Miracle-dz/UniFAR-FTUs huggingface dataset:
General anesthetics and cytotoxicity: possible implications for brain health

Abstract Background: The search for agents that bring about faster induction and quicker recovery in the operating room have yielded numerous anesthetics whose mechanisms of action and potential toxic side effects remain unknown, especially in the young and aging brain. Objective: Taking advantage of our clinical and basic science expertise, here we subject the reader to an interesting perspective vis-à-vis the current applications of general anesthetics, and present evidence for their neurotoxic effects on the developing and elderly brains. Results: Recent studies have called into question the safety of general anesthetics, especially with regards to potentially significant detrimental impacts on the developing brains of young children, and cognitive decline in the elderly – often following multiple episodes of anesthesia. Despite accumulating evidence from animal studies demonstrating that general anesthesia leads to neurodegeneration and cognitive impairment, to date a clear consensus on the impact of anesthetics in humans remains elusive. Because a direct impact of anesthetics on human neuronal networks is often difficult to deduce experimentally, most laboratories have resorted to animal models – albeit with limited success in translating these findings back to the clinic. Moreover, the precise mechanisms that lead to potential cognitive, learning, and memory decline in young and elderly patients also remain to be fully defined. Conclusions: This review will focus primarily on the cytotoxic effects of anesthetics, and offer some practical resolutions that may attenuate their long-term harm. An urgent need for studies on animal models and an increased focus on highly controlled prospective epidemiological studies is also reinforced.
Assessment of patient safety research from an organizational ergonomics and structural perspective

The aim of this study is to review patient safety improvement initiatives within a conceptual framework that builds upon principles of organizational ergonomics and emphasizes structural factors that influence patient safety. The literature review included 131 English language published studies of patient safety improvement strategies extracted using Medline, Ovid Healthstar, PubMed and CINAHL searches. Keywords for the search included: ‘patient safety’; ‘medical errors’; ‘adverse event’; ‘iatrogenic’; and truncated options for ‘improve’. The multilevel, hierarchical framework offered in this paper integrates quality management principles and organizational ergonomics theory and organizes patient safety initiatives according to sociotechnical system elements within three structural levels: health policies and associated health care organizations; health care delivery organizations; and health care microsystems. Utilizing the conceptual framework, this review of patient safety improvement initiatives highlights the need for consideration of the impact of all improvement proposals on each structural component within health care systems. The review also supports the need for patient safety research to evolve from exploratory, 1-D reporting to multi-level, integrated research.
CA: Computer Associates or Creative Accounting? How corporate culture can influence unethical behavior

This paper examines the establishment of a pattern of unethical behavior using Computer Associates as a case study. By incorporating their own self-interests into the firm’s corporate culture, top level managers at Computer Associates used Machiavellian techniques in order to support an unethical corporate culture. In addition, the establishment of unethical individual and group norms allowed employees a rationale for their unethical behavior. This unethical behavior was exposed when the federal government started a criminal investigation of Computer Associates. The initial alle-gations were that Computer Associates allowed monthly sales to be booked for up to 35 days representing a month in violation of Securities and Exchange Commission requirements. The former CEO was charged and was found guilty of securities fraud and obstruction of justice. Computer Associates disassociated themselves from the actions of the un-ethical managers who left the company and started with a clean slate, which included changing their name to CA.
The Diagnostic Interview for Social and Communication Disorders: algorithms for ICD-10 childhood autism and Wing and Gould autistic spectrum disorder.

BACKGROUND The Diagnostic Interview for Social and Communication Disorders (DISCO) is an interviewer-based schedule for use with parents and carers. In addition to its primary clinical purpose of helping the clinician to obtain a developmental history and description of the child or adult concerned, it can also be used to assist in providing a formal diagnostic category. METHOD In this study we compared two algorithms based on the ninth revision of the schedule (DISCO 9). The algorithm for ICD-10 childhood autism comprised 91 individual, operationally defined items covering the behaviour outlined in the ICD-10 research criteria. The algorithm for the autistic spectrum disorder, as defined by Wing and Gould (1979), was based on 5 DISCO items that represented overarching categories of behaviour crucial for the diagnosis of autistic disorders. The aim of the study was to examine the implications for clinical diagnosis of these two different approaches. Parents of 36 children with clinical diagnoses of autistic disorder, 17 children with learning disability and 14 children with language disorders were interviewed by two interviewers. Algorithm diagnoses were applied to interview items in order to analyse the relationship between clinical and algorithm diagnoses and the inter-rater reliability between interviewers. RESULTS Clinical diagnosis was significantly related to the diagnostic outputs for both algorithms. Inter-rater reliability was also high for both algorithms. The ICD childhood disorder algorithm produced more discrepant diagnoses than the Wing and Gould autistic spectrum algorithm. Analysis of the ICD-10 algorithm items and combination of items helped to explain the reason for these discrepancies. CONCLUSIONS The results indicate that the DISCO is a reliable instrument for diagnosis when sources of information are used from the whole interview. It is particularly effective for diagnosing disorders of the broader autistic spectrum.
Glial–Cytokine–Neuronal Interactions Underlying the Mechanisms of Persistent Pain

The emerging literature implicates a role for glia/cytokines in persistent pain. However, the mechanisms by which these non-neural elements contribute to CNS activity-dependent plasticity and pain are unclear. Using a trigeminal model of inflammatory hyperalgesia, here we provide evidence that demonstrates a mechanism by which glia interact with neurons, leading to activity-dependent plasticity and hyperalgesia. In response to masseter inflammation, there was an upregulation of glial fibrillary acidic proteins (GFAPs), a marker of astroglia, and interleukin-1β (IL-1β), a prototype proinflammatory cytokine, in the region of the trigeminal nucleus specifically related to the processing of deep orofacial input. The activated astroglia exhibited hypertrophy and an increased level of connexin 43, an astroglial gap junction protein. The upregulated IL-1β was selectively localized to astrocytes but not to microglia and neurons. Local anesthesia of the masseter nerve prevented the increase in GFAP and IL-1β after inflammation, and substance P, a prototype neurotransmitter of primary afferents, induced similar increases in GFAP and IL-1β, which was blocked by a nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester. Injection of IL-1 receptor antagonist and fluorocitrate, a glial inhibitor, attenuated hyperalgesia and NMDA receptor phosphorylation after inflammation. In vitro application of IL-1β induced NR1 phosphorylation, which was blocked by an IL-1 receptor antagonist, a PKC inhibitor (chelerythrine), an IP3 receptor inhibitor (2-aminoethoxydiphenylborate), and inhibitors of phospholipase C [1-[6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione] and phospholipase A2 (arachidonyltrifluoromethyl ketone). These findings provide evidence of astroglial activation by tissue injury, concomitant IL-1β induction, and the coupling of NMDA receptor phosphorylation through IL-1 receptor signaling.
Addressing the Needs of Homeless Youth Through Housing, Education, and Career Services in Kingston, Ontario, Canada

Youth homelessness is experienced by youth between ages of 16-24, where they are either homeless or at risk of becoming homeless. These youth typically lack social structures, stability, and sense of security in their lives. They also face many issues such as drugs, violence, sexually transmitted diseases, and early pregnancy. In the past decade, youth homelessness has become an increasingly important issue in Canada. Many organizations such as Covenant House in Toronto and Crisis House in Calgary are designed specifically to help homeless youth in finding shelter spaces. However, in smaller cities such as Kingston, there is a lack of reports on the conditions of homeless youth. The aim of this master’s report is to fill the gaps and provide a research base for future studies. The report provides a detailed literature review on the subject of youth homelessness, and an analysis of how agencies have met the needs of homeless youth in Kingston based on interviews with youth and agencies to identify gaps in services. The agencies interviewed include Kingston Youth Shelter (KYS), Kingston Youth Employment Services, and Passage House.
Mechanisms of Transcriptional Activation of bcl-2Gene Expression by 17β-Estradiol in Breast Cancer Cells*

bcl-2 gene expression is induced by 17β-estradiol (E2) in T47D and MCF-7 human breast cancer cells, and the mechanism of E2 responsiveness was further investigated by analysis of the bcl-2 gene promoter. The −1602 to −1534 distal region (bcl-2j) of the promoter was E2-responsive; however, in gel mobility shift assays, the estrogen receptor α (ERα) did not bind [32P]bcl-2j, whereas Sp1 protein formed a retarded band complex. Further analysis demonstrated that the upstream region (−1603 to −1579) of the bcl-2 gene promoter contained two GC/GA-rich sites at −1601 (5′-GGGCTGG-3′) and −1588 (3′-GGAGGG-5′) that bound Sp1 protein. Subsequent studies confirmed that transactivation by E2 was dependent on ERα/Sp1 interactions with both GC-rich sites, and this was confirmed byin vitro footprinting. In contrast, a 21-base pair E2-responsive downstream region (−1578 to −1534) did not bind Sp1 or ERα protein; however, analysis of a complex binding pattern with nuclear extracts showed that ATF-1 and CREB-1 bound to this motif. These data coupled with results of transient transfection studies demonstrated that transcriptional activation by E2 of the −1578 to −1534 region of the bcl-2 gene promoter was dependent on induction of cAMP and subsequent activation through a cAMP response element. Thus, hormone regulation of bcl-2 gene expression in breast cancer cells involves multiple enhancer elements and E2-mediated transactivation does not require direct binding of the estrogen receptor with promoter DNA.
Self-knowledge activation and the scope of attention

Self-knowledge is a complex structure, composed of many different aspects. Depending on what aspect is currently active (accessible) different regulatory consequences arise (5, 9). Most up-to-date studies were focused on the effects of the momentary accessibility of self-standards (e.g. 2). The present studies add to this knowledge by focusing on the can self – the element of self-knowledge, which pertains to the beliefs about one’s capabilities and potentials (1, 7). The global-local visual paradigm was used to compare the scope of attention after activating the can self vs self-standards. The impossible self was added as the additional control. Numerous studies show that positive affect leads to a global bias (broadened attentional focus), whereas negative affect leads to a local bias (narrowed attentional focus) (3, 4). Assuming that: • priming the self-standard attributes increases the accessibility between actual self and self-standard as well as the resulting negative emotional state (11), • priming can self attributes increases the accessibility of the optimistic self-knowledge regarding one’s capabilities and potentials. It was hypothesized that: • Activation of the can self results in a stronger global bias as compared to the activation of self-standards (here: the ought self). • Activation of the impossible self (the desired attributes that are perceived as impossible to be achieved) results in the stronger local bias as compared to both the can self and the ought self.
Prediction of protein domain boundaries from sequence alone

We present here a simple approach to identify domain boundaries in proteins of an unknown three‐dimensional structure. Our method is based on the hypothesis that a high‐side chain entropy of a region in a protein chain must be compensated by a high‐residue interaction energy within the region, which could correlate with a well‐structured part of the globule, that is, with a domain unit. For protein domains, this means that the domain boundary is conditioned by amino acid residues with a small value of side chain entropy, which correlates with the side chain size. On the one hand, relatively high Ala and Gly content on the domain boundary results in high conformational entropy of the backbone chain between the domains. On the other hand, the presence of Pro residues leads to the formation of hinges for a relative orientation of domains. The method was applied to 646 proteins with two contiguous domains extracted from the SCOP database with a success rate of 63%. We also report the prediction of domain boundaries for CASP5 targets obtained with the same method.
Is Drinking with Parents Associated with High-Risk Drinking among Adolescents?

Background/Aims: What are the implications of drinking with parents (DWP) on adolescents' drinking behavior? We expanded the meagre body of research on this controversial issue by assessing the association between the frequency of DWP and adolescent high-risk drinking, taking a number of parental factors into account. Method: Data stemmed from a subsample of 14-17-year-old current drinkers (n = 7,616) who participated in a cross-sectional Norwegian school survey (response rate: 84%). Results: One in four reported DWP during the past year. The higher the frequency of DWP, the higher was the prevalence of high-risk drinking. Parental drunkenness, permissive alcohol-related parenting, and indicators of suboptimal parenting more generally also correlated with DWP. After controlling for these confounders, only frequent DWP remained significantly associated with high-risk drinking. Conclusions: DWP was related to adolescent high-risk drinking, yet the association was in part attributable to parents' drinking and parenting style. The risk of involvement in high-risk drinking was about the same for adolescents reporting no DWP and infrequent DWP, while it was significantly elevated among those reporting frequent DWP. This study thus demonstrated that the frequency of DWP matters and that parents who drink with their adolescent children differ from other parents in important ways.
T cell immunodeficiency

T cell immunodeficiency can occur as one of a group of primary disorders or develop secondary to chronic infection, illness or drug therapy. Primary T cell disorders are rare, accounting for approximately 11% of reported primary immunodeficiencies, and generally present in infancy or early childhood. Early recognition is very important as many of these patients will require bone marrow transplantation prior to the onset of severe infection or other complications. Because of their rarity, these infants usually present to clinicians who have little or no prior experience of these conditions, and therefore laboratory-based clinicians with knowledge of the key laboratory/pathological abnormalities and clinical features have a valuable role in identifying the possibility of immunodeficiency. Secondary T cell deficiency is a cardinal feature of HIV infection and the specific susceptibility to infectious micro-organisms is highlighted. The possibility of T cell immunodeficiency should be considered in any patient presenting with unusual or severe viral, fungal or protozoal infection.
GBR12909 Possesses Anticonvulsant Activity in Zebrafish and Rodent Models of Generalized Epilepsy but Cardiac Ion Channel Effects Limit Its Clinical Utility

Background/Aims: GBR12909 has been reported to possess anticonvulsant activity with focal brain perfusion to the hippocampus of pilocarpine, although an earlier publication suggested any anticonvulsant effects were only mild. Here we further explored the anticonvulsant potential of GBR12909 with a suite of anticonvulsant assays in both zebrafish and mammals and then explored whether it possessed any QT effects which might limit clinical utility. Methods: We assessed the anticonvulsant effects of GBR12909 in zebrafish pentylenetetrazole (PTZ), mammalian maximal electroshock and PTZ models of generalized epilepsy and a rodent hippocampal kindling model. Cardiac effects were assessed in zebrafish and man. Results: GBR12909 possesses anticonvulsant activity in zebrafish and rodent models of generalized epilepsy. However, phase 1 human data indicated potential QT effects. Subsequent testing in a zebrafish QT assay confirmed marked arrhythmogenic potential. Conclusion: Further clinical development of GBR12909 in epilepsy was considered inappropriate because of insufficient window between the therapeutic effects and the cardiac arrhythmia problems identified in zebrafish assays. Any further development based on this mechanism of action should avoid the GBR12909 chemical scaffold, or involve structure-activity dissociation of its neurological and cardiac effects.
School based oral health promotional intervention: Effect on knowledge, practices and clinical oral health related parameters

Background: No organized school oral health program is existent in India. Aim: The aim of this study is to test the feasibility and efficacy of an economical school oral health promotional intervention with educational and preventive components. Settings and Design: School oral health promotional intervention carried out in one of the randomly selected school and evaluated through short duration prospective model. Materials and Methods: A total of 100 children with an age range of 10-12 years with no previous history of dental intervention were enrolled. Interventions comprised of oral health education (delivered through lecture and demonstrations by an undergraduate dental student) and topical antibacterial therapy (fluoride varnish and povidone iodine). Outcomes consisted of Knowledge and practices (KAP) regarding oral health, clinical oral health related parameters such as plaque index (PI), gingival index (GI) and caries activity as per Modified Snyder's test. These were reported at baseline, 3 weeks and 6 months follow-up examination by a calibrated examiner. Statistical Analysis: McNemar Bowker's test, Student's t-test, Pearson Chi-square tests were used. Results: Highly significant (P < 0.001) improvements in KAP scores, PI scores, GI scores and caries activity were reported at 3 weeks and 6 months follow-up examination. Conclusion: This small economical school oral health program positively influenced oral health related practices and parameters of oral health such as oral cleanliness, gingival health and caries activity.
Precharging and DC Fault Ride-Through of Hybrid MMC-Based HVDC Systems

Compared to half-bridge-based modular multilevel converters (MMCs), full-bridge-based systems have the advantage of blocking the dc fault, but at the expense of increased power semiconductors and power losses. In view of the relationships among ac/dc voltages and currents in full-bridge-based MMC with the negative voltage state, this paper provides a detailed analysis on the link between capacitor voltage variation and the maximum modulation index. A hybrid MMC, consisting of mixed half-bridge and full-bridge circuits to combine their respective advantages is investigated in terms of its precharging process and transient dc fault ride-through capability. Simulation and experiment results demonstrate the feasibility and validity of the proposed strategy for a full-bridge-based MMC and the hybrid MMC.
The Danish PET/depression project: PET findings in patients with major depression

Background. It is hypothesized from previous positron emission tomography (PET) studies of patients with major depression that dysfunction of regions of the limbic system and the frontal lobes in close connection with the basal ganglia is involved in the pathophysiology of major depression. Methods. By means of PET and 15O labelled radioactive water we determined an index of the neuronal activity by mapping the cerebral blood flow distribution of 42 unselected in-patients suffering from moderate to severe depression and 47 healthy controls controlling for age and gender. The PET maps were co-registered to magnetic resonance images of the anatomy of the brain. Results. The functions-of-interest analysis revealed significant gender differences in cerebral blood flow and changes in the relative distribution of the blood with increasing age. The patients had increased activity of the hippocampus and the cerebellum compared to the healthy controls when corrected for these confounders and the influence of antidepressant medication. Furthermore, data in the Danish Psychiatric Central Register showed that the patients studied were representative of the population of depressed patients admitted to the hospital during the study period. Conclusion. Our main finding is increased blood flow to the hippocampus, even when controlling for a number of confounders. This is in accordance with a rapidly expanding literature suggesting an important role for this structure in major depression.
Levetiracetam, Calcium Antagonism, and Bipolar Disorder

Abstract Hyperactive intracellular calcium ion (Ca2+) signaling in peripheral cells has been a reliable finding in bipolar disorder. Some established mood stabilizing medications, such as lithium and carbamazepine, have been found to normalize elevated intracellular Ca2+ concentrations ([Ca2+]i) in platelets and lymphocytes from bipolar disorder patients, and some medications the primary effect of which is to attenuate increased [Ca2+]i have been reported to have mood stabilizing properties. Hyperactive intracellular Ca2+ signaling has also been implicated in epilepsy, and some anticonvulsants have calcium antagonist properties. This study demonstrated that levetiracetam, an anticonvulsant that has been shown to block N and P/Q-type calcium channels in animal studies does not alter elevated [Ca2+]i in blood platelets of patients with bipolar disorder. Review of published clinical trials revealed no controlled evidence of efficacy as a mood stabilizer. This study underscores the possibility that pharmacologic actions of a medication in animals and normal subjects may not necessarily predict its pharmacologic or clinical effects in actual patients. Effects of treatments on pathophysiology that is demonstrated in clinical subtypes may be more likely to predict effectiveness in those subtypes than choosing medications based on structural similarities to established treatments.