Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemical Characterization and Antiplatelet Potential of Bioactive Extract from Tomato Pomace (Byproduct of Tomato Paste)

We examined the ability of tomato pomace extract (by-product) to affect platelet aggregation in healthy humans (clinical pilot study). In phase 1 the tolerance of participants (n = 15; 5 per dose level) ingesting tomato pomace extract across three dose levels (1, 2.5, and 10 g) was evaluated. Phase 2 was a single-blind, placebo-controlled, parallel design human (male, n = 99; 33 per group) pilot intervention trial investigating the acute and repeated dose effects (5 days) of different doses of tomato pomace extract (1 g, 2.5 g or placebo) on platelet aggregation ex vivo. Various flavonoids (coumaric acid, floridzin, floretin, procyanidin B2, luteolin-7-O-glucoside, kaempferol, and quercitin) and nucleosides (adenosine, inosine, and guanosine) were identified in the tomato pomace extract. The clinical study showed that the daily consumption of 1 g of aqueous extract of tomato pomace for 5 days exerted an inhibitory activity on platelet aggregation.
Early-life adversity programs long-term cytokine and microglia expression within the HPA axis in female Japanese quail

ABSTRACT Stress exposure during prenatal and postnatal development can have persistent and often dysfunctional effects on several physiological systems, including immune function, affecting the ability to combat infection. The neuroimmune response is inextricably linked to the action of the hypothalamic–pituitary–adrenal (HPA) axis. Cytokines released from neuroimmune cells, including microglia, activate the HPA axis, while glucocorticoids in turn regulate cytokine release from microglia. Because of the close links between these two physiological systems, coupled with potential for persistent changes to HPA axis activity following developmental stress, components of the neuroimmune system could be targets for developmental programming. However, little is known of any programming effects of developmental stress on neuroimmune function. We investigated whether developmental stress exposure via elevated prenatal corticosterone (CORT) or postnatal unpredictable food availability had long-term effects on pro- (IL-1β) and anti-inflammatory (IL-10) cytokine and microglia-dependent gene (CSF1R) expression within HPA axis tissues in a precocial bird, the Japanese quail (Coturnix japonica). Following postnatal stress, we observed increased IL-1β expression in the pituitary gland, reduced IL-10 expression in the amygdala and hypothalamus, and reduced CSF1R expression within the hypothalamus and pituitary gland. Postnatal stress disrupted the ratio of IL-1β:IL-10 expression within the hippocampus and hypothalamus. Prenatal stress only increased IL-1β expression in the pituitary gland. We found no evidence for interactive or cumulative effects across life stages on basal cytokine and glia expression in adulthood. We show that postnatal stress may have a larger impact than elevated prenatal CORT on basal immunity in HPA-axis-specific brain regions, with changes in cytokine homeostasis and microglia abundance. These results provide evidence for postnatal programming of a pro-inflammatory neuroimmune phenotype at the expense of reduced microglia, which could have implications for central nervous system health and subsequent neuroimmune responses. Summary: Developmental exposure to a non-pathogenic stressor can cause long-term changes in inflammatory and anti-inflammatory cytokine gene expression and microglia abundance in different brain regions involved in stress response regulation.
Journal Watch review of Long-term outcome of psychodynamic therapy and cognitive-behavioral therapy in social anxiety disorder

The authors of this study chose to observe, at five sites throughout Germany, the efficacy of psychodynamic psychotherapy as a treatment for people diagnosed with social anxiety disorder as compared to their receiving cognitive-behavioral therapy (CBT) or no treatment at all. The study was performed between 2007 and 2009; results of the study immediately after completion of treatment were first published last year (Leichsenring et al. 2013). This 2014 paper examines the long-term outcomes of the study following completion of treatment at 6, 12, and 24 months. An interesting aspect of this study is the attempt to manualize and define psychodynamic psychotherapy. CBT was administered using Clark and Wells’s manualized treatment for social phobia (Clark and Wells 1995; Wells 1997). Aware that no manualized form of psychodynamic psychotherapy exists, the researchers defined the therapy by adapting Luborsky’s manualized supportive-expressive therapy for social phobia (1984), a treatment not previously studied. Establishing a secure helping alliance and elaborating a core conflictual relationship theme related to the symptoms of anxiety are central features of this treatment. Both treatments were “dosed” in twenty-five individual sessions of fifty minutes each. Because CBT allows for double sessions, those in the psycho dynamic arm of the study were allowed twice-weekly sessions during the middle part of the treatment (sessions 7 to 16); the authors note that this was done to match CBT in terms of session minutes, and not necessarily to reflect the impact of session frequency on transference. In all, 1,450 patients were screened, 495 of whom met the study’s inclusion criteria. Patients were excluded if they had psychotic or acute 560793 APAXXX10.1177/0003065114560793Journal WatchJournal Watch other2014
The Response of Litter‐Associated Myxomycetes to Long‐Term Nutrient Addition in a Lowland Tropical Forest

Myxomycetes (plasmodial slime molds) are abundant protist predators that feed on bacteria and other microorganisms, thereby playing important roles in terrestrial nutrient cycling. Despite their significance, little is known about myxomycete communities and the extent to which they are affected by nutrient availability. We studied the influence of long‐term addition of N, P, and K on the myxomycete community in a lowland forest in the Republic of Panama. In a previous study, microbial biomass increased with P but not N or K addition at this site. We hypothesized that myxomycetes would increase in abundance in response to P but that they would not respond to the sole addition of N or K. Moist chamber cultures of leaf litter and small woody debris were used to quantify myxomycete abundance. We generated the largest myxomycete dataset (3,381 records) for any single locality in the tropics comprised by 91 morphospecies. In line with our hypothesis, myxomycete abundance increased in response to P addition but did not respond to N or K. Community composition was unaffected by nutrient treatments. This work represents one of very few large‐scale and long‐term field studies to include a heterotrophic protist highlighting the feasibility and value in doing so.
A more efficient ocular delivery system of triamcinolone acetonide as eye drop to the posterior segment of the eye

Abstract As a leading cause of vision impairment of the retina, macular edema (ME) has one of the highest clinical demands for treatment. Current treatment of ME relies heavily on invasive techniques resulting in complications and poor patient compliance. To enhance the efficiency of triamcinolone acetonide as eye drop to the posterior segment of the eye, we developed and characterized a novel formulation, namely, triamcinolone acetonide chitosan-coated liposomes (TA-CHL), prepared by the calcium acetate gradient method with some modifications. TA-CHL provided the mean particle size of 135.46 ± 4.49 nm and high entrapment efficiency (90.66 ± 3.21%), exhibited a sustained release profile, excellent physical stability, and no significant toxicity on cornea, conjunctiva, and retina. Optical coherence tomography system (OCT) was used to detect pharmacokinetics of CHL in vivo, indicating that CHL had good potency for drug delivery. Cellular uptake experiments showed CHL had the higher transduction efficiency into HCEC and ARPE-19 than liposomes. TA-CHL was shown to be potentially effective eye drop to contribute to the posterior segment of the eye.
Screening for Associated Autoimmunity in Children and Adolescents with Type 1 Diabetes Mellitus (T1DM)

Background/Aims: Type 1 diabetes (T1DM) is associated with autoimmune thyroid, celiac, autoimmune gastric and Addison’s disease. Our aim was to investigate the prevalence of associated autoantibodies in relation to the demographic and β-cell autoantibody status (anti-GAD). Methods: Antibodies against thyroid peroxidase (anti-TPO), thyroglobulin (anti-Tg), tissue transglutaminase (anti-tTG IgA), parietal cells (APCA) and adrenal tissue (AAA) were measured in 144 children with T1DM with a mean ± SD age of 12.3 ± 4.6 years and a diabetes duration of 4.6 ± 3.8 years. Results: The prevalence of antibody positivity among our patients was: anti-GAD 53.2%, anti-thyroid (anti-TPO 17.4%, anti-Tg 11.1%); anti-tTG IgA 7.6%, APCA 4.0%, and AAA 0%. Among the children with positive anti-thyroid antibodies, 60% developed autoimmune thyroiditis, while among those anti-tTG IgA positive, 62.5% developed biopsy-confirmed celiac disease. Female gender was more frequent among anti-tTG IgA-positive patients (OR 4.47, p = 0.068), while increasing age was associated with anti-Tg positivity (OR 22.9, p = 0.041). The presence of anti-thyroid antibodies was associated with the presence of anti-GAD (OR 1.45, p = 0.01) and parietal cell antibodies (OR 4.98, p = 0.09). Conclusion: Among T1DM patients, the prevalence rates of anti-thyroid and parietal cell antibodies increased with age and diabetes duration. As the presence of anti-GAD was associated with gastric and thyroid autoimmunity, it could serve as marker for the development of additional autoimmunity in adolescents with diabetes.
Prevalence and Predictors of Current and Former Tobacco Use among Older Adults in Indonesia

Purpose: The study aims to describe sociodemographic and health variable indices related to current and former tobacco use among older adults who participated in the Indonesia Family Life Survey (IFLS-5) in 2014-15. Materials and Methods: A national population-based cross-sectional study was conducted with a probability sample of 8,001 aged 50 years or older Indonesians. Results: The overall prevalence of current tobacco use was 33.3% (62.2% in men and 6.5% in women) and former tobacco use was 9.8% (17.4% among men and 2.8% in women), of which 64.4% quit tobacco use when 50 years and older. In multinomial regression analysis, sociodemographic factors (being male, lower education, lower economic status, living in Java and rural residence) and health variables (cancer or malignant tumour, depression symptoms, functional disability and inadequate fruit and vegetable consumption) were associated with current tobacco use. In addition, being overweight or obese, having had a stroke, and other lung conditions were inversely associated with current tobacco use. Further, in adjusted analysis, sociodemographic factors (being 70 years and older, being male, living in Sumatra) and having chronic conditions (dyslipidemia, heart problems, asthma, stomach or digestive diseases and functional disability) were associated with former tobacco use. Conclusions: A high rate of current tobacco use and low rate of former tobacco use was found, particularly among men. The identified risk factors may help to better target this vulnerable population with tobacco cessation programmes.
Risk of Metabolic Bone Disease is Increased Both during and after Weaning off Parenteral Nutrition in Pediatric Intestinal Failure

Aim: To assess bone health in pediatric intestinal failure (IF). Methods: A population-based cohort of 41 IF patients (age 9.9 years) underwent evaluation of bone mineral density (BMD), bone biochemistry, nutritional status and growth. Eleven patients remained on parenteral nutrition (PN) after 69 months. Thirty had weaned off PN 9.0 years earlier (mean), i.e. after 30 months on PN. Results: The majority of patients had lumbar spine or femoral BMD Z-score ≤-1.0 (70%), vitamin D deficiency (serum 25-hydroxyvitamin-D, S-25-OHD, <50 nmol/l, 41%) or secondary hyperparathyroidism (plasma parathyroid hormone >47 ng/l, 44%), equally during and after weaning off PN. Hyperparathyroidism was absent when S-25-OHD was >80 nmol/l. Until puberty, height (-1.4 to -0.8, age 1-12) and weight Z-scores (-1.3 to -0.5, age 1-16) were below the normal mean (p < 0.05). Small bowel length associated with S-25-OHD levels (r = 0.489, p = 0.013). In a multivariate model, time after weaning off PN (β = -0.597, p = 0.001), duration of PN (β = -0.466, p = 0.006) and calcium intake (β = -0.331, p = 0.035) predicted decreased lumbar spine BMD. Conclusions: In pediatric IF, vitamin D insufficiency, secondary hyperparathyroidism and decreased BMD are common. BMD, vitamin D, calcium and nutritional status should be closely monitored during and after weaning off PN to ensure sufficient vitamin D and mineral substitution for normal growth and bone mass attainment.
High Frequency of Either Altered Pre-Core Start Codon or Weakened Kozak Sequence in the Core Promoter Region in Hepatitis B Virus A1 Strains from Rwanda

Hepatitis B virus (HBV) is endemic in Rwanda and is a major etiologic agent for chronic liver disease in the country. In a previous analysis of HBV strains from Rwanda, the S genes of most strains segregated into one single clade of subgenotype, A1. More than half (55%) of the anti-HBe positive individuals were viremic. In this study, 23 complete HBV genomes and the core promoter region (CP) from 18 additional strains were sequenced. Phylogenetic analysis of complete genomes confirmed that most Rwandan strain formed a single unique clade, within subgenotype A1. Strains from 17 of 22 (77%) anti-HBe positive HBV carriers had either mutated the precore start codon (9 strains with either CUG, ACG, UUG, or AAG) or mutations in the Kozak sequence preceding the pre-core start codon (8 strains). These mutually exclusive mutations were also identified in subgenotypes A1 (70/266; 26%), A2 (12/255; 5%), and A3 (26/49; 53%) sequences from the GenBank. The results showed that previous, rarely described HBV variants, expressing little or no HBeAg, are selected in anti-HBe positive subgenotype Al carriers from Rwanda and that mutations reducing HBeAg synthesis might be unique for a particular HBV clade, not just for a specific genotype or subgenotype.
Treatment with Noripurum EV® is effective and safe in pediatric patients with inflammatory bowel disease and iron deficiency anemia

Abstract Objectives: To evaluate the therapeutic response and adverse effects of Noripurum EV® in children and adolescents with inflammatory bowel disease (IBD) and iron deficiency anemia. Materials and methods: Cohort study involving patients with Crohn’s disease (CD) and ulcerative colitis (UC) who received treatment for iron deficiency anemia with Noripurum EV®. Anemia was defined according to WHO 2011 criteria. Iron deficiency anemia was established when ferritin <30µg/l and transferrin saturation <16%. Iron deficiency anemia and anemia of chronic disease were established when ferritin was between 30 and 100µg/l and transferrin saturation <16%. The total dose of Noripurum EV® was estimated by the Ganzoni formula and divided into weekly administrations. When there was an increase in hemoglobin (Hb) by a minimum of 2g/dl and or when Hb reached the target determined by WHO, treatment was considered a therapeutic success. Results: Noripurum EV® was administered to 16 patients (9.3% of total patients with IBD). Ten (65.5%) were male, the mean (SD) age was 11.3(4.6) years old, 75%(12/16) had CD and 25%(4/16) had UC. All patients presented an increase in Hb (p < .001) at a mean (SD) of 2.8(1.3)g/dl, after median and interquartile range(IQR) of 4.5(3.0–6.0) weeks that iron infusions were completed. It was found that the proportion of patients that achieved therapeutic success (68.8%) was statistically higher (p = .031) than those who did not (31.2%). No adverse events were reported. Conclusion: Noripurum EV® in pediatric patients with IBD and iron deficiency anemia was effective and safe, making it an appropriate option for the clinical management of these patients.
First Report of Rhizoctonia solani AG-4 and AG-2-2 on Lupinus angustifolius in Canada.

Narrow-leaved lupine (Lupinus angustifolius L.) is grown as a grain legume crop in Australia and Europe where it is used as feedstock in the livestock and aquaculture industries. During July 2003, a stem rot disease was observed in narrow-leaved lupine (cv. Arabella) plants in a research plot at the Crop Diversification Centre North (CDCN), Edmonton, Alberta, Canada. The disease was also found on cv. Rose at the CDCN and cv. Arabella in experimental fields near Devon, Ellerslie, and Westlock, Alberta during the late spring of 2004. Diseased plants showed dark brown-to-black stems with sunken and constricted lesions at the soil level. Young leaves became shrunken and twisted and seedlings collapsed. Rhizoctonia solani was consistently isolated from lesions on taproots and basal stems of diseased plants. Colonies of cream-colored mycelia grew close to the surface of potato dextrose agar (PDA). Most sclerotia formed inside the medium. Agar disks (1 cm in diameter) of isolates LP-11Bb, LP-24C, and LP-25C were attached to the opposite sides of basal stems (180° apart) of 1-month-old lupine seedlings (cv. Arabella). Inoculated plants were incubated for 2 days in black plastic bags under a greenhouse bench at approximately 20°C. All isolates caused brown lesions on the lower stems (extending up to 7 cm above ground level), girdling, and root rot. Plants wilted within 7 to 10 days after inoculation, and aerial mycelia appeared on the basal stems. R. solani was reisolated from the infected crown tissues using PDA to complete Koch's postulates. The isolates were paired with AG tester strains of R. solani. Isolates LP-11Bb and LP-24C were identified as AG-4 while isolate LP-25C was identified as AG-2-2. In another trial, eight isolates of R. solani (unknown AG types) were tested for virulence on L. angustifolius cv. Arabella using the inoculation method described above. All isolates were pathogenic, and disease severity that was based on a 0 to 4 scale ranged from 2.7 to 3.2. The most virulent strain was LP-24C, which caused a 77% loss in fresh weight compared with the noninoculated control plants. R. solani AG-8 is associated with Rhizoctonia disease of lupine in Australia (1) and also causes bare patch disease of wheat. To our knowledge, this is the first report of R. solani on lupine in Canada. This disease could have a significant impact on the commercial production of lupine in Alberta. Reference: (1) M. W. Sweetingham et al. Pages 466-486 in: Advances in Lupin Disease Management in Australia. Proc. Int. Lupin Conf. , 8th. G. D. Hill, ed. International Lupin Association, Canterbury, New Zealand, 1999.
Clozapine Metabolism in East Asians and Caucasians: A Pilot Exploration of the Prevalence of Poor Metabolizers and a Systematic Review

Purpose/Background In clozapine therapeutic drug monitoring (TDM) studies, Chinese reached the same concentrations using half the dosage Caucasians use. Defining clozapine poor metabolizers (PMs) requires stratification by ethnicity, smoking, and sex. Methods/Procedures After sex and smoking stratification in 129 Chinese inpatients (mean, 8.8 TDM samples per patient), we explored the association between the total concentration-dose (C/D) ratio and CYP1A2 (*1C, *1F, and *7) and CYP2C19 alleles (*2 and *3). A systematic literature review identified 22 clozapine TDM prior studies (13 in Caucasians and 7 in East Asians). Findings/Results In our Chinese sample, the mean total clozapine C/D ratio (ng/mL per mg/d) was 1.96 for 22 male smokers, 2.07 for 5 female smokers, 2.47 for 36 male nonsmokers, and 2.95 for 66 female nonsmokers. CYP1A2 *1C had no significant effects, and CYP1A2 *1F had small effects. Five clozapine PMs (4%) needed low clozapine doses of 75 to 115 mg/d to get therapeutic concentrations. Using the same methodology in a published Italian sample, we found 5 PMs (3.3% of 152). In the systematic review, the clozapine C/D ratio (ng/mL per mg/d) was higher when comparing: (1) weighted mean values of 1.57 in 876 East Asians versus 1.07 in 1147 Caucasians and (2) ranks of 8 East Asians versus 13 Caucasian samples (P < 0.001). Implications/Conclusions Future TDM studies need to further explore the frequency of clozapine PMs after sex and smoking stratification in East Asian and Caucasian patients. Compared with Caucasians, East Asians appear to have a clinically relevant decrease in clozapine clearance.
Multimodal neuroimaging analysis reveals age‐associated common and discrete cognitive control constructs

The aims of this study were to determine which cognitive control functions are most sensitive to cross‐sectional age differences and to identify neural features in different neuroimaging modalities that associated cognitive control function across the adult lifespan. We employed a joint independent component analysis (jICA) approach to obtain common networks among three different brain‐imaging modalities (i.e., structural MRI, resting‐state functional MRI, and diffusion tensor imaging) in relation to the cognitive control function. We differentiated three distinct cognitive constructs: one common (across inhibition, shifting, and updating) and two specific (shifting, updating) factors. These common/specific constructs were transformed from three original performance indexes: (a) stop‐signal reaction time, (b) switch‐cost, and (c) performance sensitivity collected from 156 individuals aged 20 to 78 years old. The current results show that the cross‐sectional age difference is associated with a wide spread of brain degeneration that is not limited to the frontal region. Crucially, these findings suggest there are some common and distinct joined multimodal components that correlate with the psychological constructs of common and discrete cognitive control functions, respectively. To support current findings, other fusion ICA models were also analyzed including, parallel ICA (para‐ICA) and multiset canonical correlation analysis with jICA (mCCA + jICA). Dynamic interactions among these brain features across different brain modalities could serve as possible developmental mechanisms associated with these age effects.
Development and Characterization of a Sin Nombre Virus Transmission Model in Peromyscus maniculatus

In North America, Sin Nombre virus (SNV) is the main cause of hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with a fatality rate of 35–40%. SNV is a zoonotic pathogen carried by deer mice (Peromyscus maniculatus), and few studies have been performed examining its transmission in deer mouse populations. Studying SNV and other hantaviruses can be difficult due to the need to propagate the virus in vivo for subsequent experiments. We show that when compared with standard intramuscular infection, the intraperitoneal infection of deer mice can be as effective in producing SNV stocks with a high viral RNA copy number, and this method of infection provides a more reproducible infection model. Furthermore, the age and sex of the infected deer mice have little effect on viral replication and shedding. We also describe a reliable model of direct experimental SNV transmission. We examined the transmission of SNV between deer mice and found that direct contact between deer mice is the main driver of SNV transmission rather than exposure to contaminated excreta/secreta, which is thought to be the main driver of transmission of the virus to humans. Furthermore, increases in heat shock responses or testosterone levels in SNV-infected deer mice do not increase the replication, shedding, or rate of transmission. Here, we have demonstrated a model for the transmission of SNV between deer mice, the natural rodent reservoir for the virus. The use of this model will have important implications for further examining SNV transmission and in developing strategies for the prevention of SNV infection in deer mouse populations.