Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in patients with acute pancreatitis

Aim: Acute pancreatitis may affect cardiovascular system regardless of etiology. Electrocardiographic parameters such as QT interval, corrected QT interval (QTc), Tp-e interval and Tp-e/QT, Tp-e/QTc ratio can be used to evaluate myocardial repo- larization. We aimed to investigate the effects of acute pancreatitis on the cardiovascular system and the relationship between ventricular repolarization parameters and the severity of the disease. Methods: Ventricular repolarization parameters (QT interval, QTc interval, Tp-e/QT, Tp-e/QTc ratio) of the patients who were included in the study and diagnosed with acute pancreatitis were compared with the control group patients. In addition, these parameters and Ranson, APACHE II and amylase values were taken into account in all patients in the pancreatitis group and the relationship between the severity of the disease and cardiac parameters was investigated. Results: 60 patients (30 acute pancreatitis and 30 control) were examined. Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were significantly higher in the acute pancreatitis group compared to the control. In addition, Tp-e interval, Tp-e/QT and Tp-e/QTc ratios showed a positive correlation with the Ranson and APACHE II scores and Tp-e interval displayed a positive correlation with amylase levels. Conclusions: Tp-e interval, Tp-e/QT and Tp-e/QTc ratios can be used as a marker for the detection of ventricular arrhythmia risk in acute pancreatitis patients and Tp-e/ QT and Tp-e/QTc ratios increased depending on the severity of AP and Tp-e interval increased in parallel with higher levels of amylase. Amylase level alone could be an indicator for increased risk of ventricular arrhythmia in patients with acute pancreatitis.
Catechol-O-methyltransferase Val158Met Genotype and Resting Regional Cerebral Blood Flow in Medication-Free Patients with Schizophrenia

Background—A valine158methionine polymorphism in Catechol-O-methyltransferase (COMT) modulates cortical dopaminergic catabolism and has been associated with schizophrenia. Consistent with schizophrenia itself, during cognitive tasks, the risk (val) allele predicts less efficient prefrontal cortex (PFC) physiology and worse performance, while during aversive stimuli viewing, this allele predicts less limbic activation. Task-independent effects of this polymorphism in schizophrenia have not yet been characterized. Methods—Twenty-five medication-free patients (28±6 years; 19 male) and forty-seven healthy individuals (29±8 years; 33 male) were genotyped for the COMT val158met polymorphism and underwent two 60-second [O]H2O regional cerebral blood flow (rCBF) positron emission tomography (PET) scans (10 mCi/scan) during rest. Data were analyzed with a random-effects general linear model using COMT genotype as a covariate. Results—In patients, but not healthy individuals, val (risk) allele load predicted less regional cerebral blood flow (rCBF) in the right dorsolateral PFC (DLPFC), right superior temporal gyrus, and left precuneus, but greater rCBF in the amygdala and parahippocampal gyrus. Conclusions—In schizophrenia, brain structures important for executive and affective processing show activity that is differentially predicted by COMT allelic variation in an opposing manner even at rest, providing evidence for the salience of prefrontal dopaminergic tone in task-independent, basal-level neural activity.
Analysis of testosterone and dihydrotestosterone in mouse tissues by liquid chromatography-electrospray tandem mass spectrometry

A novel method was established for simultaneous quantitation of testosterone (T) and dihydrotestosterone (DHT) in murine tissue and serum samples. Endogenous T and DHT, together with the internal standards, 17 α -methyl-T and 17 α -methyl-DHT, were extracted from tissues, and then derivatized by reaction with 2-hydrazino-4-(trifluoromethyl)-pyrimidine (HTP). Analysis by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) resulted in production spectra of HTP derivatives of both T and DHT that showed analyte-specific fragmentations; the latter fragmentations were characterized by use of high-resolution Orbitrap MS/ MS. These specific fragmentations enabled quantitation of T and DHT in the multiple-reaction monitoring (MRM) mode. The method was validated with charcoal-stripped serum as the matrix; the LLOQ was 0.10 ng/ml for T and 0.50 ng/ml for DHT. The method was then used for determination of serum and tissue levels of T and DHT in transgenic mice carrying a hypomorphic NADPH-cytochrome P450 reductase gene (Cpr-low mice). Remarkably, ovarian T levels in Cpr-low mice were found to be 25-fold higher than those in wild-type mice, a finding that at least partly explains the female infertility seen in the Cpr-low mice. In conclusion, our method provides excellent sensitivity and selectivity for determination of endogenous levels of T and DHT in mouse tissues.
Mechanisms that limit the light stimulus frequency following through the APB sensitive and insensitive rod Off-pathways

In the retina, rod signal pathways process scotopic visual information. Light decrements are mediated by two distinct groups of rod pathways in the dark adapted retina that can be differentiated on the basis of their sensitivity to the glutamate agonist DL-2-amino-4-phosphonobutyric acid (APB). We have found that the APB sensitive and insensitive rod Off-pathways signal different light decrement information: the APB sensitive rod Off-pathway conveys slow and low frequency light signals, whereas the APB insensitive rod Off-pathways mediate fast and high frequency light signals (Wang, 2006). However, the mechanisms which limit the frequency following through the APB sensitive and insensitive rod Off-pathways remain unknown. In the current study, whole-cell patch-clamp recordings were made from ganglion cells in dark and light adapted mouse retina to identify the mechanisms that limit the frequency following through the APB sensitive and insensitive rod Offpathways. The results showed that the sites from AII amacrine cells to Off cone bipolar cells are the major mechanisms that limit the frequency following through the APB sensitive rod Off-pathway. In the APB insensitive rod Off-pathways, rods themselves limited the frequency following through these pathways. Moreover, ganglion cells were able to follow higher frequencies under photopic conditions than under scotopic conditions. The Off responses followed lower frequencies than On responses under photopic conditions. This finding was observed in cells that yielded On or Off responses only as well as in On-Off cells.
Monitoring transient Ca 2+ dynamics with BK channels at active zones in frog saccular hair cells

Neurotransmitter release from the basolateral surface of auditory and vestibular hair cells is mediated by Ca 2+ influx through voltage-gated Ca 2+ channels. Co-localization of large-conductance Ca 2+ activated K + (BK) channels at the active zones of these cells affords them with an optimal location to act as reporters of the Ca 2+ concentration changes at active zones of transmitter release. In this report we use BK channels to monitor dynamic changes in intracellular Ca 2+ concentration during transient influxes of Ca 2+ , showing that BK current magnitude and delay to onset are correlated with the rate and duration of Ca 2+ entry through Ca 2+ channels. We also show that BK channels exhibit a much higher Ca 2+ binding affinity in the open state than in the closed state.
Use and interpretation of anthropometric indicators of nutritional status*

Studies carried out during the last decade have led to a better understanding of the value of anthropometric indicators of nutritional status. The present report concentrates on data concerning 0-5-year-old children and examines the indices of weight and height and the biological significance of "wasting" and "stunting". The need for a reference population as well as for a standard or target is recognized and the advantages and dis-advantages of local versus international reference populations are discussed. In the analysis of data, preference is given to the use ofstandard deviation (SD) scores and to the presentation of whole distributions. Cut-offs, for example - 2SD, are needed for comparison of prevalences and for screening of populations. Sequential or serial measurements and the increasing use of growth velocities are discussed and their uses and difficulties are outlined.
Amyloid Beta as a Modulator of Synaptic Plasticity

Alzheimer’s disease is associated with synapse loss, memory dysfunction and pathological accumulation of amyloid beta in plaques. However, an exclusively pathological role for amyloid beta is being challenged by new evidence for an essential function of amyloid beta at the synapse. Amyloid beta protein exists in different assembly states in the central nervous system and plays distinct roles ranging from synapse and memory formation to memory loss and neuronal cell death. Amyloid beta is present in the brain of symptom-free people where it likely performs important physiological roles. New evidence indicates that synaptic activity directly evokes the release of amyloid beta at the synapse. At physiological levels, amyloid beta is a normal, soluble product of neuronal metabolism that regulates synaptic function beginning early in life. Monomeric amyloid beta 40 and 42 are the predominant forms required for synaptic plasticity and neuronal survival. With age, some assemblies of amyloid beta are associated with synaptic failure and Alzheimer’s disease pathology, possibly targeting the N-methyl-D-aspartic acid (NMDA) receptor through the α7-nicotinic acetylcholine receptor (α7-nAChR), mitochondrial amyloid-β alcohol dehydrogenase (ABAD) and cyclophilin D. But emerging data suggests a distinction between age effects on the target response in contrast to the assembly state or the accumulation of the peptide. Both aging and beta amyloid independently decrease neuronal plasticity. Our laboratory has reported that amyloid beta, glutamate and lactic acid are each increasingly toxic with neuron age. The basis of the age-related toxicity partly resides in age-related mitochondrial dysfunction and an oxidative shift in mitochondrial and cytoplasmic redox potential. In turn, signaling through phosphorylated extracellular signal-regulated protein kinases (pERK) is affected along with an age-independent increase in phosphorylated cAMP response element-binding protein (pCREB) This review examines the long-awaited functional impact of amyloid beta on synaptic plasticity.
Defining midbrain dopaminergic neuron diversity by single-cell gene profiling

Effective approaches to neuropsychiatric disorders require detailed understanding of the cellular composition and circuitry of the complex mammalian brain. Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter, using a microfluidic dynamic array to simultaneously evaluate the expression of 96 genes in single neurons. With this approach, we successfully identified multiple molecularly distinct dopamine neuron subtypes, and localized them in the adult mouse brain. To validate the anatomical and functional correlates of molecular diversity, we provide evidence that one Vip+ subtype, located in the periaqueductal region, has a discrete projection field within the extended amygdala. Another Aldh1a1+ subtype, located in the substantia nigra, is especially vulnerable in the MPTP model of Parkinson’s disease. Overall, this rapid, cost-effective approach enables the identification and classification of multiple dopamine neuron subtypes, with distinct molecular, anatomical, and functional properties.
Strain-Dependent Oxidant Release in Articular Cartilage Originates from Mitochondria

Mechanical loading is essential for articular cartilage homeostasis and plays a central role in the cartilage pathology, yet the mechanotransduction processes that underlie these effects remain unclear. Previously we showed that lethal amounts of reactive oxygen species (ROS) were liberated from the mitochondria in response to mechanical insult, and that chondrocyte deformation may be a source of ROS. To this end, we hypothesized that mechanically-induced mitochondrial ROS is related to the magnitude of cartilage deformation. To test this, we measured axial tissue strains in cartilage explants subjected to semi-confined compressive stresses of 0, 0.05, 0.1, 0.25, 0.5, or 1.0 MPa. The presence of ROS was then determined by confocal imaging with dihydroethidium (DHE), an oxidant sensitive fluorescent probe. Our results indicated that ROS levels increased linearly relative to the magnitude of axial strains (r 2 = 0.83, p < 0.05), and significant cell death was observed at strains > 40%. By contrast, hydrostatic stress, which causes minimal tissue strain, had no significant effect. Cell permeable superoxide dismutase mimetic Mn(III)tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP) significantly decreased ROS levels at 0.5 and 0.25 MPa. Electron transport chain inhibitor, rotenone, and cytoskeletal inhibitor, cytochalasin B, significantly decreased ROS levels at 0.25 MPa. Our findings strongly suggest that ROS and mitochondrial oxidants contribute to cartilage mechanobiology.
Tissue Factor and Toll Like Receptor (TLR)4 in HyperglycemiaHyperinsulinemia: Effects in Healthy Subjects, and Type 1 and Type 2 Diabetes Mellitus

SUMMARY Background— Diabetes mellitus (DM) patients have increased cardiovascular events. Blood tissue factor-procoagulant activity (TF-PCA), the initiating mechanism for blood coagulation, is elevated in DM. We have shown that hyperglycemia (HG), hyperinsulinemia (HI) and combined HG+HI (induced using 24 hr infusion clamps) increases TF-PCA in healthy and T2DM subjects, but not in T1DM subjects. The mechanisms for this are unknown. DM patients have elevated plasma lipopolysaccharide (LPS), a toll-like receptor (TLR) 4 ligand. We postulated that TLR4 plays a role in modulating TF levels. Objectives and Methods— We studied the effect of HG+HI on TLR4 and TF-PCA in vivo during 24 hr HG+HI infusion clamps in healthy subjects, and T1DM and T2DM subjects, and in vitro in blood. Results— In vivo, in healthy subjects, 24 hr HG + HI infusion increased TLR4 6-fold, which correlated with TF-PCA (r= 0.91, p<0.0001). T2DM patients showed smaller increases in both. In T1DM subjects, TLR4 declined (50%, p<0.05) and correlated with TF-PCA (r=0.55; p<0.05). In vitro , HG (200 mg/dl added glucose) and HI (1-100 nM added insulin) increased TF-PCA in healthy subjects (~2-fold, 2-4 hr). Insulin inhibited and T2DM during infusion clamps— Whole blood TLR4 levels were measured in blood samples available from our previously published studies on TF-PCA using infusion clamps in healthy non-diabetic subjects [20], and patients with type T1DM [19] and T2DM [18]; the details regarding the subjects and the protocols have been described. The study protocols were approved by the Institutional Review Board of Temple University Hospital. Informed written consent was obtained from all subjects after explanation of the nature, purpose and potential risks.
Homologous and heterologous uncoupling of muscarinic M 3 and a 1B adrenoceptors to G a q/11 in SH-SY5Y human neuroblastoma cells

1 The present study employed a [ 35 S]-GTP g S binding protocol in conjunction with immunoprecipitation (IP) of the G a subunits to investigate the desensitization of G q/11 -coupled receptors at the level of the G-protein activation. Membranes from SH-SY5Y cells expressing the recombinant human a 1B -adrenoceptor ( a 1B -AR) (and endogenously expressing the M 3 muscarinic acetylcholine receptor (M 3 -AChR)) exhibited G q/11 activation in a concentration-dependent manner in response to noradrenaline or methacholine. 2 Pre-treatment of intact cells with agonist prior to membrane preparation and use in the [ 35 S]-GTP g S IP assay demonstrated that both receptors were homologously desensitized by pre-treatment with agonist since the G q/11 activation in response to a secondary challenge with agonist was markedly reduced. Stimulation of a 1B -AR was e(cid:128)ective at heterologously desensitizing the M 3 AChR. The PKC inhibitor, Ro-31-8220 (10 m M ) was ine(cid:128)ective at preventing the agonist-mediated receptor desensitization. 3 [ 32 P]P i -labelled cells allowed the detection of increases in receptor phosphorylation. Phorbol 12,13 dibutyrate (PDBu) (1 m M ) was e(cid:128)ective at producing a Ro-31-8220 (10 m M )-sensitive, detectable increase in a 1B -AR but not M 3 -AChR phosphorylation. Noradrenaline (30 m M ) stimulated a 1B -AR phosphorylation, which could be partially inhibited by Ro-31-8220 (10 m M ). The phosphorylation of M 3 -AChR was increased by methacholine (100 m M ) incubation and this e(cid:128)ect appeared to be insensitive to Ro-31-8220 (10 m M ). 4 These ﬁndings demonstrate that [ 35 S]-GTP g S-G a -subunit IP can be used to estimate receptor desensitization as a decline in receptor-G-protein coupling. Both the a 1B -AR and M 3 -AChR undergo rapid homologous desensitization that is associated with an increase in receptor phosphorylation. The heterologous desensitization of M 3 -AChR produced by a 1B -AR stimulation is not associated with a detectable increase in M 3 -AChR phosphorylation, suggesting that receptor phosphorylation is not necessarily a prerequisite for desensitization. Pharmacology 13-acetate; [ 3 H]-prazosin, prazosin [7-methoxy- 3 H]
Graph partitioning using single commodity flows

We show that the sparsest cut in graphs with <i>n</i> vertices and <i>m</i> edges can be approximated within <i>O</i>(log<sup>2</sup> <i>n</i>) factor in Õ(<i>m</i> + n<sup>3/2</sup>) time using polylogarithmic single commodity max-flow computations. Previous algorithms are based on multicommodity flows that take time Õ(<i>m</i> + n<sup>2</sup>). Our algorithm iteratively employs max-flow computations to embed an expander flow, thus providing a certificate of expansion. Our technique can also be extended to yield an <i>O</i>(log<sup>2</sup> <i>n</i>)-(pseudo-) approximation algorithm for the edge-separator problem with a similar running time.
Noninvasive assessment of tumor microenvironment using dynamic contrast enhanced MRI and 18 F- fluoromisonidazole PET imaging in neck nodal metastases

Purpose— Pretreatment multimodality imaging can provide useful anatomical and functional data about tumors, including perfusion and possibly hypoxia status. The purpose of our study was to assess non-invasively the tumor microenvironment of neck nodal metastases in patients with head and neck (HN) cancer by investigating the relationship between tumor perfusion measured using Dynamic Contrast Enhanced MRI (DCE-MRI) and hypoxia measured by 18 F-fluoromisonidazole ( 18 F-FMISO) PET. Methods and Materials— Thirteen newly diagnosed HN cancer patients with metastatic neck nodes underwent DCE-MRI and 18 F-FMISO PET imaging prior to chemotherapy and radiation therapy. The matched regions of interests from both modalities were analyzed. To examine the correlations between DCE-MRI parameters and standard uptake value (SUV) measurements from 18 F-FMISO PET, the non-parametric Spearman correlation coefficient was calculated. Furthermore, DCE-MRI parameters were compared between nodes with 18 F-FMISO uptake and nodes with no 18 F-FMISO uptake using Mann-Whitney
CO 2 Challenge Reactivity as a Prospective Predictor of Panic Attacks

CO 2 -induced fear responding was prospectively evaluated as a risk factor for the development of anxiety pathology in a nonclinical sample ( N = 404) followed for two years. Baseline response to a CO 2 challenge was a very strong predictor of future panic attacks (though not for panic disorder or other anxiety disorders).
Recent Decrease in Acute GVHD in Children with Leukemia Receiving Unrelated Donor Bone Marrow Transplants Blood Marrow

Unrelated donor (URD) BMT is an effective treatment for leukemia in children, but success is limited by graft versus host disease (GVHD) and relapse. In this study we describe the incidence and risk factors for GVHD over time in children receiving URD BMT. We analyzed outcomes of 638 myeloablative URD BMT performed between 1990 and 2003 for treatment of AML, ALL, CML or MDS, using the Center for International Blood & Marrow Transplant Research (CIBMTR) database. Recipients were <18 years of age, and had available high resolution HLA typing for HLA A, B, C and DRB1. Overall, 27% of recipients developed aGVHD grades III-IV and risk was significantly higher in recipients of T-replete compared with T-depleted grafts (OR 3.12, 95%CI 2.02-4.83; p< 0.0001). Acute GVHD significantly reduced risk of relapse in children with ALL (OR 0.34 95% CI 0.13-0.86, p=0.0052) but not AML (OR 0.58, 95% CI 0.22-2.98; p=0.26). Risk of aGVHD was higher in children transplanted in earlier years (1990-1998, n=365) compared to 1999-2003 (OR 1.93 95%CI 1.27-2.91; p=0.002). We conclude that outcomes have changed significantly over time, with reduced risk of aGVHD in more recent transplants.
b -Carotene-9 # ,10 # -Oxygenase Status Modulates the Impact of Dietary Tomato and Lycopene on Hepatic Nuclear Receptor–, Stress-, and Metabolism-Related Gene Expression in Mice 1–3

Tomato and lycopene ( c , c -carotene) consumption is hypothesized to protect against nonalcoholic steatohepatitis and hepatocarcinogenesis, processes that may depend upon diet and gene interactions. To investigate the interaction of tomato or lycopene feeding with b -carotene-9 # ,10 # -monooxygenase ( Bco2 ) on hepatic metabolic and signaling pathways, male wild-type (WT) and Bco2 2 / 2 mice (3-wk-old; n = 36) were fed semi-puriﬁed control, 10% tomato powder–containing, or 0.25% lycopene beadlet–containing diets for 3 wk. Serum lycopene concentrations were higher in lycopene- and tomato-fed Bco2 2 / 2 mice compared with WT ( P = 0.03). Tomato- and lycopene-fed mice had detectable hepatic apolipoprotein (apo)-6 # -, apo-8 # -, and apo-12 # -lycopenal concentrations. Hepatic expression of b -carotene-15,15 (cid:1) monooxygenase was increased in Bco2 2 / 2 mice compared with WT ( P = 0.02), but not affected by diet. Evaluation of hepatic gene expression by focused quantitative reverse transcriptase-polymerase chain reaction arrays for nuclear receptors and coregulators (84 genes) and stress and metabolism (82 genes) genes indicates that tomato feeding affected 31 genes ( $ 1.5-fold, P < 0.05) and lycopene feeding affected 19 genes, 16 of which were affected by both diets. Lycopene down-regulation of 7 nuclear receptors and coregulators, estrogen-related receptor- a , histone deacetylase 3, nuclear receptor coactivator 4, RevErbA- b , glucocorticoid receptor, peroxisome proliferator-activated receptor (PPAR)- a , and PPAR- g , coactivator 1 b was dependent upon interaction with Bco2 status. Lycopene and tomato feeding induced gene expression patterns consistent with decreased lipid uptake, decreased cell proliferation and mitosis, down-regulated aryl hydrocarbon receptor signaling, and decreased expression of genes involved in retinoid X receptor heterodimer activation. Tomato feeding also caused expression changes consistent with down-regulation of DNA synthesis and terpenoid metabolism. These data suggest tomato components, particularly lycopene, affect hepatic gene expression, potentially affecting hepatic responses to metabolic, infectious, or chemical stress. J. Nutr. 144: 431–439, 2014.