Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Aldose Reductase Inhibitor (Tolrestat) on Urinary Albumin Excretion Rate and Glomerular Filtration Rate in IDDM Subjects With Nephropathy

OBJECTIVE To explore the possible link between diabetic nephropathy and the enhanced activity of the polyol pathway, known to occur in IDDM subjects. RESEARCH DESIGN AND METHODS We studied the effects of the aldose reductase inhibitor tolrestat (200 mg/day) on urinary albumin excretion rate and glomerular filtration rate in 20 IDDM patients with diabetic nephropathy. RESULTS Six months of placebo treatment produced no significant changes in glomerular filtration rate, urinary albumin excretion rate, and renal plasma flow. Consequently, filtration fraction remained unchanged. During tolrestat treatment, glomerular filtration rate decreased from the basal value of 156 ± 14 ml·min−1.73 m2 to 142 ± 13.7 ml·min−1·1.73 m2 (P < 0.001) at 2 mo; 128 ± 12.4 ml·min−1·1.73 m2 (P < 0.001) at 4 mo; and 123.7 ± 13.0 ml·min−1·1.73 m2 at 6 mo. A significant decrease of urinary albumin excretion rate was observed during the trial (basal values 219 ± 32.5 vs. 196.9 ± 28.5 μg/min at 2 mo [P < 0.05] 171.6 ± 25.5 μg/min at 4 mo [P < 0.001] and 58.6 ± 19.3 μg/min at 6 mo [P < 0.001]). No significant change in renal plasma flow was seen during tolrestat treatment. Filtration fraction significantly decreased in the tolrestat group from the basal value of 0.23 ± 0.02 to 0.21 ± 0.01 at 2 mo (P < 0.005); 0.18 ± 0.02 at 4 mo (P < 0.001); and 0.17 ± 0.02 at 6 mo (P < 0.001). CONCLUSIONS The polyol pathway is implicated in hemodynamic changes associated with early diabetic nephropathy, and aldose reductase treatment can positively influence these parameters.
The Luteinizing Hormone Surge Is Preceded by an Estrogen-Induced Increase of Hypothalamic Progesterone in Ovariectomized and Adrenalectomized Rats

As circulating estrogen levels rise on the afternoon of proestrus, they stimulate the hypothalamo-pituitary axis. This estrogen positive feedback is pivotal to stimulate the luteinizing hormone (LH) surge required for ovulation and luteinization of ovarian follicles. In addition to estrogen, pre-LH surge progesterone is critical for an LH surge as was demonstrated by blocking progesterone synthesis. In ovariectomized (OVX) rats treated with trilostane, a blocker of the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD) that catalyzes the conversion of pregnenolone to progesterone, estrogen did not induce an LH surge. Further, estrogen induced an LH surge in OVX and adrenalectomized (ADX) rats, indicating that the source of progesterone was neither the ovary nor adrenal gland. This estrogen-only LH surge was inhibited by pretreatment with trilostane, indicating that although the adrenal gland and ovary were not necessary for positive feedback, progesterone synthesis was critical for estrogen-induced positive feedback in an OVX/ADX rat. This suggested that the LH surge is dependent on the pre-LH surge synthesis of progesterone. Estrogen-induced progesterone receptors in the hypothalamus are vital for the LH surge, so a potential location for progesterone synthesis is the hypothalamus. OVX/ADX female rats were treated with 17β-estradiol (50 µg) and progesterone levels were assayed by RIA. Progesterone levels were elevated in hypothalamic tissue following estrogen treatment. No increases in tissue progesterone levels were found in parietal cortex, cerebellum, medulla, pituitary or plasma. Additionally, male rats that do not have an estrogen positive feedback-induced LH surge were examined. Castrated/ADX male rats had no increase in hypothalamic progesterone levels after estrogen treatment. Together, these data strongly suggest that estrogen enhances neuroprogesterone synthesis in the hypothalamus that is involved in the positive feedback regulating the LH surge.
Simultaneous Aortic Valve Replacement in left Ventricular Assist Device Recipients: Single-Center Experience

Introduction: Aortic valve regurgitation or the presence of a mechanical aortic valve prosthesis is a relative contraindication for implantation of left ventricular assist devices (LVAD). However, concomitant aortic valve replacement by a biological prosthesis is one of the options in this situation. We analyzed our recent experience with left ventricular assist device implantation and concomitant aortic valve replacement. Methods: Between January 1, 2008 and January 15, 2012, 318 adult patients (>18 years old) were supported with a long-term implantable LVAD in our institution. In 19, simultaneous aortic valve replacement (6 redo and 13 primary procedures) was performed. Patients were divided into 2 groups according to INTERMACS (IM) level: Group 1 (n = 7) consisted of patients with IM level 1–2 and Group 2 (n = 12) of IM level 3–4 patients. As a control cohort we analyzed all LVAD recipients during the study period (n = 299, study group excluded). The control cohort was similarly divided into two groups according to the IM level: Group 3 (n = 162) consisted of patients with IM level 1–2 and Group 4 (n = 137) of those with IM level 3–5. Perioperative data and outcomes in all groups were retrospectively analyzed and compared (Group 1 compared to Group 3; and Group 2 to Group 4). Results: In study Groups 1 and 2 all patients were male; in Groups 3 and 4, 80% and 88% respectively were male. Median age distribution in Groups was 55, 61, 54, and 57 years respectively. Patients from Group 2 were significantly older than those from Group 4 (p = 0.039). Body mass index was significantly lower in Group 1 than in Group 3 (p = 0.033). Cardio-pulmonary bypass time was significantly longer in Groups 1 and 2 compared with Groups 3 and 4 respectively (p≤0.001). Patients from Group 1 had a trend more often to develop right ventricular failure requiring a right ventricular assist device (RVAD) than those in Group 3 (p = 0.09). Intensive care unit stay duration of mechanical ventilation and in-hospital mortality in Group 1 were significantly higher than in Group 3 (p = 0.025, p = 0.005, p = 0.038). Patients from Group 2 had similar outcomes compared to those from Group 4. Conclusions: In stable patients, simultaneous aortic valve replacement and LVAD implantation are not associated with an impaired outcome. In patients with cardiogenic shock an additional aortic valve replacement may impair outcome; therefore alternative techniques should be considered.
A recombinant retrovirus encoding alkaline phosphatase confirms clonal boundary assignment in lineage analysis of murine retina.

Recombinant retroviruses encoding the histochemically detectable enzyme beta-galactosidase have been used to investigate lineage in the vertebrate nervous system. Identification of the descendants of individual progenitors is straightforward when progeny cells are arranged in a reproducible, clustered pattern, but difficulties in interpretation arise when progeny migrate extensively and/or in an irregular pattern. To better resolve clonal boundaries, additional histochemical marker viruses that engender distinctive reaction products can be used in combination with lacZ-bearing viruses. To this end, we have created a retrovirus vector, DAP, encoding an easily assayable enzyme, human placental alkaline phosphatase. DAP was found to be at least as useful as a lacZ-encoding retrovirus (e.g., BAG) with respect to high viral titer, stability of expression, and in identification of infected cells in vivo. Moreover, it was found to be neutral with respect to postnatal rodent retinal development and offered superior staining characteristics relative to lacZ. Coinfection of rodent retina with DAP and BAG allowed an examination of the clonal nature of radial arrays of labeled retinal cells that previously had been described as products of a single infected progenitor. Of 1100 radial arrays examined for the presence of both DAP- and BAG-infected cells, only 1.2% were the result of infection with more than one virus.
Prevalence and possible mechanisms of reactive hypoglycemia in polycystic ovary syndrome.

STUDY QUESTION What is the prevalence of reactive hypoglycemia (RH) in polycystic ovary syndrome (PCOS) versus age- and body mass index (BMI)-matched healthy controls. SUMMARY ANSWER The prevalence of RH was increased in PCOS versus controls. WHAT IS KNOWN ALREADY Previous studies suggested an increased prevalence of RH in PCOS. STUDY DESIGN, SIZE, DURATION Cross-sectional study of 88 women with PCOS and 34 healthy age- and BMI-matched controls. PARTICIPANTS/MATERIALS, SETTING, METHODS Eighty-eight women with PCOS and 34 age- and BMI-matched controls were included. The study was conducted at Odense University Hospital, Denmark. Participants underwent 5 h oral glucose tolerance test (5 h OGTT). Indices of insulin resistance, β-cell function, and area under the curve (AUC) for glucose, insulin and C-peptide were calculated. Insulin clearance was estimated as 5 h AUC C-peptide/insulin. RH was defined as blood glucose ≤3.3 mmol/l during 5 h OGTT. MAIN RESULTS AND THE ROLE OF CHANCE RH occurred in 15/88 (17%) women with PCOS versus 0/34 controls ( ITALIC! P = 0.01). Nine out of 15 women with RH were obese and 6 were lean ( ITALIC! P = 0.42). Obese patients with RH had significantly higher 5 h AUCs insulin and C-peptide compared with lean patients with RH ( ITALIC! P = 0.02 and 0.04, respectively). Obese patients with RH had significantly lower 5 h AUC C-peptide/insulin versus obese patients without RH ( ITALIC! P = 0.02). In lean patients with RH, 5 h AUCs insulin and C-peptide were similar to lean controls. LIMITATIONS, REASONS FOR CAUTION The 5 h OGTT was used to diagnose RH and may be a limitation of the study. Although the 5 h OGTT is the most widely accepted method, no gold standard exists in terms of diagnosing RH. The 5 h OGTT was suggested to over-estimate the incidence of RH compared with meal test. WIDER IMPLICATIONS OF THE FINDINGS The study supports previous suggestions of increased prevalence of RH in women with PCOS compared with controls. STUDY FUNDING/COMPETING INTERESTS This study was funded by Jacob Madsen's and Olga Madsen's Foundation, Institute of Clinical Research, Odense University Hospital, Kolding Hospital, AP Møller's Foundation, Bernhard and Marie Kleins Foundation, The Novo Nordisk Foundation, and The Danish Medical Association. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER The trial was registered at www.clinicaltrials. gov (registration numbers NCT00451568 (patients) and NCT01995773 (controls)).
Stability analysis of unified chaotic systems via switching control

The problem on the existence of a common quadratic Lyapunov function for switched unified chaotic systems is investigated in this paper. Switched unified chaotic systems with a varying parameter are constructed. A sufficient condition on the existence of a common quadratic Lyapunov function is derived in view of the solution to a group of matrix inequalities. By designing linear state feedback controllers, the controlled switched unified chaotic systems can be asymptotically stable via arbitrary switching. Finally, a random numerical example and its simulations illustrate the effectiveness of the switching control approach.
Equivalence of a Sprouting-and-Retraction Model and Correlation-Based Plasticity Models of Neural Development

A simple model of correlation-based synaptic plasticity via axonal sprouting and retraction (Elliott, Howarth, & Shadbolt, 1996a) is shown to be equivalent to the class of correlation-based models (Miller, Keller, & Stryker, 1989), although these were formulated in terms of weight modification of anatomically fixed synapses. Both models maximize the same measure of synaptic correlation, subject to certain constraints on connectivity. Thus, the analyses of the correlation-based models suffice to characterize the behavior of the sprouting-and-retraction model. More detailed models are needed for theoretical distinctions to be drawn between plasticity via sprouting and retraction, weight modification, or a combination. The model of Elliott et al. involves stochastic search through allowed weight patterns for those that improve correlations. That of Miller et alinstead follows dynamical equations that determine continuous changes of the weights that improve correlations. The identity of these two approaches is shown to depend on the use of subtractive constraint enforcement in the models of Miller et al. More generally, to model the idea that neural development acts to maximize some measure of correlation subject to a constraint on the summed synaptic weight, the constraint must be enforced subtractively in a dynamical model.
Physical activity levels among children attending after-school programs.

PURPOSE To describe the physical activity (PA) levels of children attending after-school programs, 2) examine PA levels in specific after-school sessions and activity contexts, and 3) evaluate after-school PA differences in groups defined by sex and weight status. METHODS One hundred forty-seven students in grades 3-6 (mean age: 10.1 +/- 0.7, 54.4% male, 16.5 % overweight (OW), 22.8% at-risk for OW) from seven after-school programs in the midwestern United States wore Actigraph GT1M accelerometers for the duration of their attendance to the program. PA was objectively assessed on six occasions during an academic year (three fall and three spring). Stored activity counts were uploaded to a customized data-reduction program to determine minutes of sedentary (SED), light (LPA), moderate (MPA), vigorous (VPA), and moderate-to-vigorous (MVPA) physical activity. Time spent in each intensity category was calculated for the duration of program attendance, as well as specific after-school sessions (e.g., free play, snack time). RESULTS On average, participants exhibited 42.6 min of SED, 40.8 min of LPA, 13.4 min of MPA, and 5.3 min of VPA. The average accumulation of MVPA was 20.3 min. Boys exhibited higher levels of MPA, VPA, and MVPA, and lower levels of SED and LPA, than girls. OW and at-risk-for-OW students exhibited significantly less VPA than nonoverweight students, but similar levels of LPA, MPA, and MVPA. MVPA levels were significantly higher during free-play activity sessions than during organized or structured activity sessions. CONCLUSION After-school programs seem to be an important contributor to the PA of attending children. Nevertheless, ample room for improvement exists by making better use of existing time devoted to physical activity.
Observations on brilliant green agar with H2S indicator

Several formulations of brilliant green agar with an added H2S indicator were evaluated. Results were optimum with variations of a basic formula consisting of 40 g of tryptic soy agar (Difco), 8 g of lactose, 8 g of sucrose, 80 mg of phenol red, 1 g of sulfanilamide, 1.5 g of ferric ammonium citrate, 5 g of sodium thiosulfate pentahydrate, and 7 mg of brilliant green dye per liter. Brilliant green dye was added after sterilization of the other components This formulation supported good growth of all of 39 strains of Salmonella tested. Normal biochemical types formed pink colonies with black centers, and an H2S-negative S. choleraesuis formed pink colonies without black centers. Of other bacteria tested, only Enterobacter, Klebsiella, and a few Citrobacter strains showed significant growth in 24 h. When lactose was omitted from the formulation, a lactose-fermenting strain formed pink colonies with black centers, and differentiation of Salmonella from the Enterobacter-Klebsiella groups was equally good. Addition of xylose (4.0 g) and L-lysine hydrochloride (5.4 g) to the above formulation improved differentiation between Salmonella and the few Citrobacter strains that grew and produced more intense blackening in Salmonella colonies. Addition of an H2S indicator to brilliant green agar formulations aided in identification of Salmonella colonies, especially in mixtures with other bacteria. These media were judged to give better differentiation of salmonellae from other bacteria than Hektoen agar with added novobiocin (10 mg/liter).
Endocytosis of Adeno-Associated Virus Type 5 Leads to Accumulation of Virus Particles in the Golgi Compartment

ABSTRACT Among the adeno-associated virus (AAV) serotypes which are discussed as vectors for gene therapy AAV type 5 (AAV5) represents a candidate with unique advantages. To further our knowledge on AAV5-specific characteristics, we studied the entry pathway of wild-type virus in HeLa cells in the absence of helper virus by immunofluorescence and electron microscopy and by Western blot analysis. We found virus binding at the apical cell surface, especially at microvilli and, with increasing incubation time, virus accumulation at cell-cell boundaries. The different binding kinetics suggest different binding properties at apical versus lateral plasma membranes. Endocytosis of viruses was predominantly by clathrin-coated vesicles from both membrane domains; however, particles were also detected in noncoated pits. AAV5 particles were mainly routed to the Golgi area, where they could be detected within cisternae of the trans-Golgi network and within vesicles associated with cisternae and with the dictyosomal stacks of the Golgi apparatus. These data suggest that AAV5 makes use of endocytic routes that have hitherto not been described as pathways for virus entry.
Involved field radiation therapy for early stage Hodgkin's disease in children. Preliminary results

Twenty Stage I and II children with Hodgkin's disease were treated with involved field radiation therapy. Twelve patients were Stage I. The histologic types were: nodular sclerosis (seven cases), mixed cellularity (two) and lymphocyte predominant (three). There were eight Stage II patients (six nodular sclerosis and two of mixed cellularity). One Stage I and 4 Stage II patients had class B disease. Involved field irradiation was used in these children after staging laparotomy showed no disease below the diaphragm. Eight of the 20 patients relapsed, five in lymph nodes adjacent to the primary site, two in areas across the diaphragm; the other had both local and distant extension. The median time to relapse after completion of radiation therapy for Stage I and II were 15 and 5 months, respectively. Two of the eight children with recurrent disease are dead. The other six were retreated and are alive and free of disease for periods ranging from 24 to 68 months after original treatment (median, 36 months). Two of the six survivors in this group received irradiation to the site of the recurrent disease only, one was given total nodal irradiation, and three had chemotherapy. The other 12 patients are in continuous first remission. They have been followed for a median time of 26 months. The actuarial relapse‐free survival and survival rates at 3 years are 57 and 89%, respectively.
CGRP infusion in unanesthetized rats increases expression of c-Fos in the nucleus tractus solitarius and caudal ventrolateral medulla, but not in the trigeminal nucleus caudalis

Background and aims Calcitonin gene-related peptide (CGRP) and glyceryl trinitrate (GTN) infusion in migraineurs provokes headache resembling spontaneous migraine, and CGRP receptor antagonists are effective in the treatment of acute migraine. We hypothesized that CGRP infusion would increase molecular markers of neuronal activation in migraine-relevant tissues of the rat. Methods CGRP was infused intravenously (i.v.) in freely moving rats to circumvent factors like anesthesia, acute surgery and severe hypotension, the three confounding factors for c-Fos expression. The trigeminal nucleus caudalis (TNC) was isolated at different time points after CGRP infusion. The level of c-Fos mRNA and protein expression in TNC were analyzed by qPCR and immunohistochemistry. c-Fos-stained nuclei were also counted in the nucleus tractus solitarius (NTS) and caudal ventrolateral medulla (CVLM), integrative sites in the brain stem for processing cardiovascular signals. We also investigated Zif268 protein expression (another immediate early gene) in TNC. The protein expression of p-ERK, p-CREB and c-Fos was analyzed in dura mater, trigeminal ganglion (TG) and TNC samples using Western blot. Results CGRP infusion caused a significant dose-dependent fall in mean arterial blood pressure. No significant activation of c-Fos in the TNC at mRNA and protein levels was observed after CGRP infusion. A significant increase in c-Fos protein was observed in the NTS and CVLM in the brain stem. Zif268 expression in the TNC was also not changed after CGRP infusion. p-ERK was increased in the dura mater 30 minutes after CGRP infusion. Conclusion CGRP infusion increased the early expression of p-ERK in the dura mater but did not increase c-Fos and Zif268 expression in the TNC. The rats may, thus, differ from migraine patients, in whom infusion of CGRP caused headache and a delayed migraine attack. The rat CGRP infusion model with c-Fos or Zif268 as neuronal pain markers in TNC is unsuitable for antimigraine drug testing.
Deuterium exchange and mass spectrometry reveal the interaction differences of two synthetic modulators of RXRα LBD

Protein amide hydrogen/deuterium (H/D) exchange was used to compare the interactions of two antagonists, UVI 2112 and UVI 3003, with that of the agonist, 9‐cis‐retinoic acid, upon binding to the human retinoid X receptor alpha ligand‐binding domain (hRXRα LBD) homodimer. Analysis of the H/D content by mass spectrometry showed that in comparison to 9‐cis‐retinoic acid, the antagonists provide much greater protection toward deuterium exchange‐in throughout the protein, suggesting that the protein–antagonist complex adopts a more restricted conformation or ensemble of conformations in which solvent accesses to amide protons are reduced. A comparison between the two antagonists shows that UVI 3003 is more protective in the C‐terminal region due to the extra hydrophobic interactions derived from the atoms in the benzene ring of the carboxylic acid chain. It was less protective within regions comprising peptides 271–278 and 326–330 due to differences in conformational orientation, and/or shorter carboxylic acid chain length. Decreased deuterium exchange‐in in the segment 234–239 where the residues do not involve interactions with the ligand was observed with the two antagonists, but not with 9‐cis‐RA. The amide protons of helix 12 of the agonist‐ or antagonist‐occupied protein in solution have the same deuterium exchange rates as the unliganded protein, supporting a suggestion made previously that helix 12 can cover the occupied binding cavity only with the cofactor present to adjust its location.
Challenges and Pitfalls in Cartel Fining

We analyze challenges and pitfalls faced by antitrust authorities in the fining of cartels. We review economics and legal approaches to cartel fining and the sometimes-conflicting objectives of restitution, deterrence, and proportionality. We also discuss various theoretical and empirical hurdles that antitrust authorities and courts must overcome to determine appropriate cartel fines, namely regarding cartel impact duration, but-for prices, and overcharges.