Miracle-dz/UniFAR-FTUs huggingface dataset:
Baseline Performance Predicts tDCS-Mediated Improvements in Language Symptoms in Primary Progressive Aphasia

Primary Progressive Aphasia (PPA) is a neurodegenerative condition characterized by insidious irreversible loss of language abilities. Prior studies suggest that transcranial direct current stimulation (tDCS) directed toward language areas of the brain may help to ameliorate symptoms of PPA. In the present sham-controlled study, we examined whether tDCS could be used to enhance language abilities (e.g., picture naming) in individuals with PPA variants primarily characterized by difficulties with speech production (non-fluent and logopenic). Participants were recruited from the Penn Frontotemporal Dementia Center to receive 10 days of both real and sham tDCS (counter-balanced, full-crossover design; participants were naïve to stimulation condition). A battery of language tests was administered at baseline, immediately post-tDCS (real and sham), and 6 weeks and 12 weeks following stimulation. When we accounted for individuals’ baseline performance, our analyses demonstrated a stratification of tDCS effects. Individuals who performed worse at baseline showed tDCS-related improvements in global language performance, grammatical comprehension and semantic processing. Individuals who performed better at baseline showed a slight tDCS-related benefit on our speech repetition metric. Real tDCS may improve language performance in some individuals with PPA. Severity of deficits at baseline may be an important factor in predicting which patients will respond positively to language-targeted tDCS therapies. Clinicaltrials.gov ID: NCT02928848
1 DIFFERENTIAL EFFECTS OF ENDOGENOUS AND SYNTHETIC CANNABINOIDS ON α 7 -NICOTINIC ACETYLCHOLINE RECEPTOR-MEDIATED RESPONSES IN XENOPUS OOCYTES.

The effects of endogenous and synthetic cannabinoid receptor agonists including 2-arachidonoylglycerol, R-methanandamide, WIN55,212-2, CP55,940 and the psychoactive constituent of marijuana, ∆ 9 -THC, on the function of homomeric α 7 nicotinic ACh receptors expressed in Xenopus oocytes was investigated using the two-electrode voltage-clamp technique. The endogenous cannabinoid receptor ligands 2-arachidonoylglycerol and the metabolically stable analogue of anandamide (arachidonylethanolamide), R-methanandamide, reversibly inhibited currents evoked with ACh (100 µM) in a concentration-dependent manner (IC 50 values of 168 nM and 183 nM, respectively). In contrast, the synthetic cannabinoid receptor agonists CP55,940, the aminoalklylindole, WIN55,212-2, and the phytochemical ∆ 9 -THC did not alter α 7 nicotinic ACh receptor function. The inhibition of α 7 -mediated currents by 2-arachidonylglycerol was found to be non-competitive and voltage-independent. Additional experiments using endocannabinoid metabolites suggested that arachidonic acid, but not ethanolamine or glycerol, could also inhibit the α 7 -nACh receptor function. Whereas the effects of arachidonic acid were also noncompetitive and voltage-independent, its potency was much lower than 2-AG and anandamide. Results of studies with chimeric α 7 -nACh-5-HT 3 receptors comprised of the amino-terminal domain of the α 7 -nACh receptor and the transmembrane and carboxyl-terminal domains of 5-HT 3 receptors indicated that the site of interaction of the endocannabinoids with the α 7 -nAChR was not located on the N-terminal region of the receptor. These data indicate that cannabinoid receptor ligands that are produced in-situ potently inhibit α 7 -nACh receptor function, whereas the synthetic cannabinoid ligands, and ∆ 9 -THC, are without effect, or are relatively ineffective at inhibiting
Effect of Verapamil on the Cyclic AMP‐Mediated Pathway for Amylase Secretion in Rat Pancreatic Acini

In dispersed acini from rat pancreas, verapamil (a phenylalkylamine calcium channel blocker) potentiated amylase secretion stimulated by vasoactive intestinal peptide (VIP), secretin, peptide histidine isoleucine, helodermin, forskolin, and 8-bromocyclic AMP. The action of verapamil on VIP-stimulated amylase secretion was detectable at 10 μM verapamil and maximal at 100 μM verapamil. Verapamil did not alter binding of 125I-VIP, basal CAMP, the increase in cAMP caused by VIP, or the increase in CAMP-dependent protein kinase caused by VIP. The effects of verapamil on stimulated amylase secretion were fully reversible and could be reproduced by nicardipine (a 1,4- dihydropryidine calcium channel blocker) and diltiazem (a benzothiazepine calcium channel blocker), but not by cinnarizine (a piperazine calcium channel blocker). Although 300 μM verapamil increased outflux of 45Ca, 100 μM verapamil, the concentration that produced maximal potentiation of VIP stimulated amylase secretion, did not alter 45Ca outflux. Our results indicate that the action of verapamil to potentiate amylase secretion stimulated by secretagogues that activate the cAMP pathway occurs at a step that is distal to the activation of CAMP-dependent protein kinase.
LPS-INDUCED VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION IN RAT LUNG PERICYTES

Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. Recent studies have shown that the VEGF levels increase in several cell types, for example, macrophages and smooth muscle cells after LPS stimulation, suggesting that it is important in the initiation and development of sepsis. In particular, LPS-regulated contractility in lung pericytes may play an important role in mediating pulmonary microvascular fluid hemodynamics during sepsis. This study investigated the production of VEGF by rat lung pericytes in response to LPS. LPS was found to enhance VEGF mRNA expression in a concentration-dependent manner peaking 2 h after stimulation in pericytes. Vascular endothelial growth factor protein levels in conditioned medium and in cell lysate also increased on increasing LPS and peaked after 24 to 48 h. LPS also significantly augmented iNOS expression in lung pericytes within 6 h. However, iNOS mRNA induction occurred later than LPS-induced VEGF mRNA increases. Interestingly, attempted inhibition with nuclear factor-&kgr;B or tyrosine kinase did not suppress LPS-induced augmented VEGF mRNA expression in lung pericytes, although both inhibitors markedly inhibited LPS-induced iNOS mRNA expression. SB203580, a p38 MAP kinase inhibitor, repressed LPS-induced VEGF mRNA expression. Furthermore, LPS stimulated a rapid and sustained phosphorylation of p38 MAP kinase. These results show that pericytes produce VEGF in response to LPS stimulation, and that this may be partly mediated by the p38 MAP kinase pathway. More research should be done to establish the regulation of capillary hemodynamics and identify mechanisms of their regulation.ABBREVIATIONS ARDS-acute respiratory distress syndrome; SIRS-systemic inflammatory response syndrome; VEGF-vascular endothelial growth factor
Venlafaxine in the treatment of depressive and vasomotor symptoms in women with perimenopausal depression

Perimenopause is often marked by vasomotor symptoms and dysphoria. Antidepressant studies have demonstrated decreased frequency and severity of hot flashes in breast cancer survivors and menopausal women. We hypothesized that venlafaxine would relieve both depressive and vasomotor symptoms in depressed perimenopausal women. Sixteen women fulfilling clinical criteria for climacteric phase and Diagnostic and Statistical Manual of Mental Disorders (DSM)‐IV criteria for a depressive episode were enrolled in an open‐label 8‐week trial of extended‐release venlafaxine. Depressive and climacteric symptoms were monitored using the Hamilton Rating Scales for Depression (Ham‐D) and Anxiety (Ham‐A), Clinical Global Impression (CGI) scale, and Greene Climacteric Scale (GCS). Serum follicular stimulating hormone (FSH) and estradiol concentrations were monitored. Significant decreases in Ham‐D and Ham‐A scores and the GCS psychiatric subscale were seen after 2 weeks of treatment. In an intention‐to‐treat analysis, 81% of the subjects demonstrated a therapeutic antidepressant response (>50% decline in Ham‐D score) and 75% achieved clinical remission (Ham‐D score ≤7) after 8 weeks of venlafaxine therapy (75–225 mg/day). Total GCS scores declined 60%, and GCS vasomotor subscores decreased among those with vasomotor symptoms at baseline. These data suggest that venlafaxine treatment improves overall well‐being, reduces depressive symptoms, and may diminish baseline vasomotor symptoms in depressed perimenopausal women. Further studies are warranted to investigate the utility of venlafaxine in perimenopausal depression. Depression and Anxiety 22:94–97, 2005. © 2005 Wiley‐Liss, Inc.
“No-Touch” versus “Endo” Vein Harvest: Early Patency on Symptom-Directed Catheterization and Harvest Site Complications

Objective “No-touch” (NT) saphenous vein harvesting preserves the adventitial vasa vasorum, prevents medial ischemia, and is associated with an improved short-term and long-term vein graft patency. It may also be associated with a higher rate of harvest site complications. Endovascular vein harvesting (endo-vein) has a low rate of harvest site complications but also a tendency toward a lower patency rate. Methods During a 2-year period (2011–2012), we compared the vein graft patency at symptom-directed cardiac catheterization as well as wound complication rates in 210 patients who received either NT (87 patients) or endo-vein (123 patients). Results The recatheterization rate for the two groups was similar: 9 (10.3%) of 87 of the NT patients versus 11 (9.0%) of 123 of the endo-vein patients. There was a significant difference in vein graft patency between the groups: 15 (94%) of 16 NT vein grafts were patent versus 6 (27%) of 22 of endo-veins (P < 0.02). The endo-vein graft patency during this 2-year period was similar to the total endo-vein patency (37%) during a 4-year period. A comparison between a more experienced and a less experienced harvester revealed no difference in patency rate. Harvest site complications were significantly higher with the NT harvest: 18% of the NT patients requiring vacuum-assisted wound closure or intravenous antibiotics versus 2% of the endo-vein patients (P < 0.0001). The application of platelet-rich plasma did not significantly lower wound complication rates (P = 0.27). Conclusions These results suggest that NT vein harvesting may be associated with improved graft patency, but methods should be developed to lower wound complication rates.
Analysis of potassium dynamics in mammalian brain tissue.

Equations are derived for potassium (K+) dynamics in simplified models of brain tissue. These describe K+ movement in extracellular space, transfer of K+ associated with current flow through cells (the so‐called spatial buffer mechanism) and equilibration between extracellular space and cytoplasm. Numerical calculations show that the principal data on K+ dynamics from various laboratories can be accounted for with simple assumptions about spatial buffer action and uptake. Much of the data is inconsistent with extracellular diffusion being the main mechanism for K+ flux through brain tissue, including some that has earlier been cited in support of this hypothesis. The buffering actions of spatial buffer transfer of K+ and of cytoplasmic equilibration, in which these mechanisms reduce rises of [K+]o that would otherwise occur, are analysed quantitatively for specific K+ source distributions and for spatial and temporal frequency components of general disturbances. Spatial buffer action has most effect in reducing [K+]o rises with net release over extensive zones of tissue (greater than ca. 200 micron in diameter) for periods of the order of minutes. Reductions greater than 75% may be achieved. With localized but prolonged release, the maximum [K+]o rise is little affected but the volume of tissue affected by more moderate rises is substantially reduced. Cytoplasmic K+ uptake also has most effect with widespread release, but its effect diminishes with prolonged periods of release. The effects of the buffering mechanisms and of K+ re‐uptake into active neurones in determining the decline of [K+]o after a period of stimulation are considered. Re‐uptake is unlikely to be the major factor responsible for [K+]o decline when this has a time course of only a few seconds. The properties necessary for the cells mediating the spatial buffer mechanisms, possibly glial cells, are assessed.
The Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Procedural Memory and Dysphoric Mood in Patients With Major Depressive Disorder

Objective:To study the effects of depression and treatment with repetitive transcranial magnetic stimulation (rTMS) on sequence learning. Background:Prefrontal dysfunction in depression may affect sequence learning and be amenable to normalization by rTMS. Method:The serial reaction time test (SRTT) was administered to 19 patients with major depressive disorder (MDD) and 20 nondepressed control participants. MDD patients were examined before and following treatment with rTMS to the left dorsolateral prefrontal cortex in daily sessions of 1600 stimuli at 10 Hz and at an intensity of 110% of the motor threshold. Treatment occurred over a 2-week interval of time. Results:MDD and nondepressed groups differed significantly with respect to baseline response speed. Following treatment with rTMS, MDD participants demonstrated significantly improved mood, improved response speed, and improved procedural learning. Conclusions:Findings suggest that rTMS over a 2-week period improves performance on tasks of response speed and procedural memory in patients with MDD. These cognitive effects are greater in those patients who showed a significant antidepressant effect to rTMS intervention.
Contending and Adapting Every Day

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood disorders, and little attention has been paid to the parents and their experiences. The aim of this study was to gain a deeper understanding of the Norwegian parents’ lived experiences of having a child with an ADHD diagnosis. A descriptive design using phenomenological approach was chosen as the research method. Individual qualitative interviews with nine parents, who were members of the ADHD Association, were conducted. The interviews were analyzed according to Colaizzi’s method. The essential structure of the parents’ experiences was Contending and Adapting Every Day—Windsurfing in unpredictable waters which was embedded in the interrelated main themes: Maintaining the Self and Parenthood, and Interacting With the Surrounding World. Being the parent of a child with ADHD is a demanding situation. Nurses need to address the needs of these parents and focus on the family unit.
Intellectual impairment in children exposed to polychlorinated biphenyls in utero.

BACKGROUND In utero exposure to polychlorinated biphenyls, a ubiquitous environmental contaminant, has been linked to adverse effects on neurologic and intellectual function in infants and young children. We assessed whether these effects persist through school age and examined their importance in the acquisition of reading and arithmetic skills. METHODS We tested 212 children, recruited as newborns to overrepresent infants born to women who had eaten Lake Michigan fish contaminated with polychlorinated biphenyls. A battery of IQ and achievement tests was administered when the children were 11 years of age. Concentrations of polychlorinated biphenyls in maternal serum and milk at delivery were slightly higher than in the general population. A composite measure of prenatal exposure was derived from concentrations in umbilical-cord serum and maternal serum and milk. RESULTS Prenatal exposure to polychlorinated biphenyls was associated with lower full-scale and verbal IQ scores after control for potential confounding variables such as socioeconomic status (P = 0.02). The strongest effects related to memory and attention. The most highly exposed children were three times as likely to have low average IQ scores (P <0.001) and twice as likely to be at least two years behind in reading comprehension (P = 0.03). Although larger quantities of polychlorinated biphenyls are transferred by breast-feeding than in utero, there were deficits only in associated with transplacental exposure, suggesting that the developing fetal brain is particularly sensitive to these compounds. CONCLUSIONS In utero exposure to polychlorinated biphenyls in concentrations slightly higher than those in the general population can have a long-term impact on intellectual function.
Postoperative outcome after coronary artery bypass grafting in chronic obstructive pulmonary disease.

BACKGROUND It is uncertain if the presence and severity of airflow obstruction in chronic obstructive pulmonary disease (COPD) is predictive of surgical morbidity and mortality after coronary artery bypass grafting (CABG). METHODS Retrospective study of patients who underwent CABG between 1998 and 2003 in a university-affiliated hospital for whom a preoperative spirometry was available. COPD was diagnosed in smokers or ex-smokers 50 years of age or older in the presence of irreversible airflow obstruction. Patients were divided into three groups depending on the spirometry: controls (forced expiratory volume in 1 s [FEV1] 80% or more, FEV1/forced vital capacity [FVC] greater than 0.7), mild to moderate COPD (FEV1 50% or more and FEV1/FVC 0.7 or less) and severe COPD (FEV1 less than 50% and FEV1/FVC 0.7 or less). RESULTS Among the 411 files studied, 322 (249 men, 68+/-8 years of age) were retained (controls, n=101; mild to moderate COPD, n=153; severe COPD, n=68). The mortality rate (3.0%, 2.6% and 0%, respectively) was comparable among the three groups. Patients with severe COPD had a slightly longer hospital stay than controls (mean difference 0.7+/-1.4 days, P<0.05). Pulmonary infections were more frequent in severe COPD (26.5%) compared with mild to moderate COPD (12.4%) and controls (12.9%), P<0.05. Atrial fibrillation tended to be more frequent in severe COPD than in the other two groups. CONCLUSION Mortality rate associated with CABG surgery is not influenced by the presence and severity of airflow obstruction in patients with COPD. The incidence of pulmonary infections and length of hospital stay were increased in patients with severe COPD.
A genotype resource for postmortem brain samples from the Autism Tissue Program

The Autism Tissue Program (ATP), a science program of Autism Speaks, provides researchers with access to well‐characterized postmortem brain tissues. Researchers access these tissues through a peer‐reviewed, project‐based approval process, and obtain related clinical information from a secure, online informatics portal. However, few of these samples have DNA banked from other sources (such as a blood sample from the same individual), hindering genotype–phenotype correlation and interpretation of gene expression data derived from the banked brain tissue. Here, we describe an initiative to extract DNA from Brodmann Area 19, and genotype these samples using both the Affymetrix Genome‐Wide Human SNP Array 6.0 and the Illumina Human1M‐Duo DNA Analysis BeadChip genome‐wide microarray technologies. We additionally verify reported gender, and infer ethnic background from the single nucleotide polymorphism data. We have also used a rigorous, multiple algorithm approach to identify genomic copy number variation (CNV) from these array data. Following an initial proof of principle study using two samples, 52 experimental samples, consisting of 27 subjects with confirmed or suspected autism and related disorders, 5 subjects with cytogenetically visible duplications of 15q, 2 with epilepsy and 18 age‐matched normal controls were processed, yielding high‐quality genotype data in all cases. The genotype and CNV data are provided via the ATP informatics portal as a resource for the autism research community. Autism Res 2011, 4: 89–97. © 2011, International Society for Autism Research, Wiley Periodicals, Inc.
Investigation into the role of apolipoprotein B gene 8344C/T variant on plasma cholesterol levels by allele-specific PCR amplification.

The 8344C/T polymorphism of the apoB gene was genotyped by an original modification of PCR allele-specific amplification consisting in a single amplification reaction double-primed by two opposite allele-specific oligonucleotides nested in a larger amplified fragment. This method was used to genotype 200 randomly selected healthy individuals (113 males, 87 females). The frequency of the rare allele in this random Italian population was 0.240, i.e. not far from the 0.282 frequency observed in hypocholesterolemic Norwegians and suggestive of a moderating effect on LDL levels of our population. However, we did not find any significant cholesterol-lowering effect of this polymorphism either by comparing the frequency of mutant alleles in the population stratified for its plasma lipoprotein levels or by studying the association between ApoB genotype and the different lipoproteins. In conclusion this ApoB polymorphism appeared to have a secondary role in LDL- and HDL-cholesterol variations of our population.
Influence of biomass burning during recent fluctuations in the slow growth of global tropospheric methane

During the past 15 years the annual growth rate of tropospheric methane (CH4) has shown striking changes over 2–3 year periods, varying from +1% yr−1 to slightly negative values (−0.2% yr−1). These fluctuations are superimposed on an overall slowdown of the CH4 growth rate since the 1980s. Here we use our complementary measurement of other compounds (ethane, tetrachloroethene) to confirm the influence of biomass burning on large global CH4 pulses in 1998 and 2002–2003. Methane growth rate fluctuations also track ENSO indices, most likely via the influence of ENSO activity on large‐scale biomass burning. We also report the seventh year of near‐zero growth of global CH4 levels (Dec. 1998–Dec. 2005). The global CH4 mixing ratio was 1772 ± 1 ppbv in 2005, and CH4 increases of 118–376 ppbv between 2000–2020 (ten scenarios in the 2001 IPCC report, to levels around 1900+ ppbv by 2020, now appear quite unlikely.