Miracle-dz/UniFAR-FTUs huggingface dataset:
Staurosporine-Induced Neuronal Apoptosis

Staurosporine, a nonselective protein kinase inhibitor, has been shown to induce apoptosis in several different nonneuronal cell types. We tested the hypothesis that staurosporine would also induce apoptosis in central neurons. Exposure of murine cortical cell cultures to 30-100 nM staurosporine induced concentration-dependent selective neuronal degeneration over the following day; at higher concentrations, staurosporine damaged glial cells as well. Staurosporine-induced neuronal death was accompanied by cell body shrinkage, chromatin condensation, and DNA laddering. In contrast, NMDA-induced neuronal death was accompanied by acute cell body swelling without DNA laddering. Staurosporine-induced neuronal death, unlike excitotoxic death, was markedly attenuated by the protein synthesis inhibitor cycloheximide; this protective effect was not reversed by a glutathione synthesis inhibitor, buthionine sulfoximine. Interestingly, the glial cell death induced by 1 microM staurosporine was markedly potentiated by cycloheximide. Staurosporine-induced neuronal death was not accompanied by an increase in intracellular free Ca2+ and was attenuated by 30 mM K+; this protective effect of high K+ was blocked by nimodipine or Co2+. Present data suggest that staurosporine can induce apoptosis in cultured cortical neurons and that this apoptosis can be blocked by raising intracellular Ca2+ or by blocking protein synthesis. Staurosporine exposure may be useful as a model for studying central neuronal apoptosis in vitro.
The effect of dilution during culture on detection of low concentrations of bacteria in blood

The standard procedure for culturing blood is to inoculate 5 ml of blood into 50 ml of broth, resulting in a blood-broth ratio of 1:10. In infants, where only 0.5 to 1.0 ml of blood is available for culture, blood:broth ratios may be as dilute as 1:100. The purpose of this study was to determine whether a blood-broth ratio of 1:100 was as sensitive as a ratio of 1:10 for detecting low concentrations of bacteria in blood. Blood (0.5 ml) seeded with 2 to 30 organisms/ml of one of four common pediatric pathogens (Escherichia coli, Streptococcus pneumoniae, Group B Streptococcus or Haemophilus influenzae type b) was inoculated into culture broth so as to provide blood-broth ratios of 1:10, 1:30 or 1:100. There were no differences in the ability to recover organisms or in the time-to-positivity of cultures with different blood-broth ratios. Cultures were positive in 24 of 40 (60%) bottles at a ratio of 1:10, 28 of 40 (70%) at 1:30 and 30 of 40 (75%) at 1:100. Common pediatric pathogens can be recovered without delay from volumes of blood as small as 0.5 ml cultured at blood-broth ratios up to 1:100.
Potential bias in a randomized trial of laparoscopic gastric bypass versus laparoscopic adjustable gastric banding.

To the Editors: I t is with great interest we read the recent randomized controlled trial by Nguyen et al., comparing the frequently performed bariatric operations, gastric bypass and adjustable gastric banding.1 The authors should be congratulated for the methodological rigor of this study, providing significant level 1 evidence in the comparison of these 2 procedures. We would, however, like to draw attention to aspects of the trial methodology that may limit the generalizability of its findings. When responding to the comment by Dr Wolfe, Dr Nguyen states that only 23% of the patients approached for this trial agreed to participate. We are concerned that the low uptake rate of this trial may mean the study participants differ systematically from the population of all patients seeking bariatric surgery. This would decrease the external validity of the trial, limiting the application of its findings to other patients seeking bariatric surgery.2 In addition, Dr Nguyen states that 14 of the 125 patients randomized to gastric bypass (11%) and 39 of the 125 patients randomized to adjustable gastric banding (31%) were excluded after randomization. This represents a
BIOLOGIC CHARACTERISTICS OF A CONTINUOUS KIDNEY CELL LINE DERIVED FROM THE AFRICAN GREEN MONKEY.

A continuous cell line derived from kidney tissue of the African green monkey, Cercopithecus aethiops and designated BS-C-1, has been maintained through 142 subcultures. Cultures of the BS-C-1 line support the growth of simian virus 40 to the same extent as do primary Cercopithecus kidney cell cultures; moreover, the pathognomonic vacuolating changes induced by this virus are as apparent in the continuous cell line as in the primary cell cultures. The BS-C-1 cell cultures are suitable for propagating several viruses, including polio, measles, Rift Valley fever, respiratory syncytial, Coxsackie A9, O'Malley's A-1 agent, and simian agents 1, 4 and 5. In contrast, several strains of influenza A and B viruses and of adenoviruses 3, 4 and 7 as well as simian virus 2 failed to multiply in BS-C-1 cells. No change in the susceptibility of the BS-C-1 cultures of SV40 virus was detected throughout 142 passages of the cell line. On the other hand, during this period of culture the cell line changed its chromosomal characteristics. Thus, the pattern remained diploid, i.e., 60 chromosomes, beyond the 20th subculture, and became subdiploid by the 41st passage after which it continued to change its characteristics with a majority of the cells in the 52nd passage having 59 chromosomes and the remainder 58; most of the cells had a dicentric chromosome. By the 111th passage, most of the cells approached the hypotetraploid state with 83% of the cells having 114 to 117 chromosomes. To our knowledge, this represents the first instance in which continuous observations have been made on the susceptibility of a tissue culture cell system to a given virus during a period when its cells changed from the diploid to the polyploid state. In this particular system the changes in chromosomal pattern were not associated with change in susceptibility to the virus. The BS-C-1 line is apparently free of extraneous microbial agents; seed cultures can be maintained in the frozen state; it grows rapidly and is not fastidious in its nutritional requirements. The BS-C-1 continuous cell line provides the virologist with another tool for diagnostic and research work and perhaps for the large scale cultivation of viral agents for vaccines. As regards the last mentioned possibility the employment of continuous cell lines has recently received a cautious endorsement (22) for use in carefully planned, progressively expanding studies.
[Bullying and its association with psychiatric disorders in a Mexican students sample].

OBJECTIVE To study the relationship between bullying behavior and psychopathology. MATERIALS AND METHODS A total of 1 092 students identified their peers' bullying status based on the Bull-S questionnaire. Parents completed the Child Behavior Checklist (CBCL) to determine psychopathology levels. RESULTS The bullying group had associations with anxiety, somatic symptoms, oppositionalism and behavior problems; the bully-victims group had associations with attention, oppositionalism and behavior problems; victims had higher anxiety scores.These differences were significant compared with the control group. CONCLUSIONS Bullying is associated with psychopathology, which requires timely psychiatric attention.
Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer.

PURPOSE ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor-positive advanced breast cancer. MATERIALS AND METHODS In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. RESULTS In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). CONCLUSION ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.
Exercise training delineates the importance of B-cell dysfunction to the glucose intolerance of human aging.

Aging has been associated with glucose intolerance, insulin resistance, hyperinsulinemia, and diminished islet B-cell function. The relative contribution of these factors to the aging-associated changes in glucose tolerance has been difficult to discern, particularly so for B-cell function, since insulin sensitivity itself is a determinant of B-cell function and, therefore, comparisons of insulin levels and responses between old and young subjects are difficult. To reduce this effect, we compared B-cell function in 14 healthy older men (aged 61-82 yr; body mass index, 21-30 kg/m2), who were exercise trained for 6 months to improve insulin sensitivity, to that of 11 healthy young men (aged 24-31 yr; body mass index, 19-31 kg/m2), who were also trained. Insulin-glucose interactions were assessed by measuring indices of insulin sensitivity (SI) and glucose effectiveness at zero insulin (GEZI) using Bergman's minimal model. B-Cell function was assessed by determining the acute insulin responses (AIR) to glucose (AIRgluc) and arginine at 3 different glucose levels: fasting, approximately 14 mM, and greater than 28 mM (AIRmax). AIRmax provides a measure of B-cell secretory capacity, while the glucose level at which 50% of AIRmax occurs is termed PG50 and is used to estimate B-cell sensitivity to glucose. The insulin sensitivity and glucose effectiveness at zero insulin of the trained older subjects was similar to that of the trained young [SI: old, 5.1 +/- 0.6; young, 6.5 +/- 0.7 x 10(-5) min-1/pM (mean +/- SEM; P = NS); GEZI: old, 1.3 +/- 0.2; young, 1.7 +/- 0.2 x 10(-2) min (P = NS)]. Under these conditions, the fasting glucose levels (old, 5.4 +/- 0.2; young, 5.1 +/- 0.1 mM) and basal insulin levels (old, 49 +/- 6; young, 63 +/- 11 pM) were also similar in the two groups. AIRgluc values were lower in the exercised elderly (old, 253 +/- 50; young, 543 +/- 101 pM; P = 0.01). This decrease in stimulated insulin release was due solely to a reduction in the AIRmax (old, 1277 +/- 179; young, 2321 +/- 225 pM; P less than 0.005); the PG50 was not different (old, 8.9 +/- 0.4; young, 8.8 +/- 0.2 mM; P = NS). These differences in the older subjects were associated with a reduction in iv glucose tolerance (old, 1.49 +/- 0.15; young, 1.95 +/- 0.13%/min; P less than 0.05). (ABSTRACT TRUNCATED AT 400 WORDS)
Relationship between insulin resistance, hs-CRP, and body fat and serum osteoprotegerin/RANKL in prediabetic patients.

BACKGROUND Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPN) are soluble members of the tumor necrosis factor superfamily. Growing evidence suggest that there is link between inflammation, insulin resistance and OPG, soluble RANKL (sRANKL). We aimed to ascertain whether OPG and sRANKL levels are altered in prediabetic subjects and there is association between OPG/sRANKL and metabolic parameters. METHODS Forty prediabetic subjects and 40 age- and BMI-matched controls were recruited for this cross-sectional study. Circulating OPG, sRANKL were measured using ELISA. Anthropometric and metabolic parameters were also determined. RESULTS Circulating sRANKL (97.74±17.67 vs. 55.00±11.19 pg/mL, P=0.010) and OPG (261.54±74.55 vs. 159.23±52.91 pg/mL, P=0.020) levels were found to be significantly higher in diabetic subjects compared with control subjects. There was a positive correlation between sRANKL and OPG. sRANKL also positively correlated with BMI, insulin resistance marker HOMA-IR, inflammatory marker hs-CRP. Logistic regression analyses revealed that the odds ratio was increased for prediabetes in subjects with having elevated sRANKL levels. CONCLUSIONS Increased sRANKL and OPG levels were associated with prediabetic subjects. sRANKL and OPG may play a role in the pathogenesis of diabetes as well as metabolic disturbance.
EFFECTS OF ARTIFICIAL INTRAOCULAR PRESSURE ELEVATION ON THE CORNEAL ENDOTHELIUM IN THE VERVET MONKEY

Both eyes of anesthetized vervet monkeys were perfused with mock aqueous humor for 3–7 hours. By adjusting the height of a reservoir connected to the anterior chamber of each eye the intraocular pressure in one eye was maintained at 33–44 mmHg and in the other eye it was a few mmHg above the spontaneous level (12–15 mmHg). Morphologically the control eyes appeared normal, whereas pronounced changes were observed in the high pressure eyes. Thus the corneal endothelium showed an uneven surface towards the anterior chamber with vacuolization, blebbing and disruption of the cytoplasm. Pycnosis, excaryocytosis and even loss of whole endothelial cells were observed as well. The morphological changes were most pronounced in the peripheral part of the cornea and furthermore differed among neighbouring cells. During the healing process one could observe mitosis, amitosis and cell surface increase.
Interplay between C-Raf kinase and Rassf1a putative tumour suppressor in liver cancer

Der Hippo/MST Signaltransduktionsweg reguliert das Zellwachstum in Metazoen und fungiert als potentieller Tumorsuppressor in Leberkarzinomen. C-RAF, der indirekte Aktivator von ERK im MAPK Signaltransduktionsweg, kann MST2 binden und inhibieren. Auβerdem schutzt C-Raf Zellen vor Apoptose und zeigt eine deutliche Uberexpression in humanen Leberkarzinomen. Diese Arbeit untersucht die potentielle Interaktion zwischen dem Hippo/Mst Signaltransduktionsweg und C-Raf in der Entstehung von Leberkrebs. Chemische Tumorinduktion in c-raf Knock-out Mausen zeigen, dass die Ablation von C-Raf in Hepatozyten zu einem gesteigerten Tumorwachstum und einer hoheren Anzahl von Tumoren fuhrt. Auf ahnliche Weise fuhrt die Ablation von C-Raf in Hepatozyten und den nicht-perenchymalen Zellen vor der Tumorinitiation zu einer hoheren Zahl von Tumoren, jedoch zu keinem gesteigerten Tumorwachstum. Die Ablation von C-Raf in Hepatozyten und den nicht-parenchymalen Zellen nach der Entstehung von makroskopische Tumoren zeigt keine Auswirkung auf deren Zahl und Wachstum. Im nachsten Schritt wurde die chemische Tumorinduktion in einem c-raf/rassf1a doppel Knock-out Stamm durchgefuhrt. Rassf1a reguliert den Hippo/Mst Signaltransduktionsweg, und fungiert als Tumorsuppressor in der Leber, verliert diese Funktion jedoch im Zuge der Tumorprogression durch Promotor-Methylierung. Der Phanotyp Verlust des c-raf Knock-outs nach der chemischen Tumorinduktion im rassf1a Knock-out Hintergrund deutet auf die genetische Interaktion zwischen c-raf und rassf1a hin. Die Mehrzahl der c-raf-Knock-out Lebern zeigt Tumore im fortgeschrittenen Karzinomstadium, wahrend in Wildtyp-Mausen nur Dysplasien detektiert werden konnten. Doppel Knockout Mause aber zeigen eine ahnliche Zahl an Karzinomen wie jene mit der alleinigen Deletion von rassf1a. Weiters war in tumorfreien Arealen in c-raf Knock-out Mausen im Vergleich zum Wild-Typ eine erhohte Proliferation zu beobachten, nicht jedoch im rassf1a-Knock-out Hintergrund. Sowohl C-raf- als auch c-raf/rassf1a doppel Knock-outs weisen eine erhohte Anzahl von der Kupfferzellen auf, was auf eine Entzundungsreaktion hindeuten konnte. Die beobachteten Phanotypen der Lebertumore wurden mit veranderten Aktivitaten in MAPK-, Hippo- und Enzundungs Signaltransduktionswegen korreliert. Im letzten Schritt wurden die Akuteffekte von, oxidativem Stress auf den Hippo Signaltransduktionsweg analysiert. Zusammenfassend konnten wir zeigen, dass C-Raf in Hepatozyten als potentieller Tumorsuppressor, in nicht-parenchymalen Leberzellen, die aus dem Knochenmark stammen, aber als Tumorpromoter fungiert. Weiters wurde die Interaktion zwischen c-raf und rassf1a im chemisch-induzierten Leberkrebsmodel analysiert.
One year outcome of intensive care patients with decompensated alcoholic liver disease.

BACKGROUND We aimed to examine the outcome of patients with decompensated alcoholic liver disease (ALD) admitted to a general intensive care unit (ICU). METHODS Retrospective observational cohort study of intensive care admissions over a 3 yr period was conducted. The study was set in an ICU in a UK university hospital with a tertiary liver referral unit. One hundred and ten admissions, involving 107 patients, with decompensated ALD were included. Intensive care, hospital, and 6 and 12 months mortality were recorded along with the outcome in diagnostic and organ system support subgroups. Intensive care, hospital, 6 month and 12 month mortality rates were 58, 71, 78 and 81%. RESULTS Hospital mortality in the sepsis/multiorgan failure group was 88%. Sixty-nine per cent of patients who were ventilated but required no other organ support survived to hospital discharge. However, the requirement for any other organ support, or a raised creatinine (>120 micromol litre(-1)) in the first 24 h, reduced the hospital survival to <15%. In those patients requiring acute renal replacement therapy, the hospital mortality was 94%. CONCLUSION Decompensated ALD requiring intensive care admission is associated with a high hospital mortality and consideration should be given to the futility of escalating organ support measures, particularly when renal replacement therapy is required.
Ethanol-induced conditioned taste aversion in male sprague-dawley rats: impact of age and stress.

BACKGROUND Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. This study was designed to examine age-related differences in sensitivity to ethanol's aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus (CS). Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed. METHODS Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings. RESULTS This study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose CS. No effects of prior stressor exposure were observed in either experiment. CONCLUSIONS Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption.
Risk of Hospital-Acquired Complications in Patients with Chronic Kidney Disease.

BACKGROUND AND OBJECTIVES Unintended injuries or complications in hospitalized patients are common, potentially preventable, and associated with adverse consequences, including greater mortality and health care costs. Patients with CKD may be at higher risk of hospital-acquired complications (HACs). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Adults from a population-based cohort (Alberta Kidney Disease Network) who were hospitalized from April 1, 2003, to March 31, 2008, made up the study cohort. Kidney function was defined using outpatient eGFR and proteinuria (protein-to-creatinine ratio or dipstick) in the year before index hospitalization. Comorbid conditions were identified using validated algorithms applied to administrative data. A specific diagnostic indicator was used to identify HACs. Complications were classified into clinically homogeneous groups and subclassified as potentially preventable (p-HACs) or always preventable (a-HACs). Multivariable logistic regressions models were used to examine the association of CKD with HACs, accounting for confounders. RESULTS Of 536,549 patients, 8.5% had CKD; those with CKD were older and more likely to be admitted for circulatory system diseases than those without CKD. In fully adjusted models, the odds ratio (OR) of any hospital complication in patients with CKD (reference: no CKD) was 1.19 (95% confidence interval [95% CI], 1.18 to 1.26); there was a graded relation between the risk of HACs and CKD severity, with an OR of 1.81 (95% CI, 1.51 to 2.17) in those with the most severe CKD (eGFR, 15-29 ml/min per 1.73 m(2) and proteinuria, >30 mg/mmol). Findings were similar for p-HACs (OR, 1.20 [95% CI, 1.16 to 1.24] and 1.78 [95% CI, 1.43 to 2.11], respectively). The a-HACs had similar point estimates. CONCLUSIONS The presence of CKD and its severity are associated with a higher risk of HACs, including those considered preventable. Targeted strategies to reduce complications in patients with CKD admitted to the hospital should be considered.
Designing for Learning and Play - The Smiley Model as a Framework

This paper presents the Smiley Model as a framework for designing engaging learning experiences in games. In a design-based research project, student game designers learned inside a gamified learning design while designing and implementing learning goals from curriculum into small digital games. Project participants were adult students in an upper secondary general education program. The Smiley Model inspired and provided a scaffold or a heuristic for the overall gamified learning design and for the students’ learning game design processes, turning the learning situation into an engaging experience while integrating learning and play. The student game designers reached cognitively complex levels of understanding by designing learning situations into the digital learning games. They experienced motivating learning situations, and the social and collaborative learning processes in the class increased.