Recent Stanford Publications in PubMed
- Control of alphavirus-based gene expression using engineered riboswitches.Bell CL, Yu D, Smolke CD, Geall AJ, Beard CW, Mason PWVirology
- Dexterous robotic manipulation of alert adult Drosophila for high-content experimentation.Savall J, Ho ET, Huang C, Maxey JR, Schnitzer MJNat Methods
- Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture.Paşca AM, Sloan SA, Clarke LE, Tian Y, Makinson CD, Huber N, Kim CH, Park JY, O'Rourke NA, Nguyen KD, Smith SJ, Huguenard JR, Geschwind DH, Barres BA, Paşca SPNat Methods
- Juvenile zebra finches learn the underlying structural regularities of their fathers' song.Menyhart O, Kolodny O, Goldstein MH, DeVoogd TJ, Edelman SFront Psychol
- Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials.Strand V, McIntyre LF, Beach WR, Miller LE, Block JEJ Pain Res
- Estimating Large-Scale Network Convergence in the Human Functional Connectome.Bell PT, Shine JMBrain Connect
- Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming.Tanaka Y, Hysolli E, Su J, Xiang Y, Kim KY, Zhong M, Li Y, Heydari K, Euskirchen G, Snyder MP, Pan X, Weissman SM, Park IHStem Cell Reports
- An unprecedented dual antagonist and agonist of human Transglutaminase 2.Yi MC, Palanski BA, Quintero SA, Plugis NM, Khosla CBioorg Med Chem Lett
- In vivo histology of the myelin g-ratio with magnetic resonance imaging.Stikov N, Campbell JS, Stroh T, Lavelée M, Frey S, Novek J, Nuara S, Ho MK, Bedell BJ, Dougherty RF, Leppert IR, Boudreau M, Narayanan S, Duval T, Cohen-Adad J, Picard P, Gasecka A, Côté D, Bruce Pike GNeuroimage
- Curricular policy as a collective effects problem: A distributional approach.Penner AM, Domina T, Penner EK, Conley ASoc Sci Res
- No place like home? Familism and Latino/a-white differences in college pathways.Ovink SM, Kalogrides DSoc Sci Res
- What drives the gender gap in charitable giving? Lower empathy leads men to give less to poverty relief.Willer R, Wimer C, Owens LASoc Sci Res
- Mutations of GPR126 Are Responsible for Severe Arthrogryposis Multiplex Congenita.Ravenscroft G, Nolent F, Rajagopalan S, Meireles AM, Paavola KJ, Gaillard D, Alanio E, Buckland M, Arbuckle S, Krivanek M, Maluenda J, Pannell S, Gooding R, Ong RW, Allcock RJ, Carvalho ED, Carvalho MD, Kok F, Talbot WS, Melki J, Laing NGAm J Hum Genet
- Recessive Mutations in the α3 (VI) Collagen Gene COL6A3 Cause Early-Onset Isolated Dystonia.Zech M, Lam DD, Francescatto L, Schormair B, Salminen AV, Jochim A, Wieland T, Lichtner P, Peters A, Gieger C, Lochmüller H, Strom TM, Haslinger B, Katsanis N, Winkelmann JAm J Hum Genet
- Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.Kesler SR, Watson CL, Blayney DWNeurobiol Aging
- Gizmo is a mean word!Koltai PJOtolaryngol Head Neck Surg
- The ins and outs of viral infection: keystone meeting review.Bird SW, Kirkegaard K, Agbandje-McKenna M, Freed EOViruses
- Inflammatory cytokines and the lymphatic endothelium.Rockson SGLymphat Res Biol
- Cellular specificity of the blood-CSF barrier for albumin transfer across the choroid plexus epithelium.Liddelow SA, Dzięgielewska KM, Møllgård K, Whish SC, Noor NM, Wheaton BJ, Gehwolf R, Wagner A, Traweger A, Bauer H, Bauer HC, Saunders NRPLoS One
- Absence of pancreatic intraepithelial neoplasia predicts poor survival after resection of pancreatic cancer.Hassid BG, Lucas AL, Salomao M, Weng C, Liu F, Khanna LG, Kumar S, Hwang C, Chabot JA, Frucht HPancreas
- Relationship between sunlight and the age of onset of bipolar disorder: an international multisite study.Bauer M, Glenn T, Alda M, Andreassen OA, Angelopoulos E, Ardau R, Baethge C, Bauer R, Bellivier F, Belmaker RH, Berk M, Bjella TD, Bossini L, Bersudsky Y, Cheung EY, Conell J, Del Zompo M, Dodd S, Etain B, Fagiolini A, Frye MA, Fountoulakis KN, Garneau-Fournier J, González-Pinto A, Harima H, Hassel S, Henry C, Iacovides A, Isometsä ET, Kapczinski F, Kliwicki S, König B, Krogh R, Kunz M, Lafer B, Larsen ER, Lewitzka U, Lopez-Jaramillo C, MacQueen G, Manchia M, Marsh W, Martinez-Cengotitabengoa M, Melle I, Monteith S, Morken G, Munoz R, Nery FG, O'Donovan C, Osher Y, Pfennig A, Quiroz D, Ramesar R, Rasgon N, Reif A, Ritter P, Rybakowski JK, Sagduyu K, Scippa ÂM, Severus E, Simhandl C, Stein DJ, Strejilevich S, Sulaiman AH, Suominen K, Tagata H, Tatebayashi Y, Torrent C, Vieta E, Viswanath B, Wanchoo MJ, Zetin M, Whybrow PCJ Affect Disord
- Prevalence and clinical correlates of co-occurring insomnia and hypersomnia symptoms in depression.Soehner AM, Kaplan KA, Harvey AGJ Affect Disord
- Human cadavers Vs. multimedia simulation: A study of student learning in anatomy.Saltarelli AJ, Roseth CJ, Saltarelli WAAnat Sci Educ
Control of alphavirus-based gene expression using engineered riboswitches.
Virology. 2015 May 22;483:302-311
Authors: Bell CL, Yu D, Smolke CD, Geall AJ, Beard CW, Mason PW
Alphavirus-based replicons are a promising nucleic acid vaccine platform characterized by robust gene expression and immune responses. To further explore their use in vaccination, replicons were engineered to allow conditional control over their gene expression. Riboswitches, comprising a ribozyme actuator and RNA aptamer sensor, were engineered into the replicon 3' UTR. Binding of ligand to aptamer modulates ribozyme activity and, therefore, gene expression. Expression from DNA-launched and VRP-packaged replicons containing riboswitches was successfully regulated, achieving a 47-fold change in expression and modulation of the resulting type I interferon response. Moreover, we developed a novel control architecture where riboswitches were integrated into the 3' and 5' UTR of the subgenomic RNA region of the TC-83 virus, leading to an 1160-fold regulation of viral replication. Our studies demonstrate that the use of riboswitches for control of RNA replicon expression and viral replication holds promise for development of novel and safer vaccination strategies.
PMID: 26005949 [PubMed - as supplied by publisher]
Dexterous robotic manipulation of alert adult Drosophila for high-content experimentation.
Nat Methods. 2015 May 25;
Authors: Savall J, Ho ET, Huang C, Maxey JR, Schnitzer MJ
We present a robot that enables high-content studies of alert adult Drosophila by combining operations including gentle picking; translations and rotations; characterizations of fly phenotypes and behaviors; microdissection; or release. To illustrate, we assessed fly morphology, tracked odor-evoked locomotion, sorted flies by sex, and dissected the cuticle to image neural activity. The robot's tireless capacity for precise manipulations enables a scalable platform for screening flies' complex attributes and behavioral patterns.
PMID: 26005812 [PubMed - as supplied by publisher]
Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture.
Nat Methods. 2015 May 25;
Authors: Paşca AM, Sloan SA, Clarke LE, Tian Y, Makinson CD, Huber N, Kim CH, Park JY, O'Rourke NA, Nguyen KD, Smith SJ, Huguenard JR, Geschwind DH, Barres BA, Paşca SP
The human cerebral cortex develops through an elaborate succession of cellular events that, when disrupted, can lead to neuropsychiatric disease. The ability to reprogram somatic cells into pluripotent cells that can be differentiated in vitro provides a unique opportunity to study normal and abnormal corticogenesis. Here, we present a simple and reproducible 3D culture approach for generating a laminated cerebral cortex-like structure, named human cortical spheroids (hCSs), from pluripotent stem cells. hCSs contain neurons from both deep and superficial cortical layers and map transcriptionally to in vivo fetal development. These neurons are electrophysiologically mature, display spontaneous activity, are surrounded by nonreactive astrocytes and form functional synapses. Experiments in acute hCS slices demonstrate that cortical neurons participate in network activity and produce complex synaptic events. These 3D cultures should allow a detailed interrogation of human cortical development, function and disease, and may prove a versatile platform for generating other neuronal and glial subtypes in vitro.
PMID: 26005811 [PubMed - as supplied by publisher]
Juvenile zebra finches learn the underlying structural regularities of their fathers' song.
Front Psychol. 2015;6:571
Authors: Menyhart O, Kolodny O, Goldstein MH, DeVoogd TJ, Edelman S
Natural behaviors, such as foraging, tool use, social interaction, birdsong, and language, exhibit branching sequential structure. Such structure should be learnable if it can be inferred from the statistics of early experience. We report that juvenile zebra finches learn such sequential structure in song. Song learning in finches has been extensively studied, and it is generally believed that young males acquire song by imitating tutors (Zann, 1996). Variability in the order of elements in an individual's mature song occurs, but the degree to which variation in a zebra finch's song follows statistical regularities has not been quantified, as it has typically been dismissed as production error (Sturdy et al., 1999). Allowing for the possibility that such variation in song is non-random and learnable, we applied a novel analytical approach, based on graph-structured finite-state grammars, to each individual's full corpus of renditions of songs. This method does not assume syllable-level correspondence between individuals. We find that song variation can be described by probabilistic finite-state graph grammars that are individually distinct, and that the graphs of juveniles are more similar to those of their fathers than to those of other adult males. This grammatical learning is a new parallel between birdsong and language. Our method can be applied across species and contexts to analyze complex variable learned behaviors, as distinct as foraging, tool use, and language.
PMID: 26005428 [PubMed]
Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials.
J Pain Res. 2015;8:217-28
Authors: Strand V, McIntyre LF, Beach WR, Miller LE, Block JE
BACKGROUND: Intra-articular injection of hyaluronic acid is a common, yet controversial, therapeutic option for patients with knee osteoarthritis (OA). The purpose of this research was to determine the safety and efficacy of US-approved viscosupplements for symptomatic knee OA.
METHODS: We searched MedLine and EMBase for randomized, sham-controlled trials evaluating safety and/or clinical efficacy of US-approved viscosupplements in patients with symptomatic knee OA. Knee pain severity and knee joint function were assessed at 4 to 13 weeks and 14 to 26 weeks. Safety outcomes included serious adverse events, treatment-related serious adverse events, patient withdrawal, and adverse event-related patient withdrawal occurring at any time during follow-up.
RESULTS: A total of 29 studies representing 4,866 unique patients (active: 2,673, control: 2,193) were included. All sham-controlled trials used saline injections as a control. Viscosupplementation resulted in very large treatment effects between 4 and 26 weeks for knee pain and function compared to preinjection values, with standardized mean difference values ranging from 1.07 to 1.37 (all P<0.001). Compared to controls, standardized mean difference with viscosupplementation ranged from 0.38 to 0.43 for knee pain and 0.32 to 0.34 for knee function (all P<0.001). There were no statistically significant differences between viscosupplementation and controls for any safety outcome, with absolute risk differences of 0.7% (95% confidence interval [CI]: -0.2 to 1.5%) for serious adverse events, 0% (95% CI: -0.4 to 0.4%) for treatment-related serious adverse events, 0% (95% CI: -1.6 to 1.6%) for patient withdrawal, and 0.2% (95% CI: -0.4 to 0.8%) for adverse event-related patient withdrawal.
CONCLUSION: Intra-articular injection of US-approved viscosupplements is safe and efficacious through 26 weeks in patients with symptomatic knee OA.
PMID: 26005358 [PubMed]
Estimating Large-Scale Network Convergence in the Human Functional Connectome.
Brain Connect. 2015 May 25;
Authors: Bell PT, Shine JM
The study of resting-state networks provides an informative paradigm for understanding the functional architecture of the human brain. Although investigating specialized resting-state networks has led to significant advances in our understanding of brain organization, the manner in which information is integrated across these networks remains unclear. Here, we have developed and validated a data-driven methodology for describing the topography of resting-state network convergence in the human brain. Our results demonstrate the importance of an ensemble of cortical and subcortical regions in supporting the convergence of multiple resting-state networks, including the rostral anterior cingulate, precuneus, posterior cingulate cortex, bilateral posterior parietal cortex, bilateral dorsal prefrontal cortex, along with the caudate head, anterior claustrum and posterior thalamus. In addition, we have demonstrated a significant correlation between voxel-wise network convergence and global brain connectivity, emphasizing the importance of resting-state network convergence in facilitating global brain communication. Finally, we examined the convergence of systems within each of the individual resting-state networks in the brain, revealing the heterogeneity by which individual resting-state networks balance the competing demands of specialized processing against the integration of information. Together, our results suggest that the convergence of resting-state networks represents an important organizational principle underpinning systems-level integration in the human brain.
PMID: 26005099 [PubMed - as supplied by publisher]
Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming.
Stem Cell Reports. 2015 May 20;
Authors: Tanaka Y, Hysolli E, Su J, Xiang Y, Kim KY, Zhong M, Li Y, Heydari K, Euskirchen G, Snyder MP, Pan X, Weissman SM, Park IH
Reprogramming of somatic cells produces induced pluripotent stem cells (iPSCs) that are invaluable resources for biomedical research. Here, we extended the previous transcriptome studies by performing RNA-seq on cells defined by a combination of multiple cellular surface markers. We found that transcriptome changes during early reprogramming occur independently from the opening of closed chromatin by OCT4, SOX2, KLF4, and MYC (OSKM). Furthermore, our data identify multiple spliced forms of genes uniquely expressed at each progressive stage of reprogramming. In particular, we found a pluripotency-specific spliced form of CCNE1 that is specific to human and significantly enhances reprogramming. In addition, single nucleotide polymorphism (SNP) expression analysis reveals that monoallelic gene expression is induced in the intermediate stages of reprogramming, while biallelic expression is recovered upon completion of reprogramming. Our transcriptome data provide unique opportunities in understanding human iPSC reprogramming.
PMID: 26004630 [PubMed - as supplied by publisher]
An unprecedented dual antagonist and agonist of human Transglutaminase 2.
Bioorg Med Chem Lett. 2015 May 15;
Authors: Yi MC, Palanski BA, Quintero SA, Plugis NM, Khosla C
Transglutaminase 2 (TG2) is a ubiquitously expressed, Ca(2+)-activated extracellular enzyme in mammals that is maintained in a catalytically dormant state by multiple mechanisms. Although its precise physiological role in the extracellular matrix remains unclear, aberrantly up-regulated TG2 activity is a hallmark of several maladies, including celiac disease. Previously, we reported the discovery of a class of acylideneoxoindoles as potent, reversible inhibitors of human TG2. Detailed analysis of one of those inhibitors (CK-IV-55) led to an unprecedented and striking observation. Whereas this compound was a non-competitive inhibitor (3.3±0.9μM) of human TG2 at saturating Ca(2+) concentrations, it activated TG2 in the presence of sub-saturating but physiologically relevant Ca(2+) concentrations (0.5-0.7mM). This finding was validated in a cellular model of TG2 activation and inhibition. Mutant TG2 analysis suggested that CK-IV-55 and its analogs bound to a low-affinity Ca(2+) binding site on the catalytic core of TG2. A mechanistic model for the dual agonistic/antagonistic action of CK-IV-55 on TG2 is presented, and the pathophysiological implications of basal activation of intestinal TG2 by small molecules are discussed.
PMID: 26004580 [PubMed - as supplied by publisher]
In vivo histology of the myelin g-ratio with magnetic resonance imaging.
Neuroimage. 2015 May 21;
Authors: Stikov N, Campbell JS, Stroh T, Lavelée M, Frey S, Novek J, Nuara S, Ho MK, Bedell BJ, Dougherty RF, Leppert IR, Boudreau M, Narayanan S, Duval T, Cohen-Adad J, Picard P, Gasecka A, Côté D, Bruce Pike G
The myelin g-ratio, defined as the ratio between the inner and the outer diameter of the myelin sheath, is a fundamental property of white matter that can be computed from a simple formula relating the myelin volume fraction to the fiber volume fraction or the axon volume fraction. In this paper, a unique combination of magnetization transfer, diffusion imaging and histology is presented, providing a novel method for in vivo magnetic resonance imaging of the axon volume fraction and the myelin g-ratio. Our method was demonstrated in the corpus callosum of one cynomolgus macaque, and applied to obtain full-brain g-ratio maps in one healthy human subject and one multiple sclerosis patient. In the human subjects, the g-ratio in multiple sclerosis lesions was higher than in normal appearing white matter, which was in turn higher than in healthy white matter. Measuring the g-ratio brings us one step closer to fully characterizing white matter non-invasively, making it possible to perform in vivo histology of the human brain during development, aging, disease and treatment.
PMID: 26004502 [PubMed - as supplied by publisher]
Curricular policy as a collective effects problem: A distributional approach.
Soc Sci Res. 2015 Jul;52:627-41
Authors: Penner AM, Domina T, Penner EK, Conley A
Current educational policies in the United States attempt to boost student achievement and promote equality by intensifying the curriculum and exposing students to more advanced coursework. This paper investigates the relationship between one such effort - California's push to enroll all 8th grade students in Algebra - and the distribution of student achievement. We suggest that this effort is an instance of a "collective effects" problem, where the population-level effects of a policy are different from its effects at the individual level. In such contexts, we argue that it is important to consider broader population effects as well as the difference between "treated" and "untreated" individuals. To do so, we present differences in inverse propensity score weighted distributions investigating how this curricular policy changed the distribution of student achievement. We find that California's attempt to intensify the curriculum did not raise test scores at the bottom of the distribution, but did lower scores at the top of the distribution. These results highlight the efficacy of inverse propensity score weighting approaches for examining distributional differences, and provide a cautionary tale for curricular intensification efforts and other policies with collective effects.
PMID: 26004485 [PubMed - in process]
No place like home? Familism and Latino/a-white differences in college pathways.
Soc Sci Res. 2015 Jul;52:219-35
Authors: Ovink SM, Kalogrides D
Recent research has argued that familism, defined as a cultural preference for privileging family goals over individual goals, may discourage some Latino/a youth from applying to and attending college, particularly if they must leave home (Desmond and López Turley, 2009). Using data from the Education Longitudinal Study, we find that Latino/a students and parents indeed have stronger preferences than white students and parents for living at home during college. For students, most differences in preferences for proximate colleges are explained by socioeconomic status, academic achievement and high school/regional differences. Moreover, controlling for socioeconomic background and prior achievement explains most racial/ethnic gaps in college application and attendance among high school graduates, suggesting that familism per se is not a significant deterrent to college enrollment above and beyond these more primary factors. However, results indicate generational differences; cultural factors may contribute to racial/ethnic gaps in parental preferences for children to remain at home.
PMID: 26004459 [PubMed - in process]
What drives the gender gap in charitable giving? Lower empathy leads men to give less to poverty relief.
Soc Sci Res. 2015 Jul;52:83-98
Authors: Willer R, Wimer C, Owens LA
We draw upon past research on gender and prosocial emotions in hypothesizing that empathy can help explain the gender gap in charitable giving. In a nationally representative survey, we found that men reported less willingness to give money or volunteer time to a poverty relief organization, gaps that were mediated by men's lower reported feelings of empathy toward others. We also experimentally tested how effective a variety of different ways of framing poverty relief were for promoting giving. Framing poverty as an issue that negatively affects all Americans increased men's willingness to donate to the cause, eliminating the gender gap. Mediation analysis revealed that this "aligned self-interest" framing worked by increasing men's reported poverty concern, not by changing their understanding of the causes of poverty. Thus, while men were generally less motivated by empathy, they responded to a framing that recast charitable giving as consistent with their self-interest. Exposure to the same framing, however, led women to report lower willingness to volunteer time for poverty relief, suggesting that framing giving as consistent with self-interest may discourage those who give because of an empathic response to poverty.
PMID: 26004450 [PubMed - in process]
Mutations of GPR126 Are Responsible for Severe Arthrogryposis Multiplex Congenita.
Am J Hum Genet. 2015 May 20;
Authors: Ravenscroft G, Nolent F, Rajagopalan S, Meireles AM, Paavola KJ, Gaillard D, Alanio E, Buckland M, Arbuckle S, Krivanek M, Maluenda J, Pannell S, Gooding R, Ong RW, Allcock RJ, Carvalho ED, Carvalho MD, Kok F, Talbot WS, Melki J, Laing NG
Arthrogryposis multiplex congenita is defined by the presence of contractures across two or more major joints and results from reduced or absent fetal movement. Here, we present three consanguineous families affected by lethal arthrogryposis multiplex congenita. By whole-exome or targeted exome sequencing, it was shown that the probands each harbored a different homozygous mutation (one missense, one nonsense, and one frameshift mutation) in GPR126. GPR126 encodes G-protein-coupled receptor 126, which has been shown to be essential for myelination of axons in the peripheral nervous system in fish and mice. A previous study reported that Gpr126(-/-) mice have a lethal arthrogryposis phenotype. We have shown that the peripheral nerves in affected individuals from one family lack myelin basic protein, suggesting that this disease in affected individuals is due to defective myelination of the peripheral axons during fetal development. Previous work has suggested that autoproteolytic cleavage is important for activating GPR126 signaling, and our biochemical assays indicated that the missense substitution (p.Val769Glu [c.2306T>A]) impairs autoproteolytic cleavage of GPR126. Our data indicate that GPR126 is critical for myelination of peripheral nerves in humans. This study adds to the literature implicating defective axoglial function as a key cause of severe arthrogryposis multiplex congenita and suggests that GPR126 mutations should be investigated in individuals affected by this disorder.
PMID: 26004201 [PubMed - as supplied by publisher]
Recessive Mutations in the α3 (VI) Collagen Gene COL6A3 Cause Early-Onset Isolated Dystonia.
Am J Hum Genet. 2015 May 13;
Authors: Zech M, Lam DD, Francescatto L, Schormair B, Salminen AV, Jochim A, Wieland T, Lichtner P, Peters A, Gieger C, Lochmüller H, Strom TM, Haslinger B, Katsanis N, Winkelmann J
Isolated dystonia is a disorder characterized by involuntary twisting postures arising from sustained muscle contractions. Although autosomal-dominant mutations in TOR1A, THAP1, and GNAL have been found in some cases, the molecular mechanisms underlying isolated dystonia are largely unknown. In addition, although emphasis has been placed on dominant isolated dystonia, the disorder is also transmitted as a recessive trait, for which no mutations have been defined. Using whole-exome sequencing in a recessive isolated dystonia-affected kindred, we identified disease-segregating compound heterozygous mutations in COL6A3, a collagen VI gene associated previously with muscular dystrophy. Genetic screening of a further 367 isolated dystonia subjects revealed two additional recessive pedigrees harboring compound heterozygous mutations in COL6A3. Strikingly, all affected individuals had at least one pathogenic allele in exon 41, including an exon-skipping mutation that induced an in-frame deletion. We tested the hypothesis that disruption of this exon is pathognomonic for isolated dystonia by inducing a series of in-frame deletions in zebrafish embryos. Consistent with our human genetics data, suppression of the exon 41 ortholog caused deficits in axonal outgrowth, whereas suppression of other exons phenocopied collagen deposition mutants. All recessive mutation carriers demonstrated early-onset segmental isolated dystonia without muscular disease. Finally, we show that Col6a3 is expressed in neurons, with relevant mRNA levels detectable throughout the adult mouse brain. Taken together, our data indicate that loss-of-function mutations affecting a specific region of COL6A3 cause recessive isolated dystonia with underlying neurodevelopmental deficits and highlight the brain extracellular matrix as a contributor to dystonia pathogenesis.
PMID: 26004199 [PubMed - as supplied by publisher]
Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.
Neurobiol Aging. 2015 May 1;
Authors: Kesler SR, Watson CL, Blayney DW
Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes.
PMID: 26004016 [PubMed - as supplied by publisher]
Gizmo is a mean word!
Otolaryngol Head Neck Surg. 2015 Apr;152(4):581-2
Authors: Koltai PJ
The editorial titled "Gizmos" in the April issue of Otolaryngology-Head and Neck Surgery was unfortunate. Intracapsular tonsillectomy is a rational surgical option for managing tonsillar hypertrophy causing obstructive sleep apnea in selected children. It is performed routinely by surgeons across the globe and has become the standard of care across northern Europe due to the high safety profile of the operation. The semirigid, dartlike design of the sinuplasty devices suggested the idea for an airway-specific set of high-pressure balloons. We began working on these in 2007 and had FDA approval in 2009. They are in wide use by many airway surgeons. Lingual tonsils are a frequent cause of obstructive sleep apnea, and there is no tool that manages this as effectively as endoscopic plasma ablation. We are all engaged in an honorable effort to improve care; surgical and creative skills are as important as analytical skills. Both are necessary for the continuous improvement of our work. Both are worthy of respect.
PMID: 25833921 [PubMed - indexed for MEDLINE]
The ins and outs of viral infection: keystone meeting review.
Viruses. 2014 Sep;6(9):3652-62
Authors: Bird SW, Kirkegaard K, Agbandje-McKenna M, Freed EO
Newly observed mechanisms for viral entry, assembly, and exit are challenging our current understanding of the replication cycle of different viruses. To address and better understand these mechanisms, a Keystone Symposium was organized in the snowy mountains of Colorado ("The Ins and Outs of Viral Infection: Entry, Assembly, Exit, and Spread"; 30 March-4 April 2014, Beaver Run Resort, Breckenridge, Colorado, organized by Karla Kirkegaard, Mavis Agbandje-McKenna, and Eric O. Freed). The meeting served to bring together cell biologists, structural biologists, geneticists, and scientists expert in viral pathogenesis to discuss emerging mechanisms of viral ins and outs. The conference was organized around different phases of the viral replication cycle, including cell entry, viral assembly and post-assembly maturation, virus structure, cell exit, and virus spread. This review aims to highlight important topics and themes that emerged during the conference.
PMID: 25256395 [PubMed - indexed for MEDLINE]
Inflammatory cytokines and the lymphatic endothelium.
Lymphat Res Biol. 2014 Sep;12(3):123
Authors: Rockson SG
PMID: 25229431 [PubMed - indexed for MEDLINE]
Cellular specificity of the blood-CSF barrier for albumin transfer across the choroid plexus epithelium.
PLoS One. 2014;9(9):e106592
Authors: Liddelow SA, Dzięgielewska KM, Møllgård K, Whish SC, Noor NM, Wheaton BJ, Gehwolf R, Wagner A, Traweger A, Bauer H, Bauer HC, Saunders NR
To maintain the precise internal milieu of the mammalian central nervous system, well-controlled transfer of molecules from periphery into brain is required. Recently the soluble and cell-surface albumin-binding glycoprotein SPARC (secreted protein acidic and rich in cysteine) has been implicated in albumin transport into developing brain, however the exact mechanism remains unknown. We postulate that SPARC is a docking site for albumin, mediating its uptake and transfer by choroid plexus epithelial cells from blood into cerebrospinal fluid (CSF). We used in vivo physiological measurements of transfer of endogenous (mouse) and exogenous (human) albumins, in situ Proximity Ligation Assay (in situ PLA), and qRT-PCR experiments to examine the cellular mechanism mediating protein transfer across the blood-CSF interface. We report that at all developmental stages mouse albumin and SPARC gave positive signals with in situ PLAs in plasma, CSF and within individual plexus cells suggesting a possible molecular interaction. In contrast, in situ PLA experiments in brain sections from mice injected with human albumin showed positive signals for human albumin in the vascular compartment that were only rarely identifiable within choroid plexus cells and only at older ages. Concentrations of both endogenous mouse albumin and exogenous (intraperitoneally injected) human albumin were estimated in plasma and CSF and expressed as CSF/plasma concentration ratios. Human albumin was not transferred through the mouse blood-CSF barrier to the same extent as endogenous mouse albumin, confirming results from in situ PLA. During postnatal development Sparc gene expression was higher in early postnatal ages than in the adult and changed in response to altered levels of albumin in blood plasma in a differential and developmentally regulated manner. Here we propose a possible cellular route and mechanism by which albumin is transferred from blood into CSF across a sub-population of specialised choroid plexus epithelial cells.
PMID: 25211495 [PubMed - indexed for MEDLINE]
Absence of pancreatic intraepithelial neoplasia predicts poor survival after resection of pancreatic cancer.
Pancreas. 2014 Oct;43(7):1073-7
Authors: Hassid BG, Lucas AL, Salomao M, Weng C, Liu F, Khanna LG, Kumar S, Hwang C, Chabot JA, Frucht H
OBJECTIVES: Pancreatic intraepithelial neoplasia (PanIN), thought to represent the dominant precursor of pancreatic adenocarcinoma (PDAC), is often found synchronously adjacent to resected PDAC tumors. However, its prognostic significance on outcome after PDAC resection is unknown.
METHODS: A total of 342 patients who underwent resection for PDAC between 2005 and 2010 at a single institution were identified and stratified according to highest grade of PanIN demonstrated surrounding the tumor. Clinical and pathologic characteristics of each patient and tissue were recorded and analyzed. The primary outcome was length of survival after resection.
RESULTS: An absence of PanIN lesions was identified in 32 patients (9%), low grade PanIN without synchronous high grade lesions was identified in 52 patients (15%), and high grade PanIN was found in 258 patients (75%). Median survival were 12.8 months for the non-PanIN group, 26.3 months for the low-grade PanIN group, and 23.8 months for the high-grade PanIN groups (P = 0.043). In multivariable analysis, absence of PanIN was independently associated with poor survival (P = 0.002).
CONCLUSIONS: The patients who demonstrate an absence of PanIN in the pancreatic tissue adjacent to the resected PDAC tumor have shorter postresection survival compared with those who demonstrate a PanIN lesion.
PMID: 24987871 [PubMed - indexed for MEDLINE]
Relationship between sunlight and the age of onset of bipolar disorder: an international multisite study.
J Affect Disord. 2014;167:104-11
Authors: Bauer M, Glenn T, Alda M, Andreassen OA, Angelopoulos E, Ardau R, Baethge C, Bauer R, Bellivier F, Belmaker RH, Berk M, Bjella TD, Bossini L, Bersudsky Y, Cheung EY, Conell J, Del Zompo M, Dodd S, Etain B, Fagiolini A, Frye MA, Fountoulakis KN, Garneau-Fournier J, González-Pinto A, Harima H, Hassel S, Henry C, Iacovides A, Isometsä ET, Kapczinski F, Kliwicki S, König B, Krogh R, Kunz M, Lafer B, Larsen ER, Lewitzka U, Lopez-Jaramillo C, MacQueen G, Manchia M, Marsh W, Martinez-Cengotitabengoa M, Melle I, Monteith S, Morken G, Munoz R, Nery FG, O'Donovan C, Osher Y, Pfennig A, Quiroz D, Ramesar R, Rasgon N, Reif A, Ritter P, Rybakowski JK, Sagduyu K, Scippa ÂM, Severus E, Simhandl C, Stein DJ, Strejilevich S, Sulaiman AH, Suominen K, Tagata H, Tatebayashi Y, Torrent C, Vieta E, Viswanath B, Wanchoo MJ, Zetin M, Whybrow PC
BACKGROUND: The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode.
METHODS: Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations.
RESULTS: There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California.
LIMITATIONS: Recall bias for onset and family history data.
CONCLUSIONS: A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.
PMID: 24953482 [PubMed - indexed for MEDLINE]
Prevalence and clinical correlates of co-occurring insomnia and hypersomnia symptoms in depression.
J Affect Disord. 2014;167:93-7
Authors: Soehner AM, Kaplan KA, Harvey AG
BACKGROUND: The aim was to examine the prevalence and consequences of co-occurring insomnia and hypersomnia symptoms in depressed adults drawn from a representative sample of the U.S. population.
METHOD: Data from 687 National Comorbidity Survey Replication (NCS-R) respondents meeting criteria for a major depressive episode (MDE) in the past year were included. Respondents completed clinical interviews that assessed 12-month DSM-IV disorders, impairment, mental health treatment, and depressive symptom severity. Outcomes were compared between respondents who experienced insomnia symptoms-only (N=404), hypersomnia symptoms-only (N=44), both insomnia and hypersomnia symptoms (N=184) and no sleep problems (N=55) during an MDE.
RESULTS: Insomnia and hypersomnia symptoms co-occurred in 27.7% of respondents with past-year MDEs, most frequently in bipolar spectrum disorders and major depressive disorder with dysthymia. Similar to the insomnia-only group, respondents with co-occurring sleep disturbances had more severe depression, and higher rates of past-year impulse control disorders and suicide planning. Similar to the hypersomnia-only group, respondents with co-occurring sleep disturbances had higher rates of past-year drug use disorders and suicide attempts. Compared to the insomnia-only and no sleep problem groups, respondents with both sleep disturbances were more frequently in mental health treatment, seeing a general practitioner, and taking antidepressants.
LIMITATIONS: The NCS-R is cross-sectional and did not evaluate sleep disorder diagnoses.
CONCLUSIONS: Co-occurring insomnia and hypersomnia symptoms were associated with a more severe MDE. Further research is warranted to more fully understand the joint presentation of insomnia and hypersomnia in depression.
PMID: 24953480 [PubMed - indexed for MEDLINE]
Human cadavers Vs. multimedia simulation: A study of student learning in anatomy.
Anat Sci Educ. 2014 Sep-Oct;7(5):331-9
Authors: Saltarelli AJ, Roseth CJ, Saltarelli WA
Multimedia and simulation programs are increasingly being used for anatomy instruction, yet it remains unclear how learning with these technologies compares with learning with actual human cadavers. Using a multilevel, quasi-experimental-control design, this study compared the effects of "Anatomy and Physiology Revealed" (APR) multimedia learning system with a traditional undergraduate human cadaver laboratory. APR is a model-based multimedia simulation tool that uses high-resolution pictures to construct a prosected cadaver. APR also provides animations showing the function of specific anatomical structures. Results showed that the human cadaver laboratory offered a significant advantage over the multimedia simulation program on cadaver-based measures of identification and explanatory knowledge. These findings reinforce concerns that incorporating multimedia simulation into anatomy instruction requires careful alignment between learning tasks and performance measures. Findings also imply that additional pedagogical strategies are needed to support transfer from simulated to real-world application of anatomical knowledge.
PMID: 24415563 [PubMed - indexed for MEDLINE]
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