Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual effect of beta-adrenergic receptors on mitogen-activated protein kinase. Evidence for a beta gamma-dependent activation and a G alpha s-cAMP-mediated inhibition.

The enzymatic activity of mitogen-activated protein kinases (MAP kinases) increases in response to agents acting on a variety of cell surface receptors, including receptors linked to heterotrimeric G proteins of the Gi and Gq family. Recently, it has been shown that stimulation of beta-adrenergic receptors, which are typical of those that act through Gs to activate adenylyl cyclases, potently activates MAP kinases in the heart, resulting in the hypertrophy of the cardiac muscle (Lazou, A., Bogoyevitch, M.A., Clerk, A., Fuller, S.J., Marshall, C.J., and Sudgen, P.H. (1994) Circ. Res. 75, 938-941). We have observed that exposure of COS-7 cells to a beta-adrenergic agonist, isoproterenol, raises intracellular levels of cAMP and effectively activates protein kinase A (PKA) and an epitope-tagged MAP kinase. However, MAP kinase stimulation by isoproterenol was neither mimicked by expression of an activated mutant of G alpha s, nor by treatment with PKA-stimulating agents. Moreover, pretreatment of COS-7 with a permeable cAMP analog, 8-Br-cAMP, markedly decreased MAP kinase activation by either isoproterenol or epidermal growth factor. Thus, in COS-7 cells cAMP and PKA do not appear to mediate MAP kinase activation by beta-adrenergic receptors. Signaling from beta-adrenergic receptors to MAP kinase was inhibited by transfection of a chimeric molecule consisting of the CD8 receptor and the carboxyl terminus of the beta-adrenergic receptor kinase, which includes the beta gamma-binding domain. MAP kinase activation by isoproterenol was not affected by depletion of protein kinase C, but it was completely abolished by expression of Ras-inhibiting molecules. We conclude that signaling from beta-adrenergic receptors to MAP kinase involves an activating signal mediated by beta gamma subunits acting on a Ras-dependent pathway and a G alpha s-induced inhibitory signal mediated by cAMP and PKA. The balance between these two opposing mechanisms of regulation would be expected to control the MAP kinase response to beta-adrenergic agonists as well as to other biologically active agents known to act on Gs coupled receptors, including a number of hormones, neurotransmitters, and lipid mediators.
Critical care medicine in the United States 1985–2000: An analysis of bed numbers, use, and costs*

Objective:To establish a database that permits description and analysis of the evolving role, patterns of use, and costs of critical care medicine (CCM) in the United States from 1985 to 2000. Design:Retrospective study combining data from federal (Hospital Cost Report Information System, Center for Medicare and Medicaid Services, Baltimore, MD) and private (Hospital Statistics, American Hospital Association, Chicago, IL) databases to analyze U.S. hospitals, hospital and CCM beds, and occupancy. CCM costs were calculated by the Russell equation and compared with national health care and financial indexes. Setting:Nonfederal, acute care hospitals with CCM units in the United States. Subjects:None. Interventions:None. Measurements and Main Results:We analyzed hospitals with CCM units and focused on hospital and CCM beds, CCM occupancy, and CCM costs. CCM costs were compared with national cost indexes. Between 1985 and 2000, the total number of U.S. hospitals decreased by 8.9% (6,032 to 5,494) and acute care hospitals offering CCM decreased by 13.7% (4,150 to 3,581). The total number of beds in hospitals with CCM units decreased by 26.4% (889,600 to 654,400). In contrast, CCM beds increased by 26.2% (69,300 to 87,400). CCM occupancy was constant at 65%. CCM bed costs per day increased by 126% ($1,185 to $2,674). Although CCM costs increased by 190.4% ($19.1 billion to $55.5 billion), the proportion of national health expenditures allocated to CCM decreased by 5.4%. In 2000, CCM costs represented 13.3% of hospital costs, 4.2% of national health expenditures, and 0.56% of the gross domestic product. Conclusions:CCM is increasingly used and prominent in a shrinking U.S. hospital system. CCM occupancy is lower than expected. Despite its increasing use and cost, CCM is using proportionally less of national health expenses and the gross domestic product than previously estimated.
A Novel Mechanism for SUMO System Control: Regulated Ulp1 Nucleolar Sequestration

ABSTRACT The small ubiquitin-related modifiers (SUMOs) are evolutionarily conserved polypeptides that are covalently conjugated to protein targets to modulate their subcellular localization, half-life, or activity. Steady-state SUMO conjugation levels increase in response to many different types of environmental stresses, but how the SUMO system is regulated in response to these insults is not well understood. Here, we characterize a novel mode of SUMO system control: in response to elevated alcohol levels, the Saccharomyces cerevisiae SUMO protease Ulp1 is disengaged from its usual location at the nuclear pore complex (NPC) and sequestered in the nucleolus. We further show that the Ulp1 region previously demonstrated to interact with the karyopherins Kap95 and Kap60 (amino acids 150 to 340) is necessary and sufficient for nucleolar targeting and that enforced sequestration of Ulp1 in the nucleolus significantly increases steady-state SUMO conjugate levels, even in the absence of alcohol. We have thus characterized a novel mechanism of SUMO system control in which the balance between SUMO-conjugating and -deconjugating activities at the NPC is altered in response to stress via relocalization of a SUMO-deconjugating enzyme.
Cardiovascular Risk among Older Hispanic Women

This study used a descriptive correlational design to describe the relationship between cardiovascular risk and anxiety, spirituality, acculturation, and the objective indices of cardiac risk among a sample of 21 adult Hispanic women. Objective indices of risk included weight, blood pressure, blood lipids, and glucose. Four survey instruments were used to assess anxiety, spirituality, acculturation, and perceived risk. Findings revealed that all study participants had 3 or more risk factors, placing them in the moderate risk category for developing heart disease or having a heart attack within 10 years. State and trait anxiety scores were lower than the normative samples for adult women. Spirituality scores were higher than average; individuals with higher anxiety scores had lower spirituality scores. More research is needed to determine the health needs of unskilled workers with limited education in employment settings.
A brief afternoon nap following nocturnal sleep restriction: which nap duration is most recuperative?

STUDY OBJECTIVES The purposes of this study were to compare the benefits of different length naps relative to no nap and to analyze the electroencephalographic elements that may account for the benefits. DESIGN A repeated-measures design included 5 experimental conditions: a no-nap control and naps of precisely 5, 10, 20, and 30 minutes of sleep. SETTING Nocturnal sleep restricted to about 5 hours in participants' homes was followed by afternoon naps at 3:00 PM and 3 hours of postnap testing conducted in a controlled laboratory environment. PARTICIPANTS Twenty-four healthy, young adults who were good sleepers and not regular nappers. MEASUREMENTS AND RESULTS The 5-minute nap produced few benefits in comparison with the no-nap control. The 10-minute nap produced immediate improvements in all outcome measures (including sleep latency, subjective sleepiness, fatigue, vigor, and cognitive performance), with some of these benefits maintained for as long as 155 minutes. The 20-minute nap was associated with improvements emerging 35 minutes after napping and lasting up to 125 minutes after napping. The 30-minute nap produced a period of impaired alertness and performance immediately after napping, indicative of sleep inertia, followed by improvements lasting up to 155 minutes after the nap. CONCLUSIONS These findings suggest that the 10-minute nap was overall the most effective afternoon nap duration of the nap lengths examined in this study. The implications from these results also suggest a need to consider a process occurring in the first 10 minutes of sleep that may account for the benefits associated with brief naps.
Phylogeny of Culturable Estuarine Bacteria Catabolizing Riverine Organic Matter in the Northern Baltic Sea

ABSTRACT The objective of our study was to isolate and determine the phylogenetic affiliation of culturable estuarine bacteria capable of catabolizing riverine dissolved organic matter (RDOM) under laboratory conditions. Additions of RDOM consistently promoted the growth of estuarine bacteria in carbon-limited dilution cultures, with seasonal variation in growth rates and yields. At least 42 different taxa were culturable on solid agar media and, according to quantitative DNA-DNA hybridizations, constituted 32 to 89% of the total bacterial number in the enriched treatments. Five species in the Cytophaga-Flexibacter-Bacteroides group and one in the γ-proteobacteria phylogenetic group (Marinomonas sp.) were numerically dominant during the stationary phase of the RDOM-enriched dilution cultures but not in the control cultures. Four of the isolates in Cytophaga-Flexibacter-Bacteroides group were putatively affiliated with the genus Flavobacterium. All dominating isolates were determined to be new species based on comparison to the current databases. The same group of species dominated independently of the season investigated, suggesting a low diversity of bacteria catabolizing RDOM in the estuary. It also suggested a broad tolerance of the dominating species to seasonal variation in hydrography, chemistry, and competition with other species. Taken together, our results suggest that a limited group of bacteria, mainly in the Flavobacterium genus, played an important role in introducing new energy and carbon to the marine system in the northern Baltic Sea.
The relationship between maximal hip abductor strength and resultant loading at the knee during walking

The peak external knee adduction moment (KAM) is implicated in progression of knee osteoarthritis (OA). Recently, hip abductor weakness has also been found in patients with knee OA; however, it remains unknown as to how or if this weakness is a consequence of OA, or a predisposing factor. If it is the latter, a direct relationship between hip strength and KAM magnitude would be expected. The purpose of this study was to evaluate the relationship between hip abductor strength and KAM magnitude during walking. In fourteen adults, maximal isometric hip abductor strength was measured, and the KAM was quantified during gait. Additionally, internal hip abductor moments, vertical and medial ground-reaction-forces (GRFs), and GRF to knee joint center lever-arms were quantified during gait. The relationship between hip strength and GRFs, lever-arms and KAM were assessed using correlation. Internal hip abductor moments were compared to maximum hip strength by paired samples t-test. Correlations between hip strength and the vertical GRF (r = −0.05, p = 0.87), medial GRF (r = −0.24, p = 0.41), lever arm (r = −0.01, p = 0.97), and KAM (r = −0.24, p = 0.41) were not statistically significant. Peak internal hip abductor moments during gait (1.1 ± 0.2 Nm/kg) were significantly lower than maximal hip abductor strength (1.8 ± 0.3 Nm/kg, p < 0.001). It is concluded that hip abductor strength is not related to KAM magnitude. It seems more likely that hip abductor weakness is a consequence of OA rather than a predisposing factor.
The role of vessel geometry and material properties on the mechanics of stenting in the coronary and peripheral arteries

Abstract There have been notably higher rates of restenosis with stents used to restore blood flow to many stenosed peripheral arteries compared with their coronary counterparts. The mechanical environment of arteries such as the femoral and popliteal (and the stent fracture that this can cause) has previously been identified as a contributing factor to the relatively low success rates for this procedure. The aim of this study was to investigate how other factors, namely the differences in geometries and mechanical properties of the arteries and the stents used in them, might influence the outcome in these different arteries. Finite element models of the stents and arteries were created, and the results compared in terms of stresses induced in the arteries, the lumen gain, and the deformation of the stent due to pulsatile loading. It was found that deploying a Nitinol stent in a peripheral artery induced lower stresses in the vessel wall than expanding a stainless steel stent in a coronary artery, although the lumen gain was also lower. The predicted strain amplitude induced in Nitinol stents by the cardiac cycle was below the value required to cause fatigue failure. This study does not provide any evidence to suggest that differences in the geometry and material properties between peripheral and coronary arteries, or the types of stent used to restore vessel patency, are the dominate factors responsible for the higher rates of restenosis observed in peripheral arteries.
Alcohol abuse and dysfunctional eating in adolescent girls: the influence of individual differences in sensitivity to reward and punishment.

OBJECTIVE An unusually high comorbidity of eating disorders and alcohol abuse has been found in clinical and community samples of young women. This paper proposes that individual differences in sensitivity to reward and punishment may influence the propensity of young women to engage in dysfunctional eating and drinking behaviour. METHOD The Drive for Thinness scale, the Alcohol Use Disorders Identification Test and the BIS/BAS scales were administered to 232 high school girls. RESULTS Heightened sensitivity to reward was the better predictor of alcohol misuse while heightened sensitivity to both reward and punishment was predictive of dysfunctional eating. When categorised by group, alcohol abusing, dysfunctional eating, and comorbid girls reported greater sensitivity to reward than non-disordered girls. Girls with dysfunctional eating with and without comorbid alcohol abuse reported greater sensitivity to punishment than alcohol abusing only girls. DISCUSSION These findings suggest that girls who abuse alcohol and have dysfunctional eating may share a vulnerability to heightened sensitivity to reward, yet be differentiated by sensitivity to punishment.
The effects of calcium buffering and cyclic AMP on mechano‐electrical transduction in turtle auditory hair cells

1 The effects of intracellular Ca2+ buffering on hair cell mechanotransduction were studied in an intact cochlear epithelium where the endolymphatic and perilymphatic surfaces could be separately perfused with different Ca2+ solutions. 2 The speed and extent of transducer adaptation increased as the concentration in the patch electrode of the Ca2+ buffer BAPTA was lowered. In 0.1 mm BAPTA or less, the transducer adapted almost completely, with a mean time constant of 0.8 ms. 3 For a fixed internal BAPTA concentration, the transducer conductance varied with hair cell location, increasing towards the high‐frequency end of the cochlea, and the time constant of adaptation decreased proportionally. At a given cochlear location, hair cells with larger transducer conductances displayed faster adaptation. We suggest that transducer adaptation accounts for a variable high‐pass filter observed in the acoustic tuning curve. 4 The effects of perfusion of 50 μm Ca2+ endolymph depended on the BAPTA concentration of the electrode: with 3 mm BAPTA, adaptation was abolished, but in most recordings with 0.01 or 0.1 mm BAPTA, rapid adaptation was retained. The current–displacement curve was also shifted less the lower the intracellular BAPTA concentration. Cells in the high‐frequency half of the papilla retained adaptation at a higher BAPTA concentration. 5 Treatment with the cAMP agonist, 8‐bromo‐cAMP, or with the phosphodiesterase inhibitor 3‐isobutyl‐1‐methylxanthine, caused a rightward shift in the current–displacement curve which was independent of the internal BAPTA concentration. 6 We conclude that the free Ca2+ and cyclic nucleotide concentrations of the hair bundle modulate the position of the activation curve of the transducer. The factors which may be important for the correct functioning of adaptation in vivo are discussed.
Strains of Streptococcus mutans and Streptococcus sobrinus attach to different pellicle receptors

We compared the levels of adsorption of Streptococcus mutans JBP and Streptococcus sobrinus 6715 to experimental pellicles formed from unsupplemented and glucosyltransferase (GTF)-supplemented saliva. Pellicles formed on hydroxyapatite beads from GTF or from saliva-GTF mixtures possessed detectable GTF activity. Low levels of GTF activity were also detected in clarified whole human saliva, but not in samples of submandibular saliva. The adsorptive behavior of S. mutans JBP to pellicles formed from saliva or saliva-GTF mixtures was strikingly different from that of S. sobrinus 6715. S. mutans JBP adsorbed in higher numbers to pellicles formed from whole or submandibular saliva than to buffer-treated hydroxyapatite under the assay conditions used, in which blocking with albumin was used. In contrast, S. sobrinus 6715 attached in lower numbers and did not show enhanced adsorption to pellicles prepared from saliva. Pellicles prepared from the high-molecular-weight mucin fraction of submandibular saliva effectively promoted adsorption of S. mutans JBP, but none of the saliva fractions tested enhanced the attachment of S. sobrinus 6715 above the levels of buffer controls. Exposure of pellicles which contained GTF to sucrose to permit in situ synthesis of glucan markedly enhanced attachment of S. sobrinus 6715 but not attachment of S. mutans JBP. Also, the presence of sucrose throughout the adsorption period did not enhance attachment of S. mutans JBP. Both organisms possessed cell-associated GTF, and GTF preparations derived from S. sobrinus 6715 and Streptococcus sanguis FC-1 behaved like GTF derived from S. mutans JBP. S. sobrinus 6715 attached in high numbers to dextran-treated hydroxyapatite, whereas S. mutans JBP did not. These observations suggest that S. mutans JBP cells possess an adhesin which binds to salivary components in the pellicles. In contrast, S. sobrinus 6715 cells appear to possess an adhesin which binds to glucan in the pellicles. Four additional strains of S. mutans and four additional strains of S. sobrinus behaved qualitatively like strains JBP and 6715, respectively, and thus the differences observed appear to be representative of these species. Collectively, our data indicate that S. mutans and S. sobrinus attach to different receptors in experimental pellicles.
Interleukin-2-Based Biochemotherapy for Patients with Stage IV Melanoma: Long-Term Survivors Outside a Clinical Trial Setting

Background: The role of Interleukin-2 (IL-2)-based biochemotherapy (BCT) for patients with metastatic melanoma remains controversial and few data of patients treated outside a specialized trial setting are available. Methods: Sixty-six consecutive patients treated with BCT for stage IV melanoma were analyzed retrospectively. All patients received BCT consisting of dacarbazine, cisplatin and vinblastine (CVD), interferon alfa-2a (IFN), and IL-2. IL-2 was administered at two different dose levels: 3 × 106 U/m2/day (BCT-3) and 9 × 106 U/m2/day (BCT-9), each intravenously on 4 consecutive days (days 5–8, 17–20, 26–29). Results: Nine of 66 patients achieved a complete (CR) and 11 patients a partial response (PR), resulting in an overall response rate of 30%. Five responses (2 CR and 3 PR) were observed in the 29 patients treated according to the BCT-3 protocol, 15 responses (7 CR and 8 PR) in the 37 patients treated according to the more IL-2 dose-intense BCT-9 protocol (17 vs. 41%; p = 0.033). Median overall survival (OS) for all 66 patients was 10 (range 3–119+) months. Responders had a superior OS than nonresponders (14 vs. 7 months, p < 0.001). After a median follow-up of 70 months, 5 patients are alive. Among them, 4 are in stable CR at 30+, 48+, 79+ and 119+ months, respectively, amounting to a disease-free survival rate of 6% (4/66). Conclusions: Long-term disease-free survival for patients with stage IV melanoma can be achieved with BCT outside a highly specialized clinical trial setting. Better selection criteria are needed in order to avoid the unnecessary toxic treatment of the majority of patients.
Development and Validation of a Celiac Disease Quality of Life Instrument for North American Children

Objective: Given the social constraints imposed by a gluten-free diet, it can be hypothesized that children with celiac disease (CD) living in the United States have a reduced health-related quality of life (HRQOL); however, there is no validated CD-specific HRQOL instrument for children living in the United States. The goals of this study were to develop and validate a CD-specific HRQOL instrument for children 8 to 18 years of age with CD and to report HRQOL in these children using both generic- and disease-specific instruments. Methods: This was a prospective study using focus group methodology to develop a CD-specific HRQOL instrument that was then administered to children 8 to 18 years of age with CD living throughout the United States. Instrument validation methods included construct, convergent, and divergent validities. Results: Two instruments were developed: CD-specific pediatric HRQOL instrument (CDPQOL) 8 to 12 and CDPQOL 13 to 18. A total of 181 children with CD completed the CDPQOL as well as a comparator generic instrument. Exploratory factor analysis restructured the CDPQOL and reduced the total number of items. The CDPQOL showed a moderate agreement with the Psychosocial dimensions of the generic instrument confirming convergent validity and low-to-moderate agreement with the Physical Health Summary dimension of the generic instrument confirming divergent validity. Conclusions: The CDPQOL, consisting of 13 to 17 questions, is a validated instrument for the measurement of HRQOL in children 8 to 18 years of age with CD living in the United States.
Development and in vitro characterization of floating sustained-release drug delivery systems of polyphenols

Abstract The aim of this study was to develop and characterize floating stomach-retentive matrix tablets that will deliver polyphenols in a controlled release manner. The tablets were prepared by direct compression. A number of polymers were examined and egg albumin was chosen in light of a better performance in terms of floating behavior and decomposition time. Dissolution studies for three representative polyphenols loaded into a number of formulations were performed using the “f2” factor in order to compare release profiles of different polyphenols and formulations. The release data showed a good fit into the power law equation and zero-order kinetics has been determined for some of the systems. Erosion and textural analysis studies revealed that higher concentration of egg albumin results in a higher gel strength that is less susceptible to erosion, potentially leading to a prolonged delivery time of drug. The ability of egg albumin-based tablets to resist high mechanical forces was also determined, while comparison to cellulose-derived polymers revealed that the latter have a much lower ability to resist the same forces. The developed delivery system has the potential to increase the efficacy of the therapy for various pathological stomach conditions and to improve patient compliance.