Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Actions of Glucose and Glucosamine on Hexosamine Biosynthesis in Isolated Adipocytes

Glucose and glucosamine (GlcN) cause insulin resistance over several hours by increasing metabolite flux through the hexosamine biosynthesis pathway (HBP). To elucidate the early events underlying glucose-induced desensitization, we treated isolated adipocytes with either glucose or GlcN and then measured intracellular levels of glucose-6-P (G-6-P), GlcN-6-P, UDP-Glc-NAc, and ATP. Glucose treatment rapidly increased G-6-P levels (t½ < 1 min), which plateaued by 15 min and remained elevated for up to 4 h (glucose ED50 = 4mm). In glucose-treated cells, GlcN-6-P was undetectable; however, GlcN treatment (2 mm) caused a rapid and massive accumulation of GlcN-6-P. Levels increased by 5 min (∼400 nmol/g) and continued to rise over 2 h (t½ ∼ 20 min) before reaching a plateau at >1,400 nmol/g (ED50 = 900 μm). Thus, at high GlcN concentrations, unrestricted flux into the HBP greatly exceeds the biosynthetic capacity of the pathway leading to a rapid buildup of GlcN-6-P. The GlcN-induced rise in GlcN-6-P levels was correlated with ATP depletion, suggesting that ATP loss is caused by phosphate sequestration (with the formation of GlcN-6-P) or the energy demands of phosphorylation. As expected, GlcN and glucose increased UDP-GlcNAc levels (t½ ∼ 14–18 min), but greater levels were obtained with GlcN (4–5-fold for GlcN, 2-fold for glucose). Importantly, we found that low doses of GlcN (<250 μm, ED50 = 80 μm) could markedly elevate UDP-GlcNAc levels without increasing GlcN-6-P levels or depleting ATP levels. These studies on the dynamic actions of glucose and GlcN on hexosamine levels should be useful in exploring the functional role of the HBP and in avoiding the potential pitfalls in the pharmacological use of GlcN.
Vaso‐occlusive painful events in sickle cell disease: Impact on child well‐being

This study describes how painful events affect the health‐related quality of life (HRQL) of children with sickle cell disease (SCD) and determines the responsiveness of a generic HRQL measure in SCD. Our hypotheses were twofold: (1) HRQL is significantly impaired at presentation to the emergency department for a painful event and (2) PedsQL 4.0 Acute Version Generic Core Scales is responsive to change in the evolution of a painful event.
Visual resolution and sensitivity of single cells in the primary visual cortex (V1) of a nocturnal primate (bush baby): correlations with cortical layers and cytochrome oxidase patterns.

1. This study describes the response properties of V1 cortical cells in a nocturnal primate and examines the receptive field organization of these cells in relationship to anatomically defined layers and cytochrome oxidase (CO) rich blobs and CO poor interblob compartments. Visual resolution and contrast sensitivity are consistent with other physiological and behavioral measures in this species. Comparisons are made with response properties of the same zones in macaque monkey, as well as of area 17 of a distantly related species (cat) that also occupies a nocturnal niche. 2. The responses of single cells to drifting sinusoidal gratings were recorded in V1 (striate cortex) of anesthetized, paralyzed bush babies (Galago crassicaudatus). Cells tended to be grouped with respect to ocular dominance, orientation preference, and direction selectivity. There was a high proportion of monocularly driven cells as in macaque monkey. Only 6% of the cells were nonoriented. These were poorly tuned complex cells and bore no resemblance to nonoriented lateral geniculate nucleus (LGN)-like cells reported in layer IV of macaque monkeys. Unidirectional cells were most frequently encountered in cortical layers that receive input from the magnocellular layers of the LGN. 3. Cells were classified as simple (31%) or complex (69%) according to standard criteria. Simple cells were significantly more narrowly tuned than complex cells for both orientation and spatial frequency. Complex cells had significantly higher average optimal spatial frequencies and spatial frequency cutoffs than simple cells. Contrast sensitivity of simple and complex cells averaged 38 and 34, respectively. Spatial resolution and sensitivity of these cells matches behavioral measures in bush baby. The spatial and temporal resolution of bush baby cells are similar to those of cats, which is likely related to the nocturnal niche of both species. 4. Cells in supragranular (I-III) and infragranular (V, VI) layers differed significantly in their response characteristics. The cells in the supragranular layers had significantly higher contrast sensitivity than did the cells in the infragranular layers. Cells in the supragranular layers likewise had higher temporal frequency cutoffs, significantly lower optimal spatial frequencies, lower spatial frequency cutoffs, and tighter orientation tuning than did cells in the infragranular layers. 5. Properties of cells in individual layers and CO blob and interblob compartments also showed differentiation. Layer III had the narrowest orientation and spatial frequency tuning with the tightest tuning in layer IIIC (IVB). (ABSTRACT TRUNCATED AT 400 WORDS)
Shape Memory and Superelastic Ceramics at Small Scales

Shape Memory Ceramics Shape memory materials convert heat into strain and vice versa. These materials are often made from metal alloys, which can generate large stresses with small shape changes. Ceramics have certain characteristics that underlie shape memory transformation, but generally crack under strain. Lai et al. (p. 1505; see the Perspective by Faber) introduce a modified ceramic structure with limited crystal grains that can withstand comparable cyclic strains to shape memory metals. Fine-scale shape memory ceramics are capable of many actuation cycles to strains up to 7%. [Also see Perspective by Faber] Shape memory materials are a class of smart materials able to convert heat into mechanical strain (or strain into heat) by virtue of a martensitic phase transformation. Some brittle materials such as intermetallics and ceramics exhibit a martensitic transformation but fail by cracking at low strains and after only a few applied strain cycles. Here we show that such failure can be suppressed in normally brittle martensitic ceramics by providing a fine-scale structure with few crystal grains. Such oligocrystalline structures reduce internal mismatch stresses during the martensitic transformation and lead to robust shape memory ceramics that are capable of many superelastic cycles up to large strains; here we describe samples cycled as many as 50 times and samples that can withstand strains over 7%. Shape memory ceramics with these properties represent a new class of actuators or smart materials with a set of properties that include high energy output, high energy damping, and high-temperature usage.
Communautés bactériennes de sols alpins et filtres environnementaux

Les bacteri es jouent un role cle dans les cycles biogeochimiques. Bien que l'effet du manteau neigeux en hiver dans la fonction et la composition des communautes bacteriennes du sol ait ete signale, l'effet de la variation spatio-temporelle du manteau neigeux reste a etudier. Dans cette etude, nous avons caracterise la dynamique spatio-temporelle des communautes bacteriennes a partir de deux sites extremes selon un gradient de couvert neigeux. Pour cela, nous avons utilise des approches moleculaires (SSCP et clonage / sequencage) et traditionnel (isolation par culture bacterienne). Les resultats presentes montrent que l'ensemble de la diversite bacterienne, sa composition et sa structure phylogenetique sont fortement lies a la duree de la couverture de neige. En outre, ces effets sont detectables au cours de la saison de vegetation des plantes. Les facteurs biotiques et abiotiques (i. E. La senescence des plantes et le pH du sol) jouent un role essentiel conduisant au regroupement de certaines bacteries en clades specifiques (Acidobacteries, Actinobacteries, α-et β-Proteobacteries). Au cours de la saison de vegetation des plantes, les clades de bacteries sont plus disperses. La presente etude montre que, a un niveau taxonomique fin, la variation temporelle est un facteur plus important que la variation spatiale sur la diversite bacterienne. A un niveau taxonomique superieur (i. E. Sousphylum), la conclusion est inverse. Seule une petite fraction du total de la diversite bacterienne est cultivable et il se peut que certains groupes bacteriens soient surrepresentes dans les plaques de culture. Cette etude apporte un nouvel eclairage sur le role de l’hiver et de la couverture neigeuse dans les distributions des communautes bacteriennes. Cette etude peut-etre utile pour predire le comportement des bacteries dans les cycles des elements nutritifs dans un contexte de rechauffement de la planete.
In vitro effects of recombinant interleukin 7 on growth and differentiation of bone marrow pro-B- and pro-T-lymphocyte clones and fetal thymocyte clones.

We have studied the effects of recombinant (r) interleukin 7 (IL-7) on growth and differentiation of marrow pro-B-lymphocyte clones (CB/Bm7, LyD9, LyB9), marrow pro-T-lymphocyte clones (C4-77/3, C4-86/18, C4-95/16), and fetal thymocyte clones (FTH5, FTA2, FTD5) in the presence or absence of the bone marrow stroma clone RP.0. 10, which was selected for its ability to promote differentiation of the pro-B clones. rIL-7 alone stimulated some DNA synthesis (measured by [3H]thymidine uptake) but not actual growth (increase in cell number) of the pro-B clones. Antibodies against IL-4 and IL-6 or against receptors for IL-2, IL-3, and IL-5 did not inhibit this effect of rIL-7 on the pro-B clones. rIL-7 alone or in various combinations with other cytokines (from rIL-1 alpha to rIL-6) could not induce differentiation of the pro-B clones into IgM+ B cells regardless of the presence of lipopolysaccharide (LPS). The RP.0. 10 marrow stroma cells by themselves do not support the growth of the pro-B clones. However, the pro-B clones grew when cultured with rIL-7 and monolayers of the RP.0. 10 stroma cells. While the RP.0. 10 stroma cells induced the pro-B clones to differentiate into IgM+ B cells but not T3+ T cells when cultured in the presence of LPS and rIL-3, the B-cell progenitor clones gave rise to significantly higher numbers of IgM+ B cells (up to 63%) and to many more B cells expressing higher levels of surface IgM when cocultured with rIL-7, LPS, and RP.0. 10 stroma cells. The pro-B clones also generated IgM+ B cells (up to 20%) when cocultured with RP.0. 10 stroma cells and rIL-7 in the absence of LPS. By using culture plates designed for testing requirements for cell-cell contact, we found that cell interactions between the pro-B cell and the marrow stroma cell are essential to induce rearrangement and expression of the immunoglobulin genes in the pro-B clones. Possible mechanisms to account for the remarkable effects of rIL-7 in the presence of RP.0. 10 stroma cells on both growth and differentiation of the pro-B clones are discussed. Finally, rIL-7 alone or together with RP.0. 10 stroma cells neither supported proliferation nor induced differentiation into T3+ T cells or IgM+ B cells of the marrow pro-T clones or the fetal thymocyte clones. In light of these findings, we postulate that the interaction of the pluripotential stem cell with marrow stroma cells like RP.0. 10 and the availability of IL-7 could play a critical role in the commitment to develop along the B-lymphocyte pathway.
Sleep endocrine effects of antigluco- and antimineralocorticoids in healthy males.

In several mammalian species the responsiveness of brain neurons to corticosteroids is mediated by mineralo- (MR) and glucocorticoid (GR) receptors. These receptors play a key role not only in the endocrine adaptation to stress but also in corticosteroid-induced changes of behavior, including sleep. We further explored the specific physiological role of this binary receptor system in the human brain by studying electroencephalogram (EEG) sleep and changes in plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, and growth hormone from 1800 to 0700 h in a series of investigations in healthy men pretreated the previous evening with the nonselective GR agonist dexamethasone (Dex) and then receiving at 1400 h either placebo, spironolactone (Spi), an MR antagonist, or mifepristone (Mif), a GR antagonist. The Dex-induced suppression of ACTH and cortisol was unaltered after Spi (200 mg) but attenuated by Mif treatment (400 mg). The sleep-associated plasma growth hormone surge was increased by Dex, an effect that remained unchanged by Spi but was reduced by Mif treatment. Pretreatment with Dex did not by itself induce recognizable effects on EEG sleep, but the Dex combination with Spi reduced the amount of rapid-eye-movement (REM) sleep. With Dex plus Mif, both REM sleep and slow wave sleep (SWS) were reduced compared with placebo. The Dex-induced endocrine effects on plasma ACTH, cortisol, and growth hormone concentrations could not be antagonized by Spi, which acts via MRs mainly located in the hippocampus, but were compensated for in part by Mif, which antagonizes GR at the pituitary and in the central nervous system. (ABSTRACT TRUNCATED AT 250 WORDS)
Endolysosomal two‐pore channels regulate autophagy in cardiomyocytes

Two‐pore channels (TPCs) were identified as a novel family of endolysosome‐targeted calcium release channels gated by nicotinic acid adenine dinucleotide phosphate, as also as intracellular Na+ channels able to control endolysosomal fusion, a key process in autophagic flux. Autophagy, an evolutionarily ancient response to cellular stress, has been implicated in the pathogenesis of a wide range of cardiovascular pathologies, including heart failure. We report direct evidence indicating that TPCs are involved in regulating autophagy in cardiomyocytes, and that TPC knockout mice show alterations in the cardiac lysosomal system. TPC downregulation implies a decrease in the viability of cardiomyocytes under starvation conditions. In cardiac tissues from both humans and rats, TPC transcripts and protein levels were higher in females than in males, and correlated negatively with markers of autophagy. We conclude that the endolysosomal channels TPC1 and TPC2 are essential for appropriate basal and induced autophagic flux in cardiomyocytes, and also that they are differentially expressed in male and female hearts.
Barriers to and enablers of healthy lifestyle behaviours in adolescents with obesity: a scoping review and stakeholder consultation

Healthy lifestyle behaviours are key to successful weight management, but have proven to be challenging to attain for adolescents with obesity. The purpose of our scoping review was to (i) describe barriers and enablers that adolescents with obesity encounter for healthy nutrition, physical activity, sedentary behaviour and sleep habits and (ii) identify gaps in the literature. We adhered to established methodology for scoping reviews. Six databases were searched (1980–June 2016) for original articles published in English or French that focused on lifestyle behaviours of 13‐ to 17‐year‐olds in paediatric weight management. Following screening and data extraction, findings of selected articles were synthesized thematically using a social ecological framework. Stakeholder consultation (n = 20) with adolescents with obesity and health professionals was completed to enhance methodological rigour. Our search yielded 17 articles for inclusion, including 546 unique participants. Barriers to healthy nutrition and physical activity were more consistently related to individual‐level and interpersonal‐level factors; enablers tended to be linked with interpersonal‐level factors. Knowledge gaps identified related to sedentary behaviour and sleep as well as environmental and policy levels of influence. Our review revealed that some barriers and enablers were unique to adolescents with obesity, which were either within or beyond their control. These findings highlight the importance of multilevel interventions to enable healthy lifestyle behaviours for weight management.
Diabetic patients' willingness to use tele-technology to manage their disease – A descriptive study.

Objectives: Diabetes mellitus is a public health concern worldwide. TeleHealth technology may be an effective tool for empowering patients in the self-management of diabetes mellitus. However despite the great impact of diabetes on healthcare in Saudi Arabia, no research has investigated diabetic patients' willingness to use this technology. This study investigates diabetic patients' willingness to use tele-technology as a tool to monitor their disease. Methods: Data were collected from diabetic patients attending the diabetes education clinic at the Ministry of National Guard Health Affairs (MNGHA) in the Eastern region of Saudi Arabia over a three month period. A survey was developed which measured patients' willingness to use tele-technology in the self-management of their diabetes as well as their perceived expectations from the technology. Results: The study found that the majority of patients were willing to use tele-technology to self- monitor their diabetes. However, a minority (11.3%) indicated willingness to use the system daily and only half indicated preference to use it once a week (53.8%). Patients who were younger, had higher education levels, were employed, had internet access and had Type II diabetes were significantly more likely to report willingness to use the technology. Conclusions: Diabetic patients could be ready to play a more active role in their care if given the opportunity. Results from this study could serve as a baseline for future studies to develop targeted interventions by trialing tele-technology on a sample of the diabetic population. Patients with diabetes need to be in charge of their own care in order to improve health outcomes across the country.
MECHANISMS IN ENDOCRINOLOGY: Main air pollutants and diabetes-associated mortality: a systematic review and meta-analysis

OBJECTIVE Exposure to high levels of air pollutants may be linked to diabetes-associated mortality, but the associations remain unclear. To assess the associations between main air pollutants and diabetes-associated mortality, a systematic review and meta-analysis was performed. METHODS PubMed, Embase and Web of Science were searched for studies investigating the associations between increments in gaseous (nitrogen dioxide (NO2), sulphur dioxide, ozone (O3) and carbon monoxide) and particulate matter (PM; diameter<2.5 μm (PM2.5) or <10 μm (PM10)) air pollutants and diabetes-associated mortality. Using a random-effects model, relative risks (RRs) and 95% CIs were calculated per interquartile range (IQR) increment or per 10 μg/m3 increment in pollutant concentrations. RESULTS Out of 925 identified articles, 36 were reviewed in depth and 12 studies from 13 articles satisfying the inclusion criteria (five time-series, five case-crossovers and two cohorts) were finally included. Increased risk of diabetes-associated mortality was associated with higher levels of PM2.5 (per 10 μg/m3: RR=1.123, 95% CI 1.036-1.217, P=0.005, I2=96.1%), PM10 (per 10 μg/m3: RR=1.008, 95% CI 1.004-1.013, P<0.001, I2=0%), NO2 (per 10 μg/m3: RR=1.024, 95% CI 1.007-1.041, P=0.006, I2=49.7%) and O3 (per IQR increment: RR=1.065, 95% CI 1.017-1.115, P=0.007, I2=0.0%). No obvious risk of publication bias was observed. CONCLUSIONS Exposure to high levels of air pollutants is significantly associated with an increased risk of diabetes-associated mortality.
Emergency department visits by persons recently discharged from U.S. hospitals.

BACKGROUND Emergency department (ED) visits are rarely used as an outcome of prior hospitalization, but could be an indicator of poor inpatient care or follow-up planning. STUDY OBJECTIVE To examine the rate and characteristics of ED visits of patients recently discharged from any hospital. METHODS Data from the 2005 and 2006 National Hospital Ambulatory Medical Care Surveys (NHAMCS) and National Hospital Discharge Surveys (NHDS) were used to produce ratios of the numbers of ED visits where patients were discharged from any hospital within the last 7 days to the numbers of hospital discharges. NHAMCS, an annual survey of visits to U.S. hospital EDs, reported data for patients discharged from any hospital within 7 days previous to the ED visit. The NHDS is an annual survey of inpatient discharges from U.S. hospitals. Data from nonnewborn patients were weighted to produce national estimates. RESULTS About 2.3 million ED visits (2.0 percent of all visits) were made by persons who had been hospitalized within the last 7 days. This corresponds to 68 ED visits per 1000 live hospital discharges. About 10 percent of patients at these ED visits presented with medical or surgical complications that may have been related to their recent hospitalization. Uninsured persons were nearly three times as likely as those privately insured to make an ED visit following hospital discharge. CONCLUSION A large number of ED visits following recent hospitalization may be related to prior hospitalization. Returning to the ED after hospitalization may be an important measure to help improve inpatient care quality. Disparities in rates of ED visits following hospitalization may be attributed to differential inpatient or follow-up care.
Recent Clinical and Pathophysiological Advances in Non-Functioning Pituitary Adenomas

Pituitary adenomas are being recognized and diagnosed with increasing frequency. One of the most common forms of pituitary lesion is the clinically non-functioning pituitary adenoma (NFPA), which is often diagnosed incidentally. The vast majority of pituitary adenomas are sporadic, but familial adenomas can occur in the multiple pituitary adenoma type 1 syndrome, in Carney complex or in familial isolated pituitary adenoma. Distinguishing NFPA from prolactinomas can occasionally cause a differential diagnostic problem due to the ‘stalk effect’. NFPA often show hormone synthesis on tissue immunostaining without causing clinical symptoms. Most often these are silent gonadotroph adenomas, with silent corticotroph or somatotroph adenomas occurring less frequently. It is unclear why these silent adenomas do not release hormones at a clinically recognizable level, although it is probable that there is a continuum between fully functional and completely silent adenomas. Another intriguing feature of NFPAs is the lack of clinical response to somatostatin analogues, despite the presence of somatostatin receptors and an often good response in the in vitro setting. Temozolomide has been successfully used for the treatment of a few aggressive pituitary adenomas, and the response to this drug could be influenced by the expression of the DNA repair enzyme O-6-methylguanine DNA methyltransferase. The early diagnosis, prediction of long-term outcome and treatment of NFPAs remain a challenge for endocrinologists.