tbuckley/cabot-search huggingface dataset:
Speech, Language, and Reading Skills After Early Cochlear Implantation
Authors: John K. Niparko
Journal: JAMA (2004)

ObjectiveTo examine whether age at cochlear implantation or duration of implant
use is associated with speech, language, and reading skills exhibited at age
8 to 9 years in children who underwent implantation by age 5 years.DesignPerformance outcomes in speech perception, speech production, language,
and reading were examined in terms of the age at which children first received
a cochlear implant (2, 3, or 4 years), the age they received an updated (Spectra)
processor, and the duration of use of an implant and an updated processor.SettingData collection was conducted at summer research camps held over 4 consecutive
years to maximize the number of children available at a specific age (8-9
years). Children were tested individually by experienced examiners, and their
parents and therapists provided background and educational history information.ParticipantsA total of 181 children from 33 different states and 5 Canadian provinces
who received a cochlear implant by age 5 years were tested. A subsample of
133 children with performance IQ scores of 80 or greater and onset of deafness
at birth were selected for the age-at-implantation analysis. Another subsample
of 39 children with deafness acquired by age 3 years was also examined.Outcome MeasuresA battery of tests of speech perception, speech production, language,
and reading was administered to each child and reduced to a single factor
score for each skill.ResultsCorrelation coefficients between age at implantation and duration of
use did not reach significance for any of the outcome skills measured. Age
at which the updated speech processor (Spectra) was fitted was significantly
related to speech production outcome (earlier use of an updated processor
was associated with greater speech intelligibility) but not to any other skill
area. However, more of the children who underwent implantation at age 2 years
(43%) achieved combined speech and language skills commensurate with their
age-matched peers with normal hearing than did children who underwent implantation
at age 4 years (16%). Furthermore, normal speech and language skills were
documented in 80% of children who lost hearing after birth and who underwent
implantation within a year of onset of deafness.ConclusionsFor children who receive a cochlear implant between the ages of 2 and
4 years, early cochlear implantation does not ensure better speech perception,
speech production, language, or reading skills. However, greater speech and
language proficiency may be expected from children who exhibit normal hearing
for even a brief period after birth and receive a cochlear implant shortly
after losing their hearing. Further research examining the benefits of cochlear
implantation before age 2 years will help families and clinicians better understand
the time-sensitive nature of the decision to conduct cochlear implant surgery.
Abstract PR06: CARM1 methylates BAF155 and perturbs chromatin remodeling machinery to enhance tumor progression
Authors: Lu Wang, Zibo Zhao, Mark Meyer, Wesley J. Pike, Wei Xu
Journal: Cancer Research (2013)

Abstract CARM1 belongs to the type I protein arginine (R) methyltransferase (PRMT) family and asymmetrically di-methylates proteins on arginines. Because CARM1 is highly expressed in high grade breast tumors and was shown to transactivate cancer-relevant transcription factors including ERα, NF-κB, p53 and E2F1, it has been strongly implicated in tumorigenesis. To fully characterize functions of CARM1 in breast cancer, we knocked-out CARM1 from several breast cancer cell lines using Zinc-Finger Nuclease technology. Western blot using an asymmetric di-methylated R antibody revealed striking differences between CARM1 KO and parental MCF7 cell lysates, indicating that CARM1 methylates a significant number of substrates in breast cancer cells. BAF155, a core subunit of SWI/SNF chromatin remodeling complex, was identified as a CARM1 substrate by mass spectrometry. Further biochemical analyses validated that BAF155 was methylated by CARM1 in vivo and in vitro and methylation was mapped to a single site, R1064. We next generated BAF155R1064K knock-in MCF7 and MDA-mb-231 cells and showed that methylation of BAF155 is essential for breast cancer cell growth, colony formation and migration. Further, we developed an antibody that selectively recognized methylated form of BAF155 (me-BAF155) and observed strong nuclear me-BAF155 staining in invasive ductal carcinoma but not in the normal breast tissue. Importantly, me-BAF155 immunostaining positively correlates with tumor stage and metastasis. To understand the molecular mechanism by which BAF155 methylation affects tumorigenesis, we performed ChIP-seq using ChIP-validated BAF155 antibody in the BAF155WT or BAF155R1064K knock-in MCF7 cells. Interestingly, C-Myc pathway genes were only identified in WT but not mutant BAF155 regulated categories. Individual ChIP assays validated differential binding of BAF155WT or BAF155R1064K to specific target genes and importantly, the mRNA levels of these genes were affected correspondingly. This result suggests that BAF155 methylation affects gene expression by altering genomic association of BAF155, and perhaps the SWI/SNF complex, to chromatin regions. Collectively, our study revealed novel mechanisms by which CARM1 perturbs the chromatin remodeling machinery to enhance tumor progression. This work is supported by DOD ERA of HOPE Scholar Award and Shaw Scientist Award to W.X. This abstract is also presented as Poster A37. Citation Format: Lu Wang, Zibo Zhao, Mark Meyer, Wesley J. Pike, Wei Xu. CARM1 methylates BAF155 and perturbs chromatin remodeling machinery to enhance tumor progression. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr PR06.
Can GPs do more to help patients with facial disfigurement?
Authors: A. Gulland
Journal: BMJ (2015)

<h3>ABSTRACT</h3> <h3>BACKGROUND</h3> The biophysical properties of red blood cells (RBCs) provide potential biomarkers for the quality of donated blood. Blood unit segments provide a simple and nondestructive way to sample RBCs in clinical studies of transfusion efficacy, but it is not known whether RBCs sampled from segments accurately represent the biophysical properties of RBCs in blood bags. <h3>STUDY DESIGN AND METHODS</h3> RBCs were sampled from blood bags and segments every two weeks during 8 weeks of storage at 4 °C. RBC deformability was measured by deformabilitybased sorting using the microfluidic ratchet device in order to derive a rigidity score. Standard hematological parameters, including mean corpuscular volume (MCV), red cell distribution width (RDW), mean cell hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and hemolysis were measured at the same time points. <h3>RESULTS</h3> Deformability of RBCs stored in blood bags was retained over 4 weeks storage but a progressive loss of deformability was observed at weeks 6 and 8. This trend was mirrored in blood unit segments with a strong correlation to the blood bag data. Strong correlations were also observed between blood bag and segment for MCV, MCHC and MCH, but not for hemolysis. <h3>CONCLUSION</h3> RBCs sampled from blood unit segments accurately represents the biophysical properties of RBCs in blood bags, but not hemolysis. Blood unit segments provide a simple and non-destructive sample for measuring RBC biophysical properties in clinical studies.
Schizophrenia and Migration: A Meta-Analysis and Review
Authors: Elizabeth Cantor-Graae, Jean-Paul Selten
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The authors synthesize findings of previous studies implicating migration as a risk factor for the development of schizophrenia and provide a quantitative index of the associated effect size. METHOD: MEDLINE was searched for population-based incidence studies concerning migrants in English-language publications appearing between the years 1977 and 2003. Article bibliographies and an Australian database were cross-referenced. Studies were included if incidence reports provided numerators and denominators and if age correction was performed or could be performed by the authors. Relative risks for migrant groups were extracted or calculated for each study. Significant heterogeneity across studies indicated the need for a mixed-effects meta-analytic model. RESULTS: The mean weighted relative risk for developing schizophrenia among first-generation migrants (40 effect sizes) was 2.7 (95% confidence interval [CI]=2.3–3.2). A separate analysis performed for second-generation migrants (seven effect sizes) yielded a relative risk of 4.5 (95% CI=1.5–13.1). An analysis performed for studies concerning both first- and second-generation migrants and studies that did not distinguish between generations (50 effect sizes) yielded a relative risk of 2.9 (95% CI=2.5–3.4). Subgroup comparisons yielded significantly greater effect sizes for migrants from developing versus developed countries (relative risk=3.3, 95% CI=2.8–3.9) and for migrants from areas where the majority of the population is black (relative risk=4.8, 95% CI=3.7–6.2) versus white and neither black nor white. CONCLUSIONS: A personal or family history of migration is an important risk factor for schizophrenia. The differential risk pattern across subgroups suggests a role for psychosocial adversity in the etiology of schizophrenia.
Agonist-induced desensitization of beta-adrenoceptor function in humans. Subtype-selective reduction in beta 1- or beta 2-adrenoceptor-mediated physiological effects by xamoterol or procaterol.
Authors: O E Brodde, A Daul, M Michel-Reher, F Boomsma, A J Man in 't Veld, P Schlieper, M C Michel
Journal: Circulation (1990)

We investigated the effects of beta 2- (procaterol 2 x 50 micrograms/day for 9 days) and beta 1- (xamoterol 2 x 200 mg/day for 14 days) adrenoceptor agonists on lymphocyte beta 2-adrenoceptor density and beta 1- and beta 2-adrenoceptor in vivo function (assessed as isoprenaline-infusion-evoked hemodynamic effects and exercise-induced tachycardia) in healthy volunteers. Procaterol decreased lymphocyte beta 2-adrenoceptor density and all beta 2-adrenoceptor-mediated in vivo effects but did not affect beta 1-adrenoceptor-mediated in vivo effects. In contrast, xamoterol neither affected lymphocyte beta 2-adrenoceptors nor beta 2-adrenoceptor-mediated in vivo effects but decreased beta 1-adrenoceptor-mediated in vivo effects. It is concluded that in humans, generally long-term application of beta 1- or beta 2-adrenoceptor agonists causes desensitization of beta-adrenoceptor function but in a beta-adrenoceptor subtype-selective fashion.
Expensive Cancer Drugs With Modest Benefit Ignite Debate Over Solutions
Authors: G. Sinha
Journal: JNCI Journal of the National Cancer Institute (2008)

L ike many oncologists, Don Dizon, M.D., doesn’t like to candy-coat bad news. “I try to be realistic about what we can accomplish with treatment,” said Dizon, who specializes in treating gynecological cancers at Women and Infants Hospital of Rhode Island. But it’s in what he tells his patients afterward that Dizon may stray from the norm. Dizon also discusses with his patients the cost of drugs and the fact that their particular insurance may not cover them. Patients then meet with a hospital-appointed nurse manager, who not only explains chemotherapy to them but also helps them navigate the morass of health insurance coverage in the U.S. The nurse manager is responsible for fi guring out whether a prescribed course of therapy will be covered by a patient’s insurance. And if it isn’t, that patient is sent to a hospital-appointed fi nancial counselor who then explains that if insurance won’t pay, the patient is responsible for all costs. Welcome to the new world of cancer care. As pharmaceutical companies charge ever-higher prices for new drugs, American health care insurers have responded by tightening their belts. Many are denying payment for treatments that aren’t backed by clinical evidence. Others are asking patients to share a portion of the costs. Consequently, oncologists can no longer focus only on prescribing the best therapy; they must also consider the price tag. Moreover, hospitals and other facilities that treat cancer have had to hire additional staff to navigate the stony path of reimbursement. “Things have changed a lot,” said AnneMarie Bradley, a nurse manager at Women and Infants Hospital who has worked there for 22 years. Oncology isn’t the only medical discipline affected by high drug prices. But the fi eld has been especially hard hit by belttightening policies because most new cancer drugs have a modest, sometimes minimal, benefi t. “In oncology, we’re looking at a lot of drugs that extend life by a matter of months. We are in the gray zone in terms of benefi t,” said Jane Weeks, M.D., Ph.D., a professor in the department of health policy and management at Harvard School of Public Health. “High costs are harder to justify.” Even though experts agree that expensive drugs with modest benefi ts present a huge dilemma in healthcare, few see signs of positive change.
Clinical contraindications to allergen immunotherapy: an <scp>EAACI</scp> position paper
Authors: C. Pitsios, P. Demoly, M. B. Bilò, R. Gerth van Wijk, O. Pfaar, G. J. Sturm, P. Rodriguez del Rio, M. Tsoumani, R. Gawlik, G. Paraskevopoulos, F. Ruëff, E. Valovirta, N. G. Papadopoulos, M. A. Calderón
Journal: Allergy (2015)

Abstract Clinical indications for allergen immunotherapy ( AIT ) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. There are some discrepancies when classifying clinical contraindications for different forms of AIT as ‘absolute’ or ‘relative’. EAACI Task Force on ‘Contraindications to AIT ’ was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with β‐blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT ‐related side‐effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient.
Chemokine receptor CXCR3 facilitates CD8+ T cell differentiation into short-lived effector cells leading to memory degeneration
Authors: Makoto Kurachi, Junko Kurachi, Fumiko Suenaga, Tatsuya Tsukui, Jun Abe, Satoshi Ueha, Michio Tomura, Kei Sugihara, Shiki Takamura, Kazuhiro Kakimi, Kouji Matsushima
Journal: The Journal of Experimental Medicine (2011)

Strength of inflammatory stimuli during the early expansion phase plays a crucial role in the effector versus memory cell fate decision of CD8(+) T cells. But it is not known how early lymphocyte distribution after infection has an impact on this process. We demonstrate that the chemokine receptor CXCR3 is involved in promoting CD8(+) T cell commitment to an effector fate rather than a memory fate by regulating T cell recruitment to an antigen/inflammation site. After systemic viral or bacterial infection, the contraction of CXCR3(-/-) antigen-specific CD8(+) T cells is significantly attenuated, resulting in massive accumulation of fully functional memory CD8(+) T cells. Early after infection, CXCR3(-/-) antigen-specific CD8(+) T cells fail to cluster at the marginal zone in the spleen where inflammatory cytokines such as IL-12 and IFN-α are abundant, thus receiving relatively weak inflammatory stimuli. Consequently, CXCR3(-/-) CD8(+) T cells exhibit transient expression of CD25 and preferentially differentiate into memory precursor effector cells as compared with wild-type CD8(+) T cells. This series of events has important implications for development of vaccination strategies to generate increased numbers of antigen-specific memory CD8(+) T cells via inhibition of CXCR3-mediated T cell migration to inflamed microenvironments.
Stereological studies of desmosomes in ichthyosis vulgaris
Authors: H. ELSAYED-ALI, S. BARTON, R. MARKS
Journal: British Journal of Dermatology (1992)

Standardized stereological methods were performed on biopsies from three subjects with normal skin and from three patients with autosomal dominant and three with autosomal recessive sex‐linked ichthyosis to determined the relative numbers and dimensions of desmosomes. The results showed an increase in the persistence of desmonsomes in the stratum corneum in both ichthyotic groups. This suggests a pathogenetic role for desmosomes in the abnormal desquamation of the two types of ichthyosis vulgaris.
A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease
Authors: Zobair M. Younossi, Ancha Baranova, Katharine Ziegler, Luca Del Giacco, Karen Schlauch, Timothy L. Born, Hazem Elariny, Francesco Gorreta, Amy VanMeter, Abraham Younoszai, Janus P. Ong, Zachary Goodman, Vikas Chandhoke
Journal: Hepatology (2005)

Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and some of its forms are progressive. This study describes the profiling of hepatic gene expression and serum protein content in patients with different subtypes of NAFLD. Liver biopsy specimens from 98 bariatric surgery patients were classified as normal, steatosis alone, steatosis with nonspecific inflammation, and nonalcoholic steatohepatitis (NASH). Microarray hybridizations were performed in triplicate and the microarray expression levels of a selected group of genes were confirmed using real-time quantitative reverse-transcriptase polymerase chain reaction. Serum protein profiles of the same patients were determined by SELDI-TOF mass spectrometry. Of 98 obese patients, 91 were diagnosed with NAFLD (12 steatosis alone, 52 steatosis with nonspecific inflammation, and 27 NASH), and 7 patients without NAFLD served as obese controls. Each group of NAFLD patients was compared with the obese controls, and 22 genes with more than twofold differences in expression levels were revealed. Proteomics analyses were performed for the same group comparisons and revealed twelve significantly different protein peaks. In conclusion , this genomic/proteomic analysis suggests differential expression of several genes and protein peaks in patients within and across the forms of NAFLD. These findings may help clarify the pathogenesis of NAFLD and identify potential targets for therapeutic intervention. (Hepatology 2005;42:665–674.)
Coronary heart disease in relation to age, sex, and the menopause.
Authors: R F Heller, H S Jacobs
Journal: BMJ (1978)

Examination of the Registrar General's mortality data suggested that women do not lose protection from coronary heart disease (CHD) after the menopause. Apparently, at around the age of 50 men begin to lose a factor that had previously put them at increased risk of developing CHD compared with women. Male sex hormones may be risk factors for CHD, and further studies are needed to clarify their role in the aetiology of CHD in men.
THE ANESTHETIC PROPERTIES OF PURE ETHER
Authors: RAYMOND L. STEHLE
Journal: JAMA (1922)

who have ready access to narcotic and liquor pedlers when their compensation checks arrive.On the other hand, at Boise, Idaho, where there is better supervision, we have one of the best equipped and managed hospitals of this country in charge of the Public Health Service.At Greenville, with an old broken-down cantonment base hospital and the build¬ ings painted in every conceivable color, there was splendid morale and splendid work being done under the most adverse conditions.The President recently transferred from the Public Health Service to the Veterans' Bureau about thirtynine hospitals.The Veterans' Bureau has not had the hos¬ pital experience of the Public Health Service.Only time will tell whether the Veterans' Bureau will go on with the splendid work the Public Health Service has been conducting, or whether we shall have just domiciliary care rather than real treatment.
The Drug Trial: Nancy Olivieri and the Science Scandal That Rocked the Hospital for Sick Children
Authors: Kim A. Carmichael
Journal: Annals of Internal Medicine (2005)

Medical Writings: Book Notes4 October 2005The Drug Trial: Nancy Olivieri and the Science Scandal That Rocked the Hospital for Sick ChildrenKim A. Carmichael, MDKim A. Carmichael, MDFrom Forest Park Hospital, St. Louis University School of Medicine, St. Louis, Missouri.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-7-200510040-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Shuchman M. 464 pages. Toronto, Ontario, Canada: Random House Canada; 2005. $34.95. ISBN 0679310843. Order at www.randomhouse.ca.Field of medicine: Ethics, research, and economics.Format: Hardcover book.Audience: Physicians and scientists who research or prescribe medications, ethicists, medical journalists, and hospital administrators.Purpose: To investigate the relationships among scientists, the academic health care system, and the pharmaceutical industry.Content: It is the best of drugs, it is the worst of drugs. It is the age of discovery, it is the age of subjugation. It is the epoch of integrity, it is the epoch of deception. This book provides an intimate ... Author, Article, and Disclosure InformationAffiliations: From Forest Park Hospital, St. Louis University School of Medicine, St. Louis, Missouri. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 October 2005Volume 143, Issue 7Page: 548KeywordsAcademic medicineChildrenComputer and information sciencesDeceptionDrugsHealth careHospital medicineResearch ethicsScientistsSoftware tools ePublished: 4 October 2005 Issue Published: 4 October 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...