Miracle-dz/UniFAR-FTUs huggingface dataset:
Perilla frutescens Sprout Extract Protect Renal Mesangial Cell Dysfunction against High Glucose by Modulating AMPK and NADPH Oxidase Signaling

Perilla frutescens (L.) Britt. var. japonica (Hassk.) Hara (PF), is a medical herb of the Lamiaceae family. We have previously reported that the PF sprout extract (PFSE) is effective in treating hyperglycemia. However, the role of PFSE on glomerular mesangial cells (MCs) proliferation and the extracellular matrix (ECM) accumulation in a diabetic condition are still unclear. Therefore, in this study, we have investigated the role of PFSE on cell proliferation and ECM accumulation in murine glomerular MCs (MMCs), cultured under a high glucose (HG) condition. PFSE treatment attenuated HG-induced MMCs proliferation and hypertrophy. Moreover, the HG-induced ECM protein, collagen IV and fibronectin, overexpression was abolished by the PFFSE treatment. In addition, PFSE inhibited reactive oxygen species (ROS) overproduction and NOX2 and NOX4 expression in MMCs under a HG condition. Our data further revealed the involvement of mesangial cell damage in AMP-activated kinase (AMPK) activation. PFSE strongly activated AMPK in MMCs under hyperglycemic conditions. These results suggest that PFSE inhibits HG-medicated MC fibrosis through suppressing the activation of NOX2/4 and the AMPK activation mechanism. PFSE may be useful for the prevention or treatment of diabetic nephropathy.
A developmental study of the neural circuitry mediating motor inhibition in bipolar disorder.

OBJECTIVE Despite increased interest in the developmental trajectory of the pathophysiology mediating bipolar disorder, few studies have compared adults and youths with bipolar disorder. Deficits in motor inhibition are thought to play an important role in the pathophysiology of the illness across the age spectrum. The authors compared the neural circuitry mediating this process in bipolar youths relative to bipolar adults and in healthy volunteers. METHOD Participants were pediatric (N=16) and adult (N=23) patients with bipolar disorder and healthy child (N=21) and adult (N=29) volunteers. Functional MRI (fMRI) data were acquired while participants performed the stop-signal task. RESULTS During failed inhibition, an age group-by-diagnosis interaction manifested in the anterior cingulate cortex, with bipolar youths exhibiting hypoactivation relative to both healthy youths and bipolar adults, and bipolar adults exhibiting hyperactivation relative to healthy adults. During successful inhibition, a main effect of diagnosis emerged in the right nucleus accumbens and the left ventral prefrontal cortex, with bipolar patients in both age groups showing less activation than healthy subjects. CONCLUSIONS Anterior cingulate cortex dysfunction during failed motor inhibition was observed in both bipolar youths and adults, although the nature of this dysfunction differed between the two groups. Adults and youths with bipolar disorder exhibited similar deficits in activation of the nucleus accumbens and the ventral prefrontal cortex during successful inhibition. Therefore, while subcortical and ventral prefrontal cortex hypoactivation was present in bipolar patients across the lifespan, anterior cingulate cortex dysfunction varied developmentally, with reduced activation in youths and increased activation in adults during failed inhibition. Longitudinal fMRI studies of the developmental trajectory of the neural circuitry mediating motor inhibition in bipolar disorder are warranted.
Higher Estradiol and Lower Dehydroepiandrosterone-Sulfate Levels Are Associated with Pulmonary Arterial Hypertension in Men.

RATIONALE Recent studies have focused on the role of female sex and estradiol (E2) in pulmonary arterial hypertension (PAH), but it is not known whether sex hormones are risk factors for PAH in men. OBJECTIVES We performed a case-control study to determine whether hormone levels (E2, dehydroepiandrosterone-sulfate [DHEA-S], and testosterone) are associated with PAH in men. METHODS Plasma sex hormone levels in men with idiopathic, heritable, or connective tissue disease-associated PAH were compared with those from age- and body mass index-matched men without clinical cardiovascular disease. MEASUREMENTS AND MAIN RESULTS There were 23 cases with PAH (70% had idiopathic PAH, 65% were functional class III/IV) and 67 control subjects. Higher E2 and E2/testosterone levels were associated with the risk of PAH (odds ratio per 1 ln[E2:testosterone], 6.0; 95% confidence interval, 2.2-16.4; P = 0.001), whereas higher levels of DHEA-S were associated with a reduced risk (odds ratio per 1 ln[DHEA-S], 0.1; 95% confidence interval, 0.0-0.3; P = 0.001). E2 and DHEA-S levels were strong predictors of case status (C statistic for both, 0.82) but testosterone was not (C statistic, 0.53). Higher levels of E2 were associated with shorter 6-minute-walk distances (P = 0.03), whereas higher levels of DHEA-S were associated with lower right atrial pressure (P = 0.02) and pulmonary vascular resistance (P = 0.01) in men with PAH. CONCLUSIONS Higher levels of E2 and lower levels of DHEA-S were associated with PAH in men. Sex-based differences in sex hormone processing and signaling may contribute to unique phenotypes in pulmonary vascular disease.
Thirty years' experience with Gamma Knife surgery for metastases to the brain.

OBJECT The aim of this study was to analyze factors influencing survival time and patterns of distant recurrences after Gamma Knife surgery (GKS) for metastases to the brain. METHODS Information was available for 1855 of 1921 patients who underwent GKS for single or multiple cerebral metastases at 4 different institutions during different time periods between 1975 and 2007. The total number of Gamma Knife treatments administered was 2448, an average of 1.32 treatments per patient. The median survival time was analyzed, related to patient and treatment parameters, and compared with published data following conventional fractionated whole-brain irradiation. RESULTS Twenty-five patients survived for longer than 10 years after GKS, and 23 are still alive. Age and primary tumor control were strongly related to survival time. Patients with single metastases had a longer survival than those with multiple metastases, but there was no difference in survival between patients with single and multiple metastases who had controlled primary disease. There were no significant differences in median survival time between patients with 2, 3-4, 5-8, or >8 metastases. The 5-year survival rate was 6% for the whole patient population, and 9% for patients with controlled primary disease. New hematogenous spread was a more significant problem than micrometastases in patients with longer survival. CONCLUSIONS Patient age and primary tumor control are more important factors in predicting median survival time than number of metastases to the brain. Long-term survivors are more common than previously assumed.
Nuclear RNA foci from C9ORF72 expansion mutation form paraspeckle-like bodies

ABSTRACT The GGGGCC (G4C2) repeat expansion mutation in the C9ORF72 gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Transcription of the repeat and formation of nuclear RNA foci, which sequester specific RNA-binding proteins, is one of the possible pathological mechanisms. Here, we show that (G4C2)n repeat RNA predominantly associates with essential paraspeckle proteins SFPQ, NONO, RBM14, FUS and hnRNPH and colocalizes with known paraspeckle-associated RNA hLinc-p21. As formation of paraspeckles in motor neurons has been associated with early phases of ALS, we investigated the extent of similarity between paraspeckles and (G4C2)n RNA foci. Overexpression of (G4C2)72 RNA results in their increased number and colocalization with SFPQ-stained nuclear bodies. These paraspeckle-like (G4C2)72 RNA foci form independently of the known paraspeckle scaffold, the long non-coding RNA NEAT1. Moreover, the knockdown of SFPQ protein in C9ORF72 expansion mutation-positive fibroblasts significantly reduces the number of (G4C2)n RNA foci. In conclusion, (G4C2)n RNA foci have characteristics of paraspeckles, which suggests that both RNA foci and paraspeckles play roles in FTD and ALS, and implies approaches for regulation of their formation. Summary: (G4C2)n repeat RNA, associated with frontotemporal dementia and amyotrophic lateral sclerosis, predominantly forms paraspeckle-like bodies independently of the known paraspeckle scaffold, the long non-coding RNA NEAT1.
Mobile Internet Telephony Improves Speech Intelligibility and Quality for Cochlear Implant Recipients.

OBJECTIVE The objective of this study was to investigate the benefit of mobile Voice over Internet protocol (VoIP) over conventional mobile phone calls (Global System for Mobile Communications, GSM) on speech intelligibility and quality for cochlear implant (CI) recipients. STUDY DESIGN Cross-sectional, prospective. SETTING Tertiary referral center. PATIENTS A volunteer sample of experienced, German-speaking, adult CI recipients was considered. Volunteers with less than 50% aided monosyllabic word discrimination were excluded. INTERVENTION Smartphone communication was changed from GSM to VoIP on two separate devices (A and B). MAIN OUTCOME MEASURES Speech intelligibility was assessed with the Hochmair-Shulz-Moser (HSM) test in noise, speech quality with the mean opinion score (MOS) survey and the perceptual evaluation of speech quality (PESQ) algorithm. RESULTS With device A, the mean HSM scores were 64.40% ± 32.41 with GSM and 77.28% ± 21.60 with VoIP (p = 0.0573). 66.7% of patients had a higher score with VoIP. For device B the means were 53.90% ± 21.77 and 69.07% ± 21.09 (p < 0.0001). 94.1% patients scored better with VoIP.With device A the average MOS scores were 3.12 ± 1.52 and 4.08 ± 0.95 (p = 0.0078). 76.9% of patients gave a higher score with VoIP. With device B the means were 2.71 ± 1.08 and 3.528 ± 1.44 (p = 0.0068). 56.3% of patients gave a higher score with VoIP. The effect was smaller when using an accessory cable. PESQ scores were significantly higher with VoIP (p < 0.001) in all configurations. CONCLUSIONS CI recipients experience speech intelligibility and quality improvements using VoIP on a smartphone compared with conventional mobile phone calls.
Zonation of Ca2+ transport and enzyme activity in the caeca of rainbow trout – a simple structure with complex functions

ABSTRACT Trout caeca are vermiform structures projecting from the anterior intestine of the gastrointestinal tract. Despite their simple gross morphology, these appendages are physically distinct along the anterior–posterior axis, and ultrastructural evidence suggests zonation of function within the structures. Individual caeca from three sections (anterior, middle and posterior) were removed from the intestine of freshwater rainbow trout and investigated for ion transport and enzyme activity. Ca2+ absorption appeared as a combination of active and passive movement, with Michaelis–Menten kinetics observable under symmetrical conditions, and was inhibited by several pharmacological agents (ouabain, La3+ and a calmodulin antagonist). There was a decrease in ion transport function from adjacent to the intestine (proximal) to the distal tip of each caecum, along with decreasing transport from anterior to posterior for the proximal portion alone. Feeding increased the JMax and KM for Ca2+ absorption within all sections, whereas ion-poor water (IPW) exposure further increased the JMax and KM for Ca2+ transport in the anterior and middle sections. Increased Na+/K+-ATPase (NKA) and citrate synthase (CS) activity rates paralleled trends seen in Ca2+ transport. Feeding in freshwater and IPW exposure increased the glycolytic capacity of the caeca via increased pyruvate kinase (PK) and decreased lactate dehydrogenase (LDH) activity, while amino acid metabolism increased with IPW exposure through increased glutamate dehydrogenase (GDH) activity. Overall, feeding and IPW exposure each altered ionoregulation within the caeca of freshwater rainbow trout in a zone-specific pattern, with the anterior and proximal portions of the caeca being most affected. Increased carbohydrate and protein metabolism fueled the increased ATP demand of NKA through CS. Summary: A novel technique revealed region-specific ion transport properties within the caeca of rainbow trout. Feeding and environmental manipulation altered ion transport characteristics, which changes in enzyme activity supported.
Integrative Genomics Reveals the Genetics and Evolution of the Honey Bee’s Social Immune System

Abstract Social organisms combat pathogens through individual innate immune responses or through social immunity—behaviors among individuals that limit pathogen transmission within groups. Although we have a relatively detailed understanding of the genetics and evolution of the innate immune system of animals, we know little about social immunity. Addressing this knowledge gap is crucial for understanding how life-history traits influence immunity, and identifying if trade-offs exist between innate and social immunity. Hygienic behavior in the Western honey bee, Apis mellifera, provides an excellent model for investigating the genetics and evolution of social immunity in animals. This heritable, colony-level behavior is performed by nurse bees when they detect and remove infected or dead brood from the colony. We sequenced 125 haploid genomes from two artificially selected highly hygienic populations and a baseline unselected population. Genomic contrasts allowed us to identify a minimum of 73 genes tentatively associated with hygienic behavior. Many genes were within previously discovered QTLs associated with hygienic behavior and were predictive of hygienic behavior within the unselected population. These genes were often involved in neuronal development and sensory perception in solitary insects. We found that genes associated with hygienic behavior have evidence of positive selection within honey bees (Apis), supporting the hypothesis that social immunity contributes to fitness. Our results indicate that genes influencing developmental neurobiology and behavior in solitary insects may have been co-opted to give rise to a novel and adaptive social immune phenotype in honey bees.
Left Ventricular Diastolic Function Is Associated With Symptom Status in Severe Aortic Valve Stenosis

Background—In aortic valve stenosis (AS), the occurrence of heart failure symptoms does not always correlate with severity of valve stenosis and left ventricular (LV) function. Therefore, we tested the hypothesis that symptomatic patients with AS have impaired diastolic, longitudinal systolic function, and left atrial dilatation compared with asymptomatic patients. Methods and Results—In a retrospective descriptive study, we compared clinical characteristics and echocardiographic parameters in 99 symptomatic and 139 asymptomatic patients with severe AS and LV ejection fraction ≥50%. Independent predictors of symptomatic state were identified using logistic regression analysis. Symptomatic patients were younger (72±10 versus 76±12 years of age; P=0.002), presented less often with atrial fibrillation (13% versus 24%; P=0.05) and chronic obstructive pulmonary disease (2% versus 19%; P<0.001), and had a lower prevalence of hypertension (73% versus 40%; P<0.001). Despite similar AS severity, symptomatic patients had higher LV mass index (120±39 versus 95±25 g/m2; P<0.0001), increased relative wall thickness (0.61±0.15 versus 0.50±0.11; P<0.0001), shorter mitral deceleration time (199±58 versus 268±62 ms; P<0.0001), and increased left atrial volume index (49±18 versus 42±15 mL/m2; P=0.02). When adjusting for age, history of hypertension, atrial fibrillation, and chronic obstructive pulmonary disease in a multivariable logistic regression analysis, LV mass index, relative wall thickness, left atrial volume index, and deceleration time were still associated with the presence of symptoms. Conclusions—The present study demonstrates that symptomatic status in severe AS is associated with impaired diastolic function, LV hypertrophy, concentric remodeling, and left atrial dilatation when corrected for indices of AS severity. Clinical Trial Registration—URL: http://www.clinicaltrials. gov. Unique identifier: NCT00294775.
Quality of life outcomes after revision lumbar discectomy.

OBJECT The authors investigated quality of life (QOL) outcomes after primary versus revision discectomy. METHODS A retrospective review was performed for all patients who had undergone a primary or revision discectomy at the Cleveland Clinic Center for Spine Health from January 2008 through December 2011. Among patients in the revision cohort, they identified those who needed a second revision discectomy. Patient QOL measures were recorded before and after surgery. These measures included responses to the EQ-5D health questionnaire, Patient Health Questionnaire-9, Pain and Disability Questionnaire, and quality-adjusted life years (QALYs). Cohorts were compared by using independent-sample t-tests and Fisher exact tests for continuous and categorical variables, respectively. Multivariable logistic regression was performed to adjust for confounding. RESULTS A total of 196 patients were identified (116 who underwent primary discectomy and 80 who underwent revision discectomy); average follow-up time was 150 days. There were no preoperative QOL differences between groups. Postoperatively, both groups improved significantly in all QOL measures. For QALYs, the primary cohort improved by 0.25 points (p<0.001) and the revision cohort improved by 0.18 points (p<0.001). QALYs improved for significantly more patients in the primary than in the revision cohort (76% vs 59%, respectively; p=0.02), and improvement exceeded the minimum clinically important difference for more patients in the primary cohort (62% vs 45%, respectively; p=0.03). Of the 80 patients who underwent revision discectomy, yet another recurrent herniation (third herniation) occurred in 14 (17.5%). Of these, 4 patients (28.6%) chose to undergo a second revision discectomy and the other 10 (71.4%) underwent conservative management. For those who underwent a second revision discectomy, QOL worsened according to all questionnaire scores. CONCLUSIONS QOL, pain and disability, and psychosocial outcomes improved after primary and revision discectomy, but the improvement diminished after revision discectomy.
Dopamine transporter forms stable dimers in the live cell plasma membrane in a phosphatidylinositol 4,5-bisphosphate–independent manner

The human dopamine transporter (hDAT) regulates the level of the neurotransmitter dopamine (DA) in the synaptic cleft and recycles DA for storage in the presynaptic vesicular pool. Many neurotransmitter transporters exist as oligomers, but the physiological role of oligomerization remains unclear; for example, it has been speculated to be a prerequisite for amphetamine-induced release and protein trafficking. Previous studies point to an oligomeric quaternary structure of hDAT; however, the exact stoichiometry and the fraction of co-existing oligomeric states are not known. Here, we used single-molecule brightness analysis to quantify the degree of oligomerization of heterologously expressed hDAT fused to monomeric GFP (mGFP–hDAT) in Chinese hamster ovary (CHO) cells. We observed that monomers and dimers of mGFP–hDAT co-exist and that higher-order molecular complexes of mGFP–hDAT are absent at the plasma membrane. The mGFP–hDAT dimers were stable over several minutes, and the fraction of dimers was independent of the mGFP–hDAT surface density. Furthermore, neither oxidation nor depletion of cholesterol had any effect on the fraction of dimers. Unlike for the human serotonin transporter (hSERT), in which direct binding of phosphatidylinositol 4,5-bisphosphate (PIP2) stabilized the oligomers, the stability of mGFP–hDAT dimers was PIP2 independent.
Psychiatric nursing staffs’ attitudes towards the use of containment methods in psychiatric inpatient care: An integrative review

One of the international objectives in psychiatric care is reducing the use of coercion. Containment methods are meant to keep patients safe, yet usually include coercion. Nurses play a key role in deciding whether or not containment should be used and, as such, their attitudes towards containment can significantly impact the extent to which these methods are applied. The aim of this integrative review was to identify, analyse, and synthesize the available research on psychiatric nursing staffs' attitudes towards containment methods in inpatient psychiatric care. An electronic search was conducted using the CINAHL, Scopus, and PsycINFO databases. In addition, the citations of identified studies were screened for relevant research. A total of 24 relevant papers published between 2002 and 2017 were selected for further analysis. These studies revealed variation in nursing staffs' attitudes towards the use of containment methods. The use of containment methods seems to be widely accepted and nurses reported rarely considering alternative measures. It appears that attitudes towards containment have continuously become more negative, although the change has not been very pronounced. The concept of attitude was only defined in two studies. Thus, future research should strive to clarify this concept, as a generally accepted definition for attitude within nursing research and the utilization of all dimensions of this concept are both essential to the nursing field. Currently, it would be important to focus on changing attitudes among psychiatric nursing staff to reduce the use of containment methods; this calls for more research on nursing staffs' attitudes.
Income and Marital Status Interact on Obesity Among Black and White Men

Racial disparities in obesity among men are accompanied by positive associations between income and obesity among Black men only. Race also moderates the positive association between marital status and obesity. This study sought to determine how race, income, and marital status interact on obesity among men. Using data from the 2007 to 2014 National Health and Nutrition Examination Survey, obesity was measured as body mass index ≥30 kg/m2 among 6,145 Black and White men. Income was measured by percentage of the federal poverty line and marital status was categorized as currently, formerly, or never married. Using logistic regression and interaction terms, the associations between income and obesity were assessed by race and marital status categories adjusted for covariates. Black compared to White (OR = 1.19, 95% CI [1.03, 1.38]), currently married compared to never married (OR = 1.45, 95% CI [1.24, 1.69]), and high-income men compared to low income men (OR = 1.26, 95% CI [1.06, 1.50]) had higher odds of obesity. A three-way interaction was significant and analyses identified that income was positively associated with obesity among currently married Black men and never married White men with the highest and lowest probabilities of obesity, respectively. High-income, currently married Black men had higher obesity rates and may be at increased risk for obesity-related morbidities.