4 T cell-DC interactions. In this study, we show that Tregs form stable conjugates with DCs before, but not after, they decrease surface expression of the costimulatory molecule CD80 on the DCs. We use supported planar bilayers to show that Tregs dramatically slow down but maintain a highly polarized and motile phenotype after recognizing Ag in the absence of costimulation. These motile cells are characterized by distinct accumulations of LFA-1-ICAM-1 in the lamella and TCR-MHC in the uropod, consistent with a motile immunological synapse or "kinapse." However, in the presence of high, but not low, concentrations of CD80, Tregs form stationary, symmetrical synapses. Using blocking Abs, we show that, whereas CTLA-4 is required for CD80 downmodulation, CD28-CD80 interactions are critical for modulating Treg motility in the presence of Ag. Taken together, these results support the hypothesis that Tregs are tuned to alter their motility depending on costimulatory signals.
PMID: 25355918 [PubMed - as supplied by publisher]
Primary progressive narcolepsy type 1: The other side of the coin.
Neurology. 2014 Oct 29;
Authors: Pizza F, Vandi S, Liguori R, Parchi P, Avoni P, Mignot E, Plazzi G
PMID: 25355832 [PubMed - as supplied by publisher]
Endoscopic molecular imaging of human bladder cancer using a CD47 antibody.
Sci Transl Med. 2014 Oct 29;6(260):260ra148
Authors: Pan Y, Volkmer JP, Mach KE, Rouse RV, Liu JJ, Sahoo D, Chang TC, Metzner TJ, Kang L, van de Rijn M, Skinner EC, Gambhir SS, Weissman IL, Liao JC
A combination of optical imaging technologies with cancer-specific molecular imaging agents is a potentially powerful strategy to improve cancer detection and enable image-guided surgery. Bladder cancer is primarily managed endoscopically by white light cystoscopy with suboptimal diagnostic accuracy. Emerging optical imaging technologies hold great potential for improved diagnostic accuracy but lack imaging agents for molecular specificity. Using fluorescently labeled CD47 antibody (anti-CD47) as molecular imaging agent, we demonstrated consistent identification of bladder cancer with clinical grade fluorescence imaging systems, confocal endomicroscopy, and blue light cystoscopy in fresh surgically removed human bladders. With blue light cystoscopy, the sensitivity and specificity for CD47-targeted imaging were 82.9 and 90.5%, respectively. We detected variants of bladder cancers, which are diagnostic challenges, including carcinoma in situ, residual carcinoma in tumor resection bed, recurrent carcinoma following prior intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), and excluded cancer from benign but suspicious-appearing mucosa. CD47-targeted molecular imaging could improve diagnosis and resection thoroughness for bladder cancer.
PMID: 25355698 [PubMed - in process]
Graphene Nanoribbons Under Mechanical Strain.
Adv Mater. 2014 Oct 29;
Authors: Chen C, Wu JZ, Lam KT, Hong G, Gong M, Zhang B, Lu Y, Antaris AL, Diao S, Guo J, Dai H
Uniaxial strains are introduced into individual graphene nanoribbons (GNRs) with highly smooth edges to investigate the strain effects on Raman spectroscopic and electrical properties of GNRs. It is found that uniaxial strain downshifts the Raman G-band frequency of GNRs linearly and tunes their bandgap significantly in a non-monotonic manner. The strain engineering of GNRs is promising for potential electronics and photonics applications.
PMID: 25355690 [PubMed - as supplied by publisher]
Bibliometrics: Is your most cited work your best?
Nature. 2014 Oct 29;514(7524):561-2
Authors: Ioannidis JP, Boyack KW, Small H, Sorensen AA, Klavans R
PMID: 25355346 [PubMed - in process]
Developing sustainable global health technologies: Insight from an initiative to address neonatal hypothermia.
J Public Health Policy. 2014 Nov 13;
Authors: Gupta R, Patel R, Murty N, Panicker R, Chen J
Relative to drugs, diagnostics, and vaccines, efforts to develop other global health technologies, such as medical devices, are limited and often focus on the short-term goal of prototype development instead of the long-term goal of a sustainable business model. To develop a medical device to address neonatal hypothermia for use in resource-limited settings, we turned to principles of design theory: (1) define the problem with consideration of appropriate integration into relevant health policies, (2) identify the users of the technology and the scenarios in which the technology would be used, and (3) use a highly iterative product design and development process that incorporates the perspective of the user of the technology at the outset and addresses scalability. In contrast to our initial idea, to create a single device, the process guided us to create two separate devices, both strikingly different from current solutions. We offer insights from our initial experience that may be helpful to others engaging in global health technology development.Journal of Public Health Policy advance online publication, 13 November 2014; doi:10.1057/jphp.2014.44.
PMID: 25355235 [PubMed - as supplied by publisher]
Unique Function of Kinesin Kif5A in Localization of Mitochondria in Axons.
J Neurosci. 2014 Oct 29;34(44):14717-32
Authors: Campbell PD, Shen K, Sapio MR, Glenn TD, Talbot WS, Marlow FL
Mutations in Kinesin proteins (Kifs) are linked to various neurological diseases, but the specific and redundant functions of the vertebrate Kifs are incompletely understood. For example, Kif5A, but not other Kinesin-1 heavy-chain family members, is implicated in Charcot-Marie-Tooth disease (CMT) and Hereditary Spastic Paraplegia (HSP), but the mechanism of its involvement in the progressive axonal degeneration characteristic of these diseases is not well understood. We report that zebrafish kif5Aa mutants exhibit hyperexcitability, peripheral polyneuropathy, and axonal degeneration reminiscent of CMT and HSP. Strikingly, although kif5 genes are thought to act largely redundantly in other contexts, and zebrafish peripheral neurons express five kif5 genes, kif5Aa mutant peripheral sensory axons lack mitochondria and degenerate. We show that this Kif5Aa-specific function is cell autonomous and is mediated by its C-terminal tail, as only Kif5Aa and chimeric motors containing the Kif5Aa C-tail can rescue deficits. Finally, concurrent loss of the kinesin-3, kif1b, or its adaptor kbp, exacerbates axonal degeneration via a nonmitochondrial cargo common to Kif5Aa. Our results shed light on Kinesin complexity and reveal determinants of specific Kif5A functions in mitochondrial transport, adaptor binding, and axonal maintenance.
PMID: 25355224 [PubMed - in process]
Dissociable Roles of Right Inferior Frontal Cortex and Anterior Insula in Inhibitory Control: Evidence from Intrinsic and Task-Related Functional Parcellation, Connectivity, and Response Profile Analyses across Multiple Datasets.
J Neurosci. 2014 Oct 29;34(44):14652-67
Authors: Cai W, Ryali S, Chen T, Li CS, Menon V
The right inferior frontal cortex (rIFC) and the right anterior insula (rAI) have been implicated consistently in inhibitory control, but their differential roles are poorly understood. Here we use multiple quantitative techniques to dissociate the functional organization and roles of the rAI and rIFC. We first conducted a meta-analysis of 70 published inhibitory control studies to generate a commonly activated right fronto-opercular cortex volume of interest (VOI). We then segmented this VOI using two types of features: (1) intrinsic brain activity; and (2) stop-signal task-evoked hemodynamic response profiles. In both cases, segmentation algorithms identified two stable and distinct clusters encompassing the rAI and rIFC. The rAI and rIFC clusters exhibited several distinct functional characteristics. First, the rAI showed stronger intrinsic and task-evoked functional connectivity with the anterior cingulate cortex, whereas the rIFC had stronger intrinsic and task-evoked functional connectivity with dorsomedial prefrontal and lateral fronto-parietal cortices. Second, the rAI showed greater activation than the rIFC during Unsuccessful, but not Successful, Stop trials, and multivoxel response profiles in the rAI, but not the rIFC, accurately differentiated between Successful and Unsuccessful Stop trials. Third, activation in the rIFC, but not rAI, predicted individual differences in inhibitory control abilities. Crucially, these findings were replicated in two independent cohorts of human participants. Together, our findings provide novel quantitative evidence for the dissociable roles of the rAI and rIFC in inhibitory control. We suggest that the rAI is particularly important for detecting behaviorally salient events, whereas the rIFC is more involved in implementing inhibitory control.
PMID: 25355218 [PubMed - in process]
Oxytocin treatment for amphetamine-induced social impairments.
J Neurosci. 2014 Oct 29;34(44):14503-5
Authors: Carson DS
PMID: 25355204 [PubMed - in process]
Supracricoid Partial Laryngectomy with Cricohyoidoepiglottopexy: Surgical Technique Illustrated in the Anatomy Lab.
Head Neck. 2014 Oct 30;
Authors: Holsinger FC, Tomeh C, Moore MW, Yan W, Chen C, Laccourreye O
Despite its first introduction by Majer and Rieder in 1959 and its widespread implementation by French surgeons, supracricoid partial laryngectomy (SCPL) only started to be discussed in the English literature in the early 1990s. The procedure has been employed for decades as a partial laryngectomy that preserves laryngeal function, namely speaking, swallowing, and breathing. SCPL is similar to an extended supraglottic laryngectomy; however, while the glottis remains intact with a supraglottic laryngectomy, a neolarynx is recreated in SCPL using the fundamental elements of the cricoarytenoid unit. In SCPL with cricohyoidoepiglottopexy (CHEP), a pexy is created between the cricoid cartilage below and the preserved epiglottis and hyoid bone above. Remarkably, but reliably, this reconstruction recreates the airway and improves swallowing to the point where even one arytenoid can be sacrificed. Head Neck, 2014.
PMID: 25354982 [PubMed - as supplied by publisher]
A Protocol for Eliciting Nonmaterial Values Through a Cultural Ecosystem Services Frame.
Conserv Biol. 2014 Oct 29;
Authors: Gould RK, Klain SC, Ardoin NM, Satterfield T, Woodside U, Hannahs N, Daily GC, Chan KM
Stakeholders' nonmaterial desires, needs, and values often critically influence the success of conservation projects. These considerations are challenging to articulate and characterize, resulting in their limited uptake in management and policy. We devised an interview protocol designed to enhance understanding of cultural ecosystem services (CES). The protocol begins with discussion of ecosystem-related activities (e.g., recreation, hunting) and management and then addresses CES, prompting for values encompassing concepts identified in the Millennium Ecosystem Assessment (2005) and explored in other CES research. We piloted the protocol in Hawaii and British Columbia. In each location, we interviewed 30 individuals from diverse backgrounds. We analyzed results from the 2 locations to determine the effectiveness of the interview protocol in elucidating nonmaterial values. The qualitative and spatial components of the protocol helped characterize cultural, social, and ethical values associated with ecosystems in multiple ways. Maps and situational, or vignette-like, questions helped respondents articulate difficult-to-discuss values. Open-ended prompts allowed respondents to express a diversity of ecosystem-related values and proved sufficiently flexible for interviewees to communicate values for which the protocol did not explicitly probe. Finally, the results suggest that certain values, those mentioned frequently throughout the interview, are particularly salient for particular populations. The protocol can provide efficient, contextual, and place-based data on the importance of particular ecosystem attributes for human well-being. Qualitative data are complementary to quantitative and spatial assessments in the comprehensive representation of people's values pertaining to ecosystems, and this protocol may assist in incorporating values frequently overlooked in decision making processes.
PMID: 25354730 [PubMed - as supplied by publisher]
Book Review: "Regenerative Medicine Applications in Organ Transplantation"
Tissue Eng Part A. 2014 Oct 29;
Authors: Gurtner GC
PMID: 25354659 [PubMed - as supplied by publisher]
Government health insurance for people below poverty line in India: quasi-experimental evaluation of insurance and health outcomes.
Authors: Sood N, Bendavid E, Mukherji A, Wagner Z, Nagpal S, Mullen P
OBJECTIVES: To evaluate the effects of a government insurance program covering tertiary care for people below the poverty line in Karnataka, India, on out-of-pocket expenditures, hospital use, and mortality.
DESIGN: Geographic regression discontinuity study.
SETTING: 572 villages in Karnataka, India.
PARTICIPANTS: 31,476 households (22,796 below poverty line and 8680 above poverty line) in 300 villages where the scheme was implemented and 28,633 households (21,767 below poverty line and 6866 above poverty line) in 272 neighboring matched villages ineligible for the scheme.
INTERVENTION: A government insurance program (Vajpayee Arogyashree scheme) that provided free tertiary care to households below the poverty line in about half of villages in Karnataka from February 2010 to August 2012.
MAIN OUTCOME MEASURE: Out-of-pocket expenditures, hospital use, and mortality.
RESULTS: Among households below the poverty line, the mortality rate from conditions potentially responsive to services covered by the scheme (mostly cardiac conditions and cancer) was 0.32% in households eligible for the scheme compared with 0.90% among ineligible households just south of the eligibility border (difference of 0.58 percentage points, 95% confidence interval 0.40 to 0.75; P<0.001). We found no difference in mortality rates for households above the poverty line (households above the poverty line were not eligible for the scheme), with a mortality rate from conditions covered by the scheme of 0.56% in eligible villages compared with 0.55% in ineligible villages (difference of 0.01 percentage points, -0.03 to 0.03; P=0.95). Eligible households had significantly reduced out-of-pocket health expenditures for admissions to hospitals with tertiary care facilities likely to be covered by the scheme (64% reduction, 35% to 97%; P<0.001). There was no significant increase in use of covered services, although the point estimate of a 44.2% increase approached significance (-5.1% to 90.5%; P=0.059). Both reductions in out-of-pocket expenditures and potential increases in use might have contributed to the observed reductions in mortality.
CONCLUSIONS: Insuring poor households for efficacious but costly and underused health services significantly improves population health in India.
PMID: 25214509 [PubMed - indexed for MEDLINE]
Transcriptome sequencing of a large human family identifies the impact of rare noncoding variants.
Am J Hum Genet. 2014 Sep 4;95(3):245-56
Authors: Li X, Battle A, Karczewski KJ, Zappala Z, Knowles DA, Smith KS, Kukurba KR, Wu E, Simon N, Montgomery SB
Recent and rapid human population growth has led to an excess of rare genetic variants that are expected to contribute to an individual's genetic burden of disease risk. To date, much of the focus has been on rare protein-coding variants, for which potential impact can be estimated from the genetic code, but determining the impact of rare noncoding variants has been more challenging. To improve our understanding of such variants, we combined high-quality genome sequencing and RNA sequencing data from a 17-individual, three-generation family to contrast expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) within this family to eQTLs and sQTLs within a population sample. Using this design, we found that eQTLs and sQTLs with large effects in the family were enriched with rare regulatory and splicing variants (minor allele frequency < 0.01). They were also more likely to influence essential genes and genes involved in complex disease. In addition, we tested the capacity of diverse noncoding annotation to predict the impact of rare noncoding variants. We found that distance to the transcription start site, evolutionary constraint, and epigenetic annotation were considerably more informative for predicting the impact of rare variants than for predicting the impact of common variants. These results highlight that rare noncoding variants are important contributors to individual gene-expression profiles and further demonstrate a significant capability for genomic annotation to predict the impact of rare noncoding variants.
PMID: 25192044 [PubMed - indexed for MEDLINE]
Uncertainty of oil field GHG emissions resulting from information gaps: a Monte Carlo approach.
Environ Sci Technol. 2014 Sep 2;48(17):10511-8
Authors: Vafi K, Brandt AR
Regulations on greenhouse gas (GHG) emissions from liquid fuel production generally work with incomplete data about oil production operations. We study the effect of incomplete information on estimates of GHG emissions from oil production operations. Data from California oil fields are used to generate probability distributions for eight oil field parameters previously found to affect GHG emissions. We use Monte Carlo (MC) analysis on three example oil fields to assess the change in uncertainty associated with learning of information. Single factor uncertainties are most sensitive to ignorance about water-oil ratio (WOR) and steam-oil ratio (SOR), resulting in distributions with coefficients of variation (CV) of 0.1-0.9 and 0.5, respectively. Using a combinatorial uncertainty analysis, we find that only a small number of variables need to be learned to greatly improve on the accuracy of MC mean. At most, three pieces of data are required to reduce bias in MC mean to less than 5% (absolute). However, the parameters of key importance in reducing uncertainty depend on oil field characteristics and on the metric of uncertainty applied. Bias in MC mean can remain after multiple pieces of information are learned, if key pieces of information are left unknown.
PMID: 25110115 [PubMed - indexed for MEDLINE]
The consequences of chronic kidney disease mislabeling in living kidney donors.
Mayo Clin Proc. 2014 Aug;89(8):1126-9
Authors: Lenihan CR, Tan JC
Despite numerous studies that substantiate its long-term safety, barriers to kidney donation persist. These include issues of insurability after donation and its consequent financial and emotional burdens. We present 2 cases in which mislabeling of kidney donors as having chronic kidney disease shortly after kidney donation adversely affected their insurability. A concerted effort should be made to affect public policy such that insurability and the psychosocial well-being of living donors are protected.
PMID: 24867395 [PubMed - indexed for MEDLINE]
The role of radiosurgery for infratentorial arteriovenous malformations.
World Neurosurg. 2014 Jul-Aug;82(1-2):e85-6
Authors: Iyer A, Chang SD
PMID: 24815735 [PubMed - indexed for MEDLINE]
Three-dimensional, distendable bladder phantom for optical coherence tomography and white light cystoscopy.
J Biomed Opt. 2014 Mar;19(3):36009
Authors: Lurie KL, Smith GT, Khan SA, Liao JC, Ellerbee AK
We describe a combination of fabrication techniques and a general process to construct a three-dimensional (3-D) phantom that mimics the size, macroscale structure, microscale surface topology, subsurface microstructure, optical properties, and functional characteristics of a cancerous bladder. The phantom also includes features that are recognizable in white light (i.e., the visual appearance of blood vessels), making it suitable to emulate the bladder for emerging white light+optical coherence tomography (OCT) cystoscopies and other endoscopic procedures of large, irregularly shaped organs. The fabrication process has broad applicability and can be generalized to OCT phantoms for other tissue types or phantoms for other imaging modalities. To this end, we also enumerate the nuances of applying known fabrication techniques (e.g., spin coating) to contexts (e.g., nonplanar, 3-D shapes) that are essential to establish their generalizability and limitations. We anticipate that this phantom will be immediately useful to evaluate innovative OCT systems and software being developed for longitudinal bladder surveillance and early cancer detection.
PMID: 24623158 [PubMed - indexed for MEDLINE]
Acute lung injury in patients with subarachnoid hemorrhage: a nationwide inpatient sample study.
World Neurosurg. 2014 Jul-Aug;82(1-2):e235-41
Authors: Veeravagu A, Chen YR, Ludwig C, Rincon F, Maltenfort M, Jallo J, Choudhri O, Steinberg GK, Ratliff JK
OBJECTIVE: To determine national trends for patients with subarachnoid hemorrhage (SAH) and pulmonary complications including acute respiratory distress syndrome (ARDS).
METHODS: The Nationwide Inpatient Sample database was used to sample 193,209 admissions for SAH with and without ARDS during the period 1993-2008 using International Classification of Diseases, Ninth Revision, Clinical Modification coding. A multivariate stepwise regression analysis was performed.
RESULTS: The incidence of ARDS in patients with SAH increased from 35.51% in 1993 to 37.60% in 2008. However, the overall mortality in patients with SAH and in patients with SAH and ARDS decreased in the same period, from 42.30% to 31.99% and from 75.13% to 60.76%, respectively. Multivariate analysis showed that the predictors of developing ARDS in patients with SAH include older age; larger hospital size; and comorbidities such as epilepsy, cardiac arrest, sepsis, congestive heart failure, hypertension, chronic obstructive pulmonary disease, hematologic dysfunction, renal dysfunction, and neurologic dysfunction. Predictors of mortality in patients with SAH include age and hospital complications, such as coronary artery disease, ARDS, cancer, hematologic dysfunction, and renal dysfunction.
CONCLUSIONS: Patients with SAH are at increased risk of developing ARDS. The identification of certain risk factors may alert and aid practitioners in preventing worsening disease.
PMID: 24560705 [PubMed - indexed for MEDLINE]
Global clinical response in Cushing's syndrome patients treated with mifepristone.
Clin Endocrinol (Oxf). 2014 Apr;80(4):562-9
Authors: Katznelson L, Loriaux DL, Feldman D, Braunstein GD, Schteingart DE, Gross C
OBJECTIVE: Mifepristone, a glucocorticoid receptor antagonist, improves clinical status in patients with Cushing's syndrome (CS). We examined the pattern, reliability and correlates of global clinical response (GCR) assessments during a 6-month clinical trial of mifepristone in CS.
DESIGN: Post hoc analysis of secondary end-point data from a 24-week multicentre, open-label trial of mifepristone (300-1200 mg daily) in CS. Intraclass correlation coefficient (ICC) was used to examine rater concordance, and drivers of clinical improvement were determined by multivariate regression analysis.
PATIENTS: Forty-six adult patients with refractory CS along with diabetes mellitus type 2 or impaired glucose tolerance, and/or a diagnosis of hypertension.
MEASUREMENTS: Global clinical assessment made by three independent reviewers using a three-point ordinal scale (+1 = improvement; 0 = no change; -1 = worsening) based on eight broad clinical categories including glucose control, lipids, blood pressure, body composition, clinical appearance, strength, psychiatric/cognitive symptoms and quality of life at Weeks 6, 10, 16, and 24.
RESULTS: Positive GCR increased progressively over time with 88% of patients having improved at Week 24 (P < 0·001). The full concordance among reviewers occurred in 76·6% of evaluations resulting in an ICC of 0·652 (P < 0·001). Changes in body weight (P < 0·0001), diastolic blood pressure (P < 0·0001), two-hour postoral glucose challenge glucose concentration (P = 0·0003), and Cushingoid appearance (P = 0·022) were strong correlates of GCR.
CONCLUSIONS: Mifepristone treatment for CS results in progressive clinical improvement. Overall agreement among clinical reviewers was substantial and determinants of positive GCR included change in weight, blood pressure, glucose levels and appearance.
PMID: 24102404 [PubMed - indexed for MEDLINE]
Temporary artery occlusion in ruptured aneurysms.
World Neurosurg. 2014 Jul-Aug;82(1-2):43-5
Authors: Mukerji N, Cook DJ, Steinberg GK
PMID: 23920285 [PubMed - indexed for MEDLINE]
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