tbuckley/cabot-search huggingface dataset:
Neurocognitive Growth Charting in Psychosis Spectrum Youths
Authors: Ruben C. Gur, Monica E. Calkins, Theodore D. Satterthwaite, Kosha Ruparel, Warren B. Bilker, Tyler M. Moore, Adam P. Savitt, Hakon Hakonarson, Raquel E. Gur
Journal: JAMA Psychiatry (2014)

<h3>Importance</h3> Psychosis-risk studies have examined help-seeking adolescents and young adults. Population-based studies evaluating psychotic symptoms and neurocognitive performance across childhood are needed for “growth charting” cognitive development. We hypothesized that psychosis spectrum youths have delayed neurocognitive age relative to chronological age. We expected larger lags with increased symptom severity and in late adolescence and early adulthood. <h3>Objectives</h3> To examine neurocognitive age and compare typically developing participants with psychosis spectrum participants. <h3>Design, Setting, and Participants</h3> The Philadelphia Neurodevelopmental Cohort is a genotyped sample, with electronic medical records, enrolled in the study of brain behavior. In an academic and children’s hospital health care network, a structured psychiatric evaluation was performed and a computerized neurocognitive battery administered to evaluate performance in several domains. From 18 344 youths in the recruitment pool who were aged 8 to 21 years, physically and cognitively capable of participating, and proficient in English, participants were randomly selected with stratification for age, sex, and ethnicity. A total of 9138 participants were enrolled in the study between November 1, 2009, and November 30, 2011, and 2321 endorsed psychotic symptoms: 1423 significant (psychosis spectrum) and 898 limited (psychosis limited). They had no comorbid medical conditions. They were compared with 981 participants endorsing significant other psychiatric symptoms and with 1963 typically developing children with no psychiatric or medical disorders. <h3>Main Outcomes and Measures</h3> The computerized neurocognitive battery provides accuracy and speed measures on 12 tests and speed measures alone on 2, yielding 26 measures used in a regression analysis to predict chronological age. Prediction was performed on the entire set and separately for each domain (executive, episodic memory, complex cognition, social cognition, and sensorimotor speed). <h3>Results</h3> Throughout childhood and adolescence, the psychosis spectrum group had lower predicted age compared with the typically developing group and the group with other psychiatric symptoms. The psychosis spectrum group had a greater developmental lag than the psychosis limited group. The lags were most pronounced for complex cognition and social cognition and were smallest for sensorimotor speed. <h3>Conclusions and Relevance</h3> Individuals who endorse psychotic symptoms are neurocognitively delayed across the age range; this delay relates to symptom severity and is not prominent in other psychiatric disorders. Combined clinical and neurocognitive assessment can facilitate early detection and targeted intervention to delay or ameliorate disease progression.
Reduced Pulmonary Function Is Associated with Central Arterial Stiffness in Men
Authors: MAHMOUD ZUREIK, ATHANASE BENETOS, CATHERINE NEUKIRCH, DOMINIQUE COURBON, KATHRYN BEAN, FRÉDÉRIQUE THOMAS, PIERRE DUCIMETIÈRE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The association of impaired pulmonary function with cardiovascular morbidity and mortality has been reported in several prospective studies. The nature of this association and the mechanisms underlying it are unknown. Both atherosclerosis and central arterial stiffness might be involved. We recently reported, in a 4-yr longitudinal study, that reduced lung function predicts the development of carotid atherosclerotic plaques. In the present study, we report the associations of aortic stiffness with lung function measurements. One hundred and ninety-four men, aged 30 to 70 yr and free of coronary heart disease, who volunteered for a standard health examination were included. FEV(1) and FVC were used to assess lung function. Aortic stiffness was estimated from the carotid-femoral pulse-wave velocity (PWV), which increases proportionally with an increase in aortic stiffness. PWV was significantly and negatively associated with FEV(1) and FVC (partial correlation coefficients adjusted for age and height: -0.27 [p < 0.001] and -0.24 [p < 0.001], respectively). For every 1 SD increase in PWV (2.5 m/s), FEV(1) decreased by 195.2 +/- 50.1 ml (p < 0.001) in an age- and height-adjusted analysis. The corresponding decrease in FVC was 190.4 +/- 55.0 ml (p < 0.001). Further adjustment for cardiovascular risk factors (weight, smoking habits, hypercholesterolemia, diabetes, and hypertension) did not markedly alter these results. In addition, negative associations of PWV with lung function measurements were observed within each category of cardiovascular risk factors. This study suggests that reduced pulmonary function is independently associated with aortic stiffness in men. The interrelations between pulmonary and vascular alterations should be thoroughly investigated.
The Health Impact of Undiagnosed Airflow Obstruction in a National Sample of United States Adults
Authors: DAVID B. COULTAS, DOUGLAS MAPEL, ROBERT GAGNON, EVA LYDICK
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

To determine the health and functional impact of undiagnosed airflow obstruction for subjects in the general population, we used data obtained as part of the Third National Health and Nutrition Examination Survey (NHANES III). Categories of diagnosed and undiagnosed airflow obstruction were defined using questionnaire responses and spirometric results. Health and functional impact of airflow obstruction was assessed from responses to questions about general health status, walking 1/4 mile, lifting or carrying something as heavy as 10 lb, or needing help with personal care. Undiagnosed airflow obstruction (12.0%) was more common than doctor-diagnosed chronic obstructive pulmonary disease (COPD) (3.1%) or asthma (2.7%). Although undiagnosed airflow obstruction was usually very mild, approximately 5% of the entire sample had an FEV1 less than 75% predicted. After adjusting for smoking, obesity, and comorbid conditions, the risk of impaired health and functional status with undiagnosed airflow obstruction was independently associated with severity of FEV1 impairment. For males and females, ever smoking was strongly associated with all types of airflow obstruction, diagnosed or not. However, among females with airflow obstruction, 12.2% to 35.2% never smoked. Undiagnosed airflow obstruction is common in the general population of the United States and is associated with impaired health and functional status.Keywords: airflow obstruction; spirometry; health impact; screening
Downregulation of Bcl-2 by Podocytes Is Associated with Progressive Glomerular Injury and Clinical Indices of Poor Renal Prognosis in Human IgA Nephropathy
Authors: Lian-Qun Qiu, Raja Sinniah, Stephen I-Hong Hsu
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Bcl-2 defines a new class of proto-oncogenes that block cell death without promoting cell proliferation. To elucidate the role of Bcl-2 in the development of glomerular lesions in human IgA nephropathy (IgAN), we applied immunohistochemistry coupled with in situ hybridization to detect the expression of Bcl-2 products and their association with Bax, p27kip1, and p57kip2 in modulating the apoptotic, proliferative, and sclerotic events in progressive glomerular injury. Glomerular cell apoptosis was examined by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining. A total of 51 IgAN cases were categorized into four subgroups (A to D) according to the severity of their histopathological lesions. Creatinine levels, creatinine clearance, and magnitude of proteinuria based on 24-h urine collections at the time of diagnostic renal biopsy were available for the majority of subjects. Bcl-2 expression was observed predominantly in podocytes in IgAN. Podocyte expression of Bcl-2 was found to be upregulated in early-stage disease and downregulated in late-stage disease. Bcl-2 downregulation in progressive IgAN was associated with an increased Bax/Bcl-2 ratio in glomerular epithelial cells and correlated with the downregulation of high endogenous podocyte p27kip1 and p57kip2 expression. Bax/Bcl-2 ratios positively correlated with glomerular cell apoptosis and the degree of glomerulosclerosis, whereas p27kip1 and p57kip2 expression levels were inversely correlated with mesangial hypercellularity and glomerulosclerosis. Clinicopathologic correlations demonstrated that downregulation of Bcl-2 protein expression was associated with indices of poor renal prognosis in human IgAN. The results suggest that Bcl-2 expression by podocytes may exert modulatory effects on cellular processes that contribute to progressive glomerular injury and play an important role in determining renal outcome in human IgA nephropathy. E-mail: [email protected]
Angiotensin II stimulates two myelin basic protein/microtubule-associated protein 2 kinases in cultured vascular smooth muscle cells.
Authors: T Tsuda, Y Kawahara, Y Ishida, M Koide, K Shii, M Yokoyama
Journal: Circulation Research (1992)

In cultured vascular smooth muscle cells, angiotensin II (Ang II) stimulated a cytosolic protein kinase activity toward myelin basic protein (MBP) in a time- and dose-dependent manner. Phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate also increased the MBP kinase activity. Downregulation of protein kinase C by prolonged treatment of the cells with phorbol 12,13-dibutyrate markedly attenuated the Ang II- and PMA-induced MBP kinase activation. The Ang II- and PMA-stimulated MBP kinase activities were resolved almost equally into two distinct fractions on Mono-Q HR5/5 column chromatography (kinase 1 and kinase 2). The kinase assay in polyacrylamide gel revealed that apparent molecular masses of kinase 1 and kinase 2 were 40 and 45 kd, respectively. Microtubule-associated protein 2 also served as a substrate for both the kinases. Immunoblot analysis with an antiphosphotyrosine antibody suggested that both the kinases were tyrosine-phosphorylated during the action of Ang II. Phosphoamino acid analysis revealed that Ang II and PMA induced phosphorylation of both the kinases on serine/threonine as well as tyrosine residues. Phosphopeptide mapping patterns of kinase 1 and kinase 2 isolated from Ang II-stimulated cells were almost identical with those from PMA-stimulated cells. These results indicate that in vascular smooth muscle cells Ang II activates two species of MBP/microtubule-associated protein 2 kinases mainly through the protein kinase C-signaling pathway and suggest that tyrosine and serine/threonine phosphorylation may be involved in this process.
Primary and secondary transcriptional effects in the developing human Down syndrome brain and heart
Authors: Rong Mao, Xiaowen Wang, Edward L Spitznagel, Laurence P Frelin, Jason C Ting, Huashi Ding, Jung-whan Kim, Ingo Ruczinski, Thomas J Downey, Jonathan Pevsner
Journal: Genome biology (2005)

Down syndrome, caused by trisomic chromosome 21, is the leading genetic cause of mental retardation. Recent studies demonstrated that dosage-dependent increases in chromosome 21 gene expression occur in trisomy 21. However, it is unclear whether the entire transcriptome is disrupted, or whether there is a more restricted increase in the expression of those genes assigned to chromosome 21. Also, the statistical significance of differentially expressed genes in human Down syndrome tissues has not been reported.We measured levels of transcripts in human fetal cerebellum and heart tissues using DNA microarrays and demonstrated a dosage-dependent increase in transcription across different tissue/cell types as a result of trisomy 21. Moreover, by having a larger sample size, combining the data from four different tissue and cell types, and using an ANOVA approach, we identified individual genes with significantly altered expression in trisomy 21, some of which showed this dysregulation in a tissue-specific manner. We validated our microarray data by over 5,600 quantitative real-time PCRs on 28 genes assigned to chromosome 21 and other chromosomes. Gene expression values from chromosome 21, but not from other chromosomes, accurately classified trisomy 21 from euploid samples. Our data also indicated functional groups that might be perturbed in trisomy 21.In Down syndrome, there is a primary transcriptional effect of disruption of chromosome 21 gene expression, without a pervasive secondary effect on the remaining transcriptome. The identification of dysregulated genes and pathways suggests molecular changes that may underlie the Down syndrome phenotypes.
Randomized Trial Evaluating a Predominately Fetal Growth–Based Strategy to Guide Management of Gestational Diabetes in Caucasian Women
Authors: Ute M. Schaefer-Graf
Journal: Diabetes Care (2004)

We truly understand the concerns raised by our study (1) investigating a mainly fetal growth–based management strategy of gestational diabetes mellitus (GDM), since our data questioned the maternal glycemia-based management that we have used for decades. We are grateful for the opportunity of discussion.

Kitzmiller (2) is right that two profiles per week may not be considered as intensified management and that we might have missed occasional events of hyperglycemia. The large-for-gestational-age (LGA) rate in the standard group might have been slightly lower with more insulin therapy. But then we would have ended up with a rate of LGA newborns lower than the normal 10%. The tight blood glucose treatment in the ultrasound group is part of the concept of ultrasound-based management that concentrates intensive intervention on fetuses at risk (3,4).

In contrast to most areas of medicine, …
Characterising the expression and function of CCL28 and its corresponding receptor, CCR10, in RA pathogenesis
Authors: Zhenlong Chen, Seung-Jae Kim, Abdul B Essani, Michael V Volin, Olga M Vila, William Swedler, Shiva Arami, Suncica Volkov, Latriese V Sardin, Nadera Sweiss, Shiva Shahrara
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> This study was conducted to determine the expression pattern, regulation and function of CCL28 and CCR10 in rheumatoid arthritis (RA) pathogenesis. <h3>Methods</h3> Expression of CCL28 and CCR10 was assessed in RA compared with other arthritis synovial tissues (STs) or fluids (SFs) by histology or ELISA. The factors modulating CCL28 and CCR10 expression were identified in RA myeloid and endothelial cells by ELISA, FACS and Western blotting. The mechanism by which CCL28 ligation promotes RA angiogenesis was examined in control and CCR10-knockdown endothelial cell chemotaxis and capillary formation. <h3>Results</h3> CCL28 and/or CCR10 expression levels were accentuated in STs and SFs of patients with joint disease compared with normal controls and they were predominately coexpressed in RA myeloid and endothelial cells. We show that protein expression of CCL28 and CCR10 was modulated by tumour necrosis factor (TNF)-α and toll-like receptor 4 ligation in RA monocytes and endothelial cells and by interleukin (IL)-6 stimulation in RA macrophages. Neutralisation of CCL28 in RA SF or blockade of CCR10 on human endothelial progenitor cells (EPCs) significantly reduced SF-induced endothelial migration and capillary formation, demonstrating that ligation of joint CCL28 to endothelial CCR10+ cells is involved in RA angiogenesis. We discovered that angiogenesis driven by ligation of CCL28 to CCR10 is linked to the extracellular signal regulated kinase (ERK) cascade, as CCR10-knockdown cells exhibit dysfunctional CCL28-induced ERK signalling, chemotaxis and capillary formation. <h3>Conclusions</h3> The overexpression of CCL28 and CCR10 in RA ST and their contribution to EPC migration into RA joints support the CCL28/CCR10 cascade as a potential therapeutic target for RA.
Aerosolized STAT1 Antisense Oligodeoxynucleotides Decrease the Concentrations of Inflammatory Mediators in Bronchoalveolar Lavage Fluid in Bleomycin-Induced Rat Pulmonary Fibrosis
Authors: Ming Zeng, Bin Liao, Chen Zhu, Wenjun Wang, Xiaoqin Zhan, Xianming Fan
Journal: Cellular and Molecular Immunology (2008)
Sickle cell disease associated with uric acid deposition disease.
Authors: B M Rothschild, C W Sienknecht, S B Kaplan, J S Spindler
Journal: Annals of the Rheumatic Diseases (1980)

The infrequent occurrence of gout in patients with sickle cell anaemia contrast with the high incidence of hyperuricaemia and impaired renal function. This report records the third case of synovial membrane uric acid deposition and the first case of tophaceous deposits in haemoglobin SS patients. The limitations of a diagnosis of gout on the basis of hyperuricaemia and arthritis are confirmed. Analysis of reported cases suggests the existence of 2 forms of arthritis associated with sickle cell anaemia--noninflammatory and inflammatory. Paradoxically, gout appears to be associated with the former, in which the pathophysiological changes probably prevent or diminish the acute inflammatory response.
Target volume settings for home mechanical ventilation: great progress or just a gadget?: Table 1
Authors: Wolfram Windisch, Jan Hendrik Storre
Journal: Thorax (2012)

Home mechanical ventilation (HMV) is a well-established treatment option for patients with chronic hypercapnic respiratory failure, whereby non-invasive positive pressure ventilation (NPPV) serves as the predominant means of HMV delivery.1 ,2 In general, there are two physiologically-different modes of NPPV deliveries, volume-preset NPPV and pressure-preset NPPV. During volume-preset NPPV a fixed inspiratory volume (Vinsp) is set at the ventilator, while the inspiratory positive airway pressure (IPAP) varies depending on airway resistance. Conversely, Vinsp varies during pressure-preset NPPV, while IPAP remains fixed. The advantage of volume-preset NPPV is that Vinsp, and hence tidal volume, are relatively stable; however, this can lead to a breath-by-breath variation in IPAP levels that can become a burden for the patient, and the leakages that regularly occur during NPPV are not compensated for. In contrast, the Vinsp that is delivered during pressure-preset NPPV may be unstable due to increased airway resistance; however, given that the variation in IPAP is lower, this is often better tolerated by the patient. In addition, leak compensation is provided by pressure-preset NPPV, as shown by in vitro3 and in vivo4 studies. In addition, ventilators providing pressure-preset NPPV are cheaper. Thus, pressure-preset NPPV has become the predominant means of delivering HMV. Nevertheless, randomised controlled trials have shown that volume- and pressure-preset NPPV generally have comparable effects on improvements in blood gases, sleep quality and health-related quality of life (HRQL),5 ,6 although pressure-preset NPPV is reportedly better tolerated due to fewer gastrointestinal side effects.5 However, clinicians should always weigh the advantages and disadvantages of the two different approaches on an individual patient basis.

Recently, the so-called hybrid modes have been developed to overcome the disadvantages of volume- and pressure-preset NPPV, respectively. …
Nutrition Instruction in Medical Schools
Authors: Alan S. Kaplan
Journal: JAMA (1977)

<h3>To the Editor.—</h3> We read with interest the editorial by Dr Nelson on nutrition instruction in medical schools (236:2534, 1976). We were not surprised by the results. In fact, because we were so concerned that the teaching of nutrition, not only in medical schools but in other health professional schools, was so deficient, we contracted with the University of North Carolina to develop an educational program in the area of nutrition for health science students. Recognizing that curricula in medical schools and other similar institutions are already overcrowded, we elected to have much of the course materials developed in self-instructional format. We expect the results of this work to be completed by June 1977. We would be pleased to share the results with any interested parties, simply on request.
Concurrent drug use and the risk of perforated colonic diverticular disease: a population-based case-control study
Authors: D. J. Humes, K. M. Fleming, R. C. Spiller, J. West
Journal: Gut (2010)

<h3>Objective</h3> To determine the risk of diverticular perforation associated with current and ever use of corticosteroids, opiate analgesics, non-steroidal anti-inflammatory drugs, aspirin, cyclo-oxygenase-2 inhibitors, statins and calcium antagonists. <h3>Design, setting and participants</h3> Case–control analysis using conditional logistic regression analysis of data from the UK General Practice Research Database. The study involved 899 cases of incident diverticular perforation and 8980 population controls from 1990 to 2005. <h3>Main outcome measures</h3> Odds ratios (ORs) are presented for perforation associated with use of corticosteroids, opiate analgesics, non-steroidal anti-inflammatory drugs, aspirin, cyclo-oxygenase-2 inhibitors, statins and calcium antagonists. Data were adjusted for smoking, comorbidity, prior abdominal pain and body mass index. <h3>Results</h3> A total of 899 patients with an incident diagnosis of perforated diverticular disease were identified. Current use of opiate analgesics (OR=2.16; 95% CI 1.55 to 3.01) and oral corticosteroids (OR=2.74; 95% CI 1.63 to 4.61) was associated with a two- and threefold increase in the risk of diverticular perforation, respectively. Current use of a calcium antagonist and aspirin were not associated with an increased risk of diverticular perforation. Current statin use was associated with a reduction in the risk of perforation (OR=0.44; 95% CI 0.20 to 0.95). <h3>Conclusion</h3> Perforated diverticular disease is a serious surgical emergency with <i>current</i> opiate analgesics and oral corticosteroids being strongly associated with an increased risk of diverticular perforation.
Antibody-Radionuclide Conjugates for Cancer Therapy: Historical Considerations and New Trends
Authors: Martina Steiner, Dario Neri
Journal: Clinical Cancer Research (2011)

Abstract When delivered at a sufficient dose and dose rate to a neoplastic mass, radiation can kill tumor cells. Because cancer frequently presents as a disseminated disease, it is imperative to deliver cytotoxic radiation not only to the primary tumor but also to distant metastases, while reducing exposure of healthy organs as much as possible. Monoclonal antibodies and their fragments, labeled with therapeutic radionuclides, have been used for many years in the development of anticancer strategies, with the aim of concentrating radioactivity at the tumor site and sparing normal tissues. This review surveys important milestones in the development and clinical implementation of radioimmunotherapy and critically examines new trends for the antibody-mediated targeted delivery of radionuclides to sites of cancer. Clin Cancer Res; 17(20); 6406–16. ©2011 AACR.