Miracle-dz/UniFAR-FTUs huggingface dataset:
Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE The purposes of this study were to examine the impact of 3 weeks of amphetamine administration on intrinsic connectome-wide connectivity patterns in adults with attention-deficit/hyperactivity disorder (ADHD) and explore the association between stimulant-induced symptom improvement and functional connectivity alteration. METHODS Participants included 19 adults (age 20-55 years) diagnosed with ADHD using the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria per the Adult Clinician Diagnostic Scale taking part in amphetamine trials. For each patient, two 6-minute resting-state functional magnetic resonance imaging (R-fMRI) scans were acquired at baseline and after treatment. A fully data-driven multivariate analytic approach (i.e., multivariate distance matrix regression [MDMR]) was applied to R-fMRI data to characterize the distributed pharmacological effects in the entire functional connectome. Clinical efficacy was assessed using ADHD rating scale with adult prompts and the Adult Self-Report Scale v1.1 Symptom Checklist. We linked stimulant-induced functional connectivity changes to symptom amelioration using Spearman's correlation. RESULTS Three weeks of administration of a stimulant significantly reduced ADHD symptoms. MDMR-based analyses on R-fMRI data highlighted the left dorsolateral prefrontal cortex (DLPFC, a key cognitive control region) and the medial prefrontal cortex (MPFC, the anterior core of default network) whose distributed patterns of functional connectivity across the entire brain were altered by psychostimulants. Follow-up intrinsic functional connectivity revealed that stimulants specifically decreased the positive functional connectivity between DLPFC-insula, DLPFC-anterior cingulate cortex, and MPFC-insula. Importantly, these functional connectivity changes are associated with symptom improvement. CONCLUSION These results suggested that ADHD is associated with increased functional integration or decreased functional segregation between core regions of cognitive control, default, and salience networks. The apparent normalization of intrinsic functional interaction in these circuits (i.e., increased functional segregation) may underlie the clinical benefits produced by 3 weeks of amphetamine treatment.
Timing of Neutrophil Depletion Influences Long-Term Neuroprotection in Neonatal Rat Hypoxic-Ischemic Brain Injury

In neonatal rats, neutrophils do not accumulate in ischemic brain parenchyma to the extent that they do in adult rodents. They are also confined to the intravascular compartment during the first few hours of recovery. However, neonatal rats rendered neutropenic have less brain swelling after a hypoxic-ischemic (HI) insult. In this study, we used the Rice-Vannucci model of HI brain injury in 7-d-old rats, and we depleted neutrophils before injury in one group and 4–8 h after injury in another group to determine 1) whether neutrophils contribute to cerebral atrophy, 2) whether neutropenia induced within 8 h after recovery from HI is neuroprotective, and 3) whether neutropenia preserved energy metabolites during the HI insult. Brain energy metabolites were measured at 0 h and 6 h of recovery. Brain atrophy was measured morphometrically on brain slices at 2 wk of recovery. In 67 rats, we found that neutropenia induced before the HI insult, but not after HI, reduced brain swelling at 42 h of recovery by about 75% (p < 0.001). In another 60 rats, we found that cerebral atrophy was reduced by 61% provided that neutropenia was induced before HI (p < 0.05). Total adenine nucleotides were better preserved in the neutropenic rats at the end of the HI insult (0 h recovery); p < 0.05. We conclude that neutrophils do contribute to vascular dysfunction either during the HI insult or early hours (<4–8 h) of recovery. Antineutrophil strategies initiated after this time are unlikely to be protective in the neonatal rat.
Neurochemical characteristics associated with ethanol preference in selected alcohol-preferring and -nonpreferring rats: a quantitative microdialysis study.

BACKGROUND Rodent lines selected for alcohol preference and nonpreference have been used extensively to determine the neurobiological basis of alcohol-seeking behavior. Evidence suggests that innate differences in the mesolimbic dopamine and serotonin systems may contribute to disparate alcohol-seeking behaviors between these selected lines. Therefore, the purpose of this study was to identify neurochemical characteristics which may predict ethanol preference in selected alcohol-preferring and -nonpreferring rats [high-alcohol-preferring (HAD), low-alcohol-preferring (LAD), Alko alcohol (AA), Alko nonalcohol (ANA), Wistar]. METHODS Basal release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of ethanol-naive rats was analyzed for its relationship with subsequent measures of ethanol preference. Initially, basal extracellular DA and 5-HT levels were measured by "no-net-flux" quantitative microdialysis. Subsequently, the dopaminergic response to systemic ethanol administration (1.5 g/kg; intraperitoneal) was determined. After completion of the neurochemical tests, the rats received unlimited two-bottle, free-choice access to 10% (w/v) ethanol and water in the home cage for 28 days. RESULTS Analysis of the data across individual animals revealed that extracellular dopamine levels ([DA]e; r = + 0.64;p < 0.006) and the percent of baseline increase in DA (%incrDA; r = + 0.77;p < 0.001) due to ethanol were significant predictors of ethanol preference. Comparison of the data between genetic lines yielded a significant relationship between preference and %incrDA (r = + 0.87; p < 0.05). Analysis of the data across animals within each line and their respective control line determined that in the AA/ANA line pair (r = + 0.67; p < 0.03) and Wistar line (r = + 0.66; p < 0.03) %incrDA was a significant predictor of preference. In the HAD/LAD line pair, %incrDA (r = + 0.56; p < 0.005) and [DA]e (r = + 0.86; p < 0.004) were significant predictors of ethanol preference. CONCLUSIONS Overall, these findings suggest that elevated extracellular levels of dopamine within the nucleus accumbens and a greater responsivity to enhancements in DA release by ethanol may be factors which contribute to high-alcohol preference. Furthermore, the data suggest that alcohol may be more reinforcing in animals that exhibit an enhanced dopaminergic response to the first ethanol exposure, and that this effect may subsequently be associated with high-alcohol-seeking behavior.
Deficit of verb generation in nondemented patients with Parkinson's disease

Clinical and neuroimaging studies have shown that verb processing suggests a preferential participation of a prefrontal network, which is dysfunctional in Parkinson's disease (PD). To assess a verb processing deficit in PD, we compared noun‐ and verb‐generation tasks for 34 nondemented PD patients (according to the Dementia Rating Scale) with 34 matched normal subjects, using two intracategory tasks (noun/noun and verb/verb generation) and two intercategory tasks (noun/verb and verb/noun generation). PD patients were significantly impaired in the two tasks involving verb production, i.e., verb/verb and noun/verb generation, whereas their performance was similar to those of controls in the two tasks requiring noun production. For the two impaired tasks, we assessed 1) the influence of lexical competition that corresponds to the presence of several candidate words for a given stimulus; 2) the influence of slight cognitive dysfunction; and 3) the influence of motor deficit. Significant correlations were found between DRS scores and performance on the noun/verb task, and no significant correlations were found between lexical competition or motor deficit and performance. The specific deficit for verb production in PD patients is discussed in relation to deficits affecting either action or grammatical representations. © 2002 Movement Disorder Society
An ultra scale‐down approach identifies host cell protein differences across a panel of mAb producing CHO cell line variants

During the manufacture of biopharmaceutical products, the final product must lie within strict pre‐set specifications, for example the host cell protein (HCP) content. A number of specific HCPs have been identified in particular products and the interactions between product/HCPs have also been recently investigated; however, a comparison of the HCP dynamics between related cell lines and their response to early downstream processing to aid process development and cell line selection has not been published. We have utilised a proteomic approach coupled with an ultra scale‐down study to determine the HCP profile dynamics, at harvest and during early downstream processing, across a panel of recombinant GS‐CHOK1SV antibody producing cell lines. The results reveal that cell culture viability upon harvest has the greatest impact upon shear sensitivity and HCP concentration. Whilst the general HCP population/profile was broadly similar across the cell lines, the actual amounts of some specific HCPs in the supernatant differed and a number of cell line specific differences in the response to early downstream processing were observed. We anticipate that such knowledge can now be applied to cell line selection and downstream processing development to target reduction/removal of general and specific problematic HCPs before and during downstream processing.
Indonesia's Commitment to Reducing GHG and Its Impact on the Indonesian Economy: CGE Approach

To achieve the carbon emission target in Indonesia in 2030, what trade offs will be carried out if viewed from an economic perspective such as GDP, energy consumption? This study employs the CGE model to see the impact of imposing carbon tax on GDP and GHG emissions in Indonesia. Five scenarios have been applied to gauge the linkage between those factors. The main finding in this study is that carbon tax can reduce emissions in large numbers in Indonesia thus that carbon tax can be used as an effective emission control instrument. However, what needs to be concerned is the impact of carbon tax on decreasing GDP. It is different from Singapore where the impact of carbon tax almost does not affect GDP, in Indonesia even though the tax is applied in small amounts but has a significant effect on changes in GDP.
Limited influence of UGT1A1*28 and no effect of UGT2B7*2 polymorphisms on UGT1A1 or UGT2B7 activities and protein expression in human liver microsomes.

AIMS UGT1A1 and UGT2B7 are enzymes that commonly contribute to drug glucuronidation. Since genetic factors have been suggested to contribute to variability in activities and expression levels of these enzymes, a quantitative assessment of the influence of the major genotypes (UGT1A1*28 or UGT2B7*2) on enzyme activities was conducted. METHODS Using a bank of microsomal samples from 59 human livers, the effect of UGT1A1*28 or UGT2B7*2 polymorphisms were investigated on rates of estradiol 3-glucuronidation (a marker of UGT1A1 enzyme activity) or zidovudine glucuronidation (a marker of UGT2B7 enzyme activity) and levels of immunoreactive protein for each enzyme. Glucuronidation rates for both enzymes were measured at K(m)/S(50) and 10 times K(m)/S(50) concentrations. RESULTS UGT1A1 and UGT2B7 enzyme activities varied up to 16-fold and sixfold, respectively. Rates at K(m)/S(50) concentration closely correlated with rates at 10 times K(m)/S(50) concentration for both enzymes (but not at 1/10th K(m) for UGT2B7). Enzyme activities correlated with relative levels of immunoreactive protein for UGT1A1 and UGT2B7. Furthermore, rates of zidovudine glucuronidation correlated well with rates of glucuronidation of the UGT2B7 substrate gemcabene, but did not correlate with UGT1A1 enzyme activities. For the UGT1A1*28 polymorphism, consistent with levels of UGT1A1 immunoreactive protein, mean UGT1A1 activity was 2.5- and 3.2-fold lower for TA(6)/TA(7) (P < 0.05) and TA(7)/TA(7) (P < 0.001) genotypes in comparison with the TA(6)/TA(6) genotype. CONCLUSIONS Relative to the observed 16-fold variability in UGT1A1 activity, these data indicate only a partial (approximately 40%) contribution of the UGT1A1*28 polymorphism to variability of interindividual differences in UGT1A1 enzyme activity. For the UGT2B7*2 polymorphism, genotype had no influence on immunoreactive UGT2B7 protein or the rate of 3'-azido-3'-deoxythymidine glucuronidation.
Laparoscopic Approach to Pheochromocytoma: Is a Lower Intraabdominal Pressure Helpful?

Laparoscopic adrenalectomy is gaining popularity because of its well-documented benefits. The aim of our study was to see if a decreased intraoperative intraabdominal pressure during laparoscopic adrenalectomy would affect the hemodynamic variables and the serum levels of catecholamines. We randomly divided 9 patients into 2 groups, maintaining either an intraabdominal pressure of 15 mm Hg (group A) or 8–10 mm Hg (group B). Norepinephrine and epinephrine blood levels were measured preoperatively, during endotracheal intubation, carboperitoneum, surgical manipulation of tumor just before the ligation of the adrenal vein, and tracheal extubation; the hemodynamic variables were recorded. The introduction of carboperitoneum resulted in an increase in heart rate and mean arterial blood pressure (MAP), although it was statistically insignificant. The norepinephrine levels showed a statistically significant increase in group A as compared with group B (P = 0.0002). Surgical manipulation of the tumor resulted in a significant increase in MAP and norepinephrine levels in group A (P = 0.007 and P = 0.0001, respectively). The epinephrine levels did not change as much because the tumor was probably predominantly norepinephrine-secreting. Norepinephrine levels continued to be high even during tracheal extubation in group A patients (P = 0.027). We conclude that a low intraabdominal pressure of 8–10 mm Hg causes less catecholamine release and fewer hemodynamic fluctuations.
Multilingualism, linguistic ownership and ethnic identity : attitudes to, and use of, Mauritian

This dissertation analyses the role of ideologies about Mauritian in influencing macrolevel and micro-level linguistic practices in Mauritian society. In multiethnic and multilingual Mauritius, language is an important index of ethnicity which in turn is an index of socio-economic status and political power. The situation of the native language of most Mauritians, Mauritian, is particularly interesting from a sociolinguistic perspective in that it is currently being re-evaluated. Because Mauritian is used in a multilingual setting, it competes with other languages, including the prestigious colonial languages, English and French, and highly valued ethnic languages like Hindi and Mandarin. Therefore, ideologies about Mauritian are inextricably linked to ideologies about other languages present on the island as well. Mauritian is in an ambiguous situation: it is simultaneously the most spoken language by all ethnic and religious groups in the country and the language of the Creole ethnic group. Through its index as the language of this socio-economically deprived ethnic group, Mauritian also becomes an index of lower social status. Its link with Creole identity, low prestige and perceived linguistic inferiority vis-a-vis other languages often leads to negative perceptions of the language. However, there is increasing pressure on the government to create an official standard for Mauritian, to introduce the language in the education system and to elevate it to the status of national language. In devising a linguistic policy, the government should consider users' language ideologies. This dissertation aims to shed more light on users' attitudes to Mauritian in two specific domains: writing and education. Through the triangulation of such methods as interviews, perceptual dialectology questionnaires and participant observation, I explain some of the local language ideologies and also provide a comprehensive view of the linguistic situation in Mauritius.
Plasma protein and lipoprotein distribution of clozapine.

OBJECTIVE The authors' goal was to determine what effect dyslipidemia has on clozapine's plasma distribution. METHOD [(3)H]Clozapine plus cold clozapine (335 ng/ml) were incubated in plasma samples with varying total cholesterol, lipoprotein cholesterol, and triglyceride concentrations. Following incubation, the plasma was separated into its lipoprotein and lipoprotein-deficient fractions by density gradient ultracentrifugation and clozapine distribution was determined. RESULTS Compared with the plasma standard, significantly more clozapine was recovered in the very-low-density lipoprotein fraction, which contained elevated total cholesterol and triglycerides. Correlation analysis revealed a positive correlation between total plasma triglyceride concentration and clozapine recovery in this fraction. CONCLUSIONS In plasma samples with elevated triglycerides, clozapine shifts from the lipoprotein-deficient fraction to the very-low-density lipoprotein fraction. This redistribution of clozapine may affect the pharmacological activity of clozapine.
LEVELS OF CHLORINATED, BROMINATED, AND PERFLUORINATED CONTAMINANTS IN BIRDS OF PREY SPANNING MULTIPLE TROPHIC LEVELS

Birds of prey occupy high trophic levels and can consequently bioaccumulate high levels of environmental contaminants. To evaluate exposure to past- and current-use pollutants, we measured legacy contaminants (i.e., polychlorinated biphenyls [PCBs]; organochlorine pesticides, e.g., DDT), contaminants of emerging concern (polybrominated diphenyl ethers [PBDEs]; perfluorinated compounds [PFCs]), and stable isotopes (δ13C, δ15N) in 26 birds of prey (10 species) from coastal South Carolina (USA) sampled in 2009 and 2010. Nitrogen isotope ratios (δ15N) ranged from 5.2% to 13.7%, indicating the birds of prey spanned two to three trophic levels. Legacy contaminant levels were highly variable but generally comparable to levels reported previously for birds of prey in the southeast US, suggesting exposure has not declined substantially over the past 40 yr. Despite their status as newly emerging environmental contaminants, PFC levels were within the same order of magnitude as legacy contaminants. Although PBDEs were less prevalent, levels were among the greatest observed in wildlife to date (ΣPBDEs max. 200 μg/g lipid). Relative contaminant profiles also varied between birds of prey utilizing low and high trophic levels; specifically PFCs contributed to a larger proportion of the contaminant burden in birds utilizing high trophic levels, whereas the legacy pesticide mirex was a larger contributor in low-trophic-level birds, indicating that relative exposure is in part dependent on foraging ecology. This study demonstrates that birds of prey continue to face exposure to legacy contaminants as well as newly emerging contaminants at levels of concern.
A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group.

BACKGROUND Weaning patients from mechanical ventilation is an important problem in intensive care units. Weaning is usually conducted in an empirical manner, and a standardized approach has not been developed. METHODS We carried out a prospective, randomized, multicenter study involving 546 patients who had received mechanical ventilation for a mean (+/- SD) of 7.5 +/- 6.1 days and who were considered by their physicians to be ready for weaning. One hundred thirty patients had respiratory distress during a two-hour trial of spontaneous breathing. These patients were randomly assigned to undergo one of four weaning techniques: intermittent mandatory ventilation, in which the ventilator rate was initially set at a mean (+/- SD) of 10.0 +/- 2.2 breaths per minute and then decreased, if possible, at least twice a day, usually by 2 to 4 breaths per minute (29 patients); pressure-support ventilation, in which pressure support was initially set at 18.0 +/- 6.1 cm of water and then reduced, if possible, by 2 to 4 cm of water at least twice a day (37 patients); intermittent trials of spontaneous breathing, conducted two or more times a day if possible (33 patients); or a once-daily trail of spontaneous breathing (31 patients). Standardized protocols were followed for each technique. RESULTS The median duration of weaning was 5 days for intermittent mandatory ventilation (first quartile, 3 days; third quartile, 11 days), 4 days for pressure-support ventilation (2 and 12 days, respectively), 3 days for intermittent (multiple) trials of spontaneous breathing (2 and 6 days, respectively), and 3 days for a once-daily trial of spontaneous breathing (1 and 6 days, respectively). After adjustment for other covariates, the rate of successful weaning was higher with a once-daily trial of spontaneous breathing than with intermittent mandatory ventilation (rate ratio, 2.83; 95 percent confidence interval, 1.36 to 5.89; P < 0.006) or pressure-support ventilation (rate ratio, 2.05; 95 percent confidence interval, 1.04 to 4.04; P < 0.04). There was no significant difference in the rate of success between once-daily trials and multiple trials of spontaneous breathing. CONCLUSIONS A once-daily trial of spontaneous breathing led to extubation about three times more quickly than intermittent mandatory ventilation and about twice as quickly as pressure-support ventilation. Multiple daily trials of spontaneous breathing were equally successful.
Two stretching treatments for the hamstrings: proprioceptive neuromuscular facilitation versus kinesio taping.

CONTEXT Recent studies have shown that the static stretch (SS) may adversely affect leg-muscle performance. OBJECTIVES The authors examined the short-term effects of 2 stretching exercises on hamstrings muscle before and after exercise. DESIGN Crossover. SETTING Laboratory. PARTICIPANTS 9 healthy, physically active men. INTERVENTIONS There were 3 protocols in a randomized order with a 7-d interval: nonstretching (CON protocol), hamstrings static stretching (SS) with proprioceptive neuromuscular facilitation (PNF), and SS with kinesio-taping application on the hamstrings. MAIN OUTCOME MEASURES Outcome measures included first-felt and maximum tolerant-felt range of motion (FROM and TROM), maximal knee-flexion peak torque (PT) at 180°/s, and hamstrings muscle stiffness. RESULTS Groups were not different at prestretching in terms of hamstrings flexibility, PT, and muscle stiffness. At poststretching, both stretching protocols showed significant increases in FROM and TROM (P < .05). Stiffer hamstrings muscle and decreased PT were found in both SS+PNF and CON protocols (P < .05). However, there was no significant difference in the SS+Taping protocol (P > .05). CONCLUSION The stretching protocols improve hamstrings flexibility immediately, but after exercise hamstrings peak torque is diminished in the SS+PNF but not in the SS+Taping group. This means that SS+Taping can prevent negative results from exercise, which may prevent muscle injury.