Miracle-dz/UniFAR-FTUs huggingface dataset:
Achievement of goals in U.S. diabetes care, 1999-2010.

BACKGROUND Tracking national progress in diabetes care may aid in the evaluation of past efforts and identify residual gaps in care. METHODS We analyzed data for adults with self-reported diabetes from the National Health and Nutrition Examination Survey and the Behavioral Risk Factor Surveillance System to examine risk-factor control, preventive practices, and risk scores for coronary heart disease over the 1999-2010 period. RESULTS From 1999 through 2010, the weighted proportion of survey participants who met recommended goals for diabetes care increased, by 7.9 percentage points (95% confidence interval [CI], 0.8 to 15.0) for glycemic control (glycated hemoglobin level <7.0%), 9.4 percentage points (95% CI, 3.0 to 15.8) for individualized glycemic targets, 11.7 percentage points (95% CI, 5.7 to 17.7) for blood pressure (target, <130/80 mm Hg), and 20.8 percentage points (95% CI, 11.6 to 30.0) for lipid levels (target level of low-density lipoprotein [LDL] cholesterol, <100 mg per deciliter [2.6 mmol per liter]). Tobacco use did not change significantly, but the 10-year probability of coronary heart disease decreased by 2.8 to 3.7 percentage points. However, 33.4 to 48.7% of persons with diabetes still did not meet the targets for glycemic control, blood pressure, or LDL cholesterol level. Only 14.3% met the targets for all three of these measures and for tobacco use. Adherence to the recommendations for annual eye and dental examinations was unchanged, but annual lipid-level measurement and foot examination increased by 5.5 percentage points (95% CI, 1.6 to 9.4) and 6.8 percentage points (95% CI, 4.8 to 8.8), respectively. Annual vaccination for influenza and receipt of pneumococcal vaccination for participants 65 years of age or older rose by 4.5 percentage points (95% CI, 0.8 to 8.2) and 6.9 percentage points (95% CI, 3.4 to 10.4), respectively, and daily glucose monitoring increased by 12.7 percentage points (95% CI, 10.3 to 15.1). CONCLUSIONS Although there were improvements in risk-factor control and adherence to preventive practices from 1999 to 2010, tobacco use remained high, and almost half of U.S. adults with diabetes did not meet the recommended goals for diabetes care.
Nondrug treatment trials in psychophysiologic insomnia.

BACKGROUND Due to a variety of potential problems with long-term hypnotic use, patients and treating physicians often try to avoid drugs in the treatment of psychophysiologic insomnia and to use nondrug treatment strategies, but these treatments must bring relief within a limited amount of time to be acceptable to patients. METHOD Thirty patients participated in the study. All had, for a minimum of 6 months, the complaint of less than 6 hours total sleep time per night in conjunction with either: (1) spending more than 30 minutes in bed before falling asleep, or (2) awakening during the night within 2 hours of sleep onset with difficulty returning to sleep. All subjects had the associated complaint of daytime impairment and none had used hypnotics for at least 3 months. Patients were randomly assigned to three parallel treatment groups: structured sleep hygiene, structured sleep hygiene with late afternoon moderate exercise, and structured sleep hygiene with early morning light therapy. Patients responded to questionnaires and filled out sleep logs. In addition, they underwent clinical evaluation, structured interviews, nocturnal monitoring, and actigraphy. The analyzed variables before and at the end of treatment were those derived from sleep logs and actigraphy. RESULTS All subjects showed a trend toward improvement, independent of the treatment received, but only the "structured sleep hygiene with light treatment" showed statistically significant improvement at the end of the trial. CONCLUSIONS Patients with chronic psychophysiologic insomnia may benefit from a nondrug treatment approach. Light therapy appears particularly promising.
Chronic Widespread Pain Drawn on a Body Diagram is a Screening Tool for Increased Pain Sensitization, Psycho‐Social Load, and Utilization of Pain Management Strategies

The aim of this study was to investigate the hypothesis that chronic widespread pain, (CWP) drawn by patients on a body diagram, could be used as a screening tool for increased pain sensitization, psycho‐social load, and utilization of pain management strategies. The triage questionnaires of 144 adults attending a chronic pain outpatients' clinic were audited and the percentage pain surface area (PPSA) drawn on their body diagrams was calculated using the “rule of nines” (RON) method for burns area assessment. Outcomes were measured using the painDETECT Questionnaire (PD‐Q) and other indices and compared using a nonrandomized, case–control method. It was found that significantly more subjects with CWP (defined as a PPSA ≥ 20%) reported high (≥ 19) PD‐Q scores (suggesting pain “sensitization” or neuropathic pain) (P = 0.0002), “severe” or “extremely severe” anxiety scores on the Depression, Anxiety and Stress Scale‐21 Items Questionnaire (P = 0.0270), ≥ 5 psycho‐social stressors (P = 0.0022), ≥ 5 significant life events (P = 0.0098), and used ≥ 7 pain management strategies (PMS) (P < 00001), compared to control subjects with a lower PPSA. A Widespread Pain Index score ≥ 7 (OR = 11.36), PD‐Q score ≥ 19 (OR = 4.46) and use of ≥ 7 PMS (OR = 5.49) were independently associated with CWP. This study demonstrates that calculating PPSA on a body diagram (using the RON method) is a valid and convenient “snapshot” screening tool to identify patients with an increased likelihood of pain sensitization, psycho‐social load, and utilizing pain management resources.
Anti-BK Virus Mechanisms of Sirolimus and Leflunomide Alone and in Combination: Toward a New Therapy for BK Virus Infection

Background. Human BK polyomavirus is the causative agent of BK nephropathy which is now the leading cause of early renal graft loss. Although no randomized clinical trials have supported this therapy, reduction of immunosuppressive drugs is the current BK nephropathy treatment. We hypothesized that inhibition of the intracellular protein kinase pathways activated by BK virus may be a more effective therapeutic strategy than reduction of immunosuppression. Methods and Results. Four days after infection of renal epithelial cells lines CCD1103, CCD1105 and human primary tubular epithelial cells with BK virus, we found increased phosphorylation of 3′-phosphoinositide-dependent kinase-1 (PDK-1), the protein kinase Akt (Akt), mammalian target of rapamycin (mTOR), and 70 kDa ribosomal protein S6 kinase (p70S6K). To inhibit this pathway, we used sirolimus, which repressed p70S6K phosphorylation and reduced BK virus large T antigen expression in a dose-dependent manner. We then used the tyrosine kinase inhibitor leflunomide (using the active metabolite A77 1726), which decreased PDK1 and Akt phosphorylation and inhibited BK virus genome replication and early gene expression. The combination of sirolimus and leflunomide inhibited BK virus genome replication, large T antigen expression, PDK1, Akt, mammalian target of rapamycin, and p70S6K phosphorylation. Conclusions. On the basis of these results, we suggest that inhibition of protein kinase pathways with a combination of sirolimus and leflunomide may be an effective therapy for BK virus reactivation. Because both sirolimus and leflunomide possess immunosuppressive activity, combination therapy may reduce BK pathogenesis while maintaining appropriate transplant immunosuppression.
Short-wavelength cone-opponent retinal ganglion cells in mammals

Abstract In all of the mammalian species studied to date, the short-wavelength-sensitive (S) cones and the S-cone bipolar cells that receive their input are very similar, but the retinal ganglion cells that receive synapses from the S-cone bipolar cells appear to be quite different. Here, we review the literature on mammalian retinal ganglion cells that respond selectively to stimulation of S-cones and respond with opposite polarity to longer wavelength stimuli. There are at least three basic mechanisms to generate these color-opponent responses, including: (1) opponency is generated in the outer plexiform layer by horizontal cells and is conveyed to the ganglion cells via S-cone bipolar cells, (2) inputs from bipolar cells with different cone inputs and opposite response polarity converge directly on the ganglion cells, and (3) inputs from S-cone bipolar cells are inverted by S-cone amacrine cells. These are not mutually exclusive; some mammalian ganglion cells that respond selectively to S-cone stimulation seem to utilize at least two of them. Based on these findings, we suggest that the small bistratified ganglion cells described in primates are not the ancestral type, as proposed previously. Instead, the known types of ganglion cells in this pathway evolved from monostratified ancestral types and became bistratified in some mammalian lineages.
Small Ubiquitin-like Modifier (SUMO) Modification of the Androgen Receptor Attenuates Polyglutamine-mediated Aggregation*♦

The neurodegenerative disorder spinal and bulbar muscular atrophy or Kennedy disease is caused by a CAG trinucleotide repeat expansion within the androgen receptor (AR) gene. The resulting expanded polyglutamine tract in the N-terminal region of the receptor renders AR prone to ligand-dependent misfolding and formation of oligomers and aggregates that are linked to neuronal toxicity. How AR misfolding is influenced by post-translational modifications, however, is poorly understood. AR is a target of SUMOylation, and this modification inhibits AR activity in a promoter context-dependent manner. SUMOylation is up-regulated in response to multiple forms of cellular stress and may therefore play an important cytoprotective role. Consistent with this view, we find that gratuitous enhancement of overall SUMOylation significantly reduced the formation of polyglutamine-expanded AR aggregates without affecting the levels of the receptor. Remarkably, this effect requires SUMOylation of AR itself because it depends on intact AR SUMOylation sites. Functional analyses, however, indicate that the protective effects of enhanced AR SUMOylation are not due to alterations in AR transcriptional activity because a branched protein structure in the appropriate context of the N-terminal region of AR is necessary to antagonize aggregation but not for inhibiting AR transactivation. Remarkably, small ubiquitin-like modifier (SUMO) attenuates AR aggregation through a unique mechanism that does not depend on critical features essential for its interaction with canonical SUMO binding motifs. Our findings therefore reveal a novel function of SUMOylation and suggest that approaches that enhance AR SUMOylation may be of clinical use in polyglutamine expansion diseases.
Genetic progression in sporadic endometrial and gastrointestinal cancers with high microsatellite instability

This study selected a series of 136 MSI‐H (microsatellite instability at high frequency) gastric, colorectal, and endometrial carcinomas combining immunohistochemical analysis for hMLH1 or hMSH2 gene products and microsatellite study. The clinico‐pathological profile of all tumours was correlated with the overall instability rates at coding and non‐coding repeats, in order to clarify the role and the mutation timing of seven target genes (TGFβRII, IGFIIR, BAX, hMSH3, hMSH6, CHK1, and BRCA2) in the progression of an MSI‐H neoplasm. Regardless of the primary site, the results confirm a model of oncogenesis in which inactivation of hMLH1, or less frequently hMSH2, may initiate a pathway culminating in a progressive accumulation of frameshifts in coding region (CDR) microsatellites. Comparing gastrointestinal and endometrial tumours, significantly lower levels of microsatellite instability at both coding and non‐coding repeats were observed. Among gastric and colorectal tumours, the detection of small shortening within Bat‐26 and Bat‐25 markers defines a subgroup of MSI‐H gastrointestinal tumours invariably characterized by early stage at diagnosis. In these tumours, mutations of TGFβRII or BAX genes precede frameshifts in the other tested genes. The analysis of correlations between the mutational and clinico‐pathological profiles of advanced gastrointestinal tumours revealed that the higher levels of microsatellite instability at both coding and non‐coding repeats were not associated with a more advanced clinico‐pathological stage or a less favourable outcome. A significant association was observed between a low number of CDR frameshifts and the presence of lymph‐node metastasis in advanced gastrointestinal tumours. The existence of advanced MSI‐H tumours with more aggressive behaviour and a ‘mild mutator phenotype’ could be explained by hypothesizing an overlapping of different mechanisms of tumourigenesis, including both the mutator and the suppressor pathways; this should be tested by further studies. Copyright © 2002 John Wiley & Sons, Ltd.
Isolated polyhydramnios in the third trimester: is a gestational diabetes evaluation of value?*

Abstract We evaluated implications of testing for gestational diabetes mellitus (GDM) in pregnancies complicated by third trimester isolated polyhydramnios with previous negative diabetes screening test. In this retrospective cohort study of 104 pregnant women with polyhydramnios between 2005 and 2013, all had normal first trimester fasting glucose and normal glucose challenge test (GCT < 140 mg/dL). Late onset GDM was diagnosed in five women (4.8%) with isolated polyhydramnios, one abnormal value in the oral glucose tolerance test (OGTT) was identified in four additional women (3.8%). No significant differences were found in risk factors for GDM, mean second trimester GCT (117.5 vs. 107.2 mg/dL, p = 0.38) or fasting glucose values (82 vs. 86 mg/dL, p = 0.29) between women in the polyhydramnios group with and without late GDM diagnosis. Moreover, no significant difference was found in relation to the mode of delivery or birth weight between the studied groups (3437 ± 611 vs. 3331 ± 515 g, p = 0.63). Diagnosis of third trimester polyhydramnios was not associated with increased risk for GDM or neonatal complications.
The competitive status of trees determines their responsiveness to increasing atmospheric humidity – a climate trend predicted for northern latitudes

The interactive effects of climate variables and tree–tree competition are still insufficiently understood drivers of forest response to global climate change. Precipitation and air humidity are predicted to rise concurrently at high latitudes of the Northern Hemisphere. We investigated whether the growth response of deciduous trees to elevated air humidity varies with their competitive status. The study was conducted in seed‐originated silver birch and monoclonal hybrid aspen stands grown at the free air humidity manipulation (FAHM) experimental site in Estonia, in which manipulated stands (n = 3 for both species) are exposed to artificially elevated relative air humidity (6–7% over the ambient level). The study period included three growing seasons during which the stands had reached the competitive stage (trees were 7 years old in the final year). A significant ‘treatment×competitive status’ interactive effect on growth was detected in all years in birch (P < 0.01) and in one year in aspen stands (P = 0.015). Competitively advantaged trees were always more strongly affected by elevated humidity. Initially the growth of advantaged and neutral trees of both species remained significantly suppressed in humidified stands. In the following years, dominance and elevated humidity had a synergistic positive effect on the growth of birches. Aspens with different competitive status recovered more uniformly, attaining similar relative growth rates in manipulated and control stands, but preserved a significantly lower total growth yield due to severe initial growth stress. Disadvantaged trees of both species were never significantly affected by elevated humidity. Our results suggest that air humidity affects trees indirectly depending on their social status. Therefore, the response of northern temperate and boreal forests to a more humid climate in future will likely be modified by competitive relationships among trees, which may potentially affect species composition and cause a need to change forestry practices.
Using the SF-36 with older adults: a cross-sectional community-based survey.

OBJECTIVES To assess the practicality and validity of using the 36-item short-form health survey (SF-36) in a community-dwelling population over 65, and to obtain population scores in this age group. DESIGN Postal survey, using a questionnaire booklet containing the SF-36 and other health-related items, of all those aged 65 or over registered with 12 general practices in Sheffield. Non-respondents received up to two reminders at 3-weekly intervals. SAMPLE 9897 subjects, aged 65-104 years. MAIN OUTCOME MEASURES Scores for the eight dimensions of the SF-36 and a modified version of the physical functioning dimension. RESULTS The SF-36 achieved a response rate of 82% (n=8117) and dimension completion rates of 86.4-97.7%. Internal consistency measured by Cronbach's alpha exceeded 0.80 for all dimensions except social functioning. These results compare favourably with postal surveys of younger adults. We calculated scores for older adults by age and sex. Comparison with data from younger people showed how physical health declines steeply with age, in marked contrast to mental health. CONCLUSIONS The SF-36 is a practical and valid instrument for use in postal surveys of older people living at home. The population scores provided here may facilitate its use in future surveys of older adults.
Immunochemical analysis of lipopolysaccharides from free-living and endosymbiotic forms of Rhizobium leguminosarum

Rhizobium leguminosarum B556 and 8002 differ only with respect to carrying symbiotic plasmids with specificity for Pisum or Phaseolus hosts, respectively. Protease-treated samples derived from free-living cultures of both strains revealed a ladder of lipopolysaccharide (LPS-1) bands after periodate-silver staining of sodium dodecyl sulfate-polyacrylamide gels. These bands were arranged as doublets. After Western (immuno-) blotting, all LPS-1 bands reacted with monoclonal antibody JIM 21, whereas monoclonal antibody MAC 57 reacted only with the upper (slower-migrating) band and monoclonal antibody MAC 114 reacted only with the lower band of each doublet pair. Preparations obtained from bacteroids of Pisum or Phaseolus nodules showed significant differences in the size distribution and antigenicity of LPS. In bacteroids from Phaseolus sp. , JIM 21 and MAC 57 each stained a ladder of LPS-1 bands on sodium dodecyl sulfate-polyacrylamide gels which corresponded in mobility to the upper band of each doublet pair seen in free-living cultures. MAC 114 did not react with the LPS from Phaseolus sp. -derived bacteroids. In bacteroids from Pisum sp. , only fast-migrating (lower-molecular-weight) forms of LPS-1 could be visualized on gels, but both upper and lower bands of each doublet were still present and could be stained by the appropriate monoclonal antibody, MAC 57 or MAC 114, respectively. Similarly, bacteroids from R. leguminosarum 3841, which nodulates Pisum species, differed with respect to the structure and antigenicity of their LPS-1 from bacteroids of a related strain, B625, which nodulates Phaseolus species. Physiological factors were investigated that could account for these differences between the structures of LPS-1 from free-living cultures of B556 and 8002 and that from bacteroids. The following modifications in growth conditions each tended to reduce the expression of MAC 114 antigen and enhance the expression of MAC 57 antigen: succinate rather than glucose as the carbon source; microaerobic (2.5%, vol/vol) oxygen concentrations; and acidic (pH 5 to 6) culture medium. When all three of these conditions were combined, the LPS-1 that resulted was very similar to that in bacteroids from Pisum nodules. However, it was not possible to reproduce the LPS-1 pattern observed for bacteroids from Phaseolus nodules, which maintained a ladder of LPS bands reacting with MAC 57 antibody.
Respiratory impedance and corresponding phase-constancy in the 7.5 to 247.5 Hz frequency interval for healthy subjects

This paper presents contributions on respiratory impedance and its phase constancy effects at high frequencies; i.e. 7.5-247.5 Hz. Measurements of 14 healthy volunteers are used to provide the input impedance values. It is shown, via the modulus-phase characteristics, that the impedance poses a typical frequency-independent behavior, known as phase constancy. We propose an electrical ladder network analogue for which we identify a set of parameters from these real-life measurements. The results presented in this paper support earlier theoretical insights on the appearance of phase constancy in ladder networks and the estimated model parameters have meaningful values. The phase constancy implies that the respiratory system is fractal and that the tissue exhibits viscoelastic properties.
Origen neonatal de la síndrome metabòlica en l'adult

Datos epidemiologicos y clinicos demuestran que un rapido aumento de peso en edades tempranas del crecimiento esta fuertemente asociado con muchos componentes del Sindrome Metabolico en subsiguientes generaciones. Con la intencion de determinar cuales son los eventos que tienen lugar durante edades tempranas determinan las consecuencias metabolicas del adulto, hemos desarrollado un modelo de raton de sobrenutricion y crecimiento postnatal acelerado, ON. Hemos forzado la sobrenutricion neonatal reduciendo el numero de crias de la camada a 4, durante el periodo de lactancia. Como se esperaba, los ratones ON muestran un crecimiento acelerado y a los 4 meses de edad desarrollan muchos de los sintomas del Sindrome Metabolico, incluyendo obesidad, alteracion de la tolerancia a la glucosa y resistencia a la insulina. La alteracion de la tolerancia a la glucosa en ratones ON parece ser debida a una resistencia periferica a la insulina, puesto que la funcion de la celula beta es normal. En contraste, la senalizacion de la insulina se encuentra alterada desde edades tempranas. Asimismo, los ratones ON muestran una alteracion del metabolismo lipidico durante las primeras semanas de vida, con una alteracion de la expresion de genes lipogenicos y de la lipogenesis de novo, que conlleva a la acumulacion de trigliceridos. Los cambios ocurridos durante edades tempranas no solo afectan a los individuos a lo largo de su vida, sino que persisten en subsiguientes generaciones. La progresion transgeneracional del fenotipo metabolico a traves del linage paterno suggiere los mecanismos epigeneticos como mediadores de estos efectos.