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Amino Acid, Organic Acid, and Sugar Profiles of 3 Dry Bean (Phaseolus vulgaris L.) Varieties. - Journal of food science
In this study, we compared the amino acid, organic acid and sugar profiles of 3 different varieties of dry beans (black bean [BB], dark red bean [DRB], and cranberry bean [CB]). The efficiency of the 2 commonly used extraction solvents (water and methanol:chloroform:water [2.5:1:1, v/v/v/]) for cultivar differentiation based on their metabolic profile was also investigated. The results showed that the BB contained the highest concentration of amino acids followed by DRB and CB samples. Phenylalanine, a precursor for the biosynthesis of phenolic secondary metabolites was detected at low concentration in CB samples and correlated with the reduced anthocyanins content in CB extract as documented in the published literature. Comparing the extractability of 2 extraction solvents, methanol:chloroform:water (2.5:1:1, v/v/v/) showed higher recoveries of amino acids from 3 beans, whereas, sugars were extracted in higher concentration with water. Analytically, gas chromatography detected sugars (9), amino acids (11), and organic acids (3) in a single run after derivatization of the extracts. In comparison, ion chromatography detected only sugars in a single run without any derivatization step with the tested procedure. Bean samples are better differentiated by the sugar content extracted with water as compared to the aqueous organic solvent extracts using partial least-square discriminant analysis.Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Tendon Adaptation to Sport-specific Loading in Adolescent Athletes. - International journal of sports medicine
Tendon adaptation due to mechanical loading is controversially discussed. However, data concerning the development of tendon thickness in adolescent athletes is sparse. The purpose of this study was to examine possible differences in Achilles (AT) and patellar tendon (PT) thickness in adolescent athletes while considering age, gender and sport-specific loading. In 500 adolescent competitive athletes of 16 different sports and 40 recreational controls both ATs and PTs were sonographically measured. Subjects were divided into 2 age groups (<â€‰13; â‰¥â€‰13 years) and 6 sport type categories (ball, combat, and water sports, combined disciplines, cycling, controls). In addition, 3 risk groups (low, moderate, high) were created according to the athlete's risk of developing tendinopathy. AT and PT thickness did not significantly differ between age groups (AT/PT:<13: 5.4Â±0.7â€‰mm/3.6Â±0.5â€‰mm;â‰¥13: 5.3Â±0.7â€‰mm/3.6Â±0.5â€‰mm). In both age groups males presented higher tendon thickness than females (p<0.001). AT thickness was highest in ball sports/cyclists and lowest in controls (pâ‰¤0.002). PT thickness was greatest in water sports and lowest in controls (p=0.02). High risk athletes presented slightly higher AT thickness compared to the low risk group (p=0.03). Increased AT and PT thickness in certain sport types compared to controls supports the hypothesis of structural tendon adaptation due to sport-specific loading.Â© Georg Thieme Verlag KG Stuttgart Â· New York.
Engineering of Human Corneal Endothelial Grafts. - Current ophthalmology reports
Human corneal endothelial cells (HCEC) play a pivotal role in maintaining corneal transparency. Unlike in other species, HCEC are notorious for their limited proliferative capacity in vivo after diseases, injury, aging, and surgery. Persistent HCEC dysfunction leads to sight-threatening bullous keratopathy with either an insufficient cell density or retrocorneal membrane due to endothelial-mesenchymal transition (EMT). Presently, the only solution to restore vision in eyes inflicted with bullous keratopathy or retrocorneal membrane relies upon transplantation of a cadaver human donor cornea containing a healthy corneal endothelium. Due to a severe global shortage of donor corneas, in conjunction with an increasing trend toward endothelial keratoplasty, it is opportune to develop a tissue engineering strategy to produce HCEC grafts. Prior attempts of producing these grafts by unlocking the contact inhibition-mediated mitotic block using trypsin-EDTA and culturing of single HCEC in a bFGF-containing medium run the risk of losing the normal phenotype to EMT by activating canonical Wnt signaling and TGF-Î² signaling. Herein, we summarize our novel approach in engineering HCEC grafts based on selective activation of p120-Kaiso signaling that is coordinated with activation of Rho-ROCK-canonical BMP signaling to reprogram HCEC into neural crest progenitors. Successful commercialization of this engineering technology will not only fulfill the global unmet need but also encourage the scientific community to re-think how cell-cell junctions can be safely perturbed to uncover novel therapeutic potentials in other model systems.
Anti-N-Methyl-D-Aspartate Receptor Encephalitis in Children and Adolescents. - Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease that is becoming increasingly recognized in the pediatric population. It may be the most common cause of treatable autoimmune encephalitis. The majority of cases of anti-NMDAR encephalitis are idiopathic in etiology, but a significant minority can be attributed to a paraneoplastic origin. Children with anti-NMDAR encephalitis initially present with a prodrome of neuropsychiatric symptoms, often with orofacial dyskinesias followed by progressively worsening seizures, agitation, and spasticity, which may result in severe neurologic deficits and even death. Definitive diagnosis requires detection of NMDAR antibodies in the cerebrospinal fluid. Optimal outcomes are associated with prompt removal of the tumor in paraneoplastic cases, as well as aggressive immunosuppressive therapy. Early detection is essential for increasing the chances for a good outcome. Close follow-up is required to screen for relapse and later onset tumor presentation. The nurse practitioner plays a major role in the research, screening, diagnosis, treatment, follow-up, and rehabilitation of a child or adolescent with anti-NMDAR encephalitis.Copyright Â© 2015 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.
Interferon-mediated cytokine induction determines sustained virus control in chronic HCV infection. - The Journal of infectious diseases
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated complications such as liver cirrhosis and hepatocellular carcinoma. Interferons (IFNs) are crucial for HCV clearance and a sustained virological response (SVR), but a significant proportion of patients do not respond to IFNÎ±. The underlying mechanisms of an insufficient IFN response remain largely unknown. In this study we found that patients responding to IFNÎ± with viral clearance revealed significantly higher serum levels of TNF-related apoptosis inducing ligand (TRAIL) as compared to patients that failed to control HCV. In addition, upon direct IFNÎ± exposure peripheral blood mononuclear cells (PBMCs) from SVR patients upregulated TRAIL as well as IFNÎ³, CXCL9 and CXCL10 much more strongly than cells from patients with antiviral treatment failure. As a possible mechanism of the stronger IFNÎ±-induced cytokine response, we identified higher expression and phosphorylation of STAT1 in PBMCs from SVR patients. Increased TRAIL expression additionally involved the NFÎºB and JNK pathway. Thus, SVR in chronic HCV infection is associated with strong IFNÎ±-induced cytokine response, which might allow for the early prediction of treatment efficacy in HCV infection.Â© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail firstname.lastname@example.org.
A replication study of 49 TypeÂ 2 diabetes risk variants in a Punjabi Pakistani population. - Diabetic medicine : a journal of the British Diabetic Association
The burden of TypeÂ 2 diabetes is alarmingly high in South Asia, a region that has many genetically diverse ethnic populations. Genome-wide association studies (GWAS) conducted largely in European populations have identified a number of loci predisposing to TypeÂ 2 diabetes risk, however, the relevance of such genetic loci in many South Asian sub-ethnicities remains elusive. The aim of this study was to replicate 49 single nucleotide polymorphisms (SNPs) previously identified through GWAS in Punjabis living in Pakistan.We examined the association of 49 SNPs in 853 TypeÂ 2 diabetes cases and 1945 controls using additive logistic regression models after adjusting for age and gender.Of the 49 SNPs investigated, eight showed a nominal association (PÂ <Â 0.05) that also remained significant after controlling for the false discovery rate. The most significant association was found for rs7903146 at the TCF7L2 locus. For a per unit increase in the risk score comprising of all the 49 SNPs, the odds ratio in association with TypeÂ 2 diabetes risk was 1.16 (95% CI 1.13-1.19, PÂ <Â 2.0E-16).These results suggest that some TypeÂ 2 diabetes susceptibility loci are shared between Europeans and Punjabis living in Pakistan. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
MicroRNA expression profiling identifies miR-31-5p/3p as associated with time to progression in wild-type RAS metastatic colorectal cancer treated with cetuximab. - Oncotarget
The aim of our study was to investigate whether microRNAs (miRNAs) could serve as predictive biomarkers to anti-EGFR therapy (cetuximab, panitumumab) in patients with RAS wild-type (wt-RAS) metastatic colorectal cancer (mCRC). Historical cohort of 93 patients with mCRC (2006-2009) was included and further divided into exploratory and validation cohorts. MiRNAs expression profiling was performed on the exploratory cohort of 41 wt-KRAS mCRC patients treated with cetuximab to identify miRNAs associated with time to progression (TTP). The validation was performed on two independent cohorts: 28 patients of wt-RAS mCRC treated with cetuximab and 24 patients of wt-RAS mCRC treated with panitumumab. We identified 9 miRNAs with significantly different expression between responders and non-responders to cetuximab therapy (P â‰¤ 0.01). These 9 miRNAs were further evaluated in two independent cohorts of patients and miR-31-3p (P < 0.001) and miR-31-5p (P < 0.001) were successfully confirmed as strongly associated with TTP in wt-RAS mCRC patients treated with cetuximab but not panitumumab. When evaluated on the complete cohort of cetuximab patients (N = 69), miR-31-3p (HR, 5.10; 95% CI, 2.52-10.32; P < 0.001) and miR-31-5p (HR, 4.80; 95% CI, 2.50-9.24; P < 0.001) were correlated with TTP on the comparable level of significance. There was no difference in miR-31-5p/3p expression levels in RAS mutated and wild-type tumor samples. MiR-31-5p/3p are promising predictive biomarkers of cetuximab response in wt-RAS mCRC patients.
Assessment of Immunological Biomarkers in the First Year after Heart Transplantation. - Disease markers
Background. Pharmacodynamic biomarkers that detect changes of immunological functions have been recognized as a helpful tool to increase the efficacy of immunosuppressive drug therapies. However, physiological changes of immunological biomarkers following transplantation are not investigated. Therefore, we assessed frequently used immunological biomarkers of the circulating blood in the first year following heart transplantation (HTx). Methods. Activation markers CD25 and CD95, intracellular cytokines IL-2 and IFNÎ³, chemokines IP10 and MIG, and subsets of dendritic cells as well as antibodies against human leukocyte antigens (HLA) and major histocompatibility complex class I-related chain A (MICA) antigens were analyzed at different time points using flow cytometry and Luminex xMAP technology. Results. Expression of IL-2, IFNÎ³, and plasmacytoid dendritic cells (pDCs) significantly increased (p < 0.01) during the first year. Anti-HLA antibodies decreased continuously, while anti-MICA antibodies showed minor increase within the first year. An association between percentage of pDCs and anti-MICA antibody positivity was proven. pDCs, IFNÎ³-producing T cells, and IP10 concentration were associated in a stronger way with age and gender of HTx recipients than with antibodies against HLA or MICA. Conclusions. We conclude that certain immunological biomarkers of the circulating blood change during the first year after HTx. These changes should be considered for interpretation of biomarkers after transplantation.
Sublobar resection is equivalent to lobectomy forÂ T1a non-small cell lung cancer in the elderly: aÂ Surveillance, Epidemiology, and End Results database analysis. - The Journal of surgical research
Anatomic lobectomy with mediastinal lymph node dissection is considered the optimal management for early stage non-small cell lung cancer (NSCLC). Limited lung resection may be preferable in the elderly population, who are more likely to have poor pulmonary reserve and multiple comorbidities. Our primary objective was to compare the survival of patients aged â‰¥75Â y who underwent sublobar resection or lobectomy for stage IA NSCLC.We queried the Surveillance, Epidemiology, and End Results database for patients aged â‰¥75Â y who were diagnosed with stage IA NSCLC from 1998-2007. Patients were divided into three groups based on the type of surgery performed (wedge resection, segmentectomy, and lobectomy). Kaplan-Meier analysis and Cox proportional hazard model were used for survival analysis.A total of 1640 patients were analyzed. Lobectomy was performed in 1051 patients, 119 underwent segmentectomy, and 470 patients had wedge resection. Overall and cancer-specific survival were significantly lower in the wedge resection group as compared with those in lobectomy (PÂ <Â 0.05). However, for T1a tumors, no significant difference was found in risk adjusted 5-y cancer-specific survival for patients who underwent wedge resection, segmentectomy (hazard ratio, 1.009; 95% confidence interval 0.624-1.631; PÂ =Â 0.972), or lobectomy (hazard ratio, 0.98; 95% confidence interval, 0.691-1.388; PÂ =Â 0.908).Sublobar resection is not inferior to lobectomy for T1a N0 M0 NSCLC in the elderly and should be considered a viable alternative in this high-risk population.Copyright Â© 2015 Elsevier Inc. All rights reserved.
Diagnostic accuracy of calculated serum osmolarity to predict dehydration in older people: adding value to pathology laboratory reports. - BMJ open
To assess which osmolarity equation best predicts directly measured serum/plasma osmolality and whether its use could add value to routine blood test results through screening for dehydration in older people.Diagnostic accuracy study.Older people (â‰¥65â€…years) in 5 cohorts: Dietary Strategies for Healthy Ageing in Europe (NU-AGE, living in the community), Dehydration Recognition In our Elders (DRIE, living in residential care), Fortes (admitted to acute medical care), SjÃ¶strand (emergency room) or Pfortmueller cohorts (hospitalised with liver cirrhosis).Directly measured serum/plasma osmolality: current dehydration (serum osmolality >300â€…mOsm/kg), impending/current dehydration (â‰¥295â€…mOsm/kg).39 osmolarity equations calculated using serum indices from the same blood draw as directly measured osmolality.Across 5 cohorts 595 older people were included, of whom 19% were dehydrated (directly measured osmolality >300â€…mOsm/kg). Of 39 osmolarity equations, 5 showed reasonable agreement with directly measured osmolality and 3 had good predictive accuracy in subgroups with diabetes and poor renal function. Two equations were characterised by narrower limits of agreement, low levels of differential bias and good diagnostic accuracy in receiver operating characteristic plots (areas under the curve >0.8). The best equation was osmolarity=1.86Ã—(Na(+)+ K(+))+1.15Ã—glucose+urea+14 (all measured in mmol/L). It appeared useful in people aged â‰¥65â€…years with and without diabetes, poor renal function, dehydration, in men and women, with a range of ages, health, cognitive and functional status.Some commonly used osmolarity equations work poorly, and should not be used. Given costs and prevalence of dehydration in older people we suggest use of the best formula by pathology laboratories using a cutpoint of 295â€…mOsm/L (sensitivity 85%, specificity 59%), to report dehydration risk opportunistically when serum glucose, urea and electrolytes are measured for other reasons in older adults.DRIE: Research Register for Social Care, 122273; NU-AGE: ClinicalTrials.gov NCT01754012.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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