tbuckley/cabot-search huggingface dataset:
Influence of imaginative teaching of diet on compliance and metabolic control in insulin dependent diabetes.
Authors: D K McCulloch, R D Mitchell, J Ambler, R B Tattersall
Journal: BMJ (1983)

Dietary non-compliance is an important cause of poor metabolic control in insulin dependent diabetes. Patients are often blamed, but teaching methods may be at fault, so a prospective study was set up to compare the effect of three different teaching methods. After a three month run in, 40 adults with longstanding poorly controlled insulin dependent diabetes (mean haemoglobin A1 13.0%) were allocated at random to three teaching methods: conventional diet sheet instruction (group 1); practical lunchtime demonstrations (group 2); videotape education (group 3). Knowledge was assessed by questionnaires, compliance by seven day food records, and glycaemic control by serial glycosylated haemoglobin measurements. During six months of follow up there was no improvement in knowledge, compliance, or HbA1 in group 1, but in groups 2 and 3 both knowledge and compliance improved. In group 2 HbA1 fell to 10.6 (SD 2.1)% and in group 3 to 9.6 (2.3)%. The change in HbA1 showed an appreciable correlation with dietary compliance as judged by day to day consistency in carbohydrate intake. These findings show that new and interesting educational methods can have a major influence on knowledge, compliance, and metabolic control in insulin dependent diabetes.
Effect of formoterol with or without budesonide in repeated low-dose allergen challenge
Authors: B. Dahlén, A-S. Lantz, E. Ihre, M. Skedinger, E. Henriksson, L. Jörgensen, T. Ekström, S-E. Dahlén, K. Larsson
Journal: European Respiratory Journal (2009)

The use of combination therapy in mild asthma is debated. The current authors evaluated the effects of formoterol alone and a formoterol/budesonide combination inhaler on asthma deterioration induced by repeated low-dose allergen exposure. In total, 15 subjects with intermittent allergic asthma inhaled low doses of allergen on seven consecutive weekdays in a three-period, crossover, double-blind, double-dummy comparison between formoterol 4.5 μg Turbuhaler TM , budesonide 160 μg/formoterol 4.5 μg Turbuhaler TM and placebo, each taken as two puffs 30 min after allergen dosing. The outcome variables were: provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD 20 ), exhaled nitric oxide fraction ( F eNO ), sputum eosinophils and prostaglandin D 2 , and diary card recordings of symptoms (on a scale of 0–10), short-acting β 2 -agonist use and evening forced expiratory volume in one second (FEV 1 ). With placebo treatment, allergen exposure caused significant increases in airway hyperresponsiveness (geometric mean (coefficient of variation) PD 20 : 397 (98) μg before versus 168 (82) μg after), F eNO (mean± sd 46±31 ppb before versus 73±46 ppb after) and asthma symptom score (mean± sd 0.39±0.55 before versus 0.68±0.67 after). Budesonide/formoterol abolished these changes and significantly improved baseline FEV 1 . Formoterol alone, while providing symptom relief, was no better than placebo in protecting against the allergen-induced increase in airway inflammation. Signs of deteriorating asthma, provoked by low-dose allergen, are prevented by short-term use of budesonide/formoterol but not by temporary use of formoterol alone.
Sickle blood contains tissue factor–positive microparticles derived from endothelial cells and monocytes
Authors: Arun S. Shet, Omer Aras, Kalpna Gupta, Mathew J. Hass, Douglas J. Rausch, Nabil Saba, Louann Koopmeiners, Nigel S. Key, Robert P. Hebbel
Journal: Blood (2003)
Brown, Beige, and White: The New Color Code of Fat and Its Pharmacological Implications
Authors: Alexander Pfeifer, Linda S. Hoffmann
Journal: The Annual Review of Pharmacology and Toxicology (2014)

Brown adipose tissue (BAT) was previously regarded as a special type of fat relevant only for defending hibernating animals and newborns against a cold environment. Recently, BAT has received considerable attention following its (re)discovery in humans. Using glucose tracers, multiple laboratories independently found metabolically active BAT in adults. The enormous metabolic powers of BAT in animal models could make it an attractive target for antiobesity therapies in humans. Here, we review the present knowledge on the role of BAT in energy homeostasis and metabolism, focusing on signaling pathways and potential targets for novel therapeutics. We also shine light on ongoing debates, including those about the true color of brown fat in adults, as well as on the requirements for translation of basic research on BAT into clinical medicine.
Novel macrolides through genetic engineering
Authors: Leonard Katz, Robert McDaniel
Journal: Medicinal Research Reviews (1999)

Erythromycin, a complex polyketide antibiotic belonging to the macrolide class, is produced as a natural product by the bacterium Saccharopolyspora erythraea. The genes encoding the enzymes responsible for the synthesis of the antibiotic have been cloned and sequenced, revealing that the polyketide backbone of the molecule in produced by a polyketide synthase (PKS) composed of multifunctional proteins that contain discrete functional domains for each step of synthesis. Genetic manipulation of the PKS-encoding genes can result in predictable changes in the structure of the polyketide component of erythromycin, many of which are not easily achievable through standard chemical derivatization or synthesis. Many of the changes can be combined to lead to the further generation of navel structures. Whereas genetic engineering of the erythromycin structure has been practiced for a number of years, the re cent and continuing discoveries of modular PKSs for the synthesis of many other important complex polyketides has raised the possibility of generating novel structures in these molecules by genetic manipulation, as well.
Biochemical and neuropsychological effects of elevated plasma phenylalanine in patients with treated phenylketonuria. A model for the study of phenylalanine and brain function in man.
Authors: W Krause, M Halminski, L McDonald, P Dembure, R Salvo, D Freides, L Elsas
Journal: Journal of Clinical Investigation (1985)

Phenylketonuria provides a human model for the study of the effect of phenylalanine on brain function. Although irreversible mental retardation is preventable through newborn diagnosis and dietary phenylalanine restriction, controversy exists regarding the effects of increased concentrations of phenylalanine in older patients. We have studied ten older, treated, phenylketonuric patients using a triple-blind, multiple trials, crossover design. Each patient was tested at the end of each of three 1-wk periods of high or low phenylalanine intakes. Tests included a repeatable battery of neuropsychological tests, analysis of plasma amino acids, and measurement of urine amino acids, phenyl organic acids, dopamine, and serotonin. In all 10 patients plasma phenylalanine rose (900-4,000 microM). In 9 of 10 patients there was an inverse relationship between plasma phenylalanine and urine dopamine excretion. When blood phenylalanine was elevated, these patients had prolonged performance times on neuropsychological tests of higher but not lower integrative function. Urinary serotonin fell during phenylalanine loading in six patients. The concentration of phenylacids in the urine was not proportional to the plasma phenylalanine at concentrations below 1.5 mM. In one patient, neither performance time nor dopamine excretion varied as blood phenylalanine rose or fell. We interpret these data as follows: blood phenylalanine above 1.3 mM impairs performance on neuropsychological tests of higher integrative function, this effect is reversible, and one mechanism may involve impaired biogenic amine synthesis.
Predictors of Suicide and Accident Death in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)
Authors: Michael Schoenbaum, Ronald C. Kessler, Stephen E. Gilman, Lisa J. Colpe, Steven G. Heeringa, Murray B. Stein, Robert J. Ursano, Kenneth L. Cox
Journal: JAMA Psychiatry (2014)

The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multicomponent study designed to generate actionable recommendations to reduce Army suicides and increase knowledge of risk and resilience factors for suicidality.To present data on prevalence, trends, and basic sociodemographic and Army experience correlates of suicides and accident deaths among active duty Regular Army soldiers between January 1, 2004, and December 31, 2009, and thereby establish a foundation for future Army STARRS investigations.Analysis of trends and predictors of suicide and accident deaths using Army and Department of Defense administrative data systems. Participants were all members of the US Regular Army serving at any time between 2004 and 2009.Death by suicide or accident during active Army service.The suicide rate rose between 2004 and 2009 among never deployed and currently and previously deployed Regular Army soldiers. The accident death rate fell sharply among currently deployed soldiers, remained constant among the previously deployed, and trended upward among the never deployed. Increased suicide risk was associated with being a man (or a woman during deployment), white race/ethnicity, junior enlisted rank, recent demotion, and current or previous deployment. Sociodemographic and Army experience predictors were generally similar for suicides and accident deaths. Time trends in these predictors and in the Army's increased use of accession waivers (which relaxed some qualifications for new soldiers) do not explain the rise in Army suicides.Predictors of Army suicides were largely similar to those reported elsewhere for civilians, although some predictors distinct to Army service emerged that deserve more in-depth analysis. The existence of a time trend in suicide risk among never-deployed soldiers argues indirectly against the view that exposure to combat-related trauma is the exclusive cause of the increase in Army suicides.
INFLUENCE OF FAT PERCENTAGE, FRONT THIGH SKINFOLD AND GIRTH ON THE MAXIMUM RADIAL DISPLACEMENT OF THE DOMINANT RECTUS FEMORIS
Authors: Ignacio Diez-Vega, David Rodriguez-Ruiz, María Fernández-del-Valle, Darío Rodríguez-Matoso, Joaquín Cerdá-Béjar, José. Molina-Martín Juan
Journal: British Journal of Sports Medicine (2013)

Background Tensiomyography (TMG) is an innovative tool to control athletic training, and prevent and follow up muscular injuries. The reliability and validity for different population (sport modality, physical activity level, medical history, body composition, etc.) have been reported (Rodriguez-Matoso et al ., 2012; Tous-Fajardo et al ., 2010). Body composition of individuals may determine the mechanical response of muscular contraction produced by electrical stimulation. The aim of this study was to analyze the correlation of the values of fat percentage (%F), front thigh skinfold (FTS) and thigh girth (TG) to the maximal radial deformation (Dm) of the Rectus Femoris (RF) obtained using TMG. Methods A total of 193 participants were assessed: 132 high performance volleyball players (79 male, and 53 female), and 61 Sport Sciences college students (40 male, and 21 female). Anthropometric variables (%F, FTS, and TG) where assessed following the ISAK guidelines (Marfell-Jones, 2001) by a certified instructor (level 3). Faulkner's equation was used to calculate %F, and the TMG was used following Rodriguez-Matoso et al (2012) guidelines. Pearson correlation was assessed for statistical analysis using the SPSS v.19.0 with a level of signification p≤0.05. Results Results did not show differences between total sample and gender-related samples (FTS vs Dm: r 2=0.0096; p=0.19, y %G vs Dm: r 2&lt;0.001; p=0.98), neither when TG is used as a control variable (FTS vs Dm: r 2=0.01; p=0.18, and %G vs Dm: r 2&lt;0.001; p=0.82). Conclusions In conclusion, the results point that Dm in this population is not affected by body composition variables such %F, FTS, or TG.
An Ethnographic Study of the Social Context of Migrant Health in the United States
Authors: Seth M Holmes
Journal: PLoS Medicine (2006)

Background Migrant workers in the United States have extremely poor health. This paper aims to identify ways in which the social context of migrant farm workers affects their health and health care. Methods and Findings This qualitative study employs participant observation and interviews on farms and in clinics throughout 15 months of migration with a group of indigenous Triqui Mexicans in the western US and Mexico. Study participants include more than 130 farm workers and 30 clinicians. Data are analyzed utilizing grounded theory, accompanied by theories of structural violence, symbolic violence, and the clinical gaze. The study reveals that farm working and housing conditions are organized according to ethnicity and citizenship. This hierarchy determines health disparities, with undocumented indigenous Mexicans having the worst health. Yet, each group is understood to deserve its place in the hierarchy, migrant farm workers often being blamed for their own sicknesses. Conclusions Structural racism and anti-immigrant practices determine the poor working conditions, living conditions, and health of migrant workers. Subtle racism serves to reduce awareness of this social context for all involved, including clinicians. The paper concludes with strategies toward improving migrant health in four areas: health disparities research, clinical interactions with migrant laborers, medical education, and policy making.
Earlier Onset of Complications in Youth With Type 2 Diabetes
Authors: Allison B. Dart, Patricia J. Martens, Claudio Rigatto, Marni D. Brownell, Heather J. Dean, Elizabeth A. Sellers
Journal: Diabetes Care (2013)

OBJECTIVE To evaluate the risk of complications in youth with type 2 diabetes. RESEARCH DESIGN AND METHODS Population-based cohorts of 342 youth (1–18 years of age) with prevalent type 2 diabetes, 1,011 youth with type 1 diabetes, and 1,710 nondiabetic control youth were identified between 1986 and 2007 from a clinical registry and linked to health care records to assess long-term outcomes using ICD-9CM and ICD-10CA codes. RESULTS Youth with type 2 diabetes had an increased risk of any complication (hazard ratio 1.47 [95% CI 1.02–2.12]). Significant adverse clinical factors included age at diagnosis (1.08 [1.02–2.12]), HbA1c (1.06 [1.01–1.12]), and, surprisingly, renin-angiotensin-aldosterone system (RAAS) inhibitor use (1.75 [1.27–2.41]). HNF-1α G319S polymorphism was protective in the type 2 diabetes cohort (0.58 [0.34–0.99]). Kaplan-Meier statistics revealed an earlier diagnosis of renal and neurologic complications in the type 2 diabetes cohort, manifesting within 5 years of diagnosis. No difference in retinopathy was seen. Cardiovascular and cerebrovascular diseases were rare; however, major complications (dialysis, blindness, or amputation) started to manifest 10 years after diagnosis in the type 2 diabetes cohort. Youth with type 2 diabetes had higher rates of all outcomes than nondiabetic control youth and an overall 6.15-fold increased risk of any vascular disease. CONCLUSIONS Youth with type 2 diabetes exhibit complications sooner than youth with type 1 diabetes. Younger age at diagnosis is potentially protective, and glycemic control is an important modifiable risk factor. The unexpected adverse association between RAAS inhibitor use and outcome is likely a confounder by indication; however, further evaluation in young people is warranted.
Successful Engraftment After Reduced-Intensity Umbilical Cord Blood Transplantation for Adult Patients with Advanced Hematological Diseases
Authors: Shigesaburo Miyakoshi, Koichiro Yuji, Masahiro Kami, Eiji Kusumi, Yukiko Kishi, Kazuhiko Kobayashi, Naoko Murashige, Tamae Hamaki, Sung-Won Kim, Jun-ichi Ueyama, Shin-ichiro Mori, Shin-ichi Morinaga, Yoshitomo Muto, Shigeru Masuo, Mineo Kanemaru, Tatsuyuki Hayashi, Yoichi Takaue, Shuichi Taniguchi
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this research was to evaluate the feasibility of reduced-intensity unrelated cord-blood transplantation (RI-UCBT) in adult patients with advanced hematological diseases. Experimental Design: Thirty patients (median age, 58.5 years; range, 20–70 years) with advanced hematological diseases underwent RI-UCBT at Toranomon Hospital between September 2002 and August 2003. Preparative regimen composed of fludarabine 25 mg/m2 on days −7 to −3, melphalan 80 mg/m2 on day −2, and 4 Gy total body irradiation on day −1. Graft-versus-host disease prophylaxis was composed of cyclosporin alone. Results: Twenty-six patients achieved primary neutrophil engraftment after a median of 17.5 days. Median infused total cell dose was 3.1 × 107/kg (range, 2.0–4.3 × 107/kg). Two transplant-related mortalities occurred within 28 days of transplant, and another 2 patients displayed primary graft failure. Cumulative incidence of complete donor chimerism at day 60 was 93%. Grade II-IV acute graft-versus-host disease occurred in 27% of patients, with median onset 36 days. Primary disease recurred in 3 patients, and transplant-related mortality within 100 days was 27%. Estimated 1-year overall survival was 32.7%. Excluding 7 patients with documented infection, 19 patients displayed noninfectious fever before engraftment (median onset, day 9). Manifestations included high-grade fever, eruption, and diarrhea. The symptoms responded well to corticosteroid treatments in 7 of 13 treated patients. Conclusion: This study demonstrated the feasibility of RI-UCBT in adults.
MicroRNA-143 Targets MACC1 to Inhibit Cell Invasion and Migration in Colorectal cancer
Authors: Yu Zhang, Zhongqiu Wang, Min Chen, Liang Peng, Xinying Wang, Qunying Ma, Fengli Ma, Bo Jiang
Journal: Molecular Cancer (2012)

MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. Metastasis-associated in colon cancer-1 (MACC1) has been newly identified to express highly in colorectal cancer (CRC) and promote tumor metastasis through transactivating metastasis-inducing HGF/MET signaling pathway. In this study, we investigated whether miRNA 143 is involved in the regulation of MACC1 and thus plays a functional role in CRC.Using both in silico prediction and western blot assay, we found the previously reported tumor suppressive miR-143 targeted MACC1 in CRC. The direct interaction between them was confirmed by 3' UTR luciferase reporter gene. In concordance with the inhibitory effects induced by siRNA mediated knockdown of MACC1, restoration of miR-143 by mimics in SW620 cells significantly attenuated cell growth, migration and invasion. It is notable that combined treatment of miR-143 mimics and MACC1 siRNA induced synergistic inhibitory effects compared to either miR-143 mimics or MACC1 siRNA treatment alone. Conversely, reduction of miR-143 by inhibitors in SW480 cells apparently stimulated these phenotypes. Furthermore, we observed that miR-143 level was inversely correlated with MACC1 mRNA expression in CRC tissues.Our findings newly described miR-143/MACC1 link and provided a potential mechanism for MACC1 dysregulation and contribution to CRC cell invasion. It may help to estimate the therapeutic utility of miR-143 in CRC.
Combined Immunostimulation and Conditional Cytotoxic Gene Therapy Provide Long-term Survival in a Large Glioma Model
Authors: Sumia Ali, Gwendalyn D. King, James F. Curtin, Marianela Candolfi, Weidong Xiong, Chunyan Liu, Mariana Puntel, Queng Cheng, Jesus Prieto, Antoni Ribas, Jerzy Kupiec-Weglinski, Nico van Rooijen, Hans Lassmann, Pedro R. Lowenstein, Maria G. Castro
Journal: Cancer Research (2005)

Abstract In spite of preclinical efficacy and recent randomized, controlled studies with adenoviral vectors expressing herpes simplex virus-1 thymidine kinase (HSV1-TK) showing statistically significant increases in survival, most clinical trials using single therapies have failed to provide major therapeutic breakthroughs. Because glioma is a disease with dismal prognosis and rapid progression, it is an attractive target for gene therapy. Preclinical models using microscopic brain tumor models (e.g., ≤0.3 mm3) may not reflect the pathophysiology and progression of large human tumors. To overcome some of these limitations, we developed a syngeneic large brain tumor model. In this model, administration of single therapeutic modalities, either conditional cytotoxicity or immunostimulation, fail. However, when various immunostimulatory therapies were delivered in combination with conditional cytotoxicity (HSV1-TK), only the combined delivery of fms-like tyrosine kinase ligand (Flt3L) and HSV1-TK significantly prolonged the survival of large tumor-bearing animals (≥80%; P ≤ 0.005). When either macrophages or CD4+ cells were depleted before administration of viral therapy, TK + Flt3L therapy failed to prolong survival. Meanwhile, depletion of CD8+ cells or natural killer cells did not affect TK + Flt3L efficacy. Spinal cord of animals surviving 6 months after TK + Flt3L were evaluated for the presence of autoimmune lesions. Whereas macrophages were present within the corticospinal tract and low levels of T-cell infiltration were detected, these effects are not indicative of an overt autoimmune disorder. We propose that combined Flt3L and HSV1-TK adenoviral-mediated gene therapy may provide an effective antiglioma treatment with increased efficacy in clinical trials of glioma.
Infliximab as a treatment for systemic amyloidosis associated with Crohn's disease
Authors: M Iizuka
Journal: Gut (2006)

Systemic AA amyloidosis is a serious and potentially fatal complication of Crohn’s disease.1 This serious complication is associated with approximately 0.9–2.5% of patients with Crohn’s disease but renal failure due to renal amyloidosis is one of the most common causes of death for patients with Crohn’s disease.2 Although drugs such as azathioprine, colchicines, and dimethylsulphoxide are suggested to delay the progression of renal amyloidosis, the efficacy of these drugs on renal amyloidosis has not been fully elucidated.2 Infliximab is a chimeric anti-tumour necrosis factor α (TNF-α) monoclonal antibody. This drug has been proven …
Individualism and cognitive development
Authors: Philip Gerrans
Journal: Behavioral and Brain Sciences (2004)

Individualism is not inconsistent with social interaction; it is required to explain it. Social exchanges, evidenced in gaze monitoring, social referencing, emotional responses, protodeclarative and imperative pointing, pretence, play, and conversation all play a role in development, but the nature of that role is opaque without an understanding of the cognitive mechanisms on which they depend.