Miracle-dz/UniFAR-FTUs huggingface dataset:
High glucose down-regulates angiotensin II binding via the PKC-MAPK-cPLA2 signal cascade in renal proximal tubule cells.

BACKGROUND It has been reported that renal renin-angiotensin system contributes to the development of diabetic nephropathy. However, the mechanism of angiotensin II receptor regulation in diabetic condition has not been elucidated. METHODS The effects of high glucose on [(3)H]-arachidonic acid (AA) release and angiotensin II (Ang II) binding and its related signal pathway were examined in primary cultured rabbit renal proximal tubule cells (PTCs). RESULTS High glucose down-regulated (125)I-Ang II binding from 12 hours and this response was sustained over 48 hours. Thus, the treatment of 25 mmol/L glucose for 48 hours was used for this study. High glucose-induced down-regulation of (125)I-Ang II binding was reversed by the removal of extracellular glucose, suggesting a role for glucose specificity. The high glucose-induced down-regulation of (125)I-Ang II binding was blocked by mepacrine, AACOCF3, phospholipase A2 inhibitors, indomethacin, ibuprofen, and cyclooxygenase inhibitors. Indeed, high glucose significantly increased prostaglandin E2 synthesis. In addition, the high glucose-induced AA release was blocked by PD 98059, a p44/42 mitogen-activated protein kinase (MAPK) inhibitor. PD 98059 also prevented the down-regulation of (125)I-Ang II binding by high glucose, suggesting a role for p44/42 MAPK. Indeed, high glucose significantly increased p44/42 MAPK activity after the 15-minute time point. Protein kinase C (PKC) inhibitor blocked high glucose-induced activation of p44/42 MAPK, increase of the [(3)H]-AA release, and down-regulation of 125I-Ang II binding. W-7 and KN-62 also blocked the high glucose-induced increase of [(3)H]-AA release and down-regulation of (125)I-Ang II binding. However, phospholipase A2 inhibitor did not block high glucose-induced activation of p44/42 MAPK. CONCLUSION High glucose down-regulates (125)I-Ang II binding via the PKC-MAPK-cPLA2 signal pathway.
Intraocular Mantle Cell Lymphoma of the Iris

Purpose Non-Hodgkin lymphoma (NHL) is a neoplastic process of the lymphatic system in which tumors develop from lymphocytes. The absence of Reed-Sternberg cells differentiates NHL from Hodgkin lymphoma (HL). Mantle cell lymphoma is a mature B-cell NHL, typically with an aggressive course. Manifestations of intraocular mantle cell lymphoma include anterior uveitis, morphologic changes to the uvea, vitritis, intraocular masses, as well as subretinal or choroidal infiltrates. Case Report A 71-year-old white man with known mantle cell lymphoma presents with recent-onset blurred vision in the left eye resulting from an atypical anterior chamber cellular reaction. Iris examination reveals topographic and morphologic atypia suggestive of neoplasia. He subsequently developed posterior cervical lymph node involvement indicating recurrence of his mantle cell lymphoma. He was restarted on chemotherapy and radiation. The iris and anterior chamber reaction responded to systemic oncological therapy. Conclusions Mantle cell lymphoma may present with ocular manifestations such as an anterior chamber cellular reaction and morphologic changes to the uvea. This case stresses the importance of seeking an etiology in any secondary or atypical uveitis.
The role of olfactory cues in the sequential radiation of a gall‐boring beetle, Mordellistena convicta

1. Herbivorous insects often have close associations with specific host plants, and their preferences for mating and ovipositing on a specific host‐plant species can reproductively isolate populations, facilitating ecological speciation. Volatile emissions from host plants can play a major role in assisting herbivores to locate their natal host plants and thus facilitate assortative mating and host‐specific oviposition.
The financial impact of ambulance diversions and patient elopements.

OBJECTIVES Admission process delays and other throughput inefficiencies are a leading cause of emergency department (ED) overcrowding, ambulance diversion, and patient elopements. Hospital capacity constraints reduce the number of treatment beds available to provide revenue-generating patient services. The objective of this study was to develop a practical method for quantifying the revenues that are potentially lost as a result of patient elopements and ambulance diversion. METHODS Historical data from 62,588 patient visits to the ED of a 450-bed nonprofit community teaching hospital in central Pennsylvania between July 2004 and June 2005 were used to estimate the value of potential patient visits foregone as a result of ambulance diversion and patients leaving the ED without treatment. RESULTS The study hospital may have lost 3,881,506 dollars in net revenue as a result of ambulance diversions and patient elopements from the ED during a 12-month period. CONCLUSIONS Significant revenue may be foregone as a result of throughput delays that prevent the ED from utilizing its existing bed capacity for additional patient visits.
Better Selection Model for EML4-ALK Fusion Gene Test in Patients with Non-Small-Cell Lung Cancer

Background: In the last decade, the search for gene mutations in lung cancer has been constantly growing. EGFR, KRAS mutations and, recently, the EML4-ALK fusion can guide the selection of treatment for patients who carry a specific mutation. Methods: During 2010-2011, EML4-ALK fusion test has been performed in Israel, mostly for wild type EGFR non-squamous NSCLC patients based on fluorescent in-situ hybridization (FISH) technique to detect EML4-ALK rearrangements. Results: Between January 2010 and December 2011, 3341 patients were diagnosed with lung cancer in Israel. Of the 2997 patients with NSCLC 687 had squamous cell carcinoma and 2310 had non-squamous NSCLC. This study focused on available 125 non-squamous NSCLC cases in which analysis for EML4-ALK rearrangement was available. All were negative for EGFR mutation. Nineteen (15.2%) were found positive for the fusion, a figure 2 - 10 times higher compared with previously reported findings. The EML4-ALK fusion was significantly more prevalent in younger male patients (52.1 vs. 61.3 years, p = 0.049), in whom every additional year reduced the chance to find the fusion by 7% [CI = 0.93 (0.88 - 0.99), p = 0.03]. Conclusions: A stepwise approach based on histology and prior EGFR analysis to detect EML4-ALK fusion is highly efficient with a related increased yield of detection. We recommend testing patients with non-squamous cell lung carcinoma after ruling out an EGFR mutation. The chance to find the ALK fusion is significantly greater in younger men.
Occurrence of express saccades under isoluminance and low contrast luminance conditions

Abstract Saccadic reaction times (SRTs) of three human subjects were analyzed. The gap paradigm was used (i.e. fixation point offset precedes target onset) to obtain high proportions of express saccades (i.e. saccades of extremely short reaction times) in the SRT distributions. In one set of experiments, the luminance of the (red) saccade target was varied from brighter to darker than the (green) background including an isoluminance condition. Express saccades were obtained in response to pure color contrast stimuli with about the same frequency and reaction time as to stimuli with both color and luminance contrast. In a second experiment, the luminance contrast of a white target on a white background was lowered below 10%. Again the number of express saccades was not reduced. Thus, in contrast to other perceptual phenomena the visual neural mechanisms underlying the generation of express saccades are not affected by isoluminance nor low contrast luminance.
Takotsubo cardiomyopathy

2. Ishikawa K. “Takotsubo” cardiomyopathy: A syndrome characterized by transient left ventricular apical ballooning that mimics the shape of a bottle used for trapping octopus in Japan. Intern Med 2004; 43: 275 – 276. 3. Eitel I, von Knobelsdorff-Brenkenhoff F, Bernhardt P, Carbone I, Muellerleile K, Aldrovandi A, et al. Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy. JAMA 2011; 306: 277 – 286. 4. Ramaraj R, Movahed MR. Reverse or inverted takotsubo cardiomyopathy (reverse left ventricular apical ballooning syndrome) presents at a younger age compared with the mid or apical variant and is always associated with triggering stress. Congest Heart Fail 2010; 16: 284 – 286. 5. Win CM, Pathak A, Guglin M. Not takotsubo: A different form of stress-induced cardiomyopathy: A case series. Congest Heart Fail 2011; 17: 38 – 41. 6. Mrdovic I, Kostic J, Perunicic J, Asanin M, Vasiljevic Z, Ostojic M. Right ventricular takotsubo cardiomyopathy. J Am Coll Cardiol 2010; 55: 1751. 7. Pant S, Deshmukh A, Mehta K, Badheka AO, Tuliani T, Patel NJ, et al. Burden of arrhythmias in patients with Takotsubo cardiomyopathy (apical ballooning syndrome). Int J Cardiol 2013; 170: 64 – 68. 8. Deshmukh A, Kumar G, Pant S, Rihal C, Murugiah K, Mehta JL. Prevalence of Takotsubo cardiomyopathy in the United States. Am Heart J 2012; 164: 66 – 71. 9. Deshmukh A, Pant S, Badheka A, Deshmukh AA, Kumar G. Seasonal variation of takotsubo cardiomyopathy. Am J Cardiol 2013; 111: 627 – 628.
In Memoriam: Lynne Morishita

potential serious side effects. The Food and Drug Administration (FDA) has approved duloxetine, but it must be obtained by prescription. There are limitations based on potential side effects, drug-to-drug interactions, and recommendations not to combine it with other therapies for depression. Acetaminophen therapy has been the mainstay of osteoarthritis pain since the 1950s, and its efficacy and safety are still promoted today. No long-term toxicity has been demonstrated with up to 4 g of acetaminophen per day for various sources of pain. Other options for systemic analgesia such as NSAIDS and opioids can be effective but have limitations. NSAIDS have been found to have in shortand long-term toxicities in cardiovascular disease and hypertension and mortality in gastrointestinal bleeding. NSAIDs are widely used in the treatment of osteoarthritis and pain. They are readily available over the counter and have 17 prescription variants. NSAIDs have underlying risks. Hypertension, cardiovascular, renal, hepatic, central nervous system, and gastrointestinal complications can be profound and even lethal. The FDA revised the warning and precaution on all nonaspirin forms of NSAIDs in July 2015. The new FDA warning includes greater risk of heart attack or stroke as early as the first few weeks of use. This risk is greater with higher doses and exists for individuals with or without cardiac risk factors, and greater mortality is associated with NSAID use after myocardial infarction. Opioids, although effective, have complications including sedation, constipation, drug diversion, polypharmacy, and respiratory depression. The use of acetaminophen in the vast majority of individuals with osteoarthritis makes it a viable choice based on a blend of efficacy, safety, and cost. Monitoring is important, especially when taken with other acetaminophen-containing products or in severe hepatic disease. Intentional misuse is rare, and hepatic consequences with the use of even maximum doses of 4 g per day are almost nonexistent. Health Canada conducted a retrospective review in July 2015 of 4 billion doses in 1 year. Two hundred fifty individuals developed serious liver consequences only when exceeding the maximum dose of 4 g because of suicide attempts or unintentional overdoses. No evidence was found that doses of 4 g were toxic. It is important to be aware of all of potential sources of acetaminophen, including combination products, and the cumulative dose of acetaminophen so as not to exceed the maximal dose in 24 hours. Physicians and allied health professionals should educate people about the efficacy of acetaminophen and the unsurpassed safety of this class of drugs. The costs of education and monitoring of medications are minimal. In summary, people trust that the pharmacological options for their osteoarthritis pain are safe. The abundant, long-term clinical trial data for acetaminophen support its use in the management of osteoarthritis pain.
Interoception in emotional experience

Purpose of reviewMany theories of emotion have postulated a close relationship of the feedback of physiological changes and their perception with emotional experience. This paper reviews recent advances in theory and brain-imaging research on this topic of interoception and describes a hypothetical model of the potential mechanisms. Recent findingsResearch from patients with spinal-cord injuries and pure autonomic failure suggests that emotion-related peripheral autonomic changes are not necessary for emotional experience. However, in support of a role for centrally integrated feedback from the whole body, imaging studies found that activations in areas commonly associated with interoception and emotion (anterior insula and anterior cingulate) were correlated with individual differences in interoception (heartbeat detection) and trait measures of emotion. Because recent theory distinguishes between two levels of emotional experience (phenomenology and awareness), this paper proposes a hypothetical model of the effects of interoception on phenomenology and awareness. This model classifies interoception into the central representation of feedback from the whole body, the perception of actual physiological changes as well as the perception of illusory changes. SummaryConsistent with recent theories of emotion, evidence from brain imaging supports the notion that centrally integrated feedback from the whole body plays a role in emotional experience. Because research on neural correlates of emotional experience is at an early stage, the hypothesized model of potential causal links between interoception and emotional experience might serve as a helpful guide to future research.
Penalizing Cartels: The Case for Basing Penalties on Price Overcharge

In this paper we set out the welfare economics based case for imposing cartel penalties on the cartel overcharge rather than on the more conventional bases of revenue or profits (illegal gains). To do this we undertake a systematic comparison of a penalty based on the cartel overcharge with three other penalty regimes: fixed penalties; penalties based on revenue, and penalties based on profits. Our analysis is the first to compare these regimes in terms of their impact on both (i) the prices charged by those cartels that do form; and (ii) the number of stable cartels that form (deterrence). We show that the class of penalties based on profits is identical to the class of fixed penalties in all welfare-relevant respects. For the other three types of penalty we show that, for those cartels that do form, penalties based on the overcharge produce lower prices than those based on profit) while penalties based on revenue produce the highest prices. Further, in conjunction with the above result, our analysis of cartel stability (and thus deterrence), shows that penalties based on the overcharge out-perform those based on profits, which in turn out-perform those based on revenue in terms of their impact on each of the following welfare criteria: (a) average overcharge; (b) average consumer surplus; (c) average total welfare.
18 Regenerated Fibre Bragg Gratings

Silica remains the key optoelectronic and photonic medium, the essence of nearly all modern optical transport systems. Engineering of silica in its various forms ranges from 1 to 3-dimensional waveguide and periodic structures, including recent interest in 3-D photonic crystals. Most of the processing methods involve complex vapour deposition and various co-dopants, which have an advantage of overcoming the lack of finesse involved with general formation of glass structure through high temperature processing and quenching. Nevertheless, to obtain micron or sub-micron precision over the processing of glass for device purposes, invariably post processing methods are commonly used, ranging from etching of systems with dopants, often through patterned masks, to laser processing using UV to mid IR lasers. Concrete examples of micron scale laser processing of glass include direct written waveguides, Bragg gratings in waveguides and optical fibres and photonic crystals. The drawback with these post-processing techniques is that they often produce glass that is structurally less stable than the starting phase. For many applications the thermal stability of laser induced glass changes determines the limits in which they can operate – an excellent example which will form the basis for this chapter, is the optical fibre Bragg grating. Fibre Bragg gratings are used in many industrial and technological applications. Within standard telecommunications applications, for example, type I fibre Bragg gratings that can operate to 80°C for 25 years are required – such gratings can in principle operate for lengthy periods up to 300°C. Gratings that can operate at temperatures well above standard telecommunication requirements are critical to the success of many real time sensing applications. In the oil and gas industries, an alternative application, although standard oil bores are typically quoted as having an environment no more than ~(180-250)°C [Schroeder et al. 1999; Kersey 2000], variations can occur and the increasing depth of the next generation bores suggest sensors that can operate to 400°C or more are desirable for long term or permanent operation. In industries involving high temperature furnaces, such as aluminium smelting or coal based power stations, it would be of interest to be able to monitor temperatures in excess of 1000°C. Similar temperature requirements span many
Rescue of PINK1 Protein Null-specific Mitochondrial Complex IV Deficits by Ginsenoside Re Activation of Nitric Oxide Signaling*

Background: PINK1 null results in severe mitochondrial complex IV deficits. Results: PINK1 regulates complex IV through interactions with Hsp60 upstream regulators, and ginsenoside Re can rescue complex IV deficits. Conclusion: Complex IV deficiency was rescued by restoration of optimal NO signaling by ginsenoside Re. Significance: NO-complex IV signaling provides potential for new therapeutics targeting mitochondrial dysfunction in PD. PINK1, linked to familial Parkinson's disease, is known to affect mitochondrial function. Here we identified a novel regulatory role of PINK1 in the maintenance of complex IV activity and characterized a novel mechanism by which NO signaling restored complex IV deficiency in PINK1 null dopaminergic neuronal cells. In PINK1 null cells, levels of specific chaperones, including Hsp60, leucine-rich pentatricopeptide repeat-containing (LRPPRC), and Hsp90, were severely decreased. LRPPRC and Hsp90 were found to act upstream of Hsp60 to regulate complex IV activity. Specifically, knockdown of Hsp60 resulted in a decrease in complex IV activity, whereas antagonistic inhibition of Hsp90 by 17-(allylamino) geldanamycin decreased both Hsp60 and complex IV activity. In contrast, overexpression of the PINK1-interacting factor LRPPRC augmented complex IV activity by up-regulating Hsp60. A similar recovery of complex IV activity was also induced by coexpression of Hsp90 and Hsp60. Drug screening identified ginsenoside Re as a compound capable of reversing the deficit in complex IV activity in PINK1 null cells through specific increases of LRPPRC, Hsp90, and Hsp60 levels. The pharmacological effects of ginsenoside Re could be reversed by treatment of the pan-NOS inhibitor l-NG-Nitroarginine Methyl Ester (l-NAME) and could also be reproduced by low-level NO treatment. These results suggest that PINK1 regulates complex IV activity via interactions with upstream regulators of Hsp60, such as LRPPRC and Hsp90. Furthermore, they demonstrate that treatment with ginsenoside Re enhances functioning of the defective PINK1-Hsp90/LRPPRC-Hsp60-complex IV signaling axis in PINK1 null neurons by restoring NO levels, providing potential for new therapeutics targeting mitochondrial dysfunction in Parkinson's disease.
Carrier Phase Relative RAIM Algorithms and Protection Level Derivation

The concept of Relative Receiver Autonomous Integrity Monitoring (RRAIM) using time differential carrier phase measurements is investigated in this paper. The precision of carrier phase measurements allows for mitigation of integrity hazards by implementing RRAIM monitors with tight thresholds without significantly affecting continuity. In order to avoid the need for cycle ambiguity resolution, time differences in carrier phase measurements are used as the basis for detection. In this work, we examine RRAIM within the context of the GNSS Evolutionary Architecture Study (GEAS), which explores potential architectures for aircraft navigation utilizing the satellite signals available in the mid-term future with GPS III. The objectives of the GEAS are focused on system implementations providing worldwide coverage to satisfy LPV-200 operations, and potentially beyond. In this work, we study two different GEAS implementations of RRAIM. General formulas are derived for positioning, fault detection, and protection level generation to meet a given set of integrity and continuity requirements.
Effect of play activities on hospitalized children's stress: a randomized clinical trial

Abstract Objective:The use of unstructured play as an intervention to help children cope with the stress of a hospitalization period was tested in this randomized clinical trial. Methods:Urinary cortisol (a stress marker) was examined in 53 pediatric patients hospitalized for respiratory diseases in a public hospital, divided into two groups that did or did not play. Results:Boys and girls from the play group, 7–11 years old, showed a decrease in cortisol levels after participating in play activities. In younger participants (4–7 years old) the intervention did not seem as efficient, probably because in this group maturity levels may have influenced how children cognitively engaged in play as a coping strategy. Conclusions:The study showed the importance of using interventions that consider age ranges and gender in enhancing coping strategies, as well as the importance of such techniques that are employed by occupational therapists since they are professionals with expertise in the use of activities as therapeutic instruments.
A multisite study of implementing supported employment in the Netherlands.

OBJECTIVE This article reports on the implementation of the individual placement and support model of supported employment in four Dutch regions. METHODS The authors used structured site visits, employment data, and semistructured interviews to assess fidelity, employment outcomes, and facilitators of and barriers to successful implementation. RESULTS At 24 months, the four sites reached a mean+/-SD fidelity score of 4.1+/-. 3 (possible scores range from 1 to 5, with higher scores indicating closer adherence to the model). Of the 316 persons with mental illnesses, 57 (18%) obtained competitive jobs. Barriers to implementation included lack of organizational standards, loss of vocational staff, funding problems, insufficient time for program leaders, and inadequate cooperation between the involved organizations. Important facilitators were the skills and commitment of the vocational team members and the integration of vocational and mental health staff. CONCLUSIONS To implement evidence-based supported employment in the Netherlands will require changes in financing, organizational structures, attitudes, cultural beliefs, and labor and disability regulations.