Miracle-dz/UniFAR-FTUs huggingface dataset:
Ischemic tolerance in an in vivo model of glutamate preconditioning

Ischemia initiates a complicated biochemical cascade of events that triggers neuronal death. This study focuses on glutamate‐mediated neuronal tolerance to ischemia–reperfusion. We employed an animal model of lifelong excess release of glutamate, the glutamate dehydrogenase 1 transgenic (Tg) mouse, as a model of in vivo glutamate preconditioning. Nine‐ and twenty‐two‐month‐old Tg and wild‐type (wt) mice were subjected to 90 min of middle cerebral artery occlusion, followed by 24 hr of reperfusion. The Tg mice suffered significantly reduced infarction and edema volume compared with their wt counterparts. We further analyzed proteasomal activity, level of ubiquitin immunostaining, and microtubule‐associated protein‐2A (MAP2A) expression to understand the mechanism of neuroprotection observed in the Tg mice. We found that, in the absence of ischemia, the Tg mice exhibited higher activity of the 20S and 26S proteasomes, whereas there was no significant difference in the level of hippocampal ubiquitin immunostaining between wt and Tg mice. A surprising, significant increase was observed in MAP2A expression in neurons of the Tg hippocampus following ischemia–reperfusion compared with that in wt hippocampus. The results suggest that increased proteasome activity and MAP2A synthesis and transport might account for the effectiveness of glutamate preconditioning against ischemia–reperfusion. © 2014 Wiley Periodicals, Inc.
Silibinin prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease via mitochondrial stabilization

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the selective loss of dopaminergic neurons in the nigrostriatal pathway. The lipophile 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) can cross the blood–brain barrier and is subsequently metabolized into toxic1‐methyl‐4‐phenylpyridine (MPP+), which causes mitochondrial dysfunction and the selective cell death of dopaminergic neurons. The present article reports the neuroprotective effects of silibinin in a murine MPTP model of PD. The flavonoid silibinin is the major active constituent of silymarin, an extract of milk thistle seeds, and is known to have hepatoprotective, anticancer, antioxidative, and neuroprotective effects. In the present study, silibinin effectively attenuated motor deficit and dopaminergic neuronal loss caused by MPTP. Furthermore, in vitro study confirmed that silibinin protects primary cultured neurons against MPP+‐induced cell death and mitochondrial membrane disruption. The findings of the present study indicate that silibinin has neuroprotective effects in MPTP‐induced models of PD rather than antioxidative or anti‐inflammatory effects and that the neuroprotection afforded might be mediated by the stabilization of mitochondrial membrane potential. Furthermore, these findings suggest that silibinin protects mitochondria in MPTP‐induced PD models and that it offers a starting point for the development of treatments that ameliorate the symptoms of PD. © 2015 Wiley Periodicals, Inc.
Risk and Efficacy in Biomedical Media Representations of Herbal Medicine and Complementary and Alternative Medicine (CAM)

The objective of the research was to map the discourse about herbal medicine in Australia’s primary medical journal, the Medical Journal of Australia, over 4 decades. Manifest content analysis of 148 articles about herbal or complementary and alternative medicine (CAM) in journal articles from 1966 to 2008 was undertaken. Issues of risk dominated the discourse about herbal medicine in the journal (70%), with a focus on adverse events (42%) as the most significant risk of herbal and other complementary medicines. Toxicity (23%) and drug interactions (18%) were the most frequently mentioned specific risk items. Items that acknowledged efficacy (32%) outweighed those suggesting ineffectiveness (11%). Case reports, reviews, research articles, and letters all had risk frequencies of more than 70%. Review articles and research articles had a high rate of reference to both risk and benefit. Review articles were found to have greater reference to benefit than risk. Possible reasons for these findings are discussed.
Inhibition of endogenous heat shock protein 70 attenuates inducible nitric oxide synthase induction via disruption of heat shock protein 70/Na+/H+ exchanger 1‐Ca2+‐calcium‐calmodulin‐dependent protein kinase II/transforming growth factor β‐activated kinase 1‐nuclear factor‐κB signals in BV‐2 microgl

Inducible nitric oxide synthase (iNOS) critically contributes to inflammation and host defense. The inhibition of heat shock protein 70 (Hsp70) prevents iNOS induction in lipopolysaccharide (LPS)‐stimulated macrophages. However, the role and mechanism of endogenous Hsp70 in iNOS induction in microglia remains unclear. This study addresses this issue in BV‐2 microglia, showing that Hsp70 inhibition or knockdown prevents LPS‐induced iNOS protein expression and nitric oxide production. Real‐time PCR experiments showed that LPS‐induced iNOS mRNA transcription was blocked by Hsp70 inhibition. Further studies revealed that the inhibition of Hsp70 attenuated LPS‐stimulated nuclear translocation and phosphorylation of nuclear factor (NF)‐κB as well as the degradation of inhibitor of κB (IκB)‐α and phosphorylation of IκB kinase β (IKKβ). This prevention effect of Hsp70 inhibition on IKKβ–NF‐κB activation was found to be dependent on the Ca2+/calcium–calmodulin‐dependent protein kinase II (CaMKII)/transforming growth factor β‐activated kinase 1 (TAK1) signals based on the following observations: 1) chelation of intracellular Ca2+ or inhibition of CaMKII reduced LPS‐induced increases in TAK1 phosphorylation and 2) Hsp70 inhibition reduced LPS‐induced increases in CaMKII/TAK1 phosphorylation, intracellular pH value, [Ca2+]i, and CaMKII/TAK1 association. Mechanistic studies showed that Hsp70 inhibition disrupted the association between Hsp70 and Na+/H+ exchanger 1 (NHE1), which is an important exchanger responsible for Ca2+ influx in LPS‐stimulated cells. These studies demonstrate that the inhibition of endogenous Hsp70 attenuates the induction of iNOS, which likely occurs through the disruption of NHE1/Hsp70‐Ca2+‐CaMKII/TAK1–NF‐κB signals in BV‐2 microglia, providing further insight into the functions of Hsp70 in the CNS. © 2015 Wiley Periodicals, Inc.
Vision in Multiple Sclerosis: The Story, Structure-Function Correlations, and Models for Neuroprotection

Abstract Visual dysfunction is one of the most common clinical manifestations of multiple sclerosis (MS). Just over a decade ago, MS clincial trials did not include visual outcomes, but experts recognized the need for more sensitive measures of visual function. Low-contrast letter acuity emerged as the leading candidate to measure visual disability in MS, and subsequent studies found low-contrast acuity testing to correlate well with brain MRI lesion burden, visual-evoked potentials, quality of life (QOL), and retinal nerve fiber layer (RNFL) loss, as measured by optical coherence tomography (OCT). OCT in MS has allowed for assessment of structure-function correlations that make the anterior visual pathway and acute optic neuritis (ON) ideal models for testing novel agents for neuroprotection and repair. New therapies that reduce axonal loss by neuroprotective or myelin repair mechanisms can now be assessed noninvasively by OCT and coupled with visual function data. Based on OCT studies in MS, RNFL thickness is reduced significantly among patients (92 &mgr;m) vs controls (105 &mgr;m) and is particularly reduced in MS eyes with a history of ON (85 &mgr;m). Worsening of visual function by a clinically significant ≥7 letters or approximately 1.5 lines for low-contrast acuity is associated with approximately 4.5 &mgr;m reductions in RNFL thickness in MS eyes. Longitudinal studies of OCT have also shown RNFL axonal loss over time that occurs even in the absence of acute ON and that correlates with clinically meaningful worsening of vision and QOL, even in patients with benign MS. The latest OCT investigations involve high-resolution spectral-domain (SD) OCT with segmentation and measurement of specific retinal layers using computerized algorithms. These methods allow quantitation of ganglion cell (neuronal) layer loss and axonal degeneration in MS in vivo. In this review, we examine the data from these studies and ongoing trials that highlight the entity of ON as a model to investigate neuroprotection and neurorepair. In doing so, we also present representative group data from studies that have examined visual function, OCT measures, and QOL scales in patients with MS and ON and disease-free controls. These data, and those from recent meta-analyses, may be used to provide reference values for the development of clinical trial protocols.
Deimination level and peptidyl arginine deiminase 2 expression are elevated in astrocytes with increased incubation temperature

Astrocytes respond to environmental cues, including changes in temperatures. Increased deimination, observed in many progressive neurological diseases, is thought to be contributed by astrocytes. We determined the level of deimination and expression of peptidyl arginine deiminase 2 (PAD2) in isolated primary astrocytes in response to changes on either side (31°C and 41°C) of the optimal temperature (37°C). We investigated changes in the astrocytes by using a number of established markers and accounted for cell death with the CellTiter‐Blue assay. We found increased expression of glial fibrillary acidic protein, ALDH1L1, and J1‐31, resulting from increased incubation temperature and increased expression of TSP1, S100β, and AQP4, resulting from decreased incubation temperature vs. optimal temperature, suggesting activation of different biochemical pathways in astrocytes associated with different incubation temperatures. Mass spectrometric analyses support such trends. The PAD2 level was increased only as a result of increased incubation temperature with a commensurate increased level of deimination. Actin cytoskeleton and iso[4]LGE, a lipid peroxidase modification, also showed an increase with higher incubation temperature. Altogether, these results suggest that temperature, as an environmental cue, activates astrocytes in a different manner on either side of the optimal temperature and that increase in deimination is associated only with the higher temperature side of the spectrum. © 2015 Wiley Periodicals, Inc.
Prevalence of poor sleep quality and its relationship with body mass index among teenagers: evidence from Taiwan.

BACKGROUND The linkage between sleep quality and weight status among teenagers has gained more attention in the recent literature and health policy but no consensus has been reached. METHODS Using both a propensity score method and multivariate linear regression for a cross-sectional sample of 2,113 teenagers, we analyzed their body mass index (BMI) in relation to sleep quality while controlling for family characteristics (household income, parent/guardian level of education, disability status, work night shift, and smoking) and individual factors (age, sex, regular exercise, smoking, employment, and feeling secure in the neighborhood). Sleep quality was assessed using 3 scales: difficulty in initiating sleep, difficulty in maintaining sleep, and non-restorative sleep, based on Diagnostic and Statistical Manual of Mental Disorders-IV-defined insomnia. RESULTS Considering all 3 types of poor sleep quality, 20.9% of teenagers in Taiwan experienced some form of sleep problems. After adjusting for the other variables, 2 factors independently and statistically predicted sleep problems: current smoking and working night shifts by the head of the household. Teens experiencing difficulty in initiating sleep had higher BMIs ranging from 0.86 to 1.41 units. CONCLUSIONS Efforts to address childhood obesity need to take into consideration sleep problems that are highly prevalent among teenagers.
Corneal endothelial decompansation and ocular hypotony in a case with temporal arteritis.

I n patients with giant cell arteritis (GCA), anterior segment ischemia can cause anterior uveitis, corneal edema, corneal ulceration, and ocular hypotony (1–3). We present a patient who developed severe anterior segment ischemia because of GCA, despite the use of high-dose intravenous corticosteroid therapy. A 71-year-old man, with a 15-day history of right-sided headaches, experienced sudden complete loss of vision in his right eye. He had a history of hypertension, which had been well controlled with medication. Visual acuity was no light perception, right eye, and 20/70, left eye. The right pupil was amaurotic. Anterior segment examination of the right eye revealed folds in Descemet membrane and marked corneal edema (Fig. 1A) with a dense cataract. Intraocular pressures were 4 mm Hg, right eye and 12 mm Hg, left eye. The right fundus could not be visualized. There was a cataract present on examination of the left anterior segment while the left fundus was normal including fluorescein angiography. Confocal microscopy of the right cornea showed irregularities in endothelial cell size and morphology with loss and shift in cell nuclei (Fig. 1B). The patient was hospitalized and treated immediately with intravenous pulse methylprednisolone at a dose of 1,000 mg/day for 3 days. Erythrocyte sedimentation rate was 97 mm per hour, and temporal artery biopsy showed chronic inflammation with giant cells. Carotid doppler revealed moderate stenosis of the right internal carotid artery and mild stenosis of the left internal carotid artery with normal flow. The patient was given a 6-week course of systemic corticosteroids, but at 3-month follow up, there was no recovery of vision in the right eye. There are several reports of corneal involvement in GCA (3–5). However, hypotony occurs infrequently, and it is thought to be caused by a reduction in aqueous production as a result of inflammation of the ciliary body (2–4,6–8). Hypotony was detected in one third of patients without other signs of anterior segment ischemia in a study by Huna-Baron et al (2). They suggested that low intraocular pressure may help distinguish arteritic from nonarteritic anterior ischemic optic neuropathy. Mild corneal edema and Descemet folds have been reported in GCA (3–5) in several cases, but severe corneal edema and corneal decompensation is unusual. Our patient had a 15-day history of visual loss prior to beginning corticosteroids, and this delay possibly contributed to the poor visual outcome. Our report is similar to that of Hwang et al (6) documenting that severe corneal edema and hypotony in patients with GCA may be refractory to even high-dose corticosteroid therapy.
Human Rights and Social Wrongs: Issues in Safeguarding Adults with Learning Disabilities

This paper uses a framework of human rights to explore the high levels of bullying and abuse experienced by adults with learning disabilities. It will identify the different needs of people with different degrees of learning disability before moving on to focus on the particular needs of those with mild learning disabilities who are targeted within local communities. It goes on to suggest a need for a change in assessment practice, away from task-oriented functional assessments and towards assessments which pay greater attention to social abilities and community dynamics. In concluding, the authors argue that present policies and their underpinning principles are at times too dogmatic and call for a greater recognition of the diversity of needs and vulnerabilities which exist across the learning disability spectrum.
Intracranial hypertension in a patient preparing for gestational surrogacy with leuprolide acetate and estrogen.

O'Donnell BA. Idiopathic sclerosing orbital inflammation. Arch Ophthalmol. 2006;124:1244–1250. 3. Rootman J, McCarthy M, White V, Harris G, Kennerdell J. Idiopathic sclerosing inflammation of the orbit. A distinct clinicopathologic entity. Ophthalmology. 1994;101:570–584. 4. Liu CH, Ma L, Ku WJ, Kao LY, Tsai YJ. Bilateral idiopathic sclerosing inflammation of the orbit: a report of three cases. Chang Gung Med J. 2004;27:758–765. 5. Brannan PA. A review of sclerosing idiopathic orbital inflammation. Curr Opin Ophthalmol. 2007;18:402–404. 6. Berry-Brincat A, Rose GE. Idiopathic orbital inflammation: a new dimension with the discovery of immunoglobulin G4-related disease. Curr Opin Ophthalmol. 2012;23:415–419. 7. Cheuk W, Yuen HK, Chan AC, Shih LY, Kuo TT, Ma MW, Lo YF, Chan WK, Chan JK. Ocular adnexal lymphoma associated with IgG41 chronic sclerosing dacryoadenitis: a previously undescribed complication of IgG4-related sclerosing disease. Am J Surg Pathol. 2008;32:1159–1167.
Physiotherapy in early phase of low back pain

Low back pain (LBP) is a substantial health problem and has subsequently attracted a considerable amount of research both in the early and chronic phases. Chronic, nonspecific LBP indicates limited effectiveness from most commonly applied interventions and approaches, but it seems to be opposite in the early phase. Intervention is more effective than advice on staying active in acute LBP, leading to more rapid improvement in function, mood, quality of life, and general health. We compared physiotherapy (PT) that involved 3-7 treatment sessions based on subclassification in early phase LBP (acute and subacute LBP lasting ,3 months) to one session of PT that advised staying active, in 134 LBP patients. Low back and leg pain, disability, and days of sick-leave were evaluated. After 12 months, all groups had only mini- mal pain and disability. In the advice-only group, those patients who had radiating pain had less improvement compared with other groups, and increasing days of sick-leave because of LBP after 12 months. Compared with the advice-only group, orthopedic manual therapy and McKenzie methods seemed to be slightly more effective than one session of assessment in pain and disability.
The Retinal Nerve Fiber Layer of Patients With Neuromyelitis Optica and Chronic Relapsing Optic Neuritis is More Severely Damaged than Patients With Multiple Sclerosis

Backgroud: To compare the retinal nerve fiber layer (RNFL) in eyes of patients with relapsing remitting multiple sclerosis (RRMS), neuromyelitis optica (NMO) and chronic relapsing inflammatory optic neuritis (CRION). Methods: Evaluation of 62 patients with RRMS, NMO, and CRION in a cross-sectional study with spectral domain optical coherence tomography. Results: A total of 124 eyes were evaluated (96 RRMS, 18 NMO, and 10 CRION). Frequency of optic neuritis for each disease was: 34% for RRMS, 84% for NMO, and 100% for CRION. Visual acuity and RNFL thickness were significantly worse in NMO and CRION eyes than in RRMS, but there were no differences between NMO and CRION eyes. A RNFL of 41 &mgr;m was 100% specific for optic neuritis associated with NMO and CRION when compared to RRMS. Conclusion: This study established RNFL values to differentiate optic neuritis of RRMS from NMO and CRION. Although similarities observed between NMO and CRION eyes might suggest that they are within the same disease spectrum, it is still recommended that these 2 conditions be differentiated on clinical grounds. Optical coherence tomography serves as an additional diagnostic tool and can be used to monitor disease progression.
Cellular transplant therapies for globoid cell leukodystrophy: Preclinical and clinical observations

Globoid cell leukodystrophy (GLD) is a progressive neurodegenerative disorder caused by the deficiency of galactocerebrosidase (GALC), resulting in accumulation of toxic metabolites in neural tissues. Clinically variable based on age of onset, infantile GLD is generally a rapidly fatal syndrome of progressive neurologic and cognitive decline, whereas later‐onset GLD has a more indolent, protracted clinical course. Animal models, particularly the twitcher mouse, have allowed investigation of both the pathophysiology of and the potential treatment modalities for GLD. Cellular therapy for GLD, notably hematopoietic cell transplantation (HCT; transplantation of bone marrow, peripheral blood stem cells, or umbilical cord blood cells) from a normal related or unrelated allogeneic donor provides a self‐renewing source of GALC in donor‐derived cells. The only currently available treatment option in human GLD, allogeneic HCT, can slow the progression of the disease and improve survival, especially when performed in presymptomatic infants. Because persistent neurologic dysfunction still occurs after HCT in GLD, preclinical studies are evaluating combinations of HCT with other treatment modalities. © 2016 Wiley Periodicals, Inc.
Can Triggered Electromyography Be Used to Evaluate Pedicle Screw Placement in Hydroxyapatite-Coated Screws: An Electrical Examination

Objectives: To assess if hydroxyapatite (HA)-coated titanium pedicle screws exhibit the same electroconductive characteristics as non–HA-coated screws. Methods: Resistance measurements were obtained from a random sampling of 10 HA-coated pedicle screws and 10 non–HA-coated screws, and surgical conditions simulated. Surface resistivity measurements were taken for each screw to determine voltage drop over its entire length. Results: The non–HA-coated screws tested showed low resistive properties and proved to be an ideal conductor of electrical current. The resistive properties associated with the HA-coated pedicle screws were found to be similar to those of commonly used insulators removing the effectiveness of triggered electromyographic responses. Conclusions: Based on test results, these data suggest that the resistance value of the HA-coated screw is large enough to prevent modern Intra-Operative Monitoring (IOM) equipment from delivering the necessary current through the shank of the screw to create a diagnostic electromyographic response. Any response that would be produced would be because of shunting of electric current from the non-coated head of the screw into adjacent tissue and not through the shank of the screw. These study results suggest that HA-coated screws cannot be stimulated to assist in determining the accuracy of pedicle screw placement.
Aggressive and violent behaviors in the school environment among a nationally representative sample of adolescent youth.

BACKGROUND The purpose of this study was to describe the prevalence of aggressive and violent behaviors in the context of the school environment in a nationally representative sample of adolescent youth and to illustrate these patterns during 2001-2011. METHODS We analyzed data from 84,734 participants via the Youth Risk Behavior Surveillance System (YRBSS). Frequencies were visualized using heatmaps. One-way analyses of variance and corresponding post hoc tests helped to identify if differences in prevalence fluctuated significantly across all years. RESULTS Rates of youth feeling unsafe in their school environment, bringing weapons to school, and engaging in physical fighting on school property continue to persist. Findings illustrated that Hispanic youth and youth classified as "other" have emerged as particularly high-risk demographic subgroups over the past decade. Peer victimization and sexual victimization continue to affect girls disproportionately. CONCLUSIONS Though some variation within demographic subgroups exists, rates of aggressive and violent behaviors in the context of the school environment continue to persist. Implications for the coordinated prevention of aggressive and violent behaviors among adolescent youth are discussed and recommendations for school-based prevention efforts are identified.