Miracle-dz/UniFAR-FTUs huggingface dataset:
The Phosphodiesterase 3 Inhibitor Cilostazol Dilates Large Cerebral Arteries in Humans without Affecting Regional Cerebral Blood Flow

Cilostazol, an inhibitor of phosphodiesterase (PDE) type 3, is used clinically in peripheral artery disease. PDE3 inhibitors may be clinically useful in the treatment of delayed cerebral vasospasm after subarachnoid hemorrhage. The authors present the first results on the effect of cilostazol on cerebral hemodynamics in normal participants. In this double-blind, randomized, crossover study, 200 mg cilostazol or placebo was administered orally to 12 healthy participants. Cerebral blood flow was measured using 133Xe inhalation and single photon emission computerized tomography. Mean flow velocity in the middle cerebral arteries (VMCA) was measured with transcranial Doppler, and the superficial temporal and radial arteries diameters were measured with ultrasonography. During the 4-hour observation period, there was no effect on systolic blood pressure (P = 0.28), but diastolic blood pressure decreased slightly compared with placebo (P = 0.04). VMCA decreased 21.5 ± 5.7% after cilostazol and 5.5 ± 12.2% after placebo (P = 0.02, vs. placebo), without any change in global or regional cerebral blood flow. The superficial temporal artery diameter increased 17.6 ± 12.3% (P < 0.001 vs. baseline) and radial artery diameter increased 12.6 ± 8.6% (P < 0.001 vs. baseline). Adverse events, especially headache, were common. The findings suggest that cilostazol is an interesting candidate for future clinical trials of delayed cerebral vasospasm.
Microcontact Peeling as a New Method for Cell Micropatterning

Micropatterning is becoming a powerful tool for studying morphogenetic and differentiation processes of cells. Here we describe a new micropatterning technique, which we refer to as microcontact peeling. Polydimethylsiloxane (PDMS) substrates were treated with oxygen plasma, and the resulting hydrophilic layer of the surface was locally peeled off through direct contact with a peeling stamp made of aluminum, copper, or silicon. A hydrophobic layer of PDMS could be selectively exposed only at the places of the physical contact as revealed by water contact angle measurements and angle-resolved X-ray photoelectron spectroscopy, which thus enabled successful micropatterning of cells with micro-featured peeling stamps. This new micropatterning technique needs no procedure for directly adsorbing proteins to bare PDMS in contrast to conventional techniques using a microcontact printing stamp. Given the several unique characteristics, the present technique based on the peel-off of inorganic materials may become a useful option for performing cell micropatterning.
Failure modes characterization of impacted carbon fibre reinforced plastics laminates under compression loading using acoustic emission

Composite laminates have low resistance under dynamic loading, particularly impact loading. A low-velocity impact on laminated composites causes various types of damage, such as delamination, fibre breakage, matrix cracking and fibre matrix interfacial debonding. Post-impact compressive strength is one of the greatest weaknesses in carbon fibre reinforced plastics laminates. After impact, due to the delaminations present in the laminates, local instability is triggered, which ultimately reduces considerably their residual strength. In this work, symmetric cross ply carbon fibre reinforced plastics laminates [(0°/90°)2]12 were subjected to falling weight impact at two different velocities, 2.5 and 3.5 m/s. Compression after impact studies showed substantial differences in failure mode between the two cases, passing from end crushing to crack propagation with higher impact energy. Acoustic emission technique was able to confirm this result and characterize the different types of failure modes during compression after impact test, in particular by frequency distribution.
Investigating neighborhood and area effects on health.

The past few years have witnessed an explosion of interest in neighborhood or area effects on health. Several types of empiric studies have been used to examine possible area or neighborhood effects, including ecologic studies relating area characteristics to morbidity and mortality rates, contextual and multilevel analyses relating area socioeconomic context to health outcomes, and studies comparing small numbers of well-defined neighborhoods. Strengthening inferences regarding the presence and magnitude of neighborhood effects will require addressing a series of conceptual and methodological issues. Many of these issues relate to the need to develop theory and specific hypotheses on the processes through which neighborhood and individual factors may jointly influence specific health outcomes. Important challenges include defining neighborhoods or relevant geographic areas, identifying significant area or neighborhood characteristics, specifying the role of individual-level variables, incorporating life-course and longitudinal dimensions, combining a variety of research designs, and avoiding reductionism in the way in which "neighborhood" factors are incorporated into models of disease causation and quantitative analyses.analyses.
Microsatellite instability, prognosis and metastasis in gastric cancers from a low‐risk population

We examined 169 cases of gastric adenocarcinoma for microsatellite instability (MSI), using a panel of 8 microsatellite markers. Of these cases, 142 were from the United States, a country of relatively low risk for gastric cancer. Comparing microdissected tumors to normal cells from the same patient, we classified tumors as being microsatellite‐stable (MSS) or having a low frequency of MSI (MSI‐L, up to 30% of markers different in the tumor) or a high frequency of MSI (MSI‐H, 30% or more of markers different). Among our American cases, we identified 26 (18.2%) showing MSI‐H and 15 (10.6%) showing MSI‐L. Twenty cases were from Korean patients, and they showed no significant differences in proportions of MSI‐H and MSI‐L from the American cases. MSI‐H tumors in the American patients were characterized by elevated frequencies of band shifts in repeat sequences of the BAX (50%), transforming growth factor‐β receptor type II (TGFβRII, 68.9%), β2‐microglobulin (21.4%) and E2F4 (51.7%) genes. Alterations in E2F4 in MSI‐H tumors were always integral multiples of 3 nucleotides lost or gained, which would not cause a frameshift mutation, and within the range of normal polymorphisms for this sequence. North American patients (n = 127) with MSI‐H and MSI‐L tumors had a longer median survival of 541 days and 587 days, respectively, compared to 265 days for patients with MSS tumors (p = 0.027). This survival difference may result from a significantly greater tendency for metastases in the MSS group (p = 0.031). Int. J. Cancer 89:444–452, 2000. © 2000 Wiley‐Liss, Inc.
Inactivation of the PVN during hypoglycemia partially simulates hypoglycemia-associated autonomic failure.

The anatomic connections of the paraventricular nucleus of the hypothalamus (PVN) are such that it is ideally situated to modulate and/or control autonomic responses to a variety of stressors, including hypoglycemia. In our experimental model of hypoglycemia-associated autonomic failure (HAAF), a syndrome in which the counterregulatory response to hypoglycemia is partially compromised via unknown mechanisms, activation of the PVN is blunted (15). We hypothesized that this blunted PVN activation during HAAF may be sufficient to cause the impaired counterregulatory response. To test this hypothesis, we anesthetized the PVN with lidocaine during insulin-induced hypoglycemia in rats and measured counterregulatory hormone levels. PVN inactivation decreased indexes of the sympathoadrenal response (plasma epinephrine and norepinephrine) and the hypothalamic-pituitary axis response (ACTH). Inactivation decreased the peak epinephrine response to hypoglycemia by almost half (-42 +/- 6% from control; P = 0.04) and the peak norepinephrine response by 34 +/- 5% (P = 0.01). The peak plasma ACTH levels attained were suppressed by 35 +/- 6% (P = 0.02). Adrenal corticosterone and pancreatic glucagon responses were not impaired. This pattern of neuroendocrine response is unlike that previously seen with our HAAF model. Control infusions of lidocaine >or=1 mm anterior or posterior to the PVN did not simulate this neuroendocrine pattern. Thus it appears that decreased PVN activation, as occurs with HAAF, may be involved in specific components of HAAF (i.e., blunting the sympathoadrenal and hypothalamic-pituitary-adrenocortical axis response), but not in others (i.e., blunting the glucagon response).
Comparison of clomipramine and fluoxetine treatment of dogs with tail chasing

Summary Objective: The aim of the study was to determine the response to treatment with clomipramine and fluoxetine in dogs with tail chasing. Material and methods: Twenty-five client owned dogs with tail chasing were included in this study. Diagnosis of tail chasing was made on the basis of the dog’s behavioral history, clinical signs, and results of laboratory parameters. The study had a randomized, placebo-controlled, double-blind design. Dogs were allocated to three groups. During 12 weeks, dogs of one group were given 2 mg/kg clomipramine hydro-chloride orally, dogs of the second group received 1 mg/kg fluoxetine orally and placebo was administered to control dogs. Changes in signs of tail chasing were weekly reported by the owners. Treatment was assessed in four intervals: weeks 1–3, 4–6, 7–9, and weeks 10–12, respectively. Results: German shepherd dogs and Anatolian sheepdogs were overrepresented. In all four intervals improvement of tail chasing did not differ significantly between clomipramine and fluoxetine (p > 0.05). Improvement of behavior in the clomipramine group was significantly better than in the placebo group between weeks 1–3 and 4–6 and between weeks 7–9 and 10–12 (p < 0.05). Furthermore, there was a significantly better improvement in the fluoxetine group between weeks 7–9 and weeks 10–12 when compared to the placebo group (p < 0.05). Conclusion and clinical relevance: Clomipramine and fluoxetine seem to be equally effective in the treatment of tail chasing. Treated dogs responded well to the drugs and both drugs did not show superiority over each other.
A Major Role for Mammals in the Ecology of Mycobacterium ulcerans

Background Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU), a destructive skin disease found predominantly in sub-Saharan Africa and south-eastern Australia. The precise mode(s) of transmission and environmental reservoir(s) remain unknown, but several studies have explored the role of aquatic invertebrate species. The purpose of this study was to investigate the environmental distribution of M. ulcerans in south-eastern Australia. Methodology/Principal Findings A range of environmental samples was collected from Point Lonsdale (a small coastal town southwest of Melbourne, Australia, endemic for BU) and from areas with fewer or no reported incident cases of BU. Mycobacterium ulcerans DNA was detected at low levels by real-time PCR in soil, sediment, water residue, aquatic plant biofilm and terrestrial vegetation collected in Point Lonsdale. Higher levels of M. ulcerans DNA were detected in the faeces of common ringtail (Pseudocheirus peregrinus) and common brushtail (Trichosurus vulpecula) possums. Systematic testing of possum faeces revealed that M. ulcerans DNA could be detected in 41% of faecal samples collected in Point Lonsdale compared with less than 1% of faecal samples collected from non-endemic areas (p<0.0001). Capture and clinical examination of live possums in Point Lonsdale validated the accuracy of the predictive value of the faecal surveys by revealing that 38% of ringtail possums and 24% of brushtail possums had laboratory-confirmed M. ulcerans skin lesions and/or M. ulcerans PCR positive faeces. Whole genome sequencing revealed an extremely close genetic relationship between human and possum M. ulcerans isolates. Conclusions/Significance The prevailing wisdom is that M. ulcerans is an aquatic pathogen and that BU is acquired by contact with certain aquatic environments (swamps, slow-flowing water). Now, after 70 years of research, we propose a transmission model for BU in which terrestrial mammals are implicated as reservoirs for M. ulcerans.
In vivo endothelial dysfunction characterizes patients with impaired fasting glucose.

OBJECTIVE The American Diabetes Association has recently defined a new category of abnormal glucose homeostasis called "impaired fasting glucose" (IFG), where glucose levels do not meet the criteria of diabetes but are too high to be considered normal. We determined whether endothelial dysfunction is a characteristic of subjects with IFG. RESEARCH DESIGN AND METHODS In vivo vasodilatory responses to intra-arterial infusions of endothelium-dependent (acetylcholine [ACh]) and -independent (sodium nitroprusside [SNP]) vasoactive agents were determined in 17 IFG subjects (age 63 +/- 1 years, BMI 26.5 +/- 0.8 kg/m2, serum LDL cholesterol 3.5 +/- 0.2 mmol/l) with fasting plasma glucose levels of 117 +/- 1 mg/dl and in 12 subjects with normal fasting plasma glucose concentrations. RESULTS The blood-flow response to the low dose of ACh was 46% (5.9 +/- 0.7 vs. 10.9 +/- 1.3 ml.dl-1.min-1, IFG vs. normal, P < 0.01) and to the high dose was 31% (9.1 +/- 1.2 vs. 13.2 +/- 1.5 ml.dl-1.min-1, P < 0.05, respectively) lower in the IFG than in the normal subjects. In contrast, blood-flow responses to both low (7.8 +/- 0.5 vs. 9.0 +/- 0.9 ml.dl-1.min-1, IFG vs. normal, NS) and high (11.6 +/- 1.2 vs. 12.3 +/- 1.3 ml.dl-1.min-1, NS, respectively) doses of SNP were comparable. The ratio of endothelium-dependent to -independent blood flow was 40% lower in the IFG (0.75 +/- 0.1) than in the normal (1.24 +/- 0.1, P < 0.001) subjects. Both fasting plasma glucose (r = -0.48, P < 0.01) and glycosylated hemoglobin (r = -0.42, P < 0.05) were inversely correlated with endothelium-dependent vasodilation but not with other parameters, such as weight, blood pressure, or lipids. CONCLUSIONS We conclude that vascular dysfunction is associated with abnormal, although nondiabetic, glucose homeostasis.
Parental Scaffolding of Young Children's Spatial Communication

Two studies documented and evaluated parental scaffolding of 3- and 4-year-olds' spatial communication. In Study 1, children gave directions to parents about locations of objects. Three-year-olds gave ambiguous directions more often than 4-year-olds, and parents used directive prompts more often with 3-year-olds than 4-year-olds, Study 2 compared the effectiveness of parental prompts in a controlled experiment. Each time children gave ambiguous directions, they were given either a directive prompt, nondirective prompt, or no prompt. Both age groups benefitted from directive prompts, but 3-year-olds benefitted less than 4-year-olds from nondirective prompts. Discussion focuses on parents' sensitivity to children's scaffolding needs and on developmental differences in children's responses to scaffolding. The field of cognitive development has amassed a rich store of information about developmental differences in children's thinking and about the factors that account for these differences. Far less attention, however, has been devoted to understanding how cognitive change occurs (Siegler, 1993). In particular, little is known about the kinds of experiences that lead to cognitive change in children. As others have pointed out, one type of experience that may play an important role in children's cognitive development is guidance from older, more experienced individuals such as parents (Rogoff, 1990; Vygotsky, 1978). The basic premise underlying this approach to cognitive development is that children often acquire knowledge and skills through social interaction with more skilled individuals. Adult guidance of cognitive performance is thought to be particularly important during times of transition, sometimes referred to as the zone of proximal development (Vygotsky, 1978). During such times, children are sensitive to experiences that allow them to try out new ways of thinking and acting. More specifically, children are in a state of readiness to benefit from guidance that provides them with the necessary support to use their skills in novel ways. Over time, scaffolding can be modified or withdrawn as the child becomes increasingly competent at executing the skill. Developmental change results as responsibilit y for structuring cognitive performance shifts from the adult to the child.
Heat Shock Protein 70 and Tumor Necrosis Factor Alpha in Taiwanese Patients with Dementia

This study was to determine whether polymorphisms of heat shock protein 70-1 (HSP70-1) and tumor necrosis factor α (TNF-α) are associated with the risk of Alzheimer’s disease (AD) and vascular dementia (VaD). Using the criteria of the NINCDS-ADRDA and NINDS-AIREN, 125 AD patients, 57 VaD patients and 109 ethnically matched nondemented controls were enrolled. The HSP70-1 –110 A/C and TNF-α –1031 T/C, –863 C/A and –857 C/T polymorphisms were analyzed by means of genotype or haplotype association methods. None of the four genotypes examined showed a statistically significant difference in genotype distribution between the AD cases and controls. However, the HSP70-1 –110 CC genotype occurred more frequently among AD cases (p = 0.0821; odds ratio: 2.08; 95% confidence interval, CI: 0.92–4.98). The overall genotype distribution among the VaD cases tended to be different at the HSP70-1 –110 and TNF-α –1031 sites (p = 0.0604 and 0.0316, respectively). The HSP70-1 –110 CC genotype was more frequent (p = 0.0459), and the association of the –110 CC genotype with VaD was evident (p = 0.0207; odds ratio: 3.22; 95% CI: 1.20–8.87). The more frequent TNF-α –1031 TC genotype (p = 0.0614) was also evidently associated with VaD (p = 0.0209; odds ratio: 2.32; 95% CI: 1.14–4.78). Multivariate analysis demonstrated the synergistic effect of the HSP70-1 –110 CC and TNF-α –1031 TC/CC genotypes on VaD (p = 0.0091; odds ratio: 10.09; 95% CI: 2.01–75.97). Haplotype analysis among TNF-α –1031, –863, –857 sites revealed that –1031C–857C may act as a risk haplotype among VaD cases (p = 0.0132, odds ratio: 2.26; 95% CI: 1.19–4.33). Our results suggest a potential protective role for HSP70 in both VaD and AD, whereas TNF-α may act as a risk factor only for VaD, and not for AD.
Assessment of Artificial MiRNA Architectures for Higher Knockdown Efficiencies without the Undesired Effects in Mice

RNAi-based strategies have been used for hypomorphic analyses. However, there are technical challenges to achieve robust, reproducible knockdown effect. Here we examined the artificial microRNA (amiRNA) architectures that could provide higher knockdown efficiencies. Using transient and stable transfection assays in cells, we found that simple amiRNA-expression cassettes, that did not contain a marker gene (−MG), displayed higher amiRNA expression and more efficient knockdown than those that contained a marker gene (+MG). Further, we tested this phenomenon in vivo, by analyzing amiRNA-expressing mice that were produced by the pronuclear injection-based targeted transgenesis (PITT) method. While we observed significant silencing of the target gene (eGFP) in +MG hemizygous mice, obtaining −MG amiRNA expression mice, even hemizygotes, was difficult and the animals died perinatally. We obtained only mosaic mice having both “−MG amiRNA” cells and “amiRNA low-expression” cells but they exhibited growth retardation and cataracts, and they could not transmit the –MG amiRNA allele to the next generation. Furthermore, +MG amiRNA homozygotes could not be obtained. These results suggested that excessive amiRNAs transcribed by −MG expression cassettes cause deleterious effects in mice, and the amiRNA expression level in hemizygous +MG amiRNA mice is near the upper limit, where mice can develop normally. In conclusion, the PITT-(+MG amiRNA) system demonstrated here can generate knockdown mouse models that reliably express highest and tolerable levels of amiRNAs.
Allele-Specific Chromatin Immunoprecipitation Studies Show Genetic Influence on Chromatin State in Human Genome

Several recent studies have shown a genetic influence on gene expression variation, including variation between the two chromosomes within an individual and variation between individuals at the population level. We hypothesized that genetic inheritance may also affect variation in chromatin states. To test this hypothesis, we analyzed chromatin states in 12 lymphoblastoid cells derived from two Centre d'Etude du Polymorphisme Humain families using an allele-specific chromatin immunoprecipitation (ChIP-on-chip) assay with Affymetrix 10K SNP chip. We performed the allele-specific ChIP-on-chip assays for the 12 lymphoblastoid cells using antibodies targeting at RNA polymerase II and five post-translation modified forms of the histone H3 protein. The use of multiple cell lines from the Centre d'Etude du Polymorphisme Humain families allowed us to evaluate variation of chromatin states across pedigrees. These studies demonstrated that chromatin state clustered by family. Our results support the idea that genetic inheritance can determine the epigenetic state of the chromatin as shown previously in model organisms. To our knowledge, this is the first demonstration in humans that genetics may be an important factor that influences global chromatin state mediated by histone modification, the hallmark of the epigenetic phenomena.
Identification of a Loss-of-Function Mutation in Ube2l6 Associated With Obesity Resistance

We previously mapped a locus on BALB/c chromosome 2 associated with protection from leptin-deficiency–induced obesity. Here, we generated the corresponding congenic mouse strain by introgression of a segment of C57BL/6J chromosome 2 to the BALB/c background to confirm the genotype–phenotype associations. We found that the BALB/c alleles decreased fat mass expansion by limiting adipocyte hyperplasia and adipocyte hypertrophy. This was concomitant to an increase in adipocyte triglyceride lipase (ATGL)-mediated triglyceride breakdown and prolongation of ATGL half-life in adipose tissue. In addition, BALB/c alleles on chromosome 2 exerted a cell-autonomous role in restraining the adipogenic potential of preadipocytes. Within a 9.8-Mb critical interval, we identified a nonsynonymous coding single nucleotide polymorphism in the gene coding for the ubiquitin-conjugating enzyme E2L6 (Ube2l6, also known as Ubch8) and showed that the BALB/c allele of Ube2l6 is a hypomorph leading to the lack of UBE2L6 protein expression. Ube2l6 knockdown in 3T3-L1 adipocytes repressed adipogenesis. Thus, altered adipogenic potential caused by Ube2l6 knockdown is likely critically involved in BALB/c obesity resistance by inhibiting adipogenesis and reducing adipocyte numbers. Overall, we have identified a loss-of-function mutation in Ube2l6 that contributes to the chromosome 2 obesity quantitative trait locus.
Neuropsychological Aspects of Turner's Syndrome

Eleven patients with Turner's syndrome (ages 13 to 23 years) were compared on a battery of neuropsychological measures with a control group matched for age and subtests of the Verbal IQ Scale of the Wechsler tests. Patients performed less well than controls on word fluency, perception of left and right, visuo‐motor co‐ordination, visual memory and motor learning. They also showed a higher incidence of left‐ear advantage on a dichotic listening test for phonemic stimuli than did controls. There was no clear evidence for a specific deficit in spatial ability in the patients tested.