The effect of obesity on patients with mild chronic obstructive pulmonary disease: results from KNHANES 2010 to 2012.

Abstract:
PURPOSE
A low body mass index has been associated with high mortalities in patients with chronic obstructive pulmonary disease (COPD), and studies reveal that obesity aggravates the clinical effects of COPD. We investigated the impact of obesity on patients newly identified with COPD.

PATIENTS AND METHODS
This population-based, cross-sectional study, used data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted from 2010 to 2012. Through analyses of data from this survey, we compared concurrent comorbid diseases, symptoms, and lung functions between an obese and nonobese group of patients with COPD.

RESULTS
In total, 618 participants were diagnosed with COPD and the average forced expired volume in 1 s (FEV1) was 79.47%±0.69%. Of the total, 30.5% of the subjects were categorized into an obese group. Subjects in the obese group were likely to have metabolic syndrome (P<0.001), hypertension (P=0.02), and a higher number of comorbidities compared to the nonobese group (2.3±0.1 vs 2.0±0.1, P=0.02). In addition, subjects in the obese group showed a lower forced vital capacity (FVC) than subjects in the nonobese group, even after adjusting for covariates (average FVC%, 89.32±1.26 vs 92.52%±0.72%, P=0.037). There were no significant differences in the adjusted FEV1% and adjusted FEV1/FVC between the groups.

CONCLUSIONS
Among subjects newly identified with mild COPD, participants in the obese group had more comorbid conditions and showed a lower FVC compared with subjects in the nonobese group, even after adjustment of covariates. These findings show that a combination of obesity and COPD may be a severe phenotype; therefore, early attention should be paid to obesity for the management of COPD patients.

Park|Ju-Hee|JH|
Lee|Jung-Kyu|JK|
Heo|Eun Young|EY|
Kim|Deog Kyeom|DK|
Chung|Hee Soon|HS|

D029424:Pulmonary Disease, Chronic Obstructive

obesity
KNHANES
COPD
comorbidity
lung function
spirometry


Influence of Lipophilicity on the Antibacterial Activity of Polymyxin Derivatives and on Their Ability to Act as Potentiators of Rifampicin.

Abstract: Novel polymyxin derivatives are often classified either as having direct activity against Gram-negative pathogens or as compounds inactive in their own right, which through permeabilization of the outer membrane act as potentiators of other antibiotics. Here, we report the systematic investigation of the influence of lipophilicity on microbiological activity (including against strains with reduced susceptibility to polymyxins), potentiation of rifampicin, and in vitro toxicity within a series of next-generation polymyxin nonapeptides. We demonstrate that the lipophilicity at the N-terminus and amino acids 6 and 7 in the cyclic peptide core is interchangeable and that the activity, ability to potentiate, and cytotoxicity all appear to be primarily driven by overall lipophilicity. Our work also suggests that the characterization of a polymyxin molecule as either a direct acting compound or a potentiator is more of a continuum that is strongly influenced by lipophilicity rather than as a result of fundamentally different modes-of-action.

Brown|Pamela|P|0000-0002-1829-3695
Abdulle|Omar|O|
Boakes|Steven|S|
Divall|Naomi|N|
Duperchy|Esther|E|
Ganeshwaran|Sonia|S|
Lester|Roy|R|
Moss|Stephen|S|
Rivers|Dean|D|
Simonovic|Mona|M|
Singh|Jaspal|J|
Stanway|Steven|S|
Wilson|Antoinette|A|
Dawson|Michael J|MJ|

lipophilicity
polymyxin
potentiator
Gram-negative
antimicrobial resistance
multidrug-resistant bacteria


Development and validation of a sensitive LC-MS/MS assay for the simultaneous quantification of allitinib and its two metabolites in human plasma.

Abstract: Allitinib, also known as AST1306, is a novel irreversible inhibitor of the epidermal growth factor receptors 1 and 2. Allitinib is currently used in clinical trial to treat solid tumors. A previous study showed that allitinib is extensively metabolized in humans. Amide hydrolysis metabolite (M6) and 29,30-dihydrodiol allitinib (M10) are the major metabolites in circulation. To study the pharmacokinetics of allitinib and its two major metabolites in cancer patients, a rapid, sensitive and reliable LC-MS/MS method was developed and validated for the simultaneous determination of allitinib, M6 and M10 in human plasma. After simple protein precipitation, the analytes and the combined internal standards (lapatinib and NB-2, an analog of allitinib) were separated on a Zorbax Eclipase XDB C18 column (50 mm × 4.6 mm, 1.8 μm, Agilent) using a mobile phase of 5 mM ammonium acetate with 0.1% formic acid (phase A) and 50% (v/v) methanol in acetonitrile (phase B) with gradient elution. Mass spectrometric detection was conducted by atmospheric-pressure chemical ionization in positive ion multiple reaction monitoring modes using AB Sciex Triple Quad 6500 system. Linear calibration curves were obtained for the following concentration range: 0.300-200 ng/ml for allitinib; 0.030-20.0 ng/ml for M6; and 0.075-50.0 ng/ml for M10. Intra-day and inter-day accuracy and precision were within the acceptable limits of ±15% at all of the concentrations. The method was successfully applied to a preliminary clinical pharmacokinetic study following oral administration of allitinib tosylate tablets in cancer patients.

Lin|Lishan|L| Gao|Zhiwei|Z| Chen|Xiaoyan|X| Zhong|Dafang|D|

Liquid chromatography–tandem mass spectrometry

erythroblastic leukemia viral oncogene homolog

liquid chromatography−tandem mass spectrometry

P P P P P P P P U U U M M U M U U U U M U U M M U U M M M


Morbidity and mortality amongst infants of diabetic mothers admitted into Soba university hospital, Khartoum, Sudan.

Abstract: The prevalence of diabetes during pregnancy is increasing and this is associated with an increased risk of complications in both mother and fetus. The aim of this research is to study the neonatal complications of maternal diabetes. This was a prospective observational study that was conducted in Soba university hospital between September 2010 and March 2011. All infants born to diabetic mothers during the study period were admitted to the neonatal care unit for evaluation. Data on sex, gestational age, and birth weight, mode of delivery, complications, investigations, birth injury, and length of hospital stay were recorded. Maternal data were retrieved from records. Data was analyzed using Minitab 15. A total of 50 infants of diabetic mothers (IDMs) were included in the study. Thirty infants (60%) were females and 20 (40%) were males. Forty two (84%) of the neonates were born by caesarian section, only 7(14%) were born by spontaneous vaginal delivery. Birth injury was observed in 4% of them. The mean gestational age was 37.2±2.051 weeks. The median birth weight was 3.5 kg. 14 (28%) of the babies were macrosomic, and 17 (34%) were large for gestational age (LGA). Congenital anomalies were found in 3 (6%), hypoglycemia in 6 (12%), hyperbillirubinaemia in 10 (20%), hypocalcaemia and hypomagnesaemia each occurred in 2%, transient tachypnea of the newborn occurred in 5 (10%) of the neonates and respiratory distress syndrome in 2%. Cardiomyopathy occurred in 2% and mortality was 4%. We concluded that macrosomia, LGA, and hyperbillirubinaemia were the commonest complications in IDMs, maternal glycaemic control was found to have a significant effect on a number of outcomes.

Kheir|Abdelmoneim E M|AE|
Berair|Rabih|R|
Gulfan|Islam G I|IG|
Karrar|Mohamed Z|MZ|
Mohammed|Zuhlel A O|ZA|

Infant
mother
Khartoum
Sudan
macrosomia
diabetes mellitus


Light Chain (AL) Cardiac Amyloidosis: A Diagnostic Dilemma.

Abstract: Amyloidosis is a clinical condition characterized by amyloid fibril deposition into different organ systems. The most common types are light chain (AL) amyloidosis and transthyretin amyloidosis (ATTR) amyloidosis. Amyloidosis involves the heart with an incidence of 1.38 to 3.69 per 100,000 person-years and a prevalence of 14.85 per 100,000 person-years between 2004 and 2018. Diagnosis of cardiac amyloidosis can be made through cardiac imaging, including cardiac magnetic resonance imaging (CMR) and 99mTc-labeled pyrophosphate (PYP) cardiac scan. However, a tissue biopsy is frequently needed to confirm the diagnosis. Herein, we report such a case of cardiac amyloidosis. The patient presented with pericardial effusion and acute kidney injury as the initial presentation. The presumptive diagnosis was ATTR amyloidosis, but the endomyocardial biopsy confirmed the diagnosis of AL amyloidosis. The patient was started on bortezomib, cyclophosphamide, and dexamethasone therapy. We aimed to highlight the different diagnostic modalities of cardiac amyloidosis and the importance of obtaining tissue biopsy to confirm the amyloidosis type before starting the treatment.

Abdelazeem|Basel|B| Manasrah|Nouraldeen|N| Yousaf|Amman|A| Gjeka|Rudin|R| Kunadi|Arvind|A|

light chain
amyloidosis
transthyretin
cardiac imagings
case report


Clinical course of percutaneous cholecystostomies: A cross-sectional study.

Abstract:
BACKGROUND
Although cholecystectomy is the standard treatment modality, it has been shown that perioperative mortality is approaching 19% in critical and elderly patients. Percutaneous cholecystostomy (PC) can be considered as a safer option with a significantly lower complication rate in these patients.

AIM
To assess the clinical course of acute cholecystitis (AC) in patients we treated with PC.

METHODS
The study included 82 patients with Grade I, II or III AC according to the Tokyo Guidelines 2018 (TG18) and treated with PC. The patients' demographic and clinical features, laboratory parameters, and radiological findings were retrospectively obtained from their medical records.

RESULTS
Eighty-two patients, 45 (54.9%) were male, and the median age was 76 (35-98) years. According to TG18, 25 patients (30.5%) had Grade I, 34 (41.5%) Grade II, and 23 (28%) Grade III AC. The American Society of Anesthesiologists (ASA) physical status score was III or more in 78 patients (95.1%). The patients, who had been treated with PC, were divided into two groups: discharged patients and those who died in hospital. The groups statistically significantly differed only concerning the ASA score (P = 0.0001) and WBCC (P = 0.025). Two months after discharge, two patients (3%) were readmitted with AC, and the intervention was repeated. Nine of the discharged patients (13.6%) underwent interval open cholecystectomy or laparoscopic cholecystectomy (8/1) within six to eight weeks after PC. The median follow-up time of these patients was 128 (12-365) wk, and their median lifetime was 36 (1-332) wk.

CONCLUSION
For high clinical success in AC treatment, PC is recommended for high-risk patients with moderate-severe AC according to TG18, elderly patients, and especially those with ASA scores of ≥ III. According to our results, PC, a safe, effective and minimally invasive treatment, should be preferred in cases suffering from AC with high risk of mortality associated with cholecystectomy.

Er|Sadettin|S|
Berkem|Hüseyin|H|
Özden|Sabri|S|
Birben|Birkan|B|
Çetinkaya|Erdinç|E|
Tez|Mesut|M|
Yüksel|Bülent Cavit|BC|

Cholecystostomy
Cholecystectomy
Mortality
Acute
Cholecystitis
Catheter ablation
Morbidity


New therapeutic strategies targeting D1-type dopamine receptors for neuropsychiatric disease.

Abstract: The neurotransmitter dopamine acts via two major classes of receptors, D1-type and D2-type. D1 receptors are highly expressed in the striatum and can also be found in the cerebral cortex. Here we review the role of D1 dopamine signaling in two major domains: L-DOPA-induced dyskinesias in Parkinson's disease and cognition in neuropsychiatric disorders. While there are many drugs targeting D2-type receptors, there are no drugs that specifically target D1 receptors. It has been difficult to use selective D1-receptor agonists for clinical applications due to issues with bioavailability, binding affinity, pharmacological kinetics, and side effects. We propose potential therapies that selectively modulate D1 dopamine signaling by targeting second messengers downstream of D1 receptors, allosteric modulators, or by making targeted modifications to D1-receptor machinery. The development of therapies specific to D1-receptor signaling could be a new frontier in the treatment of neurological and psychiatric disorders.

Kim|Young-Cho|YC|
Alberico|Stephanie L|SL|
Emmons|Eric|E|
Narayanan|Nandakumar S|NS|

dyskinesia
cognition
D1DR
dopamine D1 receptor


Colorimetric detection of L-histidine based on the target-triggered self-cleavage of swing-structured DNA duplex-induced aggregation of gold nanoparticles.

Abstract: A rapid, highly sensitive and selective colorimetric assay is presented for visually detecting L-histidine. It is based on L-histidine-triggered self-cleavage of DNA duplex-induced gold nanoparticle (AuNP) aggregation. The citrate-capped AuNPs easily aggregate in a high concentration of salt environment. However, in the presence of L-histidine aptamers (DNA1 and DNA2), the partial strands of DNA1 and DNA2 hybridize to form a DNA duplex with a swing structure. The swing-like DNA duplexes are adsorbed on the surface of AuNPs to improve the stability of AuNPs, and the AuNPs also are better dispersed in high-salt media. When L-histidine is added to the solutions, it catalyzes the self-cleavage of DNA1 to form many single-stranded DNA (ssDNA) fragments. These ssDNA segments are adsorbed on the AuNPs and weaken the stability of AuNPs. Hence, the AuNPs aggregate in high-salt environment, and this results in a red-to-blue color change. Under the optimized conditions, L-histidine can be determined with a limit of detection of 3.6 nM. In addition, the sensor was successfully applied to the determination of L-histidine in spiked serum samples. Graphical abstract Schematic of a rapid and homogeneous colorimetric L-histidine assay. It combines L-histidine-triggered self-cleavage of the swing-like DNA duplexes and self-cleavage of DNA-induced AuNP aggregation.

Jiao|Yunfei|Y| Liu|Qingyun|Q| Qiang|Hong|H| Chen|Zhengbo|Z|

Colorimetric assay
Self-cleavage of DNA
Serum samples
Catalysis
Gold nanoparticle aggregation
L-Histidine detection
Ratiometric assay
Swing-like duplex
Visible color change


Nanotechnology meets 3D in vitro models: tissue engineered tumors and cancer therapies.

Abstract: Advances in nanotechnology are providing to medicine a new dimension. Multifunctional nanomaterials with diagnostics and treatment modalities integrated in one nanoparticle or in cooperative nanosystems are promoting new insights to cancer treatment and diagnosis. The recent convergence between tissue engineering and cancer is gradually moving towards the development of 3D disease models that more closely resemble in vivo characteristics of tumors. However, the current nanomaterials based therapies are accomplished mainly in 2D cell cultures or in complex in vivo models. The development of new platforms to evaluate nano-based therapies in parallel with possible toxic effects will allow the design of nanomaterials for biomedical applications prior to in vivo studies. Therefore, this review focuses on how 3D in vitro models can be applied to study tumor biology, nanotoxicology and to evaluate nanomaterial based therapies.

da Rocha|E L|EL|
Porto|L M|LM|
Rambo|C R|CR|

Nanotechnology
3D in vitro models
Cancer therapies
Nanoparticles–cell interaction


Bacterial phospholipases C as vaccine candidate antigens against cystic fibrosis respiratory pathogens: the Mycobacterium abscessus model.

Abstract:
BACKGROUND
Vaccine strategies represent one of the fighting answers against multiresistant bacteria in a number of clinical settings like cystic fibrosis (CF). Mycobacterium abscessus, an emerging CF pathogen, raises difficult therapeutic problems due to its intrinsic antibiotic multiresistance.

METHODS
By reverse vaccinology, we identified M. abscessus phospholipase C (MA-PLC) as a potential vaccine target. We deciphered here the protective response generated by vaccination with plasmid DNA encoding the MA-PLC formulated with a tetra functional block copolymer 704, in CF (ΔF508) mice. Protection was tested against aerosolized smooth and rough (hypervirulent) variants of M. abscessus.

RESULTS
MA-PLC DNA vaccination (days 0, 21, 42) elicited a strong antibody response. A significant protective effect was obtained against aerosolized M. abscessus (S variant) in ΔF508 mice, but not in wild-type FVB littermates; similar results were observed when: (i) challenging mice with the "hypervirulent" R variant, and; (ii) immunizing mice with purified MA-PLC protein. High IgG titers against MA-PLC protein were measured in CF patients with M. abscessus infection; interestingly, significant titers were also detected in CF patients positive for Pseudomonas aeruginosa versus P. aeruginosa-negative controls.

CONCLUSIONS
MA-PLC DNA- and PLC protein-vaccinated mice cleared more rapidly M. abscessus than β-galactosidase DNA- or PBS- vaccinated mice in the context of CF. PLCs could constitute interesting vaccine targets against common PLC-producing CF pathogens like P. aeruginosa.

Le Moigne|Vincent|V|
Rottman|Martin|M|
Goulard|Céline|C|
Barteau|Benoît|B|
Poncin|Isabelle|I|
Soismier|Nathalie|N|
Canaan|Stéphane|S|
Pitard|Bruno|B|
Gaillard|Jean-Louis|JL|
Herrmann|Jean-Louis|JL|

Cystic fibrosis
ΔF508
DNA vaccine
PLC
Mycobacteria
Pulmonary diseases


Bilateral peroneal neuropathy after bariatric surgery: A case report.

Abstract: The popularity of bariatric surgery (BS) began to increase due to the dramatic rise in severe obesity in the past decades. Postoperative follow-up after BS is important to avoid possible medical complications. Therefore, medical complications after BS should be well-known and defined. Herein, we present a case of bilateral peroneal neuropathy (PN) developed after successful BS. The patient lost 40 kg during 16 weeks of follow-up. The foot drop developed after 18 weeks after surgery on the left side and than 24 weeks after surgery on the right side. Peroneal neuropathy-associated weight loss is usually unilateral. Bilateral PN with weight loss is uncommon. The rate of weight loss is an important risk factor for PN. This case report highlights the importance of optimal dietary after BS to control the weight loss rate and nutrient deficiency.

peroneal neuropathy
Bariatric surgery
foot drop
weight loss
gastric banding


Current status of esophageal endoscopy including the evaluation of smoking and alcohol consumption in Japan: an analysis based on the Japan endoscopy database.

Abstract:
PURPOSE
The aim was to investigate the current status of esophageal endoscopy, including the evaluation of smoking and alcohol consumption, in Japan.

METHODS
A total of 47,441 patients who underwent 69,748 sessions of esophageal endoscopy were registered in the Japan Endoscopy Database between January 2015 and March 2017. The study variables were as follows: (1) methods for monitoring the esophagus and the time required for monitoring and (2) the status of smoking and alcohol consumption in patients with esophageal cancer and head and neck cancer.

RESULTS
Image-enhanced endoscopy was performed in 10.6%, Lugol chromoendoscopy in 4.1%, and magnifying endoscopy in 3.2%. The mean time required for gastrointestinal endoscopy was 10 min 58 s. The mean examination times in patients with or without monitoring of the head and neck were 10 min 51 s and 11 min 13 s, respectively. In 57.0% of the patients with esophageal cancer, the head and neck were monitored at the time of gastrointestinal endoscopy. The proportion of current smokers (esophageal cancer: 16.8-4.7%; head and neck cancer: 24.3-9.3%) and addicted drinkers (esophageal cancer: 52.3-40.8%; head and neck cancer: 50.2-47.3%) were lower at the second or subsequent endoscopy than at the initial endoscopy.

CONCLUSIONS
The new strategy for esophageal endoscopy has led to an evolutionary change in Japan. The patients with esophageal cancer and head and neck cancer who underwent a second or subsequent endoscopy had lower incidences of smoking and alcohol consumption, although the incidences remained high.

Japan endoscopy database
Esophageal cancer
Head and neck cancer
Image-enhanced endoscopy
Magnifying endoscopy


Mortality risk factors from converting off-pump coronary artery bypass to on-pump coronary artery bypass.

Abstract:
INTRODUCTION
A number of large-scale retrospective studies revealed that off-pump coronary artery bypass (OPCAB) was superior to on-pump coronary artery bypass (ONCAB). The aim of the study was to investigate risk factors for mortality when OPCAB is converted to ONCAB.

METHODS
Patients who underwent OPCAB conversion to ONCAB at the Beijing Anzhen Hospital between January 2003 and January 2013 were assigned to the non-survivor and survivor groups. Background demographics, illness history and preoperative, intraoperative and postoperative variables were compared.

RESULTS
Of the 247 cases, 15.4% of the patients died. Patients in the non-survivor group were older and more frequently had diabetes mellitus (DM), arrhythmia, myocardial infarction (MI) in the past 30 days (all p<0.05) and MI combined with mitral regurgitation (p<0.0001); they more frequently had bigger left ventricular end-diastolic dimension (p=0.0019), greater fall in blood pressure, ventricular fibrillation for longer periods, longer conversion time and bypass graft occlusion. All patients in the non-survivor group received intra-aortic balloon pump compared to 89.5% in the survivor group and extracorporeal membrane oxygenation was more common. Left main coronary artery disease (OR=4.431, 95%CI: 2.440-8.048, p<0.0001), blood pressure decline ⩽40 mmHg (OR=0.509, 95%CI: 0.447-0.580, p<0.0001) and time for conversion to ONCAB ⩾20 min were independently associated with mortality. Rates of postoperative complications, such as renal failure, cerebral infarction or hemorrhage, MI and redo sternotomy, were higher in the non-survivor group.

CONCLUSIONS
Conversion from OPCAB to ONCAB is associated with high mortality. Risk factors include left main artery disease and duration of blood pressure decline >40 min.

Miao|Na|N| Yang|Feng|F| Du|Zhongtao|Z| Jiang|Chunjing|C| Hao|Xing|X| Wang|Jinhong|J| Jiang|Yu|Y| Yang|Xiaofang|X| Xie|Haixiu|H| Hou|Xiaotong|X|

D047549:Coronary Artery Bypass, Off-Pump

coronary artery disease
cardiopulmonary bypass
coronary artery bypass grafts
off-pump surgery


Systematic review adherence to methodological or reporting quality.

Abstract:
BACKGROUND
Guidelines for assessing methodological and reporting quality of systematic reviews (SRs) were developed to contribute to implementing evidence-based health care and the reduction of research waste. As SRs assessing a cohort of SRs is becoming more prevalent in the literature and with the increased uptake of SR evidence for decision-making, methodological quality and standard of reporting of SRs is of interest. The objective of this study is to evaluate SR adherence to the Quality of Reporting of Meta-analyses (QUOROM) and PRISMA reporting guidelines and the A Measurement Tool to Assess Systematic Reviews (AMSTAR) and Overview Quality Assessment Questionnaire (OQAQ) quality assessment tools as evaluated in methodological overviews.

METHODS
The Cochrane Library, MEDLINE®, and EMBASE® databases were searched from January 1990 to October 2014. Title and abstract screening and full-text screening were conducted independently by two reviewers. Reports assessing the quality or reporting of a cohort of SRs of interventions using PRISMA, QUOROM, OQAQ, or AMSTAR were included. All results are reported as frequencies and percentages of reports and SRs respectively.

RESULTS
Of the 20,765 independent records retrieved from electronic searching, 1189 reports were reviewed for eligibility at full text, of which 56 reports (5371 SRs in total) evaluating the PRISMA, QUOROM, AMSTAR, and/or OQAQ tools were included. Notable items include the following: of the SRs using PRISMA, over 85% (1532/1741) provided a rationale for the review and less than 6% (102/1741) provided protocol information. For reports using QUOROM, only 9% (40/449) of SRs provided a trial flow diagram. However, 90% (402/449) described the explicit clinical problem and review rationale in the introduction section. Of reports using AMSTAR, 30% (534/1794) used duplicate study selection and data extraction. Conversely, 80% (1439/1794) of SRs provided study characteristics of included studies. In terms of OQAQ, 37% (499/1367) of the SRs assessed risk of bias (validity) in the included studies, while 80% (1112/1387) reported the criteria for study selection.

CONCLUSIONS
Although reporting guidelines and quality assessment tools exist, reporting and methodological quality of SRs are inconsistent. Mechanisms to improve adherence to established reporting guidelines and methodological assessment tools are needed to improve the quality of SRs.

Pussegoda|Kusala|K|
Turner|Lucy|L|
Garritty|Chantelle|C|
Mayhew|Alain|A|
Skidmore|Becky|B|
Stevens|Adrienne|A|
Boutron|Isabelle|I|
Sarkis-Onofre|Rafael|R|
Bjerre|Lise M|LM|
Hróbjartsson|Asbjørn|A|
Altman|Douglas G|DG|
Moher|David|D|0000-0003-2434-4206

D019317:Evidence-Based Medicine
D019983:Guideline Adherence
D006801:Humans
D012107:Research Design
D058028:Research Report
D012196:Review Literature as Topic

Systematic reviews
Reporting quality
Methodological quality
Guideline adherence


Vagus nerve stimulation initiated late during ischemia, but not reperfusion, exerts cardioprotection via amelioration of cardiac mitochondrial dysfunction.

Abstract:
BACKGROUND
We previously reported that vagus nerve stimulation (VNS) applied immediately at the onset of cardiac ischemia provides cardioprotection against cardiac ischemic-reperfusion (I/R) injury.

OBJECTIVE
This study aimed to determine whether VNS applied during ischemia or at the onset of reperfusion exerts differential cardioprotection against cardiac I/R injury.

METHODS
Twenty-eight swine (25-30 kg) were randomized into 4 groups: Control (sham-operated, no VNS), VNS-ischemia (VNS applied during ischemia), VNS-reperfusion (VNS applied during reperfusion), and VNS-ischemia+atropine (VNS applied during ischemia with 1 mg/kg atropine administration). Ischemia was induced by left anterior descending (LAD) coronary artery occlusion for 60 minutes, followed by 120 minutes of reperfusion. VNS was applied either 30 minutes after LAD coronary artery occlusion or at the onset of reperfusion and continued until the end of reperfusion. Cardiac function, infarct size, myocardial levels of connexin 43, cytochrome c, tumor necrosis factor α, and interleukin 4, and cardiac mitochondrial function were determined.

RESULTS
VNS applied 30 minutes after LAD coronary artery occlusion, but not at reperfusion, markedly reduced ventricular fibrillation incidence and infarct size (~59%), improved cardiac function; attenuated cardiac mitochondrial reactive oxygen species production, depolarization, swelling, and cytochrome c release; and increased the amount of phosphorylated connexin 43 and interleukin 4 as compared with the Control group. These beneficial effects of VNS were abolished by atropine.

CONCLUSION
VNS could provide significant cardioprotective effects even when initiated later during ischemia, but was not effective after reperfusion. These findings indicate the importance of timing of VNS initiation and warrant the potential clinical application of VNS in protecting myocardium at risk of I/R injury.

Shinlapawittayatorn|Krekwit|K|
Chinda|Kroekkiat|K|
Palee|Siripong|S|
Surinkaew|Sirirat|S|
Kumfu|Sirinart|S|
Kumphune|Sarawut|S|
Chattipakorn|Siriporn|S|
KenKnight|Bruce H|BH|
Chattipakorn|Nipon|N|

D000818:Animals
D001285:Atropine
D004195:Disease Models, Animal
D004562:Electrocardiography
D008929:Mitochondria, Heart
D009203:Myocardial Infarction
D017202:Myocardial Ischemia
D015428:Myocardial Reperfusion Injury
D011897:Random Allocation
D012016:Reference Values
D018570:Risk Assessment
D013552:Swine
D016896:Treatment Outcome
D055536:Vagus Nerve Stimulation
D016277:Ventricular Function, Left

Vagus nerve stimulation
Cardioprotection
Acetylcholine
Heart
Ischemic-reperfusion injury


The association between MRI findings and breast cancer subtypes: focused on the combination patterns on diffusion-weighted and T2-weighted images.

Abstract:
PURPOSE
To assess morphology on diffusion-weighted imaging (DWI) and intratumoral signal intensity (SI) on T2-weighted images (T2WI) of breast carcinomas, and to evaluate the association between the combined DWI and T2WI findings and breast cancer subtypes.

METHODS
Two hundred and eighty breast cancer patients who underwent breast MRI prior to therapy were included in this retrospective study. All had invasive carcinomas, which were classified into five subtypes: Luminal A-like (n = 149), Luminal B-like (n = 63), Hormone receptor-positive HER2 (n = 31), Hormone receptor-negative HER2 (n = 13), or Triple-negative (TN) (n = 24). Based on the morphology on DWI, the tumors were classified into two patterns: DWI-homogeneous or DWI-heterogeneous. If DWI-heterogeneous, an assessment of intratumoral SI on T2WI was performed: tumors with intratumoral high/low SI on T2WI were classified as Hete-H/Hete-L, respectively. The associations between (1) the morphological patterns on DWI and the five subtypes, and (2) the intratumoral SI patterns on T2WI and the five subtypes in DWI-heterogeneous were evaluated.

RESULTS
There was a significant association between (1) the morphological patterns on DWI and the five subtypes (p < 0.0001), and (2) the intratumoral SI patterns on T2WI and the five subtypes in DWI-heterogeneous (p < 0.0001). DWI-homogeneous was dominant in Luminal A-like (67.1%), and Hete-H was dominant in TN type (75%). Hete-H, suggesting the presence of intratumoral necrosis, included high proliferative and/or aggressive subtypes more frequently (80%) than Hete-L, suggesting the presence of fibrotic focus. Fibrotic focus was seen more commonly in the luminal subtypes.

CONCLUSION
The combined findings on DWI and T2WI revealed breast carcinomas that were associated with particular subtypes.

Yuen|Sachiko|S| Monzawa|Shuichi|S| Yanai|Seiji|S| Matsumoto|Hajime|H| Yata|Yoshihiro|Y| Ichinose|You|Y| Deai|Teruyuki|T| Hashimoto|Takashi|T| Tashiro|Takashi|T| Yamagami|Kazuhiko|K|

D038524:Diffusion Magnetic Resonance Imaging

Breast cancer
T2-weighted imaging
Diffusion-weighted imaging
Magnetic resonance imaging
Molecular subtype


From consumption to harvest: Environmental fate prediction of excreted ionizable trace organic chemicals.

Abstract: Excreted trace organic chemicals, e.g., pharmaceuticals and biocides, typically undergo incomplete elimination in municipal wastewater treatment plants (WWTPs) and are released to surface water via treated effluents and to agricultural soils through sludge amendment and/or irrigation with freshwater or reclaimed wastewater. Recent research has shown the tendency for these substances to accumulate in food crops. In this study, we developed and applied a simulation tool to predict the fate of three ionizable trace chemicals (triclosan-TCS, furosemide-FUR, ciprofloxacin-CIP) from human consumption/excretion up to the accumulation in soil and plant, following field amendment with sewage sludge or irrigation with river water (assuming dilution of WWTP effluent). The simulation tool combines the SimpleTreat model modified for fate prediction of ionizable chemicals in a generic WWTP and a recently developed dynamic soil-plant uptake model. The simulation tool was tested using country-specific (e.g., consumption/emission rates, precipitation and temperature) input data. A Monte Carlo-based approach was adopted to account for the uncertainty associated to physico-chemical and biokinetic model parameters. Results obtained in this study suggest significant accumulation of TCS and CIP in sewage sludge (1.4-2.8 mg kgDW(-1)) as compared to FUR (0.02-0.11 mg kgDW(-1)). For the latter substance, more than half of the influent load (60.1%-72.5%) was estimated to be discharged via WWTP effluent. Specific emission rates (g ha(-1) a(-1)) of FUR to soil via either sludge application or irrigation were up to 300 times lower than for TCS and CIP. Nevertheless, high translocation potential to wheat was predicted for FUR, reaching concentrations up to 4.3 μg kgDW(-1) in grain. Irrigation was found to enhance the relative translocation of FUR to plant (45.3%-48.9% of emission to soil), as compared to sludge application (21.9%-27.6%). A comparison with peer-reviewed literature showed that model predictions were close to experimental data for elimination in WWTP, concentrations in sewage and sludge and bioconcentration factors (BCFs) in plant tissues, which showed however a large variability. The simulation tool presented here can thus be useful for priority setting and for the estimation of human exposure to trace chemicals via intake of food crops.

Polesel|Fabio|F|
Plósz|Benedek Gy|BG|
Trapp|Stefan|S|

D008962:Models, Theoretical
D009930:Organic Chemicals
D014865:Waste Disposal, Fluid
D018508:Water Purification

Wastewater treatment
Irrigation
Agricultural sludge reuse
Fate modeling
Ionizable organic trace chemicals
Plant uptake


Liver elastography: what it is, how it is done, and how it is interpreted.

Abstract: Liver elastography is a noninvasive method for diagnosing fibrosis that has been developed over the last decade in response to the limitations of liver biopsies, blood markers, and traditional imaging modalities. There are different methods of measuring tissue stiffness through ultrasound; thus far, shear wave elastography has proven superior for diagnosing clinically significant liver fibrosis, where early detection modifies the approach to treatment and improves prognosis. This article aims to provide a brief review of the different methods for performing elastography with ultrasound, focusing especially on shear wave elastography and on technical aspects for carrying out the procedure and key points for interpreting the findings.

Murad Gutiérrez|V|V|
Romero Enciso|J A|JA|

Liver
Elastografía por ultrasonido
Fibrosis hepática
Hepatic fibrosis
Hígado
Metavir
Ultrasound elastography


Translating Biobank Science into Patient-Centered Language.

Abstract:
INTRODUCTION
This project used Boot Camp Translation (BCT) to translate the complex medical jargon of biobanking into locally relevant evidence-based messages and materials to support increased knowledge and understanding in the local community.

METHODS
Biobank BCT was a partnership of 16 community members and 5 academic researchers. The partnership met for 8 months.

RESULTS
The partnership developed five main and seven submessages to assist patients and community members in making an informed decision about enrollment in a biobank.

DISCUSSION
The resulting messages balance an individual's right to privacy and choice, while encouraging participation for the greater good.

Coors|Marilyn E|ME|
Westfall|Noah|N|
Zittleman|Linda|L|
Taylor|Matthew|M|
Westfall|John M|JM|

biobank
biomedical ethics
community engagement


Epigenetic mechanism causes Wnt9b deficiency and nonsyndromic cleft lip and palate in the A/WySn mouse strain.

Abstract:
BACKGROUND
The heritable multifactorial etiology of human nonsyndromic cleft lip with or without cleft palate (CL ± P) is not understood. CL ± P occurs in 15% of neonates in the homozygous A/WySn mouse strain, with a multifactorial genetic etiology, the clf1 and clf2 variant genes. Clf1 acts as a mutant allele of Wnt9b but its coding sequence is normal. An IAP (intracisternal A particle) retrotransposon inserted near the Wnt9b gene is associated with clf1.

METHODS
Transcription of noncoding sequence between the IAP and the Wnt9b gene was examined in A/WySn embryos. The levels of Wnt9b transcript and of an "IAP antisense" transcript initiated in the IAP and extending into the noncoding interval were assayed in A/WySn and C57BL/6J whole embryos or heads across embryonic days 8 to 12. Methylation of the 5' LTR of the IAP was examined in E12 A/WySn embryo heads.

RESULTS
Mean Wnt9b transcript levels were lower in A/WySn than in C57BL/6J at all ages examined and lower in CL ± P embryos than in their normal littermates. The "IAP antisense" transcript was found in all A/WySn embryos and was highest in CL ± P embryos. The IAP at Wnt9b was generally unmethylated in CL ± P embryos and approximately 50% methylated in normal littermates.

CONCLUSION
The clf1 mutation in A/WySn is a "metastable epiallele", in which stochastic deficiency in some individuals of DNA methylation of a retrotransposon uniquely inserted near the Wnt9b gene allows transcriptional activity of the retrotransposon and interference with transcription from Wnt9b. Methylation of metastable epialleles should be investigated in human nonsyndromic CL ± P.

Juriloff|Diana M|DM|
Harris|Muriel J|MJ|
Mager|Dixie L|DL|
Gagnier|Liane|L|

D060888:Real-Time Polymerase Chain Reaction

epigenetic
Wnt9b
cleft lip
mouse
genetic
retrotransposon
methylation
metastable epiallele


Gefitinib frequently induces liver damage in patients with lung adenocarcinoma previously treated by chemotherapy.

Abstract:
BACKGROUND
Gefitinib is known as one of the agents for treating patients with both advanced lung cancer and an epidermal growth-factor receptor mutation. In the epidermal growth-factor receptor-mutant advanced non-small-cell lung cancer population, gefitinib therapy has been associated with increased response rate, longer progression-free survival, and better quality of life compared to other anticancer drugs. However, gefitinib has to be discontinued for patients in whom adverse events occur, even if it is still effective. Here, we retrospectively assessed the clinical course of patients receiving gefitinib therapy, with a particular focus on liver damage.

PATIENTS AND METHODS
Of 24 Asian patients treated with 250 mg gefitinib daily at Kanagawa National Hospital, Japan, between January 2008 and June 2012, grade 3 liver damage (Common Terminology Criteria for Adverse Events, version 4.0) occurred in nine and were eligible for our assessment. The regimen was subsequently changed to alternate-day administration. The relationships between liver damage and each clinical factor were retrospectively examined using Fisher's exact test.

RESULTS
Of the nine patients with liver damage, seven had previous exposure to another anticancer drug. There was a significant relationship between the incidence of liver damage and previous chemotherapy (P = 0.009). The objective response rates of patients treated with daily gefitinib 250 mg and alternate-day gefitinib following liver damage were 66.7% and 46.7%, respectively; these were not significantly different (P = 0.597).

CONCLUSION
Gefitinib for advanced adenocarcinoma patients who have previously undergone chemotherapy should be used cautiously and liver function monitored closely, because it frequently induces significant liver damage. The alternate-day administration of gefitinib may be a suitable option for patients in whom daily gefitinib therapy induces liver damage.

Sugiura|Yasoo|Y| Nemoto|Etsuo|E| Kawai|Osamu|O| Ohkubo|Yasuyuki|Y| Fusegawa|Hisae|H| Kaseda|Shizuka|S|

gefitinib
liver damage
alternate-day administration
previous chemotherapy
adjuvant chemotherapy


Clustering of multiple health risk behaviors and its association with diabetes in a Southern Chinese adult population: a cross-sectional study.

Abstract:
Background
Identifying the clustering patterns of health risk behaviors (HRBs) within individuals and their health impacts are essential to develop lifestyle promotion strategies. This study aimed to explore the clustering of a range of HRBs and the associations between such identified clusters and diabetes in Southern Chinese adults.

Methods
Data from 5,734 adults aged 35-75 years and underwent health examinations from November 2012 to December 2013 at a tertiary hospital in Guangzhou were analyzed. Behavioral characteristics, including smoking, alcohol use, physical activity, and sleep duration and quality, were measured by questionnaires. Latent class analysis was conducted by gender to identify HRBs clustering patterns, and logistic regression models were used to estimate the associations between behavioral patterns and diabetes.

Results
Three distinct behavioral clusters emerged in both genders. Male classes were defined as: (1) healthy lifestyle (Class 1, 62.9%); (2) cumulate harmful habits (Class 2, 27.1%); (3) poor sleep and risky habits (Class 3, 10.0%). Female classes were: (1) healthy lifestyle (Class 1, 83.0%); (2) inactive, daytime dysfunction (Class 2, 5.7%); (3) poor sleep habits (Class 3, 11.3%). Individuals of Class 2 and Class 3 showed a higher likelihood of diabetes across genders (multivariable-adjusted ORs [95% CIs], 2.03 [1.49-2.76] and 2.61 [1.78-3.81] among males, 2.64 [1.16-5.98] and 1.81 [1.07-3.06] among females) when compared with those of Class 1.

Conclusions
Our data provided additional evidence of HRBs clustering among adults, and such clustering was associated with an increased risk of diabetes. These findings have implications for identifying vulnerable subgroups and developing diabetes prevention programs.

Zhang|Guanrong|G| Luo|Caibing|C| Cui|Ying|Y| Lu|Yifan|Y| Yang|Yang|Y|

Clustering
Health risk behavior
Diabetes
Latent class analysis


Intramembrane attenuation of the TLR4-TLR6 dimer impairs receptor assembly and reduces microglia-mediated neurodegeneration.

Abstract: Recently, a single study revealed a new complex composed of Toll-like receptor 4 (TLR4), TLR6, and CD36 induced by fibrillary Aβ peptides, the hallmark of Alzheimer's disease. Unlike TLRs located on the plasma membrane that dimerize on the membrane after ligand binding to their extracellular domain, the TLR4-TLR6-CD36 complex assembly has been suggested to be induced by intracellular signals from CD36, similar to integrin inside-out signaling. However, the assembly site of TLR4-TLR6-CD36 and the domains participating in Aβ-induced signaling is still unknown. By interfering with TLR4-TLR6 dimerization using a TLR4-derived peptide, we show that receptor assembly is abrogated within the plasma membrane. Furthermore, we reveal that the transmembrane domains of TLR4 and TLR6 have an essential role in receptor dimerization and activation. Inhibition of TLR4-TLR6 assembly was associated with reduced secretion of proinflammatory mediators from microglia cells, ultimately rescuing neurons from death. Our findings support TLR4-TLR6 dimerization induced by Aβ. Moreover, we shed new light on TLR4-TLR6 assembly and localization and show the potential of inhibiting TLR4-TLR6 dimerization as a treatment of Alzheimer's disease.

Shmuel-Galia|Liraz|L| Klug|Yoel|Y| Porat|Ziv|Z| Charni|Meital|M| Zarmi|Batya|B| Shai|Yechiel|Y|

D031541:Fluorescence Resonance Energy Transfer

toll-like receptor
TLR4
TLR6
CD36
microglia
Alzheimer disease
amyloid-β
inflammation
neurodegenerative disease
neuroinflammation


Alcids 'fly' at efficient Strouhal numbers in both air and water but vary stroke velocity and angle.

Abstract: Birds that use their wings for 'flight' in both air and water are expected to fly poorly in each fluid relative to single-fluid specialists; that is, these jacks-of-all-trades should be the masters of none. Alcids exhibit exceptional dive performance while retaining aerial flight. We hypothesized that alcids maintain efficient Strouhal numbers and stroke velocities across air and water, allowing them to mitigate the costs of their 'fluid generalism'. We show that alcids cruise at Strouhal numbers between 0.10 and 0.40 - on par with single-fluid specialists - in both air and water but flap their wings ~ 50% slower in water. Thus, these species either contract their muscles at inefficient velocities or maintain a two-geared muscle system, highlighting a clear cost to using the same morphology for locomotion in two fluids. Additionally, alcids varied stroke-plane angle between air and water and chord angle during aquatic flight, expanding their performance envelope.

strouhal number
wing
flight
locomotion
ecology
evolutionary biology
muscle efficiency
swimming


Parental issues and concerns for their children treated under general anaesthesia for early childhood caries: A qualitative research approach.

Abstract:
Context
Most often, young children with early childhood caries (ECC) may need oral rehabilitation under general anaesthesia (GA) as treatment cannot be done chairside. A procedure under GA can be traumatic and stressful for both the parents and the children. Hence, it becomes necessary to understand the parents' opinions and address their concerns to provide better treatment. Aims: This qualitative study was conducted to explore the parental issues and concerns for their children treated under GA for ECC. Qualitative research approach was used so that it would enable us to address these issues better and prepare parents by counselling them in advance.

Settings and Design
An in-depth interview was conducted with the parents of children who underwent oral rehabilitation under GA for ECC in the M.S. Ramaiah Memorial Hospital, admitted under the Department of Pedodontics and Preventive Dentistry.

Participants and Methods
Data were audio-recorded and transcribed.

Statistical Analysis Used
Data collected were analysed using thematic analysis. Results: The themes derived were 'Concerns and Issues of GA Procedures and Improved Oral-health-related Quality of Life'.

Conclusions
The parents of children who underwent oral rehabilitation under GA initially had a few concerns and were reluctant about the procedure but were happy with the improvement post-operatively.

D000768:Anesthesia, General
D002648:Child
D002675:Child, Preschool
D003731:Dental Caries
D003733:Dental Caries Susceptibility
D006801:Humans
D009909:Oral Health
D010290:Parents
D036301:Qualitative Research
D011788:Quality of Life


Seeing liquids from static snapshots.

Abstract: Perceiving material properties can be crucial for many tasks-such as determining food edibility, or avoiding getting splashed-yet the visual perception of materials remains poorly understood. Most previous research has focussed on optical characteristics (e.g., gloss, translucency). Here, however, we show that shape also provides powerful visual cues to material properties. When liquids pour, splash or ooze, they organize themselves into characteristic shapes, which are highly diagnostic of the material's properties. Subjects viewed snapshots of simulated liquids of different viscosities, and rated their similarity. Using maximum likelihood difference scaling (Maloney & Yang, 2003), we reconstructed perceptual scales for perceived viscosity as a function of the physical viscosity of the simulated fluids. The resulting psychometric function revealed a distinct sigmoidal shape, distinguishing runny liquids that flow easily from viscous gels that clump up into piles. A parameter-free model based on 20 simple shape statistics predicted the subjects' data surprisingly well. This suggests that when subjects are asked to compare the viscosity of static snapshots of liquids that differ only in terms of viscosity, they rely primarily on relatively simple measures of shape similarity.

Paulun|Vivian C|VC|
Kawabe|Takahiro|T|
Nishida|Shin'ya|S|
Fleming|Roland W|RW|

Shape
Viscosity
Image statistics
Material perception
Object recognition
Perceptual organization


Cardiovascular risk of circulating endotoxin level in prevalent hemodialysis patients.

Abstract:
Background
Cardiovascular diseases (CVDs) are a major cause of morbidity and mortality in patients with end stage renal disease (ESRD). Circulating endotoxins may have toxic effect on myocardial functions and are speculated as pathogens of accelerated atherosclerosis and hemodialysis (HD) patients.

Objective
We aimed to assess the possible relation between circulating endotoxin levels and left ventricular functions parameters, common carotid artery intimal media thickness (CIMT) in prevalent HD patients.

Patients and Methods
Forty stable prevalent HD patients with mean age (47.97 ± 14.42) year using regular conventional hemodialysis sessions in Ain shams university hemodialysis unit, Cairo, Egypt were randomly selected. Diabetics, congestive heart failure and those with history of myocardial infarction or coronary artery disease were excluded from the study. All patients were studied by CBC and routine chemistry, as well as hs CRP, Intact PTH, lipid profile and endotoxin level by ELISA before and after the HD session, Delta change of endotoxin (pre dialysis endotoxin-post dialysis endotoxin) was calculated, resting Doppler echocardiographic and carotid duplex.

Results
Mean of Pre-HD session serum endotoxin level was (0.356 ± 0.090) EU/mL and the mean of post -HD endotoxin levels was (0.367 ± 0.110) EU/mL. Significant positive correlation between post dialysis endotoxin, MV E/A ratio and grades of left ventricular diastolic dysfunction (P < 0.05) and significant correlation between delta change in endotoxin and EF% (r = -0.36,P = 0.02). By stepwise linear regression analysis for determinants of MVE/A post -HD endotoxin level independently associated with MV E/A ratio (ß = 0.350, P = 0.027). We did not detect any significant correlation between CCA atherosclerosis and neither pre nor post- HD endotoxin level nor with delta change of pre and post HD endotoxin levels.

Conclusion
Acute increase in post dialytic circulating endotoxin level in prevalent HD patients may be associated with both left ventricular systolic and diastolic dysfunction and that attempts to reduce endotoxin level may have a positive impact on cardiovascular complications in HD Patients.

Ibrahim|Mohamed|M|
Behairy|Maha|M|
El-Ashry|Marwa|M|
Mostafa|Ahmad E|AE|

Endotoxin
Hemodialysis
Diastolic dysfunction
Carotid atherosclerosis


Comparative analysis of the Parent Attitudes about Childhood Vaccines (PACV) short scale and the five categories of vaccine acceptance identified by Gust et al.

Abstract:
BACKGROUND
There is a need to develop a standardized tool to aid in identifying, measuring and classifying the unique needs of vaccine-hesitant parents (VHPs). This will also assist in designing tailored interventions to address these needs. The Parental Attitude about Childhood Vaccines (PACV) short scale developed by Opel et al., and the Gust et al. vaccine acceptance categories have been acknowledged as potentially useful tools to measure parental vaccine hesitancy. The PACV short scale requires further validation. In our study, we evaluated how the Gust et al. vaccine acceptance categories correspond with the PACV short scale.

METHODS
As part of a larger study on vaccine attitudes, using the PACV short scale and Gust et al. vaccine acceptance categories, we assessed the correlation between the two measures using Spearman correlation coefficient, and the association between the two measures using the Cochran-Mantel-Haentszel test of association. We used logistic regression modelling to compare the association between a child's up-to-date immunization status and (a) PACV short scale and (b) Gust et al. vaccine acceptance categories.

RESULTS
The PACV short scale and Gust et al. vaccine acceptance categories were positively correlated (r=0.6, df=198, p<0.05), and the Cochran-Mantel-Haentszel test of association yielded a statistically significant association (p<0.05). The two scales similarly predicted children's up-to-date immunization status for all recommended childhood vaccines.

CONCLUSION
The ability of the PACV short scale to identify and classify parental vaccine hesitancy is similar to classification using Gust et al. vaccine acceptance categories, and both measure linear entities. The PACV short scale is recommended for screening parents at their first pediatric visit because it is easier to administer. A clearer understanding of how to classify parental vaccine hesitancy can be used to design tailored interventions based on these classifications, to address their specific needs.

Oladejo|Omolade|O|
Allen|Kristen|K|
Amin|Avnika|A|
Frew|Paula M|PM|
Bednarczyk|Robert A|RA|
Omer|Saad B|SB|

D007722:Health Knowledge, Attitudes, Practice

D010342:Patient Acceptance of Health Care


In Silico target fishing: addressing a "Big Data" problem by ligand-based similarity rankings with data fusion.

Abstract:
BACKGROUND
Ligand-based in silico target fishing can be used to identify the potential interacting target of bioactive ligands, which is useful for understanding the polypharmacology and safety profile of existing drugs. The underlying principle of the approach is that known bioactive ligands can be used as reference to predict the targets for a new compound.

RESULTS
We tested a pipeline enabling large-scale target fishing and drug repositioning, based on simple fingerprint similarity rankings with data fusion. A large library containing 533 drug relevant targets with 179,807 active ligands was compiled, where each target was defined by its ligand set. For a given query molecule, its target profile is generated by similarity searching against the ligand sets assigned to each target, for which individual searches utilizing multiple reference structures are then fused into a single ranking list representing the potential target interaction profile of the query compound. The proposed approach was validated by 10-fold cross validation and two external tests using data from DrugBank and Therapeutic Target Database (TTD). The use of the approach was further demonstrated with some examples concerning the drug repositioning and drug side-effects prediction. The promising results suggest that the proposed method is useful for not only finding promiscuous drugs for their new usages, but also predicting some important toxic liabilities.

CONCLUSIONS
With the rapid increasing volume and diversity of data concerning drug related targets and their ligands, the simple ligand-based target fishing approach would play an important role in assisting future drug design and discovery.

Liu|Xian|X| Xu|Yuan|Y| Li|Shanshan|S| Wang|Yulan|Y| Peng|Jianlong|J| Luo|Cheng|C| Luo|Xiaomin|X| Zheng|Mingyue|M| Chen|Kaixian|K| Jiang|Hualiang|H|

Target fishing
Big data
Data fusion
Similarity searching
Molecular fingerprints


Systematic analysis of gut microbiome reveals the role of bacterial folate and homocysteine metabolism in Parkinson's disease.

Abstract: Parkinson's disease (PD) is the most common progressive neurological disorder compromising motor functions. However, nonmotor symptoms, such as gastrointestinal (GI) dysfunction, precede those affecting movement. Evidence of an early involvement of the GI tract and enteric nervous system highlights the need for better understanding of the role of gut microbiota in GI complications in PD. Here, we investigate the gut microbiome of patients with PD using metagenomics and serum metabolomics. We integrate these data using metabolic modeling and construct an integrative correlation network giving insight into key microbial species linked with disease severity, GI dysfunction, and age of patients with PD. Functional analysis reveals an increased microbial capability to degrade mucin and host glycans in PD. Personalized community-level metabolic modeling reveals the microbial contribution to folate deficiency and hyperhomocysteinemia observed in patients with PD. The metabolic modeling approach could be applied to uncover gut microbial metabolic contributions to PD pathophysiology.

Rosario|Dorines|D|
Bidkhori|Gholamreza|G|
Lee|Sunjae|S|
Bedarf|Janis|J|
Hildebrand|Falk|F|
Le Chatelier|Emmanuelle|E|
Uhlen|Mathias|M|
Ehrlich|Stanislav Dusko|SD|
Proctor|Gordon|G|
Wüllner|Ullrich|U|
Mardinoglu|Adil|A|
Shoaie|Saeed|S|

gut microbiota
metagenomics
metabolic modeling
Parkinson’s disease
gut-brain axis


Determination of occlusal vertical dimension for complete dentures patients: an updated review.

Abstract: Determination of the occlusal vertical dimension (OVD) is an integral part of complete dentures fabrication. Due to the lack of teeth, the clinician faces the challenge of how to accurately establish the OVD of the new denture. Therefore, the purpose of this review article was to present, discuss and critique the available methods used in determining the OVD for complete dentures patients. This review identified two main streams to determine the OVD: (i) pre-extraction methods and (ii) post-extraction methods. For the pre-extraction methods, the OVD of the natural dentition is transferred to the new dentures mainly by intra-oral measurements, profile tracing and cephalometric analysis. The post-extraction methods rely on mandibular rest position, facial aesthetic appearance, swallowing pattern, craniofacial landmarks measurements, cephalometric analysis, phonetics and existing dentures. In general, all the available techniques have merits and are helpful for routine clinical use. However, they are empirical in nature, controversial and lack the scientific support. Further, there is no single accurate method for OVD determination. To overcome the limitations of the techniques, the clinician will benefit from applying combination of techniques to approximate the OVD.

D016302:Centric Relation
D002508:Cephalometry
D003779:Denture Design
D003824:Denture, Complete
D006801:Humans
D009066:Mouth, Edentulous
D013499:Surface Properties
D014716:Vertical Dimension

occlusion
vertical dimension
complete dentures
review
measurements
rest position


The comparative accuracy of the ROSA stereotactic robot across a wide range of clinical applications and registration techniques.

Abstract: Robot-assisted stereotactic neurosurgery is an emerging technology with a growing range of applications. The ROSA system is a robotic stereotactic system that has been shown to be accurate in laboratory studies and large case series. The goal of this study was to examine the accuracy of the ROSA across different registration methods as well as different clinical applications. Sixteen patients with one hundred and seventeen stereotactic trajectories were examined. Accuracy was compared by measuring the distance between the trajectory target and the actual termination of the device as determined by imaging. Entry error and angular deviation were also measured. Variables included bone fiducials vs. laser facial scanning, the clinical indication for stereotactic surgery, and the effect of lead deflection on accuracy. Bone fiducials did not offer an accuracy benefit over laser facial scanning (mean target error 4.5-3.9 mm, p = 0.34) in these clinical scenarios. Laser interstitial thermal therapy, responsive neurostimulation, and stereo electroencephalography were equally accurate when placed by the ROSA (mean target error 4.4-4.3-4.0 mm, respectively, p = 0.69). Deflection did not affect lead accuracy (mean target error 4.4-3.9 mm, p = 0.11). Similar results are seen for entry error and angular deviation. ROSA is a highly accurate stereotactic system. Laser facial scanning provides the same accuracy as bone fiducials in these stereotactic applications. The ROSA is equally accurate across a wide spectrum of applications. The ROSA is effective at limiting lead deflection, and when it does occur, it does not impact target accuracy in a significant way.

Accuracy ROSA Stereotactic Robot Fiducial Frameless Neuronavigation


The Plantain Proteome, a Focus on Allele Specific Proteins Obtained from Plantain Fruits.

Abstract: Proteomics has been applied with great potential to elucidate molecular mechanisms in plants. This is especially valid in the case of non-model crops of which their genome has not been sequenced yet, or is not well annotated. Plantains are a kind of cooking bananas that are economically very important in Africa, India, and Latin America. The aim of this work was to characterize the fruit proteome of common dessert bananas and plantains and to identify proteins that are only encoded by the plantain genome. We present the first plantain fruit proteome. All data are available via ProteomeXchange with identifier PXD005589. Using our in-house workflow, we found 37 alleles to be unique for plantain covered by 59 peptides. Although we do not have access (yet) to whole-genome sequencing data from triploid banana cultivars, we show that proteomics is an easily accessible complementary alternative to detect different allele specific SNPs/SAAPs. These unique alleles might contribute toward the differences in the metabolism between dessert bananas and plantains. This dataset will stimulate further analysis by the scientific community, boost plantain research, and facilitate plantain breeding.

Campos|Nádia A|NA|
Swennen|Rony|R|
Carpentier|Sebastien C|SC|

plantain
allele
amino acid polymorphisms
non-model proteomics


Ratite oils promote keratinocyte cell growth and inhibit leukocyte activation.

Abstract: Traditionally, native Australian aborigines have used emu oil for the treatment of inflammation and to accelerate wound healing. Studies on mice suggest that topically applied emu oil may have anti-inflammatory properties and may promote wound healing. We investigated the effects of ratite oils (6 emu, 3 ostrich, 1 rhea) on immortalized human keratinocytes (HaCaT cells) in vitro by culturing the cells in media with oil concentrations of 0%, 0.5%, and 1.0%. Peking duck, tea tree, and olive oils were used as comparative controls. The same oils at 0.5% concentration were evaluated for their influence on peripheral blood mononuclear cell (PBMC) survival over 48 hr and their ability to inhibit IFNγ production in PBMCs activated by phytohemagglutinin (PHA) in ELISpot assays. Compared to no oil control, significantly shorter population doubling time durations were observed for HaCaT cells cultured in emu oil (1.51×faster), ostrich oil (1.46×faster), and rhea oil (1.64×faster). Tea tree oil demonstrated significant antiproliferative activity and olive oil significantly prolonged (1.35×slower) cell population doubling time. In contrast, almost all oils, particularly tea tree oil, significantly reduced PBMC viability. Different oils had different levels of inhibitory effect on IFNγ production with individual emu, ostrich, rhea, and duck oil samples conferring full inhibition. This preliminary investigation suggests that emu oil might promote wound healing by accelerating the growth rate of keratinocytes. Combined with anti-inflammatory properties, ratite oil may serve as a useful component in bandages and ointments for the treatment of wounds and inflammatory skin conditions.

Bennett|Darin C|DC|
Leung|Gigi|G|
Wang|Eddy|E|
Ma|Sam|S|
Lo|Blanche K K|BK|
McElwee|Kevin J|KJ|
Cheng|Kimberly M|KM|

Emu oil
anti-inflammatory
skin
keratinocyte growth
wound treatment


Differential Regulation of Human Bone Marrow Mesenchymal Stromal Cell Chondrogenesis by Hypoxia Inducible Factor-1α Hydroxylase Inhibitors.

Abstract: The transcriptional profile induced by hypoxia plays important roles in the chondrogenic differentiation of marrow stromal/stem cells (MSC) and is mediated by the hypoxia inducible factor (HIF) complex. However, various compounds can also stabilize HIF's oxygen-responsive element, HIF-1α, at normoxia and mimic many hypoxia-induced cellular responses. Such compounds may prove efficacious in cartilage tissue engineering, where microenvironmental cues may mediate functional tissue formation. Here, we investigated three HIF-stabilizing compounds, which each have distinct mechanisms of action, to understand how they differentially influenced the chondrogenesis of human bone marrow-derived MSC (hBM-MSC) in vitro. hBM-MSCs were chondrogenically-induced in transforming growth factor-β3-containing media in the presence of HIF-stabilizing compounds. HIF-1α stabilization was assessed by HIF-1α immunofluorescence staining, expression of HIF target and articular chondrocyte specific genes by quantitative polymerase chain reaction, and cartilage-like extracellular matrix production by immunofluorescence and histochemical staining. We demonstrate that all three compounds induced similar levels of HIF-1α nuclear localization. However, while the 2-oxoglutarate analog dimethyloxalylglycine (DMOG) promoted upregulation of a selection of HIF target genes, desferrioxamine (DFX) and cobalt chloride (CoCl2 ), compounds that chelate or compete with divalent iron (Fe2+ ), respectively, did not. Moreover, DMOG induced a more chondrogenic transcriptional profile, which was abolished by Acriflavine, an inhibitor of HIF-1α-HIF-β binding, while the chondrogenic effects of DFX and CoCl2 were more limited. Together, these data suggest that HIF-1α function during hBM-MSC chondrogenesis may be regulated by mechanisms with a greater dependence on 2-oxoglutarate than Fe2+ availability. These results may have important implications for understanding cartilage disease and developing targeted therapies for cartilage repair. Stem Cells 2018;36:1380-1392.

Taheem|Dheraj K|DK|0000-0002-0252-6677
Foyt|Daniel A|DA|
Loaiza|Sandra|S|
Ferreira|Silvia A|SA|
Ilic|Dusko|D|
Auner|Holger W|HW|
Grigoriadis|Agamemnon E|AE|
Jell|Gavin|G|
Gentleman|Eileen|E|

D051795:Hypoxia-Inducible Factor 1, alpha Subunit

Differentiation
Chondrogenesis
Hypoxia
Bone marrow stromal cells (BMSCs)
Cell signaling
Mesenchymal stem cells (MSCs)
Tissue regeneration


Development of pre and post-operative nomograms to predict individual survival for ideal liver resection candidates with hepatocellular carcinoma.

Abstract:
BACKGROUND
Liver resection is currently the only recommended treatment option for solitary hepatocellular carcinoma (HCC) at an early stage, with well-preserved liver function and no clinically significant portal hypertension. However, this population is heterogeneous, rendering it crucial to develop a risk stratification tool. Therefore, this study aimed to develop preoperative and post-operative nomograms to predict individual survival and stratify patient risk in the ideal candidates for liver resection.

METHODS
A total of 1405 ideal liver resection candidates were recruited. Independent risk factors were identified by Cox regression model and used to establish two ideal liver resection for overall survival (IROS) nomograms in training cohort. Model performance was assessed by discrimination, calibration, clinical usefulness. The two model also compared with six other prognostic nomograms and six other staging systems.

RESULTS
Multivariate COX analysis revealed that ALP, ln(AFP), NrLR, PNI, ln(tumor size), microvascular invasion, Edmondson-Steiner grade and tumour capsular were the independent risk factors associated with mortality. 5 preoperative variables were incorporated to construct IROS-pre model; All eight available variables were used to draw IROS-post model. The C-index, K-index, time-dependent AUC and DCA of the two models showed significantly better predictive performances than other models. The models could stratify patients into three different risk groups. The web-based tools are convenient for clinical practice.

CONCLUSIONS
These two nomograms were developed to estimate survival probability and stratify three strata with significantly different outcomes, outperforming other models in training and validation cohorts, as well as different subgroups. Both IROS models will help guide individualized follow-up.

nomogram
ideal liver resection candidates
hepatocellular carcinoma
overall survival
individualized prediction


Dual-binding benzene and rhodamine B conjugate derivatives as fluorescent chemodosimeter for hypochlorite in living cell imaging.

Abstract: A new probe (SRh) which based on dual-binding benzene and rhodamine B conjugate derivatives for hypochlorite detection was developed. By desulfurization effect, probe SRh displayed"Off-On" switching in its fluorogenic and chromogenic responses to hypochlorite. The detection limit of ClO- was at a low level (up to 2.43 nM). Moreover, probe SRh has been applied in bioimaging with good biocompatibility and low cytotoxicity.

Zhang|Di|D| Ma|Zhiwei|Z| Wang|Yanliang|Y| Yin|Haiyan|H| Li|Man|M| Wang|Yun|Y| Wang|Hongqi|H| Jia|Bin|B| Liu|Jihong|J|

Rhodamine Fluorescence Hypochlorite Desulfurization Bioimaging


Challenges of Population-based Measurement of Suicide Prevention Activities Across Multiple Health Systems.

Abstract: Suicide is a preventable public health problem. Zero Suicide (ZS) is a suicide prevention framework currently being evaluated by Mental Health Research Network investigators embedded in six Health Care Systems Research Network (HCSRN) member health systems implementing ZS. This paper describes ongoing collaboration to develop population-based process improvement metrics for use in, and comparison across, these and other health systems. Robust process improvement metrics are sorely needed by the hundreds of health systems across the country preparing to implement their own best practices in suicide care. Here we articulate three examples of challenges in using health system data to assess suicide prevention activities, each in ascending order of complexity: 1) Mapping and reconciling different versions of suicide risk assessment instruments across health systems; 2) Deciding what should count as adequate suicide prevention follow-up care and how to count it in different health systems with different care processes; and 3) Trying to determine whether a safety planning discussion took place between a clinician and a patient, and if so, what actually happened. To develop broadly applicable metrics, we have advocated for standardization of care processes and their documentation, encouraged standardized screening tools and urged they be recorded as discrete electronic health record (EHR) variables, and engaged with our clinical partners and health system data architects to identify all relevant care processes and the ways they are recorded in the EHR so we are not systematically missing important data. Serving as embedded research partners in our local ZS implementation teams has facilitated this work.

population-based
suicide prevention
health systems
zero suicide
electronic health record


Small bowel adenocarcinoma: Results from a nationwide prospective ARCAD-NADEGE cohort study of 347 patients.

Abstract: Small bowel adenocarcinoma (SBA) is a rare tumour. We conducted a prospective cohort to describe the prevalence, survival and prognostic factors in unselected SBA patients. The study enrolled patients with all stages of newly diagnosed or recurrent SBA at 74 French centres between January 2009 and December 2012. In total, 347 patients were analysed; the median age was 63 years (range 23-90). The primary tumour was in the duodenum (60.6%), jejunum (20.7%) and ileum (18.7%). The prevalence of predisposing disease was 8.7%, 6.9%, 1.7%, 1.7% and 0.6% for Crohn disease, Lynch syndrome, familial adenomatous polyposis, celiac disease and Peutz-Jeghers syndrome, respectively. At diagnosis, 58.9%, 5.5% and 35.6% of patients had localised and resectable, locally advanced unresectable and metastatic disease, respectively. Crohn disease was significantly associated with younger age, poor differentiation and ileum location, whereas Lynch syndrome with younger age, poor differentiation, early stage and duodenum location. Adjuvant chemotherapy (oxaliplatin-based in 89.9%) was performed in 61.5% of patients with locally resected tumours. With a 54-months median follow-up, the 5-year overall survival (OS) was 87.9%, 78.2% and 55.5% in Stages I, II and III, respectively. The median OS of patients with Stage IV was 12.7 months. In patients with resected tumours, poor differentiation (p = 0.047) and T4 stage (p = 0.001) were associated with a higher risk of death. In conclusion, our study showed that the prognosis of advanced SBA remains poor. Tumour characteristics differed according to predisposing disease. In SBA-resected tumours, the prognostic factors for OS were grade and T stage.

Aparicio|Thomas|T|0000-0001-8834-6927 Henriques|Julie|J| Manfredi|Sylvain|S| Tougeron|David|D|0000-0002-8065-9635 Bouché|Olivier|O| Pezet|Denis|D| Piessen|Guillaume|G| Coriat|Romain|R| Zaanan|Aziz|A|0000-0001-8372-5653 Legoux|Jean-Louis|JL| Terrebone|Eric|E| Pocard|Marc|M| Gornet|Jean-Marc|JM| Lecomte|Thierry|T| Lombard-Bohas|Catherine|C| Perrier|Hervé|H| Lecaille|Cédric|C| Lavau-Denes|Sandrine|S| Vernerey|Dewi|D| Afchain|Pauline|P| |||

cohort study
Crohn disease
Lynch syndrome
epidemiology
small intestine adenocarcinoma


Human papillomavirus vaccine increases high-risk sexual behaviors: a myth or valid concern.

Abstract: In 2006, the first human pappilomavirus (HPV) vaccine was approved for females aged 9 to 26. However, the national HPV vaccination rate among young women has been low. Public concerns were raised in regard to the fact that HPV vaccination might encourage unsafe sex. This cross-sectional study examined the differences in sexual practices between college women who have and have not obtained the HPV vaccine. Participants were 209 vaccinees and 175 nonvaccinees. A web-based survey was used. Sexual practices (numbers of sexual partners in a lifetime and in the past 12 months, condom use, condom use frequency) were not significantly different between the two groups. Among the vaccinees, the numbers of sexual partners before and after vaccination was also not significantly different. School nurses are at the frontier to advise young girls/parents on HPV vaccination before the girls engage in sexual intercourse. They may utilize these findings to address the misunderstanding that HPV vaccination encourages unsafe sex.

human papillomavirus
sexual behavior
HPV vaccine


Acute pyelonephritis in children.

Abstract: Acute pyelonephritis is one of the most serious bacterial illnesses during childhood. Escherichia coli is responsible in most cases, however other organisms including Klebsiella, Enterococcus, Enterobacter, Proteus, and Pseudomonas species are being more frequently isolated. In infants, who are at major risk of complications such as sepsis and meningitis, symptoms are ambiguous and fever is not always useful in identifying those at high risk. A diagnosis of acute pyelonephritis is initially made on the basis of urinalysis; dipstick tests for nitrites and/or leukocyte esterase are the most accurate indicators of infection. Collecting a viable urine sample for urine culture using clean voided methods is feasible, even in young children. No gold standard antibiotic treatment exists. In children appearing well, oral therapy and outpatient care is possible. New guidelines suggest less aggressive imaging strategies after a first infection, reducing radiation exposure and costs. The efficacy of antibiotic prophylaxis in preventing recurrence is still a matter of debate and the risk of antibiotic resistance is a warning against its widespread use. Well-performed randomized controlled trials are required in order to better define both the imaging strategies and medical options aimed at preserving long-term renal function.

Morello|William|W|
La Scola|Claudio|C|
Alberici|Irene|I|
Montini|Giovanni|G|

Acute pyelonephritis
Guidelines
Antibiotic prophylaxis
Antibiotic resistance
Urinary tract infections
Vesicoureteral reflux


Extracellular proteases are released by ciliates in defined seawater microcosms.

Abstract: The biodegradation of proteins in seawater requires various proteases which are commonly thought to be mainly derived from heterotrophic bacteria. We, however, found that protists showed a high protease activity and continuously produced trypsin-type enzymes. The free-living marine heterotrophic ciliate Paranophrys marina together with an associated bacterium was isolated and used for microcosm incubation with different concentrations of killed bacteria as food for 10 days. The results showed that the co-existence of the ciliate with its associated bacterium produced a significant protease activity in both cell-associated and cell-free fractions while that in the associated bacterium only microcosm was negligible. The protease profiles are different between cell-associated and cell-free fractions, and a trypsin-type enzyme hydrolyzing Boc-Val-Leu-Lys-MCA was detected throughout the period in the presence of ciliates. This suggests that ciliates release proteases into the surrounding environment which could play a role in protein digestion outside cells. It has been previously suggested that bacteria are the major transformers in seawater. We here present additional data which indicates that protists, or at least ciliates with their specific enzymes, are a potential player in organic matter degradation in water columns.

Thao|Ngo Vy|NV|
Nozawa|Akino|A|
Obayashi|Yumiko|Y|
Kitamura|Shin-Ichi|S|
Yokokawa|Taichi|T|
Suzuki|Satoru|S|

Protease
Ciliate
Seawater
Bacteria
Paranophrys marina
Pseudomonas aeruginosa


Health professional-delivered obesity prevention interventions during the first 1,000 days: A systematic review of external validity reporting.

Abstract: Background: Childhood obesity prevention interventions delivered by health professionals during the first 1,000 days show some evidence of effectiveness, particularly in relation to behavioural outcomes. External validity refers to how generalisable interventions are to populations or settings beyond those in the original study. The degree to which external validity elements are reported in such studies is unclear however. This systematic review aimed to determine the extent to which childhood obesity interventions delivered by health professionals during the first 1,000 days report on elements that can be used to inform generalizability across settings and populations. Methods: Eligible studies meeting study inclusion and exclusion criteria were identified through a systematic review of 11 databases and three trial registers. An assessment tool based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework was used to assess the external validity of included studies. It comprised five dimensions: reach and representativeness of individuals, reach and representativeness of settings, implementation and adaptation, outcomes for decision making maintenance and/or institutionalisation. Two authors independently assessed the external validity of 20% of included studies; discrepancies were resolved, and then one author completed assessments of the remaining studies. Results: In total, 39 trials involving 46 interventions published between 1999 and 2019 were identified. The majority of studies were randomized controlled trials (n=24). Reporting varied within and between dimensions. External validity elements that were poorly described included: representativeness of individuals and settings, treatment receipt, intervention mechanisms and moderators, cost effectiveness, and intervention sustainability and acceptability. Conclusions: Our review suggests that more emphasis is needed on research designs that consider generalisability, and the reporting of external validity elements in early life childhood obesity prevention interventions. Important gaps in external validity reporting were identified that could facilitate decisions around the translation and scale-up of interventions from research to practice. Registration: PROSPERO CRD42016050793 03/11/16.

prevention
intervention
systematic review
External validity
childhood obesity
health professional
generalisability
implementation science
replication


Regulated Drug Release Abilities of Calcium Carbonate-Gelatin Hybrid Nanocarriers Fabricated via a Self-Organizational Process.

Abstract: In this study, we investigated the drug-releasing behavior of a calcium carbonate (CaCO3 )-gelatin hybrid nanocarrier, fabricated through a single process using biomimetic mineralization. The organic scaffold (gelatin) of the fabricated nanocarrier is responsible for its capacity to load anionic drugs and for controlling the morphology of the inorganic matrix (CaCO3 ). We studied the drug-releasing properties of the nanocarrier by investigating the response of the CaCO3 matrix to acidic conditions. We found that under neutral conditions, drug release from the nanocarrier was inhibited, whereas under acidic conditions, the drug was efficiently released. Therefore, drug release from the nanocarrier is largely dependent on the surrounding pH.

Murai|Kazuki|K|0000-0002-6916-464X Kurumisawa|Kazuya|K| Nomura|Yoshihiro|Y| Matsumoto|Mutsuyoshi|M|

D017550:Spectroscopy, Fourier Transform Infrared

gelatin
biomineralization
controlled release
drug delivery
pH responsivity


Social Disparities in Obesogenic Behaviors in Adolescents.

Abstract:
BACKGROUND/AIMS
Demographic and social characteristics, such as sex, race/ethnicity, and income, have been implicated as risk and protective factors for behavior change regarding obesogenic behaviors in adolescents. The purpose of this study was to determine the social disparities in obesogenic behaviors and compare social disparities in obesogenic behaviors between adolescents who are overweight/obese and non-overweight adolescents using an alternative methodology for calculating disparities.

METHODS
Data were obtained from the 2013 Massachusetts Youth Risk Behavior Surveillance Systems. Social disparities ratios for meeting fruit and vegetable recommendation, daily breakfast consumption, physical activity, and non-sedentary activity were calculated using the Extended Gastwirth Index Method. Independent sample t tests were used to compare social disparities between non-overweight and overweight/obese participants.

RESULTS
Racial disparities were the largest contributor to overall disparities for meeting fruit and vegetables recommendations, daily breakfast, and non-sedentary activity, while sex disparities were the largest contributor to overall disparities for meeting physical activity recommendations. The non-overweight group had lower free/reduced lunch disparities for all behaviors when compared to the overweight/obese group.

CONCLUSIONS
The results of this study confirmed that social disparities exist for obesogenic behaviors. The methodology allowed for the determination of the percentage change needed in behavior to eliminate disparities between groups. These calculations are a useful tool for identifying groups that should be targeted for intervention if disparities are to be reduced.

Social disparities
Obesogenic behaviors
Adolescents
Obesity
Health disparities
Social determinants of health


Clinical outcomes of complex lesions treated with an abluminal groove-filled biodegradable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent.

Abstract:
BACKGROUND
The Firehawk stent (Shanghai MicroPort Medical Group, Shanghai, China), a novel biodegradable polymer sirolimus-eluting coronary stent has been evaluated in the randomized TARGET I trial in which low-risk patients were enrolled with strict eligibility criteria. Recently, the TARGET All Comers study has shown similar results of the Firehawk compared to the XIENCE stent (Abbott Vascular, Santa Clara). However, clinical outcomes in high-risk patients are unclear.

METHODS
The TARGET All Comer study was a randomized trial that assigned patients to either Firehawk or XIENCE implantation. This TARGET AC subanalysis sought to evaluate the 2 year clinical outcomes of patients according to two risk groups; patients meeting all inclusion criteria and no exclusion criteria of the TARGET I trial were classified as "low-risk," while their counterparts were classified as "high-risk." The primary endpoint was target lesion failure.

RESULTS
A total of 1,585 patients were included, of which 1,334 (84%) were classified as high-risk. At 2 years, the high-risk group had a significantly higher rate of TLF than the low-risk group (9.5% vs. 3.6%, p = .003), mainly driven by increased target vessel myocardial infarction (6.3% vs. 2.4%, p = .02). The Firehawk and XIENCE had no significant differences in TLF among both low-risk (3.1% vs. 4.2%, p = .66) and high-risk (9.9% vs. 9.1%, p = .57) patients.

CONCLUSIONS
High-risk patients had worse clinical outcomes at 2 years in the TARGET All Comer study. Outcomes with the Firehawk were similar to the XIENCE stent among both low-risk and high-risk patients at 2 years.

everolimus-eluting stent
Firehawk
eligibility
drug-eluting stent


AT1-receptor blockade attenuates outward aortic remodeling associated with diet-induced obesity in mice.

Abstract: The renin-angiotensin system (RAS) and obesity have been implicated in vascular outward remodeling, including aneurysms, but the precise mechanisms are not yet understood. We investigated the effect of the angiotensin receptor type 1 (AT1-receptor) antagonist telmisartan on aortic outward remodeling in a diet-induced obesity model in mice. C57/Black6J mice were fed either a low-fat diet (LFD) or a high-fat diet (HFD) for 14 weeks. One group of HFD mice was additionally exposed to telmisartan (3 mg/kg per day) for the last 4 weeks. HFD led to aortic outward remodeling, characterized by increased proteolysis, along with structural changes, such as fragmentation of elastic fibers and decreased elastin content. Vascular damage was associated with up-regulation of matrix metalloproteinase (MMP)-2 (MMP-2), MMP-3, MMP-12, cathepsin D, and cathepsin B. HFD aortae exhibited an enhanced inflammatory status, characterized by tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) colocalized with adipocytes in the adventitia. HFD resulted in a significant increase in aortic dimensions, evident by ultrasound measurements. Telmisartan abolished aortic dilatation and preserved elastin content. HFD induced enhanced expression of aortic MMP-2, MMP-9, and TNF-α was abrogated by telmisartan. Adventitial proteolytic and inflammatory factors were also examined in samples from human abdominal aneurysms. The expression of TNF-α, IL-1β, and MMP-9 was higher in the adventitial fat of diseased vessels compared with healthy tissues. Finally, adipocytes treated with TNF-α showed enhanced MMP-2, MMP-3, and cathepsin D, which was prevented by telmisartan. Taken together, HFD in mice induced aortic dilatation with up-regulation of matrix degrading and inflammatory pathways similar to those seen in human aortic aneurysmatic tissue. The HFD-induced vascular pathology was reduced by AT1-receptor antagonist telmisartan.

Krueger|Friedrich|F|
Kappert|Kai|K|
Foryst-Ludwig|Anna|A|
Kramer|Frederike|F|
Clemenz|Markus|M|
Grzesiak|Aleksandra|A|
Sommerfeld|Manuela|M|
Frese|Jan Paul|JP|
Greiner|Andreas|A|
Kintscher|Ulrich|U|
Unger|Thomas|T|
Kaschina|Elena|E|

D047228:Angiotensin II Type 1 Receptor Blockers

angiotensin
high-fat diet
MMP
abdominal aortic aneurysm
vascular remodeling


CD30-Positive T-Cell Lymphoproliferative Disease of the Oral Mucosa in Children: A Manifestation of Epstein-Barr Virus-Associated T-Lymphoproliferative Disorder.

Abstract: Eosinophilic ulcer of the oral mucosa (EUOM) is a very rare, benign, self-limiting ulcerative lesion of the oral cavity of unknown pathogenesis, and belongs to the same spectrum of CD30(+) T-cell lymphoproliferative disease (LPD) of the oral mucosa. The etiology and pathogenesis of the disease are unknown. We report two cases in children who were initially diagnosed with EUOM and CD30(+) T-cell LPD, respectively. However, retrospective analysis revealed that a majority of infiltrated atypical T cells were positive for Epstein-Barr virus (EBV). The present cases suggest that the pathogenesis and etiology of EUOM or CD30(+) T-cell LPD occurring in children are different from those in adults. EUOM or CD30(+) T-cell LPD in children is a manifestation of EBV-positive T-cell LPD, and should therefore be distinguished from the disease in adults.

Oral mucosa
Eosinophilic ulcer
CD30 positive
Epstein-Barr virus infections
Lymphoproliferative disorders
Lymphoreticular


Clinical Features and Outcomes of 124 Italian Patients With Treatment Resistant Depression: A Real-World, Prospective Study.

Abstract: Introduction: Treatment-resistant depression (TRD) is a debilitating condition affecting 20-30% of patients with major depressive disorders (MDD). Currently, there is no established standard of care for TRD, and wide variation in the clinical approach for disease management has been documented. Real-world data could help describe TRD clinical features, disease burden, and treatment outcome and identify a potential unmet medical need. Methods: We analyzed the Italian data from a European, prospective, multicentric, observational cohort study of patients fulfilling TRD criteria by the European Medicine Agency, with moderate to severe major depressive episode, and starting a new antidepressant treatment according to routinary clinical practice. They were followed up for minimum 6 months. Treatments received throughout the study period, disease severity, health-related quality of life and functioning were prospectively recorded and analyzed. Results: The Italian subcohort included 124 TRD patients (30.2% of patients of the European cohort; mean age 53.2 [sd = 9.8], women: 82, 66.1%). At enrollement, the mean (SD) duration of MDD was 16 years (sd = 11.1) and the mean duration of the ongoing major depressive episode (MDE) was 97.5 weeks (sd = 143.5); low scores of quality of life and functioning were reported. The most frequently antidepressant classes started at baseline (data available for 98 subjects) were selective serotonin reuptake inhibitors (SSRI, 42 patients [42.9%]) and serotonin-norepinephrine reuptake inhibitors (SNRI, 32 patients [32.7%]). In terms of treatment strategies, 50 patients (51%) started augmentation therapies, 18 (18.4%) combination therapies and 24 (24.5%) monoterapies (6 patients [6%] started a non-antidepressant drug only). Fourteen patients (11.3%) were treated with a psychosocial approach, including psychotherapy. After 6 months of treatment, clinical assessments were collected for 89 patients: 64 (71.9%) showed no response, 9 (10.1%) response without remission and 16 (18.0%) were in remission; non-responder patients showed lower quality of life and higher disability scores than responder patients. Conclusions: In our sample of TRD patients, we documented substantial illness burden, low perceived quality of life and poor outcome, suggesting an unmet treatment need in TRD care in Italy. Registration Number: ClinicalTrials.gov, number: NCT03373253.

Perugi|Giulio|G|
Calò|Paola|P|
De Filippis|Sergio|S|
Rosso|Gianluca|G|
Vita|Antonio|A|
Adami|Marina|M|
Ascione|Giuseppe|G|
Morrens|Joachim|J|
Delmonte|Dario|D|

treatment resistant depression
major depressive disorder
treatment outcome
cohort study
health-related quality of life
real-world study
treatment pattern


Sacroiliac joint cut accuracy: Comparing new technologies in an idealized sawbones model.

Abstract:
BACKGROUND AND OBJECTIVES
The anatomical complexity of the pelvis creates challenges for orthopaedic oncologists to accurately and safely resect tumors involving the sacroiliac joint. Current technology may help overcome these obstacles.

METHODS
Four fellowship-trained orthopaedic oncologists performed 22 all-posterior sacroiliac cuts using freehand, computerized navigation, and patient-specific cutting guides on a Sawbones male pelvis model. Cut accuracies to preoperative planned margins were analyzed via a high-resolution optical scanner. Soft tissue damage was determined by visually inspecting the Sawbones foam placed on the far side of the cut.

RESULTS
Within 5 mm of the margins, the freehand technique resulted in 67.0% cut accuracy, the navigation technique had 71.1%, and the patient-specific cutting guide technique had 85.6% (P = .093). Within 2 mm, the techniques showed an accuracy of 25.8%, 32.5%, and 47.5%, respectively (P = .022). Regarding soft tissue damage, the freehand technique exhibited minimal penetration damage for 16.7% of the cuts, while navigation and patient-specific guide techniques exhibited 25.0% and 75.0%, respectively (P = .046). Years of surgical experience of the operator (1-7) did not influence the cut accuracy for any method.

CONCLUSIONS
Under ideal conditions, patient-specific guide technology possesses the same or better accuracy as other cutting techniques as well as the circumvention of soft tissue damage.

D001859:Bone Neoplasms
D006801:Humans
D008297:Male
D000072662:Margins of Excision
D008954:Models, Biological
D010027:Osteotomy
D010384:Pelvic Bones
D012446:Sacroiliac Joint
D025321:Surgery, Computer-Assisted
D014057:Tomography, X-Ray Computed

computer assisted
margins of excision
orthopedic procedures
patient-specific instruments
pelvic neoplasms
surgery


From sample preparation to NMR-based metabolic profiling in food commodities: The case of table olives.

Abstract:
INTRODUCTION
Nuclear magnetic resonance (NMR)-based metabolic profiling has been widely used in food and plant sciences. Despite its simplicity and inherent reproducibility, the determination of the appropriate pre-processing procedures greatly affects the obtained metabolic profile.

OBJECTIVES
The current study represents a detailed guide of use for untargeted NMR-based metabolic profiling of table olives (Olea europaea L.).

METHODS
Greek Kalamon table olives from different geographical origins were selected as reference materials. Differently treated samples were extracted using different solvents and/or solvent systems. Chemical profiles were evaluated with high-performance thin layer chromatography (HPTLC). Different deuterated solvents and sample concentrations were evaluated for the recording of optimal quality spectra.

RESULTS
The methanol extract of freeze-dried table olives was found to contain the most representative secondary metabolites, in higher concentrations, as well. The optimal deuterated solvent for the NMR analysis was methanol-d4 , while final sample concentration should be within the range of 10 to 15 mg/mL. Multivariate data analysis was also used to estimate and confirm the variation and clustering caused by different characteristics of the samples.

CONCLUSIONS
Results of the present study make evident the necessity for thorough planning and method development prior to any extensive metabolomic study based on NMR spectroscopy. Pre-processing and sample preparation stages seemed to greatly affect the metabolic profile and spectral quality in the case of table olives, which by extrapolation could apply to other food commodities. Nevertheless, the nature of the samples must be fully described in general, in order to proceed to solid conclusions.

sample preparation
NMR-based metabolic profiling
table olives
extraction
Olea europaea L
protocol optimisation


Kidney cancer demographics and outcome data from 2013 at a tertiary cancer hospital in India.

Abstract:
INTRODUCTION
The stage at diagnosis of renal cell cancer (RCC) in developed countries is lower due to increased utilization of routine health checkups by patients compared to developed countries. This study aims to determine the sociodemographic and clinical distribution of RCC in patients presenting to Tata Memorial Hospital (TMH).

SUBJECTS AND METHODS
We performed a retrospective audit of all patients presenting to TMH with a diagnosis of RCC. Data were retrieved from our electronic medical record system from January 1, 2013 to December 31, 2013. The survival analysis was done by Kaplan-Meir analysis method of estimating survival. Log-rank test of comparison was applied to estimate the difference in the survival among the different stages of renal cancer.

RESULTS
Of the 35,197 new registered patients at TMH, 338 were diagnosed with RCC. Most patients were in the 50-60 years age group, with 56.6 years being the median age at presentation. Among patients treated at TMH, 84 underwent surgery and tyrosine kinase inhibitor was given in 55 (16%) patients. The patients' characteristics, clinical characteristics of RCC, treatment modalities offered, and survival of patients treated for RCC are presented in this paper.

CONCLUSION
In the absence of robust Indian data on RCC, this audit provides baseline information on epidemiology, stage at presentation, and outcomes of RCC at our center compared with the West.

Joshi|Amit|A| Anand|Amitesh|A| Prabhash|Kumar|K| Noronha|Vanita|V| Shrirangwar|Sameer|S| Bakshi|Ganesh|G| Pal|Mahendra|M| Murthy|Vedang|V| Krishnatry|Rahul|R| Desai|Sangeeta|S| Menon|Santosh|S| Patil|Deepali|D| Kulkarni|Sheetal|S| Sable|Nilesh|N| Popat|Palak|P| Agrawal|Archi|A| Rangarajan|Venkatesh|V| Prakash|Gagan|G|

kidney cancer
Tata Memorial Hospital
Indian data
renal cell carcinoma


HLA concordance between hematopoietic stem cell transplantation patients and umbilical cord blood units: Implications for cord blood banking in admixed populations.

Abstract: Umbilical cord blood stem cell transplantation is an important choice for treating a variety of hematopoietic, neoplastic, and genetic disorders. The optimal size for a cord blood bank to provide matching units for 80% of patients requiring a stem cell transplantation procedure depends on the particular characteristics of each population. In this study, we analyzed the immunogenetic diversity of a sample set of Mexican patients suffering from blood, hematopoietic, and immunological diseases, to assess the best strategy for cord blood banking. For achieving that, we analyzed HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1 genotype and allele frequencies of both units from the bioarchive of the Umbilical Cord Blood Bank from La Raza and patients requiring a stem cell transplant and compared these variables with data from the same geographic and genetic context. We were able to detect significant differences for at least half of the alleles were observed for HLA class I and class II genes between units and patients. Five Native American haplotypes had lower frequencies in patients sample than in the cord blood units. Genetic admixture estimations for both groups showed a higher contribution of Native American component in the cord blood units. Differences in ancestral components in the Umbilical Cord Blood Bank from La Raza and six virtual banks modeled from a pool of Mexican mixed ancestry individuals show that genetic background is important in cord blood collection. In conclusion, increasing diversity over quantity of new cord blood units will improve the cost effectiveness of cord blood banking and health policies regarding hematopoietic stem cell transplantation in admixed populations such as those present in Latin American countries.

Bravo-Acevedo|Alicia|A|
Barquera|Rodrigo|R|
Bekker-Méndez|Carolina|C|
Clayton|Stephen|S|
Hernández-Zaragoza|Diana Iraíz|DI|
Benítez-Arvizu|Gamaliel|G|
Guerra-Márquez|Ángel|Á|
Juárez-Cortés|Eva Dolores|ED|
Arriaga-Perea|Agustín Jericó|AJ|
Novelo-Garza|Bárbara|B|

D036101:Cord Blood Stem Cell Transplantation

D018380:Hematopoietic Stem Cell Transplantation

HLA
Umbilical cord blood banking
Ancestral genetic components
Linkage disequilibrium
Mexico
Population immunogenetics