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Κυριακή 14 Ιανουαρίου 2018

Isolation and Molecular Characterization of a Model Antagonistic Pseudomonas aeruginosa Divulging In Vitro Plant Growth Promoting Characteristics

The use of microbial technologies in agriculture is currently expanding quite rapidly with the identification of new bacterial strains, which are more effective in promoting plant growth. In the present study 18 strains of Pseudomonas were isolated from soil sample of Balochistan coastline. Among isolated Pseudomonas strains four designated as SP19, SP22, PS24, and SP25 exhibited biocontrol activities against phytopathogenic fungi, that is, Rhizopus microsporus, Fusarium oxysporum, Aspergillus niger, Alternaria alternata, and Penicillium digitatum; PS24 identified as Pseudomonas aeruginosa by 16srRNA gene bank accession number EU081518 was selected on the basis of its antifungal activity to explore its potential as plant growth promotion. PS24 showed multiple plant growth promoting attributes such as phosphate solubilization activity, indole acetic acid (IAA), siderophore, and HCN production. In order to determine the basis for antifungal properties, antibiotics were extracted from King B broth of PS24 and analyzed by TLC. Pyrrolnitrin antibiotic was detected in the culture of strain PS24. PS24 exhibited antifungal activities found to be positive for hydrogen cyanide synthase Hcn BC gene. Sequencing of gene of Hcn BC gene of strain PS24 revealed 99% homology with the Pseudomonas aeruginosa strain PA01. The sequence of PS24 had been submitted in gene bank accession number KR605499. Ps. aeruginosa PS24 with its multifunctional biocontrol possessions can be used to bioprotect the crop plants from phytopathogens.

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The Potential Protective Effect of Curcumin on Amyloid-β-42 Induced Cytotoxicity in HT-22 Cells

Background. We aimed to investigate the effect and mechanism of curcumin (CUR) in Alzheimer's disease (AD). Methods. Mouse hippocampal neuronal cell line HT-22 was treated with Aβ1–42 and/or CUR, and then cell viability was evaluated by cell counting kit 8, Beclin-l level was detected using western blotting, and the formation of autophagosomes was observed by transmission electron microscopy (TEM). Furthermore, transcriptome sequencing and analysis were performed in cells with Aβ1–42 alone or Aβ1–42 + CUR. Results. Aβ1–42 treatment significantly inhibited cell viability compared with untreated cells . After treatment for 48 h, CUR remarkably promoted cell viability compared with cell treated with Aβ1–42 alone . Compared with cells treated with Aβ1–42 alone, the expression of Beclin-1 was slightly reduced in cells with combined treatment of Aβ1–42 with CUR . Consistently, TEM results showed that CUR inhibited the formation of autophagosomes in cells treated with Aβ1–42. Furthermore, the protein-protein interaction network showed five key genes, including MYC, Cdh1, Acaca, Egr1, and CCnd1, likely involved in CUR effects. Conclusions. CUR might have a potential neuroprotective effect by promoting cell viability in AD, which might be associated with cell autophagy. Furthermore, MYC, Cdh1, and Acaca might be involved in the progression of AD.

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First Case of Stevens-Johnson Syndrome After Rabies Vaccination

Abstract

We describe the first case of Stevens-Johnson syndrome (SJS) occurring 8 days after the first dose of a 3-dose rabies vaccination series. She had no history of vaccine-related rash or other adverse drug reactions, nor had she received any other drug therapy. The temporal relationship between the development of SJS and the vaccination suggests that the rabies vaccination probably was the causal agent. This case serves as a warning of a distinct cutaneous reaction of rabies vaccination.



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Apraxia [Humanities]



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An emergency response to the opioid overdose crisis in Canada: a regulated opioid distribution program [Commentary]



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Family doctors call for guaranteed access to EMR data for research and quality improvement [News]



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Childhood trajectories of peer victimization and prediction of mental health outcomes in midadolescence: a longitudinal population-based study [Research]

BACKGROUND:

Exposure to peer victimization is relatively common. However, little is known about its developmental course and its effect on impairment associated with mental illnesses. We aimed to identify groups of children following differential trajectories of peer victimization from ages 6 to 13 years and to examine predictive associations of these trajectories with mental health in adolescence.

METHODS:

Participants were members of the Quebec Longitudinal Study of Child Development, a prospective cohort of 2120 children born in 1997/98 who were followed until age 15 years. We included 1363 participants with self-reported victimization from ages 6 to 13 years and data available on their mental health status at 15 years.

RESULTS:

We identified 3 trajectories of peer victimization. The 2 prevailing groups were participants with little or moderate exposure to victimization (441/1685 [26.2%] and 1000/1685 [59.3%], respectively); the third group (244 [14.5%]) had been chronically exposed to the most severe and long-lasting levels of victimization. The most severely victimized individuals had greater odds of reporting debilitating depressive or dysthymic symptoms (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.27–5.17), debilitating generalized anxiety problems (OR 3.27, CI 1.64–6.51) and suicidality (OR 3.46, CI 1.53–7.81) at 15 years than those exposed to the lowest levels of victimization, after adjustment for sex, childhood mental health, family hardship and victimization perpetration. The association with suicidality remained significant after controlling for concurrent symptoms of depression or dysthymia and generalized anxiety problems.

INTERPRETATION:

Adolescents who were most severely victimized by peers had an increased risk of experiencing severe symptoms consistent with mental health problems. Given that peer victimization trajectories are established early on, interventions to reduce the risk of being victimized should start before enrolment in the formal school system.



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Peripartum suicide: additional considerations [Letters]



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Addressing overestimation of the prevalence of depression based on self-report screening questionnaires [Analysis]



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Mental health needs our attention [Editorial]



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Exacerbation of psychosis triggered by a synthetic cannabinoid in a 70-year-old woman with Parkinson disease [Practice]



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Urgent care access: finding solutions that match causation [Letters]



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Physician burnout [Practice]



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Fertility advocates protest criminal sanctions in assisted reproduction act [News]



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Contact lens-related Pseudomonas aeruginosa keratitis in a 49-year-old woman [Practice]



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Doctors disappointed by income sprinkling changes [News]



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Cognitive dysfunction after generalized tonic-clonic status epilepticus in adults

Objectives

Generalized tonic-clonic status epilepticus (GTC-SE) is considered a risk for cognitive impairment. Research with standardized tools is scarce and non-conclusive. We systematically assessed short-term and long-term cognitive function after GTC-SE.

Materials and methods

Thirty-three patients were tested after the clinical post-ictal phase of GTC-SE (timepoint 1) and again after 1 year (timepoint 2). Twenty controls were examined with the same tests. Tests from Cambridge Neuropsychological Test Automated Battery were used. Motor screening test (MOT) assessed motor speed, delayed matching to sample (DMS) and paired associates learning (PAL) assessed memory, and Stockings of Cambridge (SOC) assessed executive function. Estimated premorbid IQ and radiologically visible brain lesions were controlled for in adjusted results. Outcome measures were z-scores, the number of standard deviations a score deviates from the mean of a norm population.

Results

At timepoint 1, unadjusted patient results were significantly below both norm and control group performances on all subtests. Patient mean was 1.9 z-scores below controls (< .001) on PAL total errors. Results remained significant for PAL and DMS after adjustments. Patient results improved at timepoint 2, but memory tests remained lower than norms and for controls. An executive dysfunction emerged on the most complex SOC stage (z-score difference −0.83; = .008, adjusted difference −0.94; = .02).

Conclusions

Memory and learning impairment in the early phase after SE and late developing executive dysfunction remained significant after adjusting for estimated premorbid IQ and pre-SE brain lesions. Results suggest that GTC-SE poses a risk for cognitive impairment.



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Meet Our Editorial Board Member



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Metabolic acidosis and anaemia associated with dorzolamide in a patient with impaired renal function

Topical carbonic anhydrase inhibitors (CAI), used for treatment of glaucoma, are generally regarded as safe and unconnected with systemic side effects. We report an unusual case of fatigue, metabolic acidosis, and normocytic anaemia associated with ocular administration of the CAI, dorzolamide, in a patient with impaired renal function. In chronic kidney disease, where CAI elimination may be decreased, and patients prone to develop metabolic acidosis, systemic absorption of ocular administered CAI could lead to rare, but potentially serious adverse reaction, that are a consequence of inhibition of extraocular carbonic anhydrase isoenzymes.



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Sarcoidosis with muscular involvement demonstrated on gallium-67 scintigraphy

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LETTER

Hippokratia 2016, 20(4):319

Meristoudis G1, Tryfon S2, Notopoulos A1
1Nuclear Medicine Department, Hippokration Hospital
2Pulmonary Department, Papanikolaou Hospital, Thessaloniki, Greece



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Effects of radial extracorporeal shock wave therapy on hand spasticity in poststroke patient

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CASE REPORT

Hippokratia 2016, 20(4):309-312

Gjerakaroska Savevska C, Nikolikj Dimitrova E, Gocevska M
Institute for Physical and Rehabilitation Medicine, Medical Faculty, "Ss Ciryl and Methodius" University, Skopje, F.Y.R. of Macedonia



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The Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire: cultural adaptation and validation of the Greek version

RESEARCH ARTICLE

Hippokratia 2016, 20(4):264-267

Tailachidis P1,2, Tsimtsiou­­ Z3, Galanis P2,4, Theodorou M2, Kouvelas D1, Athanasakis K2,5
1
2nd Department of Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
2Faculty of Economics and Management, Open University of Cyprus, Nicosia, Cyprus
3Department of Hygiene, Faculty of Medicine, Aristotle University of Thessaloniki Thessaloniki, Greece
4Center for Health Services Management and Evaluation, Department of Nursing, University of Athens, Athens, Greece
5Department of Health Economics, National School of Public Health, Athens, Greece



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Anesthesia management of a patient with a femoral neck fracture and hereditary hemorrhagic telangiectasia

CASE REPORT

Hippokratia 2016, 20(4):303-305

Tsoleridis T, Galanou L, Tsoleridis S
Department of Anesthesiology and Pain Treatment, General Hospital of Rhodes, Rhodes, Greece



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The relationship between neutrophil/lymphocyte and platelet/lymphocyte ratios with oxidative stress in active Crohn’s disease patients

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RESEARCH ARTICLE

Hippokratia 2016, 20(4):268-273

Eraldemir FC1, Musul M2, Duman AE3, Oztas B4, Baydemir C5, Hulagu S3
1
Department of Biochemistry, Medical School, University of Kocaeli, Kocaeli
2Laboratory of Biochemistry, Bucak State Hospital, Burdur
3Department of Gastroenterology, Medical School, University of Kocaeli, Kocaeli
4Department of Biochemistry, Sisli Hamidiye Etfal Research and Training Hospital, Istanbul
5Department of Biostatistic, Medical School, University of Kocaeli, Kocaeli, Turkey



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MicroRNA expression in patients with squamous cell carcinoma of the tongue

LETTER

Hippokratia 2016, 20(4):317

Paraskevopoulos K1, Touplikioti P2, Antoniades K1
1Department of Oral and Maxillofacial Surgery, 'G.Papanikolaou' General Hospital
2Department of Cytopathology, Theageneio Anticancer Hospital, Thessaloniki, Greece



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Epidemiology and outcome of elderly admitted to the ward for sepsis

RESEARCH ARTICLE

Hippokratia 2016, 20(4):274-278

Pyrpasopoulou A1,2, Pateinakis P1, Varouktsi A1, Georgianou E1, Zografou I1, Roilides E2,3, Karagiannis A1
12nd Propedeutic Department of Internal Medicine
2Infectious Diseases Unit
33rd Pediatric Department, Hippokration Hospital, Thessaloniki, Greece



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The adipokines in the pathogenesis and treatment of nonalcoholic fatty liver disease

REVIEW ARTICLE

Hippokratia 2016, 20(4):259-263

Boutari C1, Tziomalos K2, Athyros VG1
1Second Propedeutic Department of Internal Medicine, Hippokration Hospital
2First Propedeutic Department of Internal Medicine, AHEPA Hospital Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece



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Home intravenous antibiotic therapy in children with cystic fibrosis: clinical outcome, quality of life and economic benefit

RSEARCH ARTICLE

Hippokratia 2016, 20(4):279-283

Chrysochoou EA, Hatziagorou E, Kirvassilis F, Tsanakas J
3rd Pediatric Department, Pediatric Pulmonology and Cystic Fibrosis Unit, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece



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Multifocal splenic abscesses in immunocompetent adult due to cat-scratch disease

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CASE REPORT

Hippokratia 2016, 20(4):306-308

Gkamprela E1, Papadimitropoulos V1, Papadopoulos N2, Deutsch M1
1Second Department of Internal Medicine, "Hippokration" General Hospital of Athens, National and Kapodistrian University of Athens
2First Department of Internal Medicine, 417 Army Share Fund Hospital of Athens, Athens, Greece



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Prevalence and social determinants of smoking in the adult Greek Cypriot population

RESEARCH ARTICLE

Hippokratia 2016, 20(4):284-291

Nicolaou SA1, Heraclides A2, Markides KS3, Charalambous A2
1Department of Life and Health Sciences
2Medical School, Center of Primary Care and Population Health, University of Nicosia, Nicosia, Cyprus
3Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, USA



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Anal canal gastrointestinal stromal tumors - report of a rare case and review of the literature

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CASE REPORT

Hippokratia 2016, 20(4):313-316

Paramythiotis D1, Bangeas P1, Karakatsanis A1, Karayannopoulou G2, Michalopoulos A1
11st Propedeutic Surgical Department, A.H.E.P.A. University Hospital
2Pathology Department, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece



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Ultrastructural evaluation of intramuscular applied botulinum toxin type A in striated muscles of rats

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RESEARCH ARTICLE

Hippokratia 2016, 20(4):292-298

Kocaelli H1, Yaltirik M1, Ayhan M1,  Aktar F2, Atalay B1,  Yalcin S1
1Department of Oral and Maxillofacial Surgery, Faculty of Dentistry
2Department of Histology and Embryology, Faculty of Medicine, Istanbul University, Istanbul, Turkey



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Giant hypopharyngeal fibrovascular polyp

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LETTER

Hippokratia 2016, 20(4): 318

Radovanovic Z1, Stankovic M2
1Institute for Radiology
2Clinic for Otolaryngology, Clinical Center Nis, Serbia



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Endonasal endoscopic repair of cerebrospinal fluid leaks versus craniotomy: comparison of the outcomes

CASE SERIES

Hippokratia 2016, 20(4):299-302

Christoforidou A1, Tsitsopoulos PP2, Selviaridis P3, Vital V1, Constantinidis J1
11st Department of Otorhinolaryngology Head and Neck Surgery, AHEPA Hospital
22nd Department of Neurosurgery, Ippokratio General Hospital
31st Department of Neurosurgery, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece



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Rectovaginal tear after sexual intercourse in a young woman-a case report

LETTER

Hippokratia 2016, 20(4):320

Daniilidis A1, Panteleris N1, Symeonidis N2
12nd Department of Obstetrics and Gynecology
22nd Propedeutical Department of Surgery, Hippokratio General Hospital, Aristotle University of Thessaloniki, Greece



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Clinical features and treatment of nonalcoholic fatty liver disease across the Asia Pacific region—the GO ASIA initiative

Summary

Background

The Gut and Obesity Asia (GO ASIA) workgroup was formed to study the relationships between obesity and gastrointestinal diseases in the Asia Pacific region.

Aim

To study factors associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis, and medical treatment of biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients.

Methods

Retrospective study of biopsy-proven NAFLD patients from centres in the GO ASIA Workgroup. Independent factors associated with NASH and with advanced fibrosis on binary logistic regression analyses in a training cohort were used for the development of their corresponding risk score, which were validated in a validation cohort.

Results

We included 1008 patients from nine centres across eight countries (NASH 62.9%, advanced fibrosis 17.2%). Independent predictors of NASH were body mass index ≥30 kg/m2, diabetes mellitus, dyslipidaemia, alanine aminotransferase ≥88 U/L and aspartate aminotransferase ≥38 U/L, constituting the Asia Pacific NASH risk score. A high score has a positive predictive value of 80%-83% for NASH. Independent predictors of advanced fibrosis were age ≥55 years, diabetes mellitus and platelet count <150 × 109/L, constituting the Asia-Pacific NAFLD advanced fibrosis risk score. A low score has a negative predictive value of 95%-96% for advanced fibrosis. Only 1.7% of patients were referred for structured lifestyle program, 4.2% were on vitamin E, and 2.4% were on pioglitazone.

Conclusions

More severe liver disease can be suspected or ruled out based on factors identified in this study. Utilisation of structured lifestyle program, vitamin E and pioglitazone was limited despite this being a cohort of biopsy-proven NAFLD patients with majority of patients having NASH.



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Clinical and metabolic effects associated with weight changes and obeticholic acid in non-alcoholic steatohepatitis

Summary

Background

In a 72-week, randomised controlled trial of obeticholic acid (OCA) in non-alcoholic steatohepatitis (NASH), OCA was superior to placebo in improving serum ALT levels and liver histology. OCA therapy also reduced weight.

Aims

Because weight loss by itself can improve histology, to perform a post hoc analysis of the effects of weight loss and OCA treatment in improving clinical and metabolic features of NASH.

Methods

The analysis was limited to the 200 patients with baseline and end-of-treatment liver biopsies. Weight loss was defined as a relative decline from baseline of 2% or more at treatment end.

Results

Weight loss occurred in 44% (45/102) of OCA and 32% (31/98) of placebo-treated patients (P = 0.08). The NAFLD Activity score (NAS) improved more in those with than without weight loss in both the OCA- (−2.4 vs −1.2, P<0.001) and placebo-treated patients (−1.2 vs −0.5, P = 0.03). ALT levels also improved in those with vs without weight loss in OCA- (−43 vs −34 U/L, P = 0.12) and placebo-treated patients (−29 vs −10 U/L, P = 0.02). However, among those who lost weight, OCA was associated with opposite effects from placebo on changes in alkaline phosphatase (+21 vs −12 U/L, P<0.001), total (+13 vs −14 mg/dL, P = 0.02) and LDL cholesterol (+18 vs −12 mg/dL, P = 0.01), and HbA1c (+0.1 vs −0.4%, P = 0.01).

Conclusions

OCA leads to weight loss in up to 44% of patients with NASH, and OCA therapy and weight loss have additive benefits on serum aminotransferases and histology. However, favourable effects of weight loss on alkaline phosphatase, lipids and blood glucose seen in placebo-treated patients were absent or reversed on OCA treatment. These findings stress the importance of assessing concomitant metabolic effects of new therapies of NASH. Clinical trial number: NCT01265498.



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RAS testing for colorectal cancer patients is reliable in European laboratories that pass external quality assessment

Abstract

Wild-type status of KRAS and the NRAS gene (exon 2, 3, and 4) in the tumor should be determined before treatment of metastatic colorectal cancer (mCRC) patients with EGFR-targeting agents. There is a large variation in test methods to determine RAS status, and more sensitive detection methods were recently introduced. Data from quality assessment programs indicate substantial error rates. This study assessed the completeness and correctness of RAS testing in European laboratories that successfully passed external quality assessment (EQA). Participants were requested to send material of their most recent ten patients with mCRC who had been tested for RAS status. Isolated DNA, a hematoxylin and eosin stained tissue slide with a marked area for macrodissection and accompanying patient reports were requested. Samples were reevaluated in a reference laboratory by using a next-generation sequencing approach. In total, 31 laboratories sent in the requested material (n = 309). Despite regulations for anti-EGFR therapy, one institute did not perform full RAS testing. Reanalysis was possible for 274 samples with sufficient DNA available. In the hotspot codons of KRAS and NRAS, seven discordant results were obtained in total, five of them leading to a different prediction of anti-EGFR therapy efficacy (2%; n = 274). Results show that oncologists can rely on the quality of laboratories with good performance in EQA. Oncologists need to be aware that the testing laboratory participates successfully in EQA programs. Some EQA providers list the good performing laboratories on their website.



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Examining patterns of multimorbidity, polypharmacy and risk of adverse drug reactions in chronic obstructive pulmonary disease: a cross-sectional UK Biobank study

Objective

This study aims: (1) to describe the pattern and extent of multimorbidity and polypharmacy in UK Biobank participants with chronic obstructive pulmonary disease (COPD) and (2) to identify which comorbidities are associated with increased risk of adverse drug reactions (ADRs) resulting from polypharmacy.

Design

Cross-sectional.

Setting

Community cohort.

Participants

UK Biobank participants comparing self-reported COPD (n=8317) with no COPD (n=494 323).

Outcomes

Multimorbidity (≥4 conditions) and polypharmacy (≥5 medications) in participants with COPD versus those without. Risk of ADRs (taking ≥3 medications associated with falls, constipation, urinary retention, central nervous system (CNS) depression, bleeding or renal injury) in relation to the presence of COPD and individual comorbidities.

Results

Multimorbidity was more common in participants with COPD than those without (17% vs 4%). Polypharmacy was highly prevalent (52% with COPD taking ≥5 medications vs 18% in those without COPD). Adjusting for age, sex and socioeconomic status, those with COPD were significantly more likely than those without to be prescribed ≥3 medications contributing to falls (OR 2.27, 95% CI 2.13 to 2.42), constipation (OR 3.42, 95% CI 3.10 to 3.77), urinary retention (OR 3.38, 95% CI 2.94 to 3.87), CNS depression (OR 3.75, 95% CI 3.31 to 4.25), bleeding (OR 4.61, 95% CI 3.35 to 6.19) and renal injury (OR 2.22, 95% CI 1.86 to 2.62). Concomitant cardiovascular disease was associated with the greatest risk of taking ≥3 medications associated with falls/renal injury. Concomitant mental health conditions were most strongly associated with medications linked with CNS depression/urinary retention/bleeding.

Conclusions

Multimorbidity is common in COPD and associated with high levels of polypharmacy. Co-prescription of drugs with various ADRs is common. Future research should examine the effects on healthcare outcomes of co-prescribing multiple drugs with similar potential ADRs. Clinical guidelines should emphasise assessment of multimorbidity and ADR risk.



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Alteration of Mevalonate Pathway in Rat Splenic Lymphocytes: Possible Role in Cytokines Secretion Regulated by L-Theanine

L-Theanine is a nonprotein amino acid in tea, and its immunomodulatory function has been confirmed. This study aimed to investigate the effect of L-theanine addition on cytokines secretion in rat splenic lymphocytes and explore its potential immunomodulatory effects on the mevalonate biosynthetic pathway. Our results showed that L-theanine treatment did not influence the proliferation and division indexes of the splenic lymphocytes subsets. Interestingly, L-theanine treatment had regulated the contents of IFN-, IL-2, IL-4, IL-10, IL-12, and TNF-   except IL-6 and upregulated the mRNA and protein expression of Ras-related protein Rap-1A (Rap1A), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and farnesyl diphosphate synthase (FDPs) . Additionally, there was a positive correlation between Rap1A and HMGCR proteins expression and IFN-γ, IL-4, and IL-6 levels. In conclusion, L-theanine regulated the secretion of cytokines probably by activating expression of Rap1A and HMGCR proteins involved in the mevalonate biosynthetic pathway in rat splenic lymphocytes. Therefore, L-theanine might be a promising potential drug candidate as immunopotentiator.

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Glycyrrhizin Suppresses the Growth of Human NSCLC Cell Line HCC827 by Downregulating HMGB1 Level

Lung cancer has very high mortality and glycyrrhizin was found to significantly inhibit the growth of lung cancer cells in vitro and tissues in mice. However, the detailed inhibitory role of glycyrrhizin in the growth of lung cancer is still unclear. In this study, we first found that glycyrrhizin inhibited the growth of lung tumor in PDX mice. And high level of HMGB1 promoted the migration and invasion of lung cancer cells, which was suppressed by glycyrrhizin. Moreover, glycyrrhizin reduced the activity of JAK/STAT signaling pathway, which is the upstream regulator of HMGB1. Therefore, this study revealed a potential mechanism by which glycyrrhizin can inhibit the progression of lung cancer.

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Targeted Next-Generation Sequencing of a Deafness Gene Panel (MiamiOtoGenes) Analysis in Families Unsuitable for Linkage Analysis

Hearing loss (HL) is a common sensory disorder in humans with high genetic heterogeneity. To date, over 145 loci have been identified to cause nonsyndromic deafness. Furthermore, there are countless families unsuitable for the conventional linkage analysis. In the present study, we used a custom capture panel (MiamiOtoGenes) to target sequence 180 deafness-associated genes in 5 GJB2 negative deaf probands with autosomal recessive nonsyndromic HL from Iran. In these 5 families, we detected one reported and six novel mutations in 5 different deafness autosomal recessive (DFNB) genes (TRIOBP, LHFPL5, CDH23, PCDH15, and MYO7A). The custom capture panel in our study provided an efficient and comprehensive diagnosis for known deafness genes in small families.

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The Differential Expression of Core Genes in Nucleotide Excision Repair Pathway Indicates Colorectal Carcinogenesis and Prognosis

Background. Nucleotide excision repair (NER) plays a critical role in maintaining genome integrity. This study aimed to investigate the expression of NER genes and their associations with colorectal cancer (CRC) development. Method. Expressions of NER genes in CRC and normal tissues were analysed by ONCOMINE. The Cancer Genome Atlas (TCGA) data were downloaded to explore relationship of NER expression with clinicopathological parameters and survival of CRC. Results. ERCC1, ERCC2, ERCC5, and DDB2 were upregulated while ERCC4 was downregulated in CRC. For colon cancer, high ERCC3 expression was related to better T stage; ERCC5 expression indicated deeper T stage and distant metastasis; DDB2 expression suggested earlier TNM stage. For rectal cancer, ERCC2 expression correlated with favourable T stage; XPA expression predicted worse TNM stage. ERCC2 expression was associated with worse overall survival (OS) in colon cancer (, ). Colon cancer patients with high ERCC4 expression showed favorable OS in males (, ). High XPC expression demonstrated decreased death hazards in rectal cancer (, ). Conclusion. ERCC1, ERCC2, ERCC4, ERCC5, and DDB2 were differently expressed in CRC and normal tissues; ERCC2, ERCC3, ERCC5, XPA, and DDB2 correlated with clinicopathological parameters of CRC, while ERCC2, ERCC4, and XPC might predict CRC prognosis.

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Monoamine Oxidase-A Inhibition and Associated Antioxidant Activity in Plant Extracts with Potential Antidepressant Actions

Monoamine oxidase (MAO) catalyzes the oxidative deamination of amines and neurotransmitters and is involved in mood disorders, depression, oxidative stress, and adverse pharmacological reactions. This work studies the inhibition of human MAO-A by Hypericum perforatum, Peganum harmala, and Lepidium meyenii, which are reported to improve and affect mood and mental conditions. Subsequently, the antioxidant activity associated with the inhibition of MAO is determined in plant extracts for the first time. H. perforatum inhibited human MAO-A, and extracts from flowers gave the highest inhibition (IC50 of 63.6 μg/mL). Plant extracts were analyzed by HPLC-DAD-MS and contained pseudohypericin, hypericin, hyperforin, adhyperforin, hyperfirin, and flavonoids. Hyperforin did not inhibit human MAO-A and hypericin was a poor inhibitor of this isoenzyme. Quercetin and flavonoids significantly contributed to MAO-A inhibition. P. harmala seed extracts highly inhibited MAO-A (IC50 of 49.9 μg/L), being a thousand times more potent than H. perforatum extracts owing to its content of β-carboline alkaloids (harmaline and harmine). L. meyenii root (maca) extracts did not inhibit MAO-A. These plants may exert protective actions related to antioxidant effects. Results in this work show that P. harmala and H. perforatum extracts exhibit antioxidant activity associated with the inhibition of MAO (i.e., lower production of H2O2).

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Construction and Characterization of a Recombinant Human Respiratory Syncytial Virus Encoding Enhanced Green Fluorescence Protein for Antiviral Drug Screening Assay

Human respiratory syncytial virus (RSV) is the single most important cause of lower respiratory tract disease in infants and young children and a major viral agent responsible for respiratory tract disease in immunosuppressed individuals and the elderly, but no vaccines and antiviral drugs are available. Herein the recombinant RSV (rRSV) encoding enhanced green fluorescence protein (EGFP, rRSV-EGFP) was constructed and the potential for screening anti-RSV drugs was investigated. The recombinant plasmid of pBRATm-rRSV-EGFP, containing T7 transcription cassette composed of T7 promoter, RSV antigenomic cDNA with EGFP gene, HDV ribozyme (δ), and T7 terminator in the order of 5′ to 3′, was constructed and cotransfected into BHK/T7-9 cells together with helper plasmids encoding N, P, L, and M2-1 gene, respectively. The rescued rRSV-EGFP was confirmed by increasing expression of EGFP over blind passages and by RT-PCR. rRSV-EGFP was comparable to the other two recombinant RSVs encoding red fluorescent protein (RFP, rRSV-RFP) or luciferase (Luc, rRSV-Luc) in the growth kinetic, and there was a difference in sensitivity between them for screening anti-RSV agents based on infection of HEp-2 cells. The EGFP-encoding rRSV has been constructed and rescued successfully and has the potential for high-throughput anti-RSV drug screening in vitro.

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Polyphenols in Colorectal Cancer: Current State of Knowledge including Clinical Trials and Molecular Mechanism of Action

Polyphenols have been reported to have wide spectrum of biological activities including major impact on initiation, promotion, and progression of cancer by modulating different signalling pathways. Colorectal cancer is the second most major cause of mortality and morbidity among females and the third among males. The objective of this review is to describe the activity of a variety of polyphenols in colorectal cancer in clinical trials, preclinical studies, and primary research. The molecular mechanisms of major polyphenols related to their beneficial effects on colorectal cancer are also addressed. Synthetic modifications and other future directions towards exploiting of natural polyphenols against colorectal cancer are discussed in the last section.

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Temporal Change of Interleukin-6, C-Reactive Protein, and Skin Temperature after Total Knee Arthroplasty Using Triclosan-Coated Sutures

The risk of surgical site infections (SSIs) after total knee arthroplasty (TKA) can never be eliminated. Antimicrobial sutures containing triclosan have been used to decrease SSIs, but whether triclosan-coated sutures are effective with TKA is unclear. Between 2011 and 2012, 102 patients randomly assigned to a triclosan or a control group were prospectively assessed. The incidence of SSI within 3 months of surgery, length of hospital stay, pain scale, functional scores, wound condition, and serum inflammatory markers during hospitalization and within 3 months postoperatively were compared. At the final follow-up, there were 2 patients with superficial infections (3.9%) in the control group but none in the triclosan group. Lower serum IL-6 was detected in the triclosan group at 4 weeks and 3 months. The local skin temperature of the knees—recorded at 3 months using infrared thermography—was lower in the triclosan group than in the control group. More precise analytical measurements are needed to investigate local and systemic complications, especially in the early subclinical stage. This prospective, randomized, open-label clinical trial is in the public registry: ClinicalTrials.gov (NCT02533492).

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Coronary Atherosclerosis Assessment by Coronary CT Angiography in Asymptomatic Diabetic Population: A Critical Systematic Review of the Literature and Future Perspectives

The prognostic impact of diabetes mellitus (DM) on cardiovascular outcomes is well known. As a consequence of previous studies showing the high incidence of coronary artery disease (CAD) in diabetic patients and the relatively poor outcome compared to nondiabetic populations, DM is considered as CAD equivalent which means that diabetic patients are labeled as asymptomatic individuals at high cardiovascular risk. Lessons learned from the analysis of prognostic studies over the past decade have challenged this dogma and now support the idea that diabetic population is not uniformly distributed in the highest risk box. Detecting CAD in asymptomatic high risk individuals is controversial and, what is more, in patients with diabetes is challenging, and that is why the reliability of traditional cardiac stress tests for detecting myocardial ischemia is limited. Cardiac computed tomography angiography (CCTA) represents an emerging noninvasive technique able to explore the atherosclerotic involvement of the coronary arteries and, thus, to distinguish different risk categories tailoring this evaluation on each patient. The aim of the review is to provide a wide overview on the clinical meaning of CCTA in this field and to integrate the anatomical information with a reliable therapeutic approach.

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Analysis of the Registration Information on Interventions of Acupuncture and Moxibustion Trials in the International Clinical Trials Registry Platform

Purpose. To analyze and compare the clinical registration information about acupuncture and moxibustion for intervention characteristics. Methods. Clinical trials from the International Clinical Trials Registry Platform of the World Health Organization in acupuncture and moxibustion were comprehensively collected from 2013 to 2015; data were independently screened and extracted by two retrievers, and relevant data involving either basic descriptions or intervention characteristics were analyzed. Results. 425 acupuncture and moxibustion registered clinical trials were included; 88.00% (374/425) were designed as controlled studies, among which 38.59% (164/425) had sham acupuncture as the control group. The most common diseases were pain-related at approximately 19.29% (82/425) of trials. Reports on the intervention information in these acupuncture and moxibustion clinical studies were not sufficiently presented; these reports included the reporting of names of points (39.8%), the method of needle stimulation (32.5%), needle type (29.6%), needle retention time (34.1%), the number of treatment sessions (22.4%), and the frequency and duration of treatment sessions (38.1%). Conclusion. The registration information for the clinical trials of acupuncture and moxibustion was quite low according to this investigational study. Steps should be taken to improve the quality of acupuncture and moxibustion registration information.

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In Vivo Single-Molecule Tracking at the Drosophila Presynaptic Motor Nerve Terminal

Here we illustrate how single molecule photo-activated localization microscopy can be carried out on the motor nerve terminal of a live Drosophila melanogaster third instar larva.

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Mass Isolation and In Vitro Cultivation of Intramolluscan Stages of the Human Blood Fluke Schistosoma Mansoni

This article describes a protocol for the large-scale axenic isolation and collection of free-swimming miracidia of the human blood fluke Schistosoma mansoni and their subsequent processing for introduction into in vitro culture.

http://ift.tt/2EGAzwc

Refractory Ventricle Arrhythmias Alternating with Pulseless Electrical Activity in a Young Woman Rescued by Extracorporeal Cardiopulmonary Resuscitation

Introduction. Extracorporeal cardiopulmonary resuscitation (ECPR) is a challenging approach for treating refractory out-of-hospital cardiac arrest (OHCA). Case Presentation. The authors describe a case of a 40-year-old Caucasian female who suffered from refractory OHCA, was admitted to a hospital while receiving ongoing cardiopulmonary resuscitation, and was connected to venoarterial extracorporeal membrane oxygenation 73 minutes after collapse. Ventricular tachyarrhythmias alternating with pulseless electrical activity resolved after eight hours. Following complete cardiac and neurological recovery, only adenoviral genome was found in myocardial biopsy. After 11 months, another episode of identical arrhythmias was rescued by an implantable cardioverter-defibrillator. Conclusion. Adequate prehospital and early hospital logistics is a prerequisite for successfully implementing extracorporeal cardiopulmonary resuscitation for refractory OHCA.

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Watchful Waiting Versus Surgery of Mildly Symptomatic or Asymptomatic Inguinal Hernia in Men Aged 50 Years and Older: A Randomized Controlled Trial

imageObjective: To compare if watchful waiting is noninferior to elective repair in men aged 50 years and older with mildly symptomatic or asymptomatic inguinal hernia. Background: The role of watchful waiting in older male patients with mildly symptomatic or asymptomatic inguinal hernia is still not well-established. Methods: In this noninferiority trial, we randomly assigned men aged 50 years and older with mildly symptomatic or asymptomatic inguinal hernia to either elective inguinal hernia repair or watchful waiting. Primary endpoint was the mean difference in a 4-point pain/discomfort score at 24 months of follow-up. Using a 0.20-point difference as a clinically relevant margin, it was hypothesized that watchful waiting was noninferior to elective repair. Secondary endpoints included quality of life, event-free survival, and crossover rates. Results: Between January 2006 and August 2012, 528 patients were enrolled, of whom 496 met the inclusion criteria: 234 were assigned to elective repair and 262 to watchful waiting. The mean pain/discomfort score at 24 months was 0.35 [95% confidence interval (CI) 0.28–0.41)] in the elective repair group and 0.58 (95% CI 0.52–0.64) in the watchful waiting group. The difference of these means (MD) was −0.23 (95% CI −0.32 to −0.14). In the watchful waiting group, 93 patients (35·4%) eventually underwent elective surgery and 6 patients (2·3%) received emergent surgery for strangulation/incarceration. Postoperative complication rates and recurrence rates in these 99 operated individuals were comparable with individuals originally assigned to the elective repair group (8.1% vs 15.0%; P = 0.106, 7.1% vs 8.9%; P = 0.668, respectively). Conclusions: Our data could not rule out a relevant difference in favor of elective repair with regard to the primary endpoint. Nevertheless, in view of all other findings, we feel that our results justify watchful waiting as a reasonable alternative compared with surgery in men aged 50 years and older.

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Isolation and Biological Evaluation of Prenylated Flavonoids from Maclura pomifera

Phytochemical analysis of the ethanolic extract of Maclura pomifera fruits yielded four new compounds (I–IV) along with eleven known compounds (V–XV). The crude extract exhibited significant activity towards cannabinoid receptors (CB1: 103.4% displacement; CB2: 68.8% displacement) and possibly allosteric interaction with and opioid receptors (−49.7 and −53.8% displacement, resp.). Compound I was found to be possibly allosteric for and opioid receptors (−88.4 and −27.2% displacement, resp.) and showed moderate activity (60.5% displacement) towards CB1 receptor. Compound II exhibited moderate activity towards cannabinoid receptors CB1 and CB2 (47.9 and 42.3% displacement, resp.). The known compounds (V–VIII) exhibited prominent activity towards cannabinoid receptors: pomiferin (V) (IC50 of 2.110 and 1.318 μM for CB1 and CB2, resp.), auriculasin (VI) (IC50 of 8.923 μM for CB1), warangalone (VII) (IC50 of 1.670 and 4.438 μM for CB1 and CB2, resp.), and osajin (VIII) (IC50 of 3.859 and 7.646 μM for CB1 and CB2, resp.). The isolated compounds were also tested for inhibition of human monoamine oxidase-A and monoamine oxidase-B enzymes activities, where all the tested compounds showed fewer inhibitory effects on MAO-A compared to MAO-B activities: auriculasin (VI) (IC50 of 1.91 and 45.98 μM for MAO-B and MAO-A, resp.).

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Themes Underlying Australian General Practitioner Views towards Chiropractic and Osteopathy: An Assessment of Free Text Data from a Cross-Sectional Survey

The Australian chiropractic and osteopathic professions underwent a period of significant transformation between 1960 and 2000. This resulted in an improvement in the views held by the medical profession towards the two professions. However, a recent survey of Australian general practitioners (GPs) reported that a number of GPs still hold negative views towards chiropractors and osteopaths. This paper examines these views from the perspective of critical realism and explores the generative mechanisms that can influence the willingness of health practitioners to collaborate over patient care. A qualitative analysis of open-ended responses to a survey of 630 Australian GPs was conducted. Unfavourable attitudes of GPs towards chiropractors and osteopaths included perceived lack of safety, efficacy, and inadequacy of training, despite chiropractic's and osteopathy's reliance on the same evidence base and similar training to those of other manual therapy professions such as physiotherapy. These attitudes may be underpinned by the professional biases against chiropractic and osteopathy that continue to marginalise the professions within the Australian healthcare system. Continued investment in the research base for chiropractic and osteopathic practice is required, along with raising the awareness of GPs about the education and skills of chiropractors and osteopaths.

http://ift.tt/2mujNZQ

Effect of Qufengtongluo Decoction on PI3K/Akt Signaling Pathway in the Kidney of Type 2 Diabetes Mellitus Rat (GK Rat) with Diabetic Nephropathy

Qufengtongluo (QFTL) decoction is an effective treatment for diabetic nephropathy (DN). However, the underlying molecular mechanism is still unclear. In this study, we try to investigate whether QFTL decoction acts via inhibiting PI3K/Akt signaling pathway. Twenty-four GK rats were randomly divided into 3 groups: blank group, sham-operated group, and QFTL group. After model establishment, rats in QFTL group were given QFTL decoction by gavage, while the rest were given pure water. During the 8-week intervention, 24 hr urinal protein was measured every 2-3 weeks. After intervention, kidneys were removed for pathological smear, quantitative real-time PCR, and western blotting to detect expression levels of p-PI3K, p-Akt, PTEN, TGF-β, PI3K mRNA, Akt mRNA, PTEN mRNA, and TGF-β mRNA. QFTL group showed a slighter degree of renal fibrosis in Masson and PASM staining and a greater reduction of 24 hr urinal protein than blank group. Compared to blank group, expression levels of p-PI3K, p-Akt, PI3K mRNA, and Akt mRNA were lower in QFTL group, while expression levels of PTEN and PTEN mRNA were higher. Besides, TGF-β was downregulated by QFTL decoction. In conclusion, this study suggests that QFTL decoction might inhibit PI3K/Akt signaling pathway via activating PTEN and inhibiting TGF-β.

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Efficient FIR Filter Implementations for Multichannel BCIs Using Xilinx System Generator

Background. Brain computer interface (BCI) is a combination of software and hardware communication protocols that allow brain to control external devices. Main purpose of BCI controlled external devices is to provide communication medium for disabled persons. Now these devices are considered as a new way to rehabilitate patients with impunities. There are certain potentials present in electroencephalogram (EEG) that correspond to specific event. Main issue is to detect such event related potentials online in such a low signal to noise ratio (SNR). In this paper we propose a method that will facilitate the concept of online processing by providing an efficient filtering implementation in a hardware friendly environment by switching to finite impulse response (FIR). Main focus of this research is to minimize latency and computational delay of preprocessing related to any BCI application. Four different finite impulse response (FIR) implementations along with large Laplacian filter are implemented in Xilinx System Generator. Efficiency of 25% is achieved in terms of reduced number of coefficients and multiplications which in turn reduce computational delays accordingly.

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Cancers, Vol. 10, Pages 20: Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity

Cancers, Vol. 10, Pages 20: Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity

Cancers doi: 10.3390/cancers10010020

Authors: Alessia Stornetta Valeria Guidolin Silvia Balbo

Alcohol is classified by the International Agency for Research on Cancer (IARC) as a human carcinogen and its consumption has been associated to an increased risk of liver, breast, colorectum, and upper aerodigestive tract (UADT) cancers. Its mechanisms of carcinogenicity remain unclear and various hypotheses have been formulated depending on the target organ considered. In the case of UADT cancers, alcohol's major metabolite acetaldehyde seems to play a crucial role. Acetaldehyde reacts with DNA inducing modifications, which, if not repaired, can result in mutations and lead to cancer development. Despite alcohol being mainly metabolized in the liver, several studies performed in humans found higher levels of acetaldehyde in saliva compared to those found in blood immediately after alcohol consumption. These results suggest that alcohol-derived acetaldehyde exposure may occur in the oral cavity independently from liver metabolism. This hypothesis is supported by our recent results showing the presence of acetaldehyde-related DNA modifications in oral cells of monkeys and humans exposed to alcohol, overall suggesting that the alcohol metabolism in the oral cavity is an independent cancer risk factor. This review article will focus on illustrating the factors modulating alcohol-derived acetaldehyde exposure and effects in the oral cavity.



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Autumn Royal and Ribier Grape Juice Extracts Reduced Viability and Metastatic Potential of Colon Cancer Cells

Antioxidants are known to be beneficial to health. This paper evaluates the potential chemopreventive and anticancer properties of phenolic compounds present in grape juice extracts (GJE) from Autumn Royal and Ribier varieties. The effects of these GJE on viability (SRB day assay) and metastatic potential (migration and invasion parameters) of colon cancer cell lines HT-29 and SW-480 were evaluated. The effects of GJE on two matrix metalloproteinase gene expressions (MMP2 and MMP9) were also evaluated via qRT-PCR. In the former, GJE reduced cell viability in both cell lines in a dose-dependent manner. GJE treatment also reduced cell migration and invasion. Moreover, MMP-2 and MMP-9 gene expression diminished depending on extract and on cell type. Conclusions. These results provide novel information concerning anticancer properties of selected GJE by revealing selective cytotoxicity and the ability to reduce invasiveness of colon cancer cells.

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Danhong Injection Alleviates Mechanical Allodynia via Inhibiting ERK1/2 Activation and Elevates BDNF Level in Sciatic Nerve in Diabetic Rat

Danhong injection (DHI) has been widely used in China for cardiocerebrovascular diseases treatments. And in this study, we demonstrated the therapeutic effect of DHI on experimental diabetic neuropathy for the first time. Methods. Streptozotocin- (STZ-) induced SD rats were used. In experiment 1, 4-week treatment with DHI or saline started 4 weeks after STZ injection; mechanical allodynia was measured before and every 2 weeks after STZ injection. In experiment 2, chronic intrathecal infusion of U0126 was conducted during the 8th week of diabetes. Phosphorylated and total ERK1/2 in spinal cord were analyzed by western blot. BDNF level in sciatic nerve was evaluated by ELISA. Results. DHI treatment significantly alleviated mechanical allodynia at the end of the study and downregulated the expression of phosphorylated ERK1/2 in spinal cord. In addition, DHI treatment also elevated brain-derived neurotrophic factor (BDNF) level in sciatic nerve of DPN rat. In experiment 2, inhibition of ERK1/2 activation was confirmed to result in the alleviation of mechanical allodynia. Conclusions. We demonstrated that DHI was able to alleviate mechanical allodynia in diabetic neuropathy rat through inhibiting the activation of ERK1/2. The reduction of BDNF content in sciatic nerve was also partially reversed by DHI treatment.

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