Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypersomnia following paramedian thalamic stroke: A report of 12 patients

Paramedian thalamic stroke (PTS) is a cause of organic hypersomnia, which in the absence of systematic sleep‐wake studies has been attributed to disruption of ascending activating impulses and considered a “earoused” state. However, an increasing amount of data suggests a role of the thalamus in sleep regulation and raises the possibility that a sleep disturbance contributes to hypersomnia in PTS. We evaluated 12 patients with magnetic resonance imaging‐proven isolated PTS and hypersomnia with 10 to >20 hours of sleep behavior per day. Nocturnal polysomnographic findings paralleled the severity of hypersomnia. All subjects had increased stage 1 NREM sleep, reduced stage 2 NREM sleep, and reduced numbers of sleep spindles. In patients with severe hypersomnia, slow‐wave (stages 3‐4) NREM sleep was often reduced, but there were no major REM sleep alterations. Daytime sleep behavior was associated mostly with stage 1 sleep by electroencephalogram; there was no correlation between hypersomnia and results of nap tests. We conclude that hypersomnia following PTS is accompanied by deficient arousal during the day and insufficient spindling and slow‐wave sleep production at night. These observations support the hypothesis of a dual role of the paramedian thalamus as “final common pathway” for both maintenance of wakefulness and promotion of NREM sleep.
Prevention of metastasis by inhibition of the urokinase receptor.

The plasminogen activator urokinase (u-PA) mediates proteolysis by a variety of human tumor cells. Competitive displacement of u-PA from cellular binding sites results in decreased proteolysis in vitro, suggesting that the cell surface is the preferred site for u-PA-mediated protein degradation. We studied the effect of u-PA receptor blockade on the metastatic capacity of human PC3 prostate carcinoma cells, using transfectants which expressed chloramphenicol acetyl-transferase (CAT). Eight weeks after subcutaneous inoculation of these cells into nude mice, CAT activity was detected in regional lymph nodes, femurs, lungs, and brain, thereby mimicking the organ tropism observed for naturally occurring metastases of prostate cancer. In a second transfection, CAT-expressing PC3 cells received cDNA encoding a mutant u-PA (Ser356-->Ala) which lacks enzymatic activity but which retains full receptor binding affinity. Three mutant u-PA expressors, each with < 5% of wild-type cell-associated u-PA activity, were compared in vivo with independently derived controls. Primary tumor growth was similar in each group of animals and all tumors expressed comparable CAT activity. In contrast, metastasis (as assessed by CAT activity) was markedly inhibited when cell surface u-PA activity was blocked. Levels of CAT activity were reduced by a factor of > 300 in regional lymph nodes, 40-100 in brain tissue, and 10-20 in lung tissue. Metastatic capacity was inhibited similarly when animals were given intermittent intraperitoneal injections of a u-PA/IgG fusion protein capable of displacing u-PA activity from the tumor cell surface. Our results indicate that cell surface u-PA activity is essential to the metastatic process. In addition, the assay system employed in these experiments may be generally useful in testing other therapeutic modalities to limit the spread of primary tumors.
Benchmark dose and the three Rs. Part II. Consequences for study design and animal use

Abstract OECD test guidelines for standard toxicity studies prescribe (minimal) numbers of animals, but these are not substantiated by a quantitative analysis of the relationship between number of animals and the required performance of the associated study design. This paper provides a general approach of how this relationship may be established and discusses the approach in more detail by focusing on the three typical repeated-dose studies (subacute, subchronic, and chronic). Quantitative results derived from simulation studies, including some new results, are summarized and their consequences for study guidelines are discussed. The currently prescribed study designs for repeated-dose studies do not appear to be sufficient when the NOAEL is used for evaluating the data—the probability of not detecting toxicologically significant effects is high. The ensuing need for increasing the number of animals may be avoided by replacing the NOAEL approach by the BMD approach as it increases the probability of detecting the same effects without increasing the number of animals. Hence, applying the BMD approach will result in a virtual reduction in the number of animals. Further, the BMD approach allows for a real reduction in the number of animals on various grounds. It allows for analyzing combined similar datasets, resulting in an increase in precision, which can be translated in animal reduction while keeping the same precision. In addition, applying the BMD approach may be expected to result in animal reduction in the long run, as it allows for distributing the same number of animals over more doses without loss of precision. The latter will reduce the need to repeat studies due to unfortunate dose location.
Comparative study on the ALA photodynamic effects of human glioma and meningioma cells

The purpose of this study was to compare the differential susceptibility to photodynamic therapy (PDT) mediated damage in human U‐105MG glioma cells and CH‐157MN meningioma cells in vitro using 5‐aminolevulinic acid (ALA) as photosensitizer, and to determine if growth factors would enhance PDT‐mediated damage of these cells.
Erasure of kinase phosphorylation in astrocytes during oxygen–glucose deprivation is controlled by ATP levels and activation of phosphatases

We have examined the relationship between adenosine triphosphate (ATP) concentration and loss of maintenance of kinase‐signalling cascades in primary cortical astrocytes during oxygen–glucose deprivation (OGD) as this may constitute an irreversible step that commits astrocytes to cell death. We report that the phosphorylation of Akt, ERK, JNK and p38 kinases, whose activities depend on serine, threonine and tyrosine phosphorylation, were all increased during OGD. All these phosphorylations were reduced to below detection limits when ATP levels were less than 10% of normal levels. Using ERK and Akt as representative examples, we show that this erasure is not irreversible as both ERK and Akt phosphorylations can be partially restored by addition of glucose under anoxic conditions. We further investigated whether OGD caused any change in phosphatase activity. The PP1/PP2A phosphatase inhibitors okadaic acid and caliculyn A, but not cyclosporine A, delayed the removal of ERK and Akt phosphorylation under OGD. By comparing the extent of phosphorylation increase under OGD and normoxic conditions, we calculate that phosphatase activity was increased by approximately 3.6‐fold during OGD. These data show that ATP levels control an important checkpoint in kinase function, and that ATP levels may need to be considered when studies of kinase function in relation to OGD are conducted.
Donepezil: a clinical review of current and emerging indications

This article reviews the piperidine derivative, donepezil hydrochloride (E2020, Aricept®), a reversible central acetylcholinesterase inhibitor currently approved for treatment of mild-to-moderate Alzheimer’s disease. Donepezil is well absorbed orally, unaffected by food or by time of administration; it reaches therapeutic levels in doses of 5 – 10 mg/day and peak plasma concentrations are obtained 3 – 4 h after oral administration. A single bedtime dose is recommended due to the long elimination half-life of the drug (70 h). Donepezil does not cause liver toxicity or significant drug interactions and is relatively well-tolerated. Initial side effects include nausea, vomiting, diarrhoea, insomnia, muscle cramps, fatigue, anorexia and syncope. Caution is advised in patients with bradycardia. Long-term use of donepezil in AD has been found to delay nursing-home placement and to result in caregiver respite. Donepezil also slows deterioration of cognition and global function in patients with moderate-to-severe AD, with improvement of abnormal behaviours. In addition to AD, donepezil demonstrates significant improvement in cognition, global function and activities of daily living in comparison with placebo-treated patients with vascular dementia and has potential therapeutic benefit for other neurological conditions.
An investigation of the association of benzodiazepines and other hypnotics with the incidence of falls in the elderly

Clinical and medication data from 2,878 admissions to a Department for Care of the Elderly were examined retrospectively to determine the association between the administration of hypnotics/benzodiazepines and the incidence of falls. Only lorazepam prescribed to females and nitrazepam prescribed to males were associated with a significantly increased incidence of falls. Women fell significantly more frequently than men, and 7.5% of falls resulted in fractures. Stroke was the most common major diagnosis in fall‐cases, followed by infection, Parkinsonism and confusion.
First nationwide survey of the health of schoolchildren in Chad

Survey data are presented from a nationwide survey of the health of schoolchildren in Chad. The country was stratified into distinct ecological zones based on satellite sensor environmental data. Twenty schools were visited and 1024 children aged between 6 and 15 years were included in the study. The overall prevalence of stunting, underweight, anaemia and goitre was 18.7, 16.5, 25.1 and 23.3%, respectively. Schistosoma haematobium, Schistosoma mansoni and hookworm were the only helminth species found with prevalences of 13.2, 1 and 32.7%, respectively. A greater proportion of boys were stunted, underweight, anaemic and infected with S. haematobium and hookworm than girls. Older children were more stunted, underweight and infected with S. haematobium and hookworm than younger children, but less anaemic. The prevalence of infection showed marked geographical heterogeneity, with hookworm prevalence being highest in the Sudanian and tropical zone, and S. haematobium being most prevalent in the Sahelian zone and the Logone and Chari basins in the west of the country. These data show that there is a high prevalence of helminth infection in Chad, but that treatment for S. haematobium and hookworm should be targeted to different geographical areas.
Heparin Potentiates the in Vivo Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2*

Although bone morphogenetic proteins (BMPs) are clinically useful for bone regeneration, large amounts are required to induce new bone formation in monkeys and humans. We found recently that heparin stimulates BMP activity in vitro (Takada, T., Katagiri, T., Ifuku, M., Morimura, N., Kobayashi, M., Hasegawa, K., Ogamo, A., and Kamijo, R. (2003) J. Biol. Chem. 278, 43229-43235). In the present study, we examined whether heparin enhances bone formation induced by BMPs in vivo and attempted to determine the molecular mechanism by which heparin stimulates BMP activity using C2C12 myoblasts. Heparin enhanced BMP-2-induced gene expression and Smad1/5/8 phosphorylation at 24 h and thereafter, although not within 12 h. Heparitinase treatment did not affect the response of cells to BMP-2. In the presence of heparin, degradation of BMP-2 was blocked, and the half-life of BMP-2 in the culture medium was prolonged by nearly 20-fold. Although noggin mRNA was induced by BMP-2 within 1 h regardless of the presence of heparin, noggin failed to inhibit BMP-2 activity in the presence of heparin. Furthermore, simultaneous administration of BMP-2 and heparin in vivo dose-dependently induced larger amounts of mineralized bone tissue compared with BMP-2 alone. These findings clearly indicate that heparin enhances BMP-induced osteoblast differentiation not only in vitro but also in vivo. This study indicates that heparin enhances BMP-induced osteoblast differentiation in vitro and in vivo by protecting BMPs from degradation and inhibition by BMP antagonists.
Cinacalcet Treatment for Secondary Hyperparathyroidism in Dialysis Patients: An Observational Study in Routine Clinical Practice

Background: Cinacalcet reduces intact parathyroid hormone (iPTH), Ca and P serum levels in patients with secondary hyperparathyroidism (SHPT). Methods: This Spanish, multicenter, observational, retrospective study collected data from SHPT dialysis patients 12 weeks before and up to 72 weeks after starting cinacalcet in clinical practice. Results: Data from 428 patients with uncontrolled SHPT despite receiving standard of care (29% with baseline iPTH 501–800 pg/ml; 51% with >800 pg/ml) were collected. Percentages of patients within National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets at baseline and 72 weeks were: iPTH, 0 versus 32.5% (p < 0.05); Ca, 40.1 versus 50% (p < 0.05); P, 47.7 versus 53.8% (p = 0.162). Vitamin D sterol use decreased from 53.3% at baseline to 36.7% at 72 weeks (p < 0.05). The mean ± SD cinacalcet dose at 72 weeks was 44.0 ± 25.8, 51.7 ± 31.3 and 57.1 ± 37.0 mg for patients with baseline iPTH 301–500, 501–800 or >800 pg/ml, respectively. The main adverse reactions were nausea (5.4%), dyspepsia (5.1%) and vomiting (3.7%). Conclusions: The introduction of cinacalcet improved the routine clinical management of SHPT in a large cohort of Spanish dialysis patients. Cinacalcet is effective and well tolerated regardless of disease severity, and maintains its efficacy over 72 weeks.
Search for the optimal channel architecture for 0.18/0.12 /spl mu/m bulk CMOS experimental study

Varied advanced architectures for 0.18/0.12 CMOS are investigated experimentally. Performances of heavy ion implanted, epitaxial and/or SiGe channels are compared through their electrical and physical characteristics. Conclusions on optimal 0.18/0.12 /spl mu/m channel architectures are drawn with respect to different applications. Very promising transport properties in SiGe channels are reported.
A CD3+ count‐based thymoglobulin induction regimen permits delayed introduction of calcineurin inhibitors in kidney transplantation

Withholding calcineurin inhibitors (CNIs) can be considered when graft function is inadequate following kidney transplantation (KT). Thymoglobulin (rATG) can be used to prevent acute rejection while CNIs are being withheld. Here, we report our results of a novel CNI‐sparing induction protocol, which utilizes a CD3+ cell count‐based rATG treatment regimen when delayed graft function (DGF) develops in the immediate postoperative period.
Increased incidence of postoperative nausea and vomiting without additional analgesic effects when a low dose of intravenous fentanyl is combined with a caudal block

Background: The use of opioids is known to increase the incidence of postoperative nausea and vomiting (PONV). In spite of this, administration of low doses of an opioid during anaesthesia is common practice, even if a regional anaesthetic technique is used. This study was designed to estimate the effects of intraoperative intravenous administration of fentanyl on PONV in paediatric daycase surgery.
Distinct Aging Effects on Motion Repulsion and Surround Suppression in Humans

Elderly exhibit accumulating deficits in visual motion perception, which is critical for humans to interact with their environment. Previous studies have suggested that aging generally reduces neuronal inhibition in the visual system. Here, we investigated how aging affects the local intra-cortical inhibition using a motion direction discrimination task based on the motion repulsion phenomenon. Motion repulsion refers to the phenomenon by which observers overestimate the perceived angle when two superimposed dot patterns are moving at an acute angle. The misperception has been interpreted as local mutual inhibition between nearby direction-tuned neurons within the same cortical area. We found that elderly exhibited much stronger motion repulsion than young adults. We then compared this effect to how aging affects the global inter-cortical inhibition by adopting the surround suppression paradigm previously used by Betts et al. (2005). We found that elderly showed less change in the discrimination threshold when the size of a high-contrast drifting Gabor was increased, indicating reduced surround suppression compared to young adults. Our results indicate that aging may not always lead to a decrease of neuronal inhibition in the visual system. These distinct effects of aging on inhibitory functions might be one of the reasons that elderly people often exhibit deficits of motion perception in a real-world situation.
Protective effects of curcumin against oxidative damage on skin cells in vitro: its implication for wound healing.

BACKGROUND Curcumin, isolated from turmeric, has been known to possess many pharmacologic properties. It has been proven to exhibit remarkable anticarcinogenic, anti-inflammatory, and antioxidant properties. Turmeric curcumin may be a good potential agent for wound healing. METHODS To further understand its therapeutic mechanisms on wound healing, the antioxidant effects of curcumin on hydrogen peroxide (H2O2) and hypoxanthine-xanthine oxidase induced damage to cultured human keratinocytes and fibroblasts were investigated. Cell viability was assessed by colorimetric assay and quantification of lactate dehydrogenase release. RESULTS Exposure of human keratinocytes to curcumin at 10 microg/mL showed significant protective effect against hydrogen peroxide. Interestingly, exposure of human dermal fibroblasts to curcumin at 2.5 microg/mL showed significant protective effects against hydrogen peroxide. No protective effects of curcumin on either fibroblasts or keratinocytes against hypoxanthine-xanthine oxidase induced damage were found in our present studies. CONCLUSION The findings indicate that curcumin indeed possessed powerful inhibition against hydrogen peroxide damage in human keratinocytes and fibroblasts.
Retrograde popliteal access as bail‐out strategy for challenging occlusions of the superficial femoral artery: A multicenter registry

Background: The concomitant use of femoral and popliteal accesses has been recommended for challenging superficial femoral artery (SFA) occlusions, but no comprehensive comparison of this approach to a strategy of femoral access only is available. We thus aimed to appraise the risk‐benefit balance of retrograde popliteal access as bail‐out strategy for SFA occlusions. Methods: Consecutive patients with symptomatic SFA occlusion and undergoing percutaneous revascularization were enrolled. We distinguished patients in whom retrograde popliteal access was required as bail‐out strategy versus those not requiring such access. The primary end‐point was procedural success. Results: A total of 130 patients (152 limbs) were included, with 23 patients (25 limbs) requiring retrograde popliteal access. Occlusion length was 20.6 ± 8.8 cm in those requiring popliteal access versus 18.5 ± 8.5 cm in those without popliteal access, with TASC C/D lesions in 23 (92%) versus 106 (83%). Procedural success was achieved in 92 out of 107 patients (86.0%) treated with a standard approach and 22 out of 23 patients (95.7%) treated with retrograde popliteal access (total 114 out of 130 [87.7%]) and 112 out of 127 limbs (88.2%) and 24 out of 25 limbs (96.0%), respectively (total 136 out of 152 [89.5%]). No significant increase in early or long‐term adverse events was associated with retrograde popliteal access. Conclusions: Whenever standard access sites do not enable successful recanalization of SFA occlusions, retrograde popliteal access can be safely and effectively envisioned as bail‐out strategy. © 2012 Wiley Periodicals, Inc.
Disappearance of Steroid Hormone Dependency During Malignant Transformation of Ovarian Clear Cell Cancer

Summary:Ovarian clear-cell carcinoma (OCCA) and ovarian endometrioid carcinoma (OEMC) are often associated with endometriosis. This study determined the immunohistochemical expression of steroid hormone receptors and cancer-related genes in OCCA and OEMC specimens containing endometriosis and atypical endometriosis. Pathological progression from endometriosis to atypical endometriosis to carcinoma was identified in 4 of 22 OCCAs and 4 of 16 OEMCs. Using paraffin-embedded tissue samples, expression and changes in expression for estrogen receptors (ERs) and progesterone receptors (PRs) were examined in relation to the observed pathological changes. A gradual reduction in ERα and PRA expression was observed with malignant transformation from endometriosis to atypical endometriosis to OCCA. In OEMC, ERα expression increased with malignant transformation. In conclusion, reductions in ERα and PRA expression were observed with progression from endometriosis to atypical endometriosis in OCCA specimens. Disappearance of hormone dependency might therefore be associated with malignant transformation to OCCA.
Measurements of the Complex Permittivity of Low Loss Polymers at Frequency Range From 5 GHz to 50 GHz

Complex permittivity of Polytetrafluoroethylene (PTFE), Polypropylene (PP), Polyethylene (PE) and cross-linked Polystyrene (Rexolite), has been measured at frequency range from 5 GHz to 50 GHz. Measurements have been performed in two cylindrical cavities employing several quasi <inline-formula> <tex-math notation="LaTeX">$\text{TE}_{0 \mathrm{mn}}$</tex-math></inline-formula> modes excited in samples under test. Measurement uncertainties for the real part of permittivity were <inline-formula> <tex-math notation="LaTeX">$\pm$</tex-math></inline-formula>0.5% while for the imaginary part of permittivity in the range from <inline-formula> <tex-math notation="LaTeX">$\pm$</tex-math></inline-formula>8% for the lowest loss materials to <inline-formula> <tex-math notation="LaTeX">$\pm$</tex-math></inline-formula>3% for Rexolite. It has been confirmed that the real part of permittivity of all measured polymers is constant in the microwave frequency spectrum to within measurement uncertainties, while the dielectric loss tangent values vary with frequency
Pigmentation in Anuran Testes: Anatomical Pattern and Variation

In amphibians, pigmented cells are present in several organs, composing an extracutaneous pigmentary system. Seventeen species from two families were studied to develop a protocol for pigmentary classification. The amount and distribution of these cells are variable, allowing the establishment of anatomical patterns for visceral pigmentation in anuran testes. Anat Rec 2009. © 2008 Wiley‐Liss, Inc.
Access to the online evidence base in general practice: a survey of the Northern and Yorkshire Region.

AIMS To assess the awareness and use of NHSnet within general practice. To investigate the presence of skills necessary to maximize the benefits of NHSnet connections. METHODS Postal survey of general practice staff in the Northern and Yorkshire Region. RESULTS At least one completed questionnaire was obtained from 65% of the general practices surveyed, and the individual response rate to the general practice survey was 44%. Ninety per cent of all respondents reported that their practice was connected to the NHSnet, with 59% of respondents reporting that they use NHSnet at least once a week. Although NHSnet was used to search for research information or guidance, all respondents in this survey still reported greater access to and use of paper-based information resources. Respondents indicated that they still needed further training on how to use NHSnet (42%), how to search the Internet (31%) and how to search electronic databases such as medline (49%). CONCLUSIONS Since our 1999 survey, reported NHSnet connectivity has increased greatly, with a majority of respondents reporting that they use NHSnet at least once a week. Although encouraging, this level of usage suggests that using the Internet/NHSnet to find research has yet to become a core activity in general practice.