Miracle-dz/UniFAR-FTUs huggingface dataset:
Cumulative effect of norepinephrine and dopamine carrier blockade on extracellular dopamine increase in the nucleus accumbens shell, bed nucleus of stria terminalis and prefrontal cortex

We investigated, by microdialysis in various brain areas, the possibility that dopamine could be captured by the norepinephrine transporter when the dopamine transporter is pharmacologically blocked. Administration of reboxetine, a selective blocker of the norepinephrine transporter, 20 min after the administration of GBR 12909, a selective blocker of the dopamine transporter, produced an increase of dopamine output in the nucleus accumbes shell (+408% above basal) greater than that obtained by GBR 12909 alone (+308% above basal). On the contrary, reboxetine did not increase further the dopamine output produced by GBR 12909 in the nucleus accumbens core or in the dorsal caudate, areas lacking a consistent noradrenergic innervations. A cumulative effect of dopamine and norepinephrine transporter blockade on the output of dopamine in dialysates was also observed in the bed nucleus of stria terminalis and in the prefrontal cortex. This study shows that dopamine extracellular concentration can be elevated by norepinephrine transporter blockade, even in areas where the dopamine transporter is predominant, when the latter is pharmacologically blocked. This phenomenon may have relevance in psychostimulant dependence as well as in antidepressant pharmacology.
Insomnia and the risk of incident heart failure: a population study.

AIMS Insomnia is highly prevalent among heart failure patients, but only a few small studies have investigated insomnia symptoms and risk of heart failure. We aimed to assess the prospective association between self-reported insomnia symptoms and the risk of incident heart failure in a large Norwegian cohort. METHODS AND RESULTS Baseline data on insomnia symptoms, including difficulty initiating sleep, difficulty maintaining sleep and having non-restorative sleep, socio-demographic variables, and health status, including established cardiovascular risk factors, were collected from 54 279 men and women 20-89 years of age who participated in the Nord-Trøndelag Health study (HUNT) between 1995 and 1997 and were free from known heart failure at baseline. The cohort was followed for incident heart failure from baseline through 2008. We used Cox proportional hazard models to assess the association of baseline insomnia symptoms with the risk of heart failure. A total of 1412 cases of heart failure occurred during a mean follow-up of 11.3 years (SD = 2.9 years), either identified at hospitals or by the National Cause of Death Registry. There was a dose-dependent association between the number of insomnia symptoms and risk of heart failure. The multi-adjusted hazard ratios were 0.96 (0.57-1.61), 1.35 (0.72-2.50), and 4.53 (1.99-10.31) for people with one, two, and three insomnia symptoms, compared with people with none of the symptoms (P for trend 0.021). CONCLUSIONS Insomnia is associated with an increased risk of incident heart failure. If our results are confirmed by others and causation is proved, evaluation of insomnia symptoms might have consequences for cardiovascular prevention.
Asymptomatic Cerebral Microbleeds in Adult Patients with Moyamoya Disease: A Prospective Cohort Study with 2 Years of Follow-Up

Objective: Risk factors for cerebral microbleeds (CMBs) in moyamoya disease (MMD) remain unknown, and whether the presence or distribution of CMBs is related to the subsequent hemorrhagic events needs to be confirmed. This study aimed to investigate the relationship between intracranial vascular morphology and the incidence/distribution patterns of CMBs as well as to determine the outcome in adult patients with MMD. Methods: Eighty-five consecutive adult patients with MMD were prospectively evaluated by 3.0-tesla high-intensity susceptibility-weighted magnetic resonance imaging and catheter-based digital subtraction angiography from June 2009 to January 2012. The differences in intracranial angiography (Suzuki stages, posterior cerebral artery stages, and angiographic features of the anterior choroidal and posterior communicating arteries) and clinical parameters (age, gender, hemorrhagic onset, antiplatelet treatment, systolic/diastolic blood pressure, diabetes, and plasma fibrinogen) among various CMB distribution patterns were analyzed with multinomial logistic regression. Moreover, after a median follow-up of 23 months, the relationship between CMB distribution patterns and subsequent intraventricular hemorrhage was also analyzed with Kaplan-Meier survival analysis and a Cox proportional hazards model. Results: Forty-five female and 40 male patients were finally enrolled in the study with an average age of 41.4 ± 12.7 years. Thirty-one CMB foci were detected in 24 (28.2%) patients. Most of the lesions (n = 22, 71.0%) were located in the region of deep and periventricular white matter (DPWM). Dilation and extension of anterior choroidal and posterior communicating arteries (AChA-PComA) was found to be an independent risk factor associated with the CMBs located in DPWM (p = 0.045; odds ratio 3.39, 95% CI 1.03-11.19). Patients with DPWM CMBs showed a statistically higher likelihood of subsequent intraventricular hemorrhage compared to patients without CMB foci and with CMBs in other regions (p = 0.014) during the follow-up period. Multivariable analysis suggested that DPWM CMBs were independent predictors of subsequent intraventricular hemorrhage (p = 0.028; hazard ratio 5.53, 95% CI 1.20-25.41). Conclusions: Dilation and extension of AChA-PComA is a determinant of CMBs involved in DPWM. CMBs in DPWM are probably predictors of subsequent intraventricular hemorrhage.
5-HT antagonists NAN-190 and SB 269970 block &agr;2-adrenoceptors in the guinea pig

Serotonin (5-HT) plays a significant role in the regulation of intestinal secretion of water and electrolytes. The initial aim of this study was to use intracellular recording and specific antagonists to identify roles of 5-HT1A and 5-HT7 receptors of submucosal noncholinergic secretomotor neurons of guinea pig ileum, in vitro. However, it was found that the widely used 5-HT receptor antagonists NAN-190 (5-HT1A) and SB 269970 (5-HT7) both blocked &agr;2-adrenoceptors, and hence depressed inhibitory synaptic potentials and hyperpolarizations evoked by noradrenaline, in these neurons. Both compounds enhanced neurally evoked contractions of the guinea pig vas deferens, an effect characteristic of blockade of &agr;2-adrenoceptors. These results raise significant concerns about studies using NAN-190 and SB 269970 as specific antagonists of serotonin receptors.
Characterization of pseudorabies virus of wild boar origin from Europe

SUMMARY Pseudorabies virus (PrV) infections appear to be more widely distributed in the European wild boar (Sus scrofa) population than assumed. In Europe, attempts to isolate and characterize the causative agents have been limited so far. We therefore collected and examined a total of 35 PrV isolates obtained from wild boar or hunting dogs in Germany, France, Spain, Italy, Slovakia and Hungary between 1993 and 2008. Restriction enzyme analysis of genomic DNA using BamHI showed that all isolates, except one, belonged to genogroup I but different subtypes were evident. For further investigations of the phylogenetic relationships, a 732-bp fragment of the glycoprotein C (gC) gene was amplified by PCR. Sequence analysis revealed about 40 variant positions within this fragment. Comparison of the nucleotide sequences supported the separation into a clade containing isolates from North-Rhine Westphalia, Rhineland-Palatinate (Germany), France and Spain (clade B) and an apparently more variable clade comprising isolates from Brandenburg, Baden-Wurttemberg, Saxony, Saxony-Anhalt (Germany), Slovakia, Hungary, Italy and France (clade A).
Difficulties in emotion regulation differentiate depressive and obsessive–compulsive symptoms and their co-occurrence

ABSTRACT Background and Objectives: Depressive and obsessive–compulsive (OC) symptoms are frequently comorbid, and the combination of these may result in additional impairment compared to the difficulties of experiencing one of these symptom groups. Emotion regulation difficulties underlie many forms of psychopathology symptoms, and this study examined whether aspects of emotion regulation could differentiate clinical levels of depressive and OC symptoms, and their co-occurrence. Design and Method: College students (N = 199; Mage = 19.47 years; 59.8% female) were grouped based on the presence of clinical levels of OC and depressive symptoms. Using a multinomial logistic regression approach, differences in odds ratios for emotion regulation difficulties were examined. Results: The co-occurring clinical-symptom group was differentiated from the single clinical-symptom groups on several aspects of emotion regulation. Impulse-control difficulties and limited access to emotion regulation strategies differentiated clinical levels of depressive from OC symptoms. Conclusions: This study highlights the importance of conducting a nuanced emotion assessment to best inform prevention and treatment of depressive and OC symptoms, and their comorbidity.
Effects of depressive symptoms on health-related quality of life in asthma patients

OBJECTIVE: To assess the effects of depressive symptoms on asthma patients’ reports of functional status and health-related quality of life.DESIGN: Cross-sectional study.SETTING: Primary care internal medicine practice at a tertiary care center in New York City.PATIENTS: We studied 230 outpatients between the ages of 18 and 62 years with moderate asthma.MEASUREMENTS AND MAIN RESULTS: Patients were interviewed in person in English or Spanish with two health-related quality-of-life measures, the disease-specific Asthma Quality of Life Questionnaire (AQLQ) (possible score range, 1 to 7; higher scores reflect better function) and the generic Medical Outcomes Study SF-36 (general population mean is 50 for both the Physical Component Summary [PCS] score and Mental Component Summary [MCS] score). Patients also completed a screen for depressive symptoms, the Geriatric Depression Scale (GDS), and a global question regarding current disease activity. Stepwise multivariate analyses were conducted with the AQLQ and SF-36 scores as the dependent variables and depressive symptoms, comorbidity, asthma, and demographic characteristics as independent variables. The mean age of patients was 41 ± SD 11 years and 83% were women. The mean GDS score was 11 ± SD 8 (possible range, 0 to 30; higher scores reflect more depressive symptoms), and a large percentage of patients, 45%, scored above the threshold considered positive for depression screening. Compared with patients with a negative screen for depressive symptoms, patients with a positive screen had worse composite AQLQ scores (3.9±SD 1.3 vs 2.8±SD 0.8, P<.0001) and worse PCS scores (40±SD 11 vs 34±SD 8, P<.0001) and worse MCS scores (48±SD 11 vs 32±SD 10, P<.0001) scores. In stepwise analyses, current asthma activity and GDS scores had the greatest effects on patient-reported health-related quality of life, accounting for 36% and 11% of the variance, respectively, for the composite AQLQ, and 11% and 38% of the variance, respectively, for the MCS in multivariate analyses.CONCLUSIONS: Nearly half of asthma patients in this study had a positive screen for depressive symptoms. Asthma patients with more depressive symptoms reported worse health-related quality of life than asthma patients with similar disease activity but fewer depressive symptoms. Given the new emphasis on functional status and health-related quality of life measured by disease-specific and general health scales, we conclude that psychological status indicators should also be considered when patient-derived measures are used to assess outcomes in asthma.
Profiles by suicide methods: an analysis of older adults

ABSTRACT Objective: The aim of this study was to investigate choice of suicide method in individuals aged 65 years and over. Methods: Data were obtained from the Queensland Suicide Register, Australia. Univariate and multi-variate logistic regression analyses were conducted. Results: The predominant methods in older adults were hanging (21.5%), firearms and explosives (20.9%), drug poisoning (18.5%), followed by other poisoning (mainly MVCO) (12.6%), suffocation by plastic bag (8.5%), and drowning (6%). Some methods (e.g. firearms and explosives, drug poisoning, suffocation) appeared characterised by profiles (e.g., socio-demographic and clinical aspects), meanwhile others were not well distinguishable. Compared to other methods, those who died by firearms and explosives were significantly more likely to be males, Australian born, live in rural and remote areas, and less likely to have a mental illness, previous suicide attempt(s) or leave a suicide note. Those who died by drug poisoning were more likely to be females, leave a suicide note, experience interpersonal conflict and live in urban areas. Similarly, those who chose suffocation by plastic bag were more likely to be older females, leave a suicide note, and pay attention to suicide in the media, but less likely to experience interpersonal conflict. Conclusion: Acceptability, availability and lethality are important factors impacting choice of means and should be considered when designing suicide prevention activities in older adults.
Dynamics of GnRH Neuron Ionotropic GABA and Glutamate Synaptic Receptors Are Unchanged during Estrogen Positive and Negative Feedback in Female Mice

Abstract Inputs from GABAergic and glutamatergic neurons are suspected to play an important role in regulating the activity of the gonadotropin-releasing hormone (GnRH) neurons. The GnRH neurons exhibit marked plasticity to control the ovarian cycle with circulating estradiol concentrations having profound “feedback” effects on their activity. This includes “negative feedback” responsible for suppressing GnRH neuron activity and “positive feedback” that occurs at mid-cycle to activate the GnRH neurons to generate the preovulatory luteinizing hormone surge. In the present study, we employed brain slice electrophysiology to question whether synaptic ionotropic GABA and glutamate receptor signaling at the GnRH neuron changed at times of negative and positive feedback. We used a well characterized estradiol (E)–treated ovariectomized (OVX) mouse model to replicate negative and positive feedback. Miniature and spontaneous postsynaptic currents (mPSCs and sPSCs) attributable to GABAA and glutamatergic receptor signaling were recorded from GnRH neurons obtained from intact diestrous, OVX, OVX + E (negative feedback), and OVX + E+E (positive feedback) female mice. Approximately 90% of GnRH neurons exhibited spontaneous GABAA-mPSCs in all groups but no significant differences in the frequency or kinetics of mPSCs were found at the times of negative or positive feedback. Approximately 50% of GnRH neurons exhibited spontaneous glutamate mPSCs but again no differences were detected. The same was true for spontaneous PSCs in all cases. These observations indicate that the kinetics of ionotropic GABA and glutamate receptor synaptic transmission to GnRH neurons remain stable across the different estrogen feedback states.
Arginase inhibition mediates cardioprotection during ischaemia-reperfusion.

AIMS Nitric oxide (NO) is vital for the integrity of the cardiovascular system and protection against ischaemic heart disease. Arginase is up-regulated during ischaemia-reperfusion (IR) and this enzyme might compete with NO synthase (NOS) for arginine. The present study investigated whether arginase blockade protects from myocardial IR injury and whether such an effect is coupled to increased NO bioavailability. METHODS AND RESULTS Sprague-Dawley rats were subjected to 30 min of coronary artery ligation, followed by 2 h of reperfusion. The animals were given either saline, or the arginase inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA) with or without the NO scavenger carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO) or the NOS inhibitor N(G)-monomethyl-l-arginine (l-NMMA) iv 15 min before ischaemia. The infarct size was 79 +/- 4% of the area at risk in the control group. Nor-NOHA treatment reduced the infarct size to 39 +/- 7% (P < 0.001). Administration of cPTIO or l-NMMA completely abolished the protective effect of nor-NOHA. Expression of arginase I was significantly (P < 0.05) increased in ischaemic myocardium. Nor-NOHA treatment resulted in higher plasma levels of nitrite (P < 0.05) and a 10-fold increase in the citrulline/ornithine ratio (P < 0.001), indicating a shift in arginine utilization towards NOS. CONCLUSION Inhibition of arginase protects from myocardial infarction by a mechanism that is dependent on NOS activity and bioavailability of NO by shifting arginine utilization from arginase towards NOS. These findings suggest that targeting of arginase is a promising future therapeutic strategy for protection against myocardial IR injury.
Severity of attempted suicide as measured by the Pierce Suicidal Intent Scale.

BACKGROUND Suicidal intent is an essential feature of suicidal behavior. Previous research has been controversial and the need for further evidence has been pointed out. AIMS The aim of the present study was to characterize the severity of attempted suicide by extracting components of suicidal intent and analyzing levels of suicidal intent by gender, age, and variables indicating the severity of attempted suicide. METHODS Data on suicide attempters (N = 469) were collected in Estonia using WHO SUPRE-MISS methodology. To measure suicidal intent, a revised version of the Pierce Suicidal Intent Scale (PSIS) was used. RESULTS The level of suicidal intent was not gender-dependent, but rose with age. Males and females were also similar in terms of discrete components. Classified in age groups, their unequivocally expressed "wish to die" was similar, but equivocal communication (components termed "arrangements" and "circumstances") increased with age. Middle-aged groups scored higher for the "alcohol/drugs" component. Psychiatric diagnosis, method of attempting suicide, and duration of hospitalization were linked to suicidal intent, but danger to life as assessed by interviewers was not. CONCLUSIONS In suicide-risk assessment, results from a Suicidal Intent Scale contribute to clinical observation and add valuable information about a suicidal person's real intention.
Angiotensin‐converting enzyme is required for normal myelopoiesis

Inhibition of angiotensin‐converting enzyme (ACE) induces anemia in humans and mice, but it is unclear whether ACE is involved in other aspects of hematopoiesis. Here, we systemically evaluated ACE‐knockout (KO) mice and found myelopoietic abnormalities characterized by increased bone marrow myeloblasts and myelocytes, as well as extramedullary myelopoiesis. Peritoneal macrophages from ACE‐KO mice were deficient in the production of effector molecules, such as tumor necrosis factor‐α, interleukin‐12p40, and CD86 when stimulated with lipopolysaccharide and interferon‐γ. ACE‐KO mice were more susceptible to Staphylococcus aureus infection. Further studies using total or fractionated bone marrows revealed that ACE regulates myeloid proliferation, differentiation, and functional maturation via angiotensin II and substance P and through the angiotensin II receptor type 1 and substance P neurokinin 1 receptors. Angiotensin II was correlated with CCAAT‐enhancer‐binding protein‐α up‐regulation during myelopoiesis. Angiotensin II supplementation of ACE‐KO mice rescued macrophage functional maturation. These results demonstrate a previous unrecognized significant role for ACE in myelopoiesis and imply new perspectives for manipulating myeloid cell expansion and maturation. —Lin, C. , Datta, V. , Okwan‐Duodu, D. , Chen, X. , Fuchs, S. , Alsabeh, R. , Billet, S. , Bernstein, K. E. , Shen, X. Z. Angiotensin‐converting enzyme is required for normal myelopoiesis. FASEB J. 25, 1145–1155 (2011). www.fasebj. org
Experimental Study and Sensing Applications of Polarization-Dependent Lossy Mode Resonances Generated by D-Shape Coated Optical Fibers

The fabrication and characterization of an optical fiber refractometer based on lossy mode resonances (LMR) is presented. TiO2/poly (sodium 4-styrenesulfonate) (PSS) coatings deposited on side-polished D-shaped optical fibers are used as LMR supporting coatings. LMRs are sensitive to the external medium refractive index, and D-shaped optical fibers enable the observation of TE and TM LMR polarizations. These refractometers based on TE and TM LMR showed an average sensitivity of 2737 nm/RIU and 2893 nm/RIU, respectively, for a surrounding medium refractive index range from 1.35 to 1.41. This study also explores the utilization of previously described refractometers in the context of two common industrial applications, such as the determination of the sugar content or °Brix in beverages and the salt concentration in sea water.
Retrospective study of surgery-related outcomes in patients with syringomyelia associated with Chiari I malformation: clinical significance of changes in the size and localization of syrinx on pain relief.

OBJECT Pain is one of the major symptoms in patients with syringomyelia; however, its origin is not fully understood, and postoperative improvement of pain is difficult to predict. The objectives of this study were to assess the surgery-related results obtained in patients who underwent treatment for syringomyelia associated with Chiari I malformation, particularly related to pain status, and to identify factors that may influence improvement in postoperative pain by comparing pre- and postoperative magnetic resonance (MR) imaging findings. METHODS The correlation between pre- and postoperative changes in the size and the location of the syrinx and pain improvement was investigated in 25 patients. The shapes of the syringes were classified into three types: central, enlarged, and deviated. In most cases in which the syrinx deviated toward the posterolateral aspect of the spinal cord at the level corresponding to dermatomal distribution of preoperative pain, the lesion remained at the same position postoperatively, and improvement in pain was poor. On the other hand, enlarged-type syringes were the most frequently observed prior to surgery, exhibited diverse changes postoperatively, and improvement in pain status was difficult to predict. When postoperative MR imaging revealed a transformation to the deviated type, poor pain improvement was noted. CONCLUSIONS Neurons in the dorsal horn were thought to be involved in the development of pain as a result of the deafferentiation mechanism in cases of syringomyelia.
p27kip1 Expression in non-small cell lung cancer is not an independent prognostic factor.

BACKGROUND p27(Kip1) (p27) plays an important role in cancer cell cycle regulation. Recent evidence however, suggests that p27 may function as an oncogene rather than a tumour suppressor gene. PATIENTS AND METHODS Ninety-two patients with previously untreated non-small cell lung cancer (NSCLC) were studied for the association between the immunohistochemical localization of p27 through a semi-quantitative method and time-to-progression (TTP) and overall survival (OS). RESULTS The relationship between p27 H-Score and both TTP and OS was polynomial. Short TTP in patients with metastasis or whose tumors progressed during the eight-month period after diagnosis was statistically associated with overexpression of PIRH2 (p<0.001). In patients whose tumours progressed later, long TTP was associated with NSCLC of the non-adenocarcinoma type (p=0.027), p27 H-Score (p=0.032) and well-differentiated adenocarcinoma (p=0.047). None of the parameters correlated with duration of OS. CONCLUSIONS This study showed that p27 H-Score may not appear to be an independent prognostic factor in patients with NSCLC.