Miracle-dz/UniFAR-FTUs huggingface dataset:
Transplantation of subventricular zone neural precursors induces an endogenous precursor cell response in a rat model of Parkinson's disease

Realistically, future stem cell therapies for neurological conditions including Parkinson's disease (PD) will most probably entail combination treatment strategies, involving both the stimulation of endogenous cells and transplantation. Therefore, this study investigates these two modes of neural precursor cell (NPC) therapy in concert in order to determine their interrelationships in a rat PD model. Human placental alkaline phosphatase (hPAP)‐labeled NPCs were transplanted unilaterally into host rats which were subsequently infused ipsilaterally with 6‐hydroxydopamine (6‐OHDA). The reaction of host NPCs to the transplantation and 6‐OHDA was tracked by bromodeoxyuridine (BrdU) labeling. Two weeks after transplantation, in animals transplanted with NPCs we found evidence of elevated host subventricular zone NPC proliferation, neurogenesis, and migration to the graft site. In these animals, we also observed a significant preservation of striatal tyrosine hydroxylase (TH) expression and substantia nigra TH cell number. We have seen no evidence that neuroprotection is a product of dopamine neuron replacement by NPC‐derived cells. Rather, the NPCs expressed glial cell line‐derived neurotrophic factor (GDNF), sonic hedgehog (Shh), and stromal cell‐derived factor 1 alpha (SDF1α), providing a molecular basis for the observed neuroprotection and endogenous NPC response to transplantation. In summary, our data suggests plausible synergy between exogenous and endogenous NPC actions, and that NPC implantation before the 6‐OHDA insult can create a host microenvironment conducive to stimulation of endogenous NPCs and protection of mature nigral neurons. J. Comp. Neurol. 515:102–115, 2009. © 2009 Wiley‐Liss, Inc.
The AMP analog AICAR modulates the Treg/Th17 axis through enhancement of fatty acid oxidation

T cells must tightly regulate their metabolic processes to cope with varying bioenergetic demands depending on their state of differentiation. The metabolic sensor AMPK is activated in states of low energy supply andmodulates cellular metabolism toward a catabolic state. Although this enzyme isknown tobeparticularly active in regulatory T (Treg) cells, its impact on T helper (Th)‐cell differentiation is poorly understood. We investigated the impact of several AMPK activators on Treg‐cell differentiation and found that the direct activator AICAR (5‐aminoimidazole‐4‐carboxamide ribonucleotide), but not the indirect activators metformin and 2‐deoxyglucose, strongly enhanced Treg‐cell induction by specifically enhancing Treg‐cell expansion. Conversely, Th17 generation was impaired by the agent. Further investigation of the metabolic background of our observations revealed that AICAR enhanced both cellular mitochondrogenesis and fatty acid uptake. Consistently, increased Treg induction was entirely reversible on inhibition of fatty acid oxidation, thus confirming the dependence of AICAR's effects on metabolic pathways alterations. Translating our findings to an in vivo model, we found that the substance enhanced Treg cell generation on IL‐2 complex–induced immune stimulation. We provide a previously unrecognized insight into the delicate interplay between immune cell function and metabolism and delineate a potential novel strategy for metabolism‐targeting immunotherapy. —Gualdoni, G. A. , Mayer, K. A. , Göschl, L. , Boucheron, N. , Ellmeier, W. , Zlabinger, G. J. The AMP analog AICAR modulates the Treg/Th17 axis through enhancement of fatty acid oxidation. FASEB J. 30, 3800–3809 (2016) www.fasebj. org
[Psychological relaxation effect of forest therapy: results of field experiments in 19 forests in Japan involving 228 participants].

OBJECTIVES In the present study, we aimed to clarify the psychological effects of shinrin-yoku (taking in the atmosphere of the forest) by conducting field experiments. METHODS The experiments were conducted in 19 forested and urban areas in Japan during the 2007-2010 period. Twelve male students participated at each of the 19 areas (a total of 228 persons). Subjective ratings of "comfortable-uncomfortable", "soothing-stimulating", and "natural-artificial" feelings were conducted after each of the participants had viewed the scenery for 15 min in the forested and urban areas. A postviewing questionnaire on "stressed-refreshed" feelings was also administered and the Profile of Mood State (POMS) questionnaire was employed to assess six aspects of mood before and after viewing the sceneries. RESULTS The forest environments were perceived as significantly more "comfortable", "soothing", and "natural" than the urban environments after viewing the sceneries. The score for "refreshed feeling" was also significantly higher in the forested areas. The score for the "vigor" subscale of POMS was significantly higher after viewing the scenery in the forested areas, whereas the scores for negative feelings such as "tension-anxiety", "depression-dejection", "anger-hostility", "fatigue", and "confusion" significantly decreased. CONCLUSION Collectively, these results suggest that the forest environments have significant beneficial and relaxing effects on human's moods compared with the urban environments.
Proton radiation-induced miRNA signatures in mouse blood: Characterization and comparison with 56Fe-ion and gamma radiation

Purpose: Previously, we showed that microRNA (miRNA) signatures derived from the peripheral blood of mice are highly specific for both radiation energy (γ-rays or high linear energy transfer [LET] 56Fe ions) and radiation dose. Here, we investigate to what extent miRNA expression signatures derived from mouse blood can be used as biomarkers for exposure to 600 MeV proton radiation. Materials and methods: We exposed mice to 600 MeV protons, using doses of 0.5 or 1.0 Gy, isolated total RNA at 6 h or 24 h after irradiation, and used quantitative real-time polymerase chain reaction (PCR) to determine the changes in miRNA expression. Results: A total of 26 miRNA were differentially expressed after proton irradiation, in either one (77%) or multiple conditions (23%). Statistical classifiers based on proton, γ, and 56Fe-ion miRNA expression signatures predicted radiation type and proton dose with accuracies of 81% and 88%, respectively. Importantly, gene ontology analysis for proton-irradiated cells shows that genes targeted by radiation-induced miRNA are involved in biological processes and molecular functions similar to those controlled by miRNA in γ ray- and 56Fe-irradiated cells. Conclusions: Mouse blood miRNA signatures induced by proton, γ, or 56Fe irradiation are radiation type- and dose-specific. These findings underline the complexity of the miRNA-mediated radiation response.
Training on hearing protector insertion improves noise attenuation.

PURPOSE To determine the efficacy of hearing protector insertion by comparing attenuation values measured by objective (MIRE) and subjective (REAT) methods in groups with and without training. METHODS The study included 80 male subjects assigned to experimental (with training) and control (without training) groups. The following procedures were performed: occupational history, objective and subjective assessment of hearing protectors. Only subjects in the experimental group received training and guidance on proper hearing protector insertion. RESULTS Attenuation values were significantly higher in the experimental group than in the control group at all frequencies (500, 1000, 2000, and 4000 Hz) investigated through the objective (MIRE) and subjective (REAT) methods. In addition, attenuation values in the control group were lower than those provided by the hearing protector manufacturer. CONCLUSION Both objective and subjective attenuation tests demonstrated the efficacy of training on insertion of hearing protectors because the group that received training on proper hearing protection insertion exhibited higher attenuation values than the untrained group.
Cruciferous Vegetables Consumption and Risk of Renal Cell Carcinoma: A Meta-Analysis

Previous cohort and case-control studies on the association between cruciferous vegetables consumption and risk of renal cell carcinoma have illustrated conflicting results so far. To demonstrate the potential association between them, a meta-analysis was performed. Eligible studies were retrieved via both computerized searches and review of references. The summary relative risks (RRs) with 95% confidence interval (CI) for the highest vs. the lowest consumption of cruciferous vegetables were calculated. Heterogeneity and publication bias were also evaluated. Stratified analyses were performed as well. Three cohort and 7 case-control studies were included. A significantly decreased risk with renal cell carcinoma was observed in overall cruciferous vegetables consumption group (RR = 0.73; 95% CI, 0.63–0.83) and subgroup of case-control studies (RR = 0.69; 95% CI, 0.60–0.78), but not in cohort studies (RR = 0.96; 95% CI, 0.71–1.21). No heterogeneity and publication bias were detected across studies. Our findings supported that cruciferous vegetables consumption was related to the decreased risk of renal cell carcinoma. Because of the limited number of studies, further well-designed prospective studies and researches need to be conducted to better clarify the protective effect of cruciferous vegetables on renal cell carcinoma and potential mechanism.
Effect of cerebral perfusion pressure augmentation on regional oxygenation and metabolism after head injury*

Objective:In this study we have used 15O positron emission tomography, brain tissue oxygen monitoring, and cerebral microdialysis to assess the effects of cerebral perfusion pressure augmentation on regional physiology and metabolism in the setting of traumatic brain injury. Design:Prospective interventional study. Setting:Neurosciences critical care unit of a university hospital. Patients:Eleven acutely head-injured patients requiring norepinephrine to maintain cerebral perfusion pressure. Interventions:Using positron emission tomography, we have quantified the response to an increase in cerebral perfusion pressure in a region of interest around a brain tissue oxygen sensor (Neurotrend) and microdialysis catheter. Oxygen extraction fraction and cerebral blood flow were measured with positron emission tomography at a cerebral perfusion pressure of ∼70 mm Hg and ∼90 mm Hg using norepinephrine to control cerebral perfusion pressure. All other aspects of physiology were kept stable. Measurements and Main Results:Cerebral perfusion pressure augmentation resulted in a significant increase in brain tissue oxygen (17 ± 8 vs. 22 ± 8 mm Hg; 2.2 ± 1.0 vs. 2.9 ± 1.0 kPa, p < .001) and cerebral blood flow (27.5 ± 5.1 vs. 29.7 ± 6.0 mL/100 mL/min, p < .05) and a significant decrease in oxygen extraction fraction (33.4 ± 5.9 vs. 30.3 ± 4.6 %, p < .05). There were no significant changes in any of the microdialysis variables (glucose, lactate, pyruvate, lactate/pyruvate ratio, glycerol). There was a significant linear relationship between brain tissue oxygen and oxygen extraction fraction (r2 = .21, p < .05); the brain tissue oxygen value associated with an oxygen extraction fraction of 40% (the mean value for oxygen extraction fraction in normal controls) was 14 mm Hg (1.8 kPa). The cerebral perfusion pressure intervention resulted in a greater percentage increase in brain tissue oxygen than the percentage decrease in oxygen extraction fraction; this suggests that the oxygen gradients between the vascular and tissue compartments were reduced by the cerebral perfusion pressure intervention. Conclusions:Cerebral perfusion pressure augmentation significantly increased levels of brain tissue oxygen and significantly reduced regional oxygen extraction fraction. However, these changes did not translate into predictable changes in regional chemistry. Our results suggest that the ischemic level of brain tissue oxygen may lie at a level below 14 mm Hg (1.8 kPa); however, the data do not allow us to be more specific.
Fragmented QRS Complex in Adult Patients With Ebstein Anomaly and Its Association With Arrhythmic Risk and the Severity of the Anomaly

Background—Fragmented QRS complex (fQRS) on 12-lead ECG, a marker of myocardial scar, is a predictor of arrhythmic events in patients with ischemic and nonischemic cardiomyopathy. We investigated whether the presence of fQRS is associated with the severity of the anomaly and with increased arrhythmic events in adult patients with Ebstein anomaly (EA). Methods and Results—In 51 consecutive adult patients with EA (median age, 37 years; 18 males), the severity index of EA calculated from echocardiographic data and clinical arrhythmic events were analyzed. The extent of fQRS in each patient was measured by counting the number of ECG leads showing fQRS. There were 35 (68.6%) patients with fQRS (fQRS group) and 16 (31.4%) patients without fQRS (non-fQRS group). fQRS was observed more frequently in the inferior (n=26) and precordial (n=25) leads versus the lateral leads (n=5). The patients in the fQRS group had a worse functional class, greater cardiothoracic ratios, more severe tricuspid regurgitation, larger atrialized right ventricular areas, higher EA severity scores, and more frequent arrhythmic events compared with those in the non-fQRS group. The atrialized right ventricular area showed a positive correlation with the fQRS extent (r=0.51; P<0.001). In multivariable Cox regression models, the presence of fQRS was independently associated with arrhythmic events (P=0.036). Conclusions—Fragmented QRS on 12-lead ECG was associated with larger atrialized right ventricular area and an increased risk of arrhythmic events in adult patients with EA.
Interferon beta-1b and intravenous methylprednisolone promote lesion recovery in multiple sclerosis

Objective: To determine whether lesion evolution in relapsing-remitting multiple sclerosis (RRMS) patients is altered by treatment with interferonβ-1b (IFNb-1b) or by intravenous methylprednisolone (IVMP) as measured by magnetization transfer imaging. Methods: Magnetization transfer ratios (MTR) of 225 contrast enhancing lesions (CEL), in four RRMS patients were serially determined for 12 months before and 12-18 months after contrast enhancement in a baseline vs treatment trial with IFNβ-1b. During the baseline period, 185 new CEL were identified: 76 were treated with IVMP (1 giday x 5 days) and designated steroid CEL (S-CEL); the remaining 109 were considered baseline lesions (B-CEL). During IFNβ-1b treatment, 40 CEL (IFN-CEL) were identified. After image co-registration, regions of interest (ROIs) defining new CEL were transferred to the MTR image set to determine the mean lesion MTR on each monthly exam. The lesion MTR was compared to MTR of normal appearing white matter (NAWM) on the same exam. Results: As early as 12 months prior to enhancement, the MTR of CEL was reduced compared to NAWM (mean 9.43±3.2%; P<0.001). The further reduction in MTR (28%±4.0) at the time of contrast enhancement was not significantly different for B-CEL, S-CEL or IFN-CEL. Following enhancement, lesion recovery for IFN-CEL (P=0.02) and S-CEL (P=0.002) was significantly higher than B-CEL. Conclusion: IFNβ-1b and IVMP reduce tissue damage and promote lesion recovery in RRMS patients. The additional benefit of IVMP compared to IFNβ-1b may be related to its inhibitory effect on demyelination.
A double-masked, randomized, 1-year study comparing the corneal effects of dorzolamide, timolol, and betaxolol. Dorzolamide Corneal Effects Study Group.

OBJECTIVE To compare the long-term effects of dorzolamide hydrochloride (Trusopt, Merck and Co Inc, White-house Station, NJ), timolol maleate, and betaxolol hydrochloride on corneal endothelial cell density and corneal thickness. METHODS This 1-year multicenter study was conducted in 298 patients with ocular hypertension or open-angle glaucoma who had a baseline central corneal endothelial cell density greater than 1500 cells/mm2 and central corneal thickness less than 0.68 mm in each eye. Patients were randomized to 0.5% betaxolol twice daily, 0.5% timolol twice daily, or 2.0% dorzolamide 3 times daily. Specular microscopy and ultrasonic pachymetry of the central cornea was performed at baseline and 6 and 12 months following institution of therapy. Endothelial cell densities were determined by a single masked observer. RESULTS The mean percent changes from baseline for both outcome measures were similar in all 3 treatment groups at both 6 and 12 months. After 1 year of treatment, the mean percent loss in endothelial cell density from baseline was 3.6%, 4.5%, and 4.2% for the dorzolamide, timolol, and betaxolol groups, respectively. The mean percent change from baseline for corneal thickness was 0.47%, -0.25%, and 0.39% for the dorzolamide, timolol, and betaxolol groups, respectively. CONCLUSIONS Dorzolamide is equivalent to timolol and betaxolol in terms of the change in central endothelial cell density and thickness after 1 year of therapy. All 3 treatments exhibit good long-term corneal tolerability in patients with normal corneas at baseline.
Antibacterial photodynamic treatment of periodontopathogenic bacteria with indocyanine green and near‐infrared laser light enhanced by TroloxTM

It has been shown that certain vitamins can significantly enhance the effect of photodynamic anti‐tumor therapy. Unfortunately, there is no sufficient information available about the impact of those antioxidants on antimicrobial Photodynamic Therapy (aPDT). The present study is aimed at investigating the antimicrobial effect of the dye indocyanine green (ICG) in the presence of TroloxTM, a vitamin E analogue, upon irradiation with near‐infrared (NIR) laser light (808 nm) on the gramnegative periodontopathogenic bacteria Aggregatibacter actinomycetemcomitans (A.a.), Porphyromonas gingivalis (P.g.) and Fusobacterium nucleatum (F.n.).
Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: Evidence for an antiinflammatory role for lipoprotein lipase

Increased levels of triglyceride-rich lipoproteins provoke lipid accumulation in the artery wall, triggering early inflammatory responses central to atherosclerosis like endothelial adhesion molecule expression. The endogenous mechanisms limiting such reactions remain poorly defined. Lipoprotein lipase (LPL) plays a central role in lipid metabolism by hydrolyzing triglyceride rich lipoproteins and releasing fatty acids. We found that LPL treatment reversed tumor necrosis factor α and very low-density lipoprotein (VLDL)-stimulated endothelial vascular cell adhesion molecule 1 (VCAM1) induction and VCAM1 promoter responses, thus recapitulating effects reported with synthetic peroxisome proliferator-activated receptor (PPAR) agonists. In fact, these LPL effects on VCAM1 were absent in endothelial cells isolated from PPARα-deficient mice. This finding suggests a novel antiinflammatory role for LPL. Further studies reveal specificity for PPAR activation through lipolysis in regards to lipoprotein substrate (VLDL ≫ LDL > HDL), PPAR isoform (PPARα ≫ PPARδ > PPARγ), and among fatty acid-releasing lipases. These PPAR responses required intact LPL catalytic activity. In vivo, transgenic mice overexpressing LPL had increased peroxisome proliferation, but not in the genetic absence of PPARα. Although human plasma possesses minimal PPARα activation despite containing abundant free fatty acids, marked PPARα activation is seen with human plasma after LPL is added in vitro or systemically released in vivo. These data suggest a previously uncharacterized pathway in which the key lipolytic enzyme LPL can act on circulating lipoproteins to generate PPARα ligands, providing a potentially important link between lipoprotein metabolism and distal PPARα transcriptional effects.
In vitro alteration of aortic vascular reactivity in hypertension induced by chronic NG-nitro-L-arginine methyl ester.

Chronic administration of NG-nitro-L-arginine methyl ester (L-NAME) induces a rise in blood pressure that is prevented by angiotensin I-converting enzyme inhibitors or angiotensin II receptor (type 1) blockade. Alterations in vascular reactivity in this model have not been extensively studied and could potentially be involved in the pathogenesis of L-NAME-induced hypertension. In the present work, we aimed to study the vascular reactivity and cGMP content of aortic ring segments isolated from Wistar rats treated for 3 weeks with L-NAME or L-NAME plus the converting enzyme inhibitor quinapril. Quinapril prevented the rise in blood pressure in L-NAME-treated rats although acetylcholine-induced dilation in aortic rings was suppressed and sodium nitroprusside-induced dilation was increased in both L-NAME- and L-NAME plus quinapril-treated rats. In isolated aortic ring segments, chronic L-NAME decreased the contractile response to K+ (125 mmol/L), phenylephrine, angiotensin II, the G protein stimulator AlF4-, and the protein kinase C activator phorbol dibutyrate. In contrast to the upregulated sodium nitroprusside-induced dilation, the contractile capacity of the aorta in response to angiotensin II, phenylephrine, AlF4-, K+, and phorbol dibutyrate was restored by quinapril. Aortic cGMP was lowered in rats treated with L-NAME (530 +/- 120 fmol/mg protein, n = 12, P < .05) and L-NAME plus quinapril (461 +/- 140 fmol/mg protein, n = 12, P < .05) compared with controls (1798 +/- 522 fmol/mg protein, n = 12). We hypothesize that the continuous nitric oxide blockade by L-NAME might attenuate a continuous endogenous relaxing tone and is associated with an upregulated endogenous vasoconstrictor tone in large arteries. Converting enzyme inhibition interfered more with the increased endogenous constrictor tone than with the decreased vasodilator tone in the wall of large arteries from L-NAME-treated rats.
Glycine‐receptor immunoreactivity in retinal bipolar cells is postsynaptic to glycinergic and GABAergic amacrine cell synapses

Glycinergic innervation of the synaptic terminals of mixed rod‐cone bipolar cells in the goldfish retina was investigated by electron microscopical immunocytochemistry with presynaptic and postsynaptic markers for glycinergic neurons: a monoclonal antibody (mAb 7A) against the 93 kDa subunit of the strychnine‐sensitive glycine receptor and polyclonal antisera against a glycine/BSA conjugate. Conventional “glycinergic” synaptic contacts, made by amacrine cell processes, accounted for 7–10% of the input to the bipolar cell terminals, whether determined by glycine receptor immunoreactivity (GlyR‐IR) or glycine‐IR. In addition to the conventional synapses, the large bipolar cell terminals in the proximal inner plexiform layer (type Mb) gave rise to spinules (spine‐like protrusions) that invaginated into presynaptic amacrine cell processes. Although 85% of the spinules were GlyR‐IR, no spinules were postsynaptic to glycine‐IR processes; yet 86% of the spinules were postsynaptic to GAD‐IR processes, suggesting that the GlyR‐IR spinules were postsynaptic to GABAergic terminals. Furthermore, a single amacrine cell process could make two synapses with an Mb terminal: a GlyR‐IR contact onto a spinule and a conventional synapse that was not GlyR‐IR. We suggest that glycinergic innervation of bipolar cell terminals involves conventional glycinergic synapses as well as an unconventional situation in which GABA and glycine may interact in as yet undetermined manner, perhaps by potentiatio.
18‐FDG‐PET in the initial staging of sinonasal malignancy

The utility of fluorine‐18 fluorodeoxyglucose‐positron emission tomography (PET) has been gradually defined for most head and neck cancers, However, its utility in the initial diagnosis of sinonasal malignancy has not been extensively studied. The aim of this study was to determine if PET scanning accurately diagnoses and stages malignant sinonasal lesions and if maximum standard uptake value (SUVmax) correlates with clinically advanced disease.