Miracle-dz/UniFAR-FTUs huggingface dataset:
Maturational alterations in constitutive activity of medial prefrontal cortex kappa‐opioid receptors in Wistar rats

Opioid receptors can display spontaneous agonist‐independent G‐protein signaling (basal signaling/constitutive activity). While constitutive κ‐opioid receptor (KOR) activity has been documented in vitro, it remains unknown if KORs are constitutively active in native systems. Using [35S] guanosine 5′‐O‐[gamma‐thio] triphosphate coupling assay that measures receptor functional state, we identified the presence of medial prefrontal cortex KOR constitutive activity in young rats that declined with age. Furthermore, basal signaling showed an age‐related decline and was insensitive to neutral opioid antagonist challenge. Collectively, the present data are first to demonstrate age‐dependent alterations in the medial prefrontal cortex KOR constitutive activity in rats and changes in the constitutive activity of KORs can differentially impact KOR ligand efficacy. These data provide novel insights into the functional properties of the KOR system and warrant further consideration of KOR constitutive activity in normal and pathophysiological behavior.
Multiple sclerosis and gestation

The gestational history of 512 women with multiple sclerosis revealed that the risk of MS-onset, exacerbation, or progression was two to three times as high during the 6 months after childbirth as during pregnancy. Using a progression-index as a measure of prognosis (disability divided by duration), the speed of deterioration was comparable for women who became pregnant and those who did not. An apparent but insignificant trend toward better prognosis for women with pregnancies after MS-onset was most likely due to their younger age at onset. The natural course of pregnancy and childbirth was comparable among women pregnant before and during the disease. There was no evidence of an increased frequency of congenital malformations in the offsprings.
Topical application of a film‐forming emulgel dressing that controls the release of stratifin and acetylsalicylic acid and improves/prevents hypertrophic scarring

Here, we evaluate the efficacy of an emulgel dressing to control the release of an antifibrogenic factor, stratifin (SFN), along with an anti‐inflammatory drug, acetylsalicylic acid (ASA), to be used as a wound dressing with hypertrophic scar reducing features. Emulgel dressings were prepared by dispersing positively charged submicron vesicles in carboxymethyl cellulose gel. Release kinetics of SFN/ASA and toxicity for primary skin cells were assessed in vitro. Antifibrogenic efficacy of medicated emulgel dressings was tested on a rabbit ear fibrotic model. Following topical application on the wounds, emulgels formed an occlusive film and controlled the release of SFN and ASA for 7 and 24 hours, respectively. Wounds treated with SFN/ASA‐containing emulgel dressings showed an 80% reduction in scar elevation compared with untreated controls. Topical formulations were nontoxic for cultured human keratinocytes and fibroblasts. Inflammation was significantly controlled in treated wounds, as shown by a reduced number of infiltrated CD3+ T cells (p < 0.001) and macrophages. SFN/ASA‐treated wounds showed a significantly higher (p < 0.001) expression of matrix metalloproteinase‐1, resulting in reduced collagen deposition and less scarring. Film‐forming emulgel dressings that control the release of antifibrogenic and anti‐inflammatory factors provide an excellent treatment option for postburn hypertrophic scar management.
Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort.

OBJECTIVE The authors previously observed an increase in striatal dopamine transmission following amphetamine challenge in 15 untreated patients with schizophrenia compared to 15 matched healthy subjects. The purpose of this study was to replicate this finding in a new cohort of schizophrenic patients and healthy subjects. METHOD Fifteen patients with schizophrenia and 15 healthy subjects matched for age, gender, ethnicity, and parental socioeconomic status were recruited for this study. Patients fulfilled DSM-IV criteria for schizophrenia, had no history of alcohol or substance abuse or dependence, and were neuroleptic free for a minimum of 21 days. Amphetamine-induced dopamine release was assessed by the reduction in dopamine D2 receptor availability induced by an acute amphetamine challenge (0.3 mg/kg, intravenous bolus). Reduction in D2 receptor availability was measured with single photon emission computed tomography and the D2 receptor radiotracer [123I]IBZM. RESULTS No differences were observed between patients with schizophrenia and the comparison group in D2 receptor availability at baseline. Patients with schizophrenia exhibited a significantly larger reduction in D2 receptor availability following acute amphetamine challenge than the comparison group. In this study, the effect size was smaller than in the first study. Excess dopamine release following amphetamine was associated with transient emergence or worsening of positive symptoms. CONCLUSIONS In this new cohort of subjects the authors replicated their initial observation of a dysregulation of striatal dopamine release in schizophrenia.
Fundamental causes of colorectal cancer mortality in the United States: understanding the importance of socioeconomic status in creating inequality in mortality.

OBJECTIVES We used the fundamental cause hypothesis as a framework for understanding the creation of health disparities in colorectal cancer mortality in the United States from 1968 to 2005. METHODS We used negative binomial regression to analyze trends in county-level gender-, race-, and age-adjusted colorectal cancer mortality rates among individuals aged 35 years or older. RESULTS Prior to 1980, there was a stable gradient in colorectal cancer mortality, with people living in counties of higher socioeconomic status (SES) being at greater risk than people living in lower SES counties. Beginning in 1980, this gradient began to narrow and then reversed as people living in higher SES counties experienced greater reductions in colorectal cancer mortality than those in lower SES counties. CONCLUSIONS Our findings support the fundamental cause hypothesis: once knowledge about prevention and treatment of colorectal cancer became available, social and economic resources became increasingly important in influencing mortality rates.
A lazaroid mitigates postresuscitation myocardial dysfunction

ObjectiveLazaroids, a series of 21-aminosteroids, reduce free radical mediated injury after ischemia and reperfusion. We hypothesized that the lazaroid U-74389G would minimize postresuscitation myocardial dysfunction and thereby improve neurologically meaningful survival in a rodent model after resuscitation from 8 mins of ventricular fibrillation. DesignRandomized, controlled laboratory study. SettingUniversity-affiliated research institute. SubjectsSprague-Dawley rats. InterventionsVentricular fibrillation was electrically induced in ten anesthetized Sprague-Dawley rats. The lazaroid agent U-74389G in a dose of 1 mg·kg−1 or its vehicle serving as a placebo was injected into the right atrium after 7 mins of untreated ventricular fibrillation. One minute after injection of the compound, precordial compression was begun together with mechanical ventilation and continued for 6 mins before attempted electrical defibrillation. Measurements and Main ResultsAll animals were successfully resuscitated. Postresuscitation cardiac index, left ventricular end-diastolic pressure, the rate of left ventricular pressure increase measured at a left ventricular pressure of 40 mm Hg, and the maximum rate of left ventricular pressure decline were significantly less impaired in lazaroid-treated animals. This contrasted with control animals, which had significantly greater myocardial impairment, greater neurologic deficit, and lesser duration of survival. ConclusionsThe lazaroid compound U-74389G, administered during cardiac arrest, mitigated postresuscitation myocardial dysfunction and improved survival.
Pseudomonas keratitis: protease IV gene conservation, distribution, and production relative to virulence and other Pseudomonas proteases.

PURPOSE To determine the distribution of the protease IV gene, the production of this and other proteases by multiple strains of Pseudomonas, and the virulence of a mutant specifically deficient in protease IV. METHODS The protease IV gene was cloned, its sequence analyzed, and its chromosomal location determined by pulse-field gel electrophoresis. Three PCR reactions were used to detect the protease IV gene in 30 Pseudomonas isolates and protease production was determined by Western blot analysis, colorimetric assay, and zymography. An allelic replacement mutant deficient in the protease IV gene was analyzed for enzyme production, corneal growth, and corneal virulence. RESULTS The protease IV gene was identified in all P. aeruginosa, but none of the non-aeruginosa strains tested. The protease IV genes of strains PA103-29 and PAO1 were in a common chromosomal site and had 98.5% sequence identity with variations occurring mainly in the promoter region. The protease IV activity of the 23 wild-type P. aeruginosa strains tested varied from 2.3 to 221.5 x 10(-3) U/mg protein in the culture supernatant. Protease IV was produced by all P. aeruginosa wild-type strains. A protease IV-deficient mutant derived from strain PA103-29 had reduced virulence compared with its parent strain and unexpectedly produced alkaline protease. CONCLUSIONS The protease IV gene and its product are common to P. aeruginosa, but not to other Pseudomonas species. Protease IV activity varies among P. aeruginosa strains, and a mutant specifically deficient in this activity produced alkaline protease and had reduced corneal virulence.
Tissue-specific Changes in the Hydroxylysine Content and Cross-links of Collagens and Alterations in Fibril Morphology in Lysyl Hydroxylase 1 Knock-out Mice*

We have generated mice with targeted inactivation of the Plod1 gene for lysyl hydroxylase 1 (LH1). Its human mutations cause Ehlers-Danlos syndrome VIA (EDS VIA) characterized by muscular hypotonia, joint laxity, and kyphoscoliosis. The Plod1-/- mice are flaccid and have gait abnormalities. About 15% of them died because of aortic rupture and smooth muscle cells in non-ruptured Plod1-/- aortas showed degenerative changes. Collagen fibrils in the Plod1-/- aorta and skin had an abnormal morphology. The LH activity level in the Plod1-/- skin and aorta samples was 35–45% of that in the wild type. The hydroxylysine content was decreased in all the Plod1-/- tissues, ranging from 22% of that in the wild type in the skin to 75 and 86% in the femur and lung. The hydroxylysylpyridinoline crosslinks likewise showed decreases in all the Plod1-/- tissues, ranging from 28 and 33% of that in the wild type in the aorta and cornea to 47 and 59% in femur and tendon, while lysylpyridinolines were increased. The hydroxylysines found in the Plod1-/- collagens and their cross-links were evidently synthesized by the other two LH isoenzymes. Few data are available on abnormalities in EDS VIA tissues other than the skin. Plod1-/- mice offer an in vivo model for systematic analysis of the tissue-specific consequences of the lack of LH1 activity and may also provide a tool for analyzing the roles of connective tissue in muscle function and the complex interactions occurring in the proper assembly of the extracellular matrix.
An Examination of the Structure and Construct Validity of the Wender Utah Rating Scale

ABSTRACT The Wender Utah Rating Scale (Ward, Wender, & Reimherr, 1993) has been widely used in adult attention-deficit/hyperactivity disorder (ADHD) research to assess childhood symptoms retrospectively, but little research has examined its factor structure and specificity in predicting ADHD versus other psychopathology. Consequently, this study had 2 goals: (a) to examine the Wender Utah Rating Scale's structure, and (b) to explicate the construct validity of this measure by relating factors from our structural analyses to other ADHD, psychopathology, and personality measures. Structural analyses in an adult community sample (N = 294) yielded a 3-factor structure of aggression (e.g., angry), internalizing distress (e.g., depressed), and academic difficulties (e.g., underachiever). Correlational and regression analyses indicated that these factors failed to display specificity in their associations with ADHD versus other psychopathology. Aggression and internalizing distress associated most strongly with indicators of externalizing (e.g., ill temper, manipulativeness) and internalizing psychopathology (e.g., depression, anxiety), respectively. Academic difficulties associated most strongly with ADHD symptoms, but these relations were relatively weak. Taken together, these findings raise concerns about the Wender Utah Rating Scale's construct validity, although additional longitudinal research is needed to clarify to what extent the Wender Utah Rating Scale validly assesses childhood ADHD symptoms.
Isolation and characterisation of lactic acid bacteria from yan-jiang (fermented ginger), a traditional fermented food in Taiwan.

BACKGROUND Yan-jiang (fermented ginger) is a popular traditional fermented food in Taiwan. The lactic acid bacteria (LAB) microflora in yan-jiang has not been studied in detail. In this study, LAB from yan-jiang were isolated, characterised and identified. RESULTS A total of 176 LAB were isolated; 160 cultures were isolated from yan-jiang samples and 16 cultures were isolated from raw ginger. These isolates were characterised phenotypically and then divided into nine groups (A to I) by restriction fragment length polymorphism analysis and sequencing of 16S ribosomal DNA. Lactobacillus sakei and Lactococcus lactis subsp. lactis were the major LAB found in the initial 2 days of fermentation without pickled plums; these species were mostly replaced by Weissella cibaria and L. plantarum after 3 days of fermentation. In the fermentation bucket with added pickled plums, W. cibaria was the most abundant LAB found during fermentation. The antibacterial activities of the isolates were determined. Twenty-four Lc. lactis subsp. lactis and 19 W. cibaria strains showed inhibitory activity against the indicator strain L. sakei JCM 1157(T) . CONCLUSION Results demonstrate that various LAB species were more numerous when fermentation was carried out without pickled plums. LAB also had effects on the aroma and flavour of yan-jiang.
The Return to Big City Experience: Evidence from Refugees in Denmark

Using a random settlement policy for refugees in Denmark between 1986-1998, we provide evidence for steeper returns to experience in big cities. Exploiting exogenous variation in initial placement, we show that the slope of an individual’s lifetime wage path depends strongly on placement in the country’s capital, Copenhagen. Conditional on observables, settled refugees initially earn similar hourly wages across regions, but those placed in Copenhagen see their wages grow 0.63% faster than others with each year of experience they accumulate. We further show that this premium is driven by greater acquisition of experience at high-wage establishments, and differential sorting across occupations. Finally, to account for dynamic selection within the city, we develop and estimate a structural model of earnings dynamics.
Energy Dysfunction as a Predictor of Outcome after Moderate or Severe Head Injury: Indices of Oxygen, Glucose, and Lactate Metabolism

The purpose of this study was to determine if the relationship between abnormalities in glucose, lactate, and oxygen metabolism were predictive of neurologic outcome after moderate or severe head injury, relative to other known prognostic factors. Serial assessments of the cerebral metabolic rates for glucose, lactate, and oxygen were performed using a modified Kety-Schmidt method. In total, 31 normal control subjects were studied once, and 49 TBI patients (mean age 36±16 years, median GCS 7) were studied five times median per patient from postinjury days 0 to 9. Univariate and multivariate analyses were performed. Univariate analysis showed that the 6-month postinjury Glasgow Outcome Scale (GOS) was most strongly associated with the mean cerebral metabolic rate of oxygen (CMRO2) (P = 0.0001), mean arterial lactate level (P = 0.0001), mean arterial glucose (P = 0.0008), mean cerebral blood flow (CBF), (P = 0.002), postresuscitation GCS (P = 0.003), and pupillary status (P = 0.004). Brain lactate uptake was observed in 44% of all metabolic studies, and 76% of patients had at least one episode of brain lactate uptake. By dichotomized GOS, patients achieving a favorable outcome (GOS 4-5) were distinguished from those with an unfavorable outcome (GOS1-3) by having a higher CMRO2 (P = 0.003), a higher rate of abnormal brain lactate uptake relative to arterial lactate levels (P = 0.04), and lesser degrees of blood-brain barrier damage based on CT findings (P = 0.03). Conclusions: During the first 6 days after moderate or severe TBI, CMRO2 and arterial lactate levels are the strongest predictors of neurologic outcome. However, the frequent occurrence of abnormal brain lactate uptake despite only moderate elevations in arterial lactate levels in the favorable outcome patients suggests the brain's ability to use lactate as a fuel may be another key outcome predictor. Future studies are needed to determine to what degree nonglycolytic energy production from alternative fuels such as lactate occurs after TBI and whether alternative fuel administration is a viable therapy for TBI patients.
Management of Oxidative Stress by Heme Oxygenase-1 in Cisplatin-induced Toxicity in Renal Tubular Cells

Induction of heme oxygenase-1 (HO-1) may serve as an immediate protective response during treatment with the cytostatic drug cisplatin (CDDP). Oxidative pathways participate in the characteristic nephrotoxicity of CDDP. In the present study, cultured tubular cells (LLC-PK1) were used to investigate whether induction of HO provided protection against CDDP by maintaining the cellular redox balance. The antioxidants, f -tocopherol (TOCO) and N -acetylcysteine (NAC), were used to demonstrate that elevation of ROS levels contribute to the development of CDDP-induced cytotoxicity. Chemical modulators of HO activity were used to investigate the role of HO herein. Hemin was used to specifically induce HO-1, while exposure of the cells to tin-protoporphyrin (SnPP) was shown to inhibit HO activity. Hemin treatment prior to CDDP-exposure significantly decreased the generation of ROS to control levels, while inhibition of HO increased the ROS levels beyond the levels measured in cells treated with CDDP alone. Furthermore, HO induction protected significantly against the cytotoxicity of CDDP, although this protection was limited. Similar results were obtained when the cells were preincubated with TOCO, suggesting that mechanisms other than impairment of the redox ratio are important in CDDP-induced loss of cell viability in vitro. In addition, SnPP treatment exacerbated the oxidative response and cytotoxicity of CDDP, especially at low CDDP concentrations. We therefore conclude that HO is able to directly limit the CDDP-induced oxidative stress response and thus serves as safeguard of the cellular redox balance.
IQ in Early Adulthood and Mortality By Middle Age: Cohort Study of 1 Million Swedish Men

Background: High premorbid IQ test scores are related to a reduced rate of later total mortality, although little is known about the shape of this association (ie, dose-response versus threshold), or the role of mediating and confounding factors in explaining it. Additionally, the link between IQ and cause-specific mortality has been little explored. Methods: A cohort of over 1 million Swedish men who underwent IQ testing at military service conscription at about 18 years of age was followed for mortality experience until middle age. Results: An average of 20 years of follow-up gave rise to 14,498 deaths in an analytical sample of 994,262. In basic analyses adjusting for age, year of birth, and conscription testing center, lower IQ scores were associated with an elevated risk of all-cause mortality (HRper 1-SD decrease in IQ; 1.32; 95% confidence interval = 1.30–1.34). This relation was incremental across the full IQ range, and was robust to adjustment for indicators of childhood social circumstances. The association did not appear to be mediated by factors measured concurrent with IQ (blood pressure, body mass index, or cigarette smoking), nor was it attributable to reverse causality. However, controlling for education (a close correlate of IQ) led to marked attenuation. IQ was also associated with mortality from accidents, coronary heart disease, and suicides, but not cancer. Conclusions: In this large cohort we found a robust stepwise relation between early adult IQ and risk of total and accident mortality in men.
Understanding the information needs of social scientists in Germany

The information needs of social science researchers are manifold and almost studied in every decade since the 1950s. With this paper, we contribute to this series and present the results of three studies. We asked 367 social science researchers in Germany for their information needs and identified needs in different categories: literature, research data, measurement instruments, support for data analysis, support for data collection, variables in research data, software support, networking/cooperation, and illustrative material. Thereby, the search for literature and research data is still the main information need with more than three‐quarter of our participants expressing needs in these categories. With comprehensive lists of altogether 154 concrete information needs, even those that are only expressed by one participant, we contribute to the holistic understanding of the information needs of social science researchers of today.
Building a theoretical framework of message authenticity in CSR communication

Purpose The purpose of this paper is to provide an integrative theoretical framework that advances the underdeveloped stream of research that analyses how message authenticity influences the persuasiveness of corporate social responsibility (CSR) communication. Design/methodology/approach Theoretical and empirical literature on authenticity is reviewed to provide a comprehensive definition of message authenticity in CSR communication. An integrative theoretical framework is also developed to understand how message authenticity is enhanced through the design of informational content and it improves consumer responses to CSR communication. Findings The framework presented in the paper defends that message authenticity can be integrated in communication models based on three streams of research: identity-based brand management model, attribution theory and heuristic-systematic model. Consumer attributions of message authenticity can be notably improved with a message design based on CSR fit, social topic information and specificity. Authenticity improves message and source credibility by reducing consumer scepticism and enhancing their attributions of corporate expertise and trustworthiness. Indirect benefits of CSR message authenticity include increased consumer purchase, loyalty and advocacy behaviours. Originality/value The value of the paper resides in making the rather underdeveloped and inconclusive literature on authenticity accessible to CSR and communication researchers and practitioners. A theoretical framework is provided for further research that would contribute to improving the knowledge on the role that message authenticity plays in CSR communication.