bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonsteroidal Anti‐Inflammatory Agents in the Treatment of Asthma in Children
Authors: Gaudreault Pierre
Published: May 2016

The increasing scientific information clearly demonstrates the important role of inflammation in asthma. This evidence has led physicians to focus their treatment on the elimination of inflammation instead of working solely against bronchoconstriction. Steroids and nonsteroidal agents are currently used to prevent this inflammatory component. This paper focuses only on nonstcroidal anti‐inflammatory agents such as sodium cromoglycate, nedocromil sodium and ketotifen and their use in pediatric asthma. The discussion on each medication addresses its mechanism of action, the evidence concerning its efficacy in pediatrics (ie, clinical pharmacology, acute bronchial challenge, late asthmatic response, bronchial hyperrcactivity, clinical efficacy) and the pediatric dose.
Asthma in Primary Care: Making Guidelines Work
Authors: Putnam Wayne , Burge Fred , Tatemichi Sue , Twohig Peter
Published: May 2016

OBJECTIVE: To determine the views of family physicians regarding selected asthma recommendations from a Canadian practice guideline and the supporting evidence, and to identify issues needing further development if family physicians are to find guideline recommendations to be truly useful clinical tools.

SETTING: Four urban communities in Nova Scotia, Prince Edward Island and New Brunswick.

PARTICIPANTS: Twenty community family physicians representing different practice settings, and varying according to age and sex, were recruited to participate.

DATA COLLECTION: Four focus groups were held, each lasting 2 h, at which recommendations from a published asthma guideline were presented for discussion on the applicability to their practices. The data were analyzed using a grounded theory method.

RESULTS: Physicians rely on clinical judgment in lieu of objective measures in diagnosing asthma and resist treating every exacerbation with steroids. They thought that the recommendations on smoking and patient education should have been stronger or more prominent. Patient noncompliance limits the usefulness of home peak flow measures. Topics such as allergy assessment and most pharmacological therapies triggered little discussion.

DISCUSSION: Asthma guideline developers and those interested in enhancing compliance with recommendations will need to attend to factors such as physician attitudes and beliefs on a variety of issues, including the use of objective measures and the availability of adequate resources to conduct the tests. Similarly, negative patient attitudes toward an increased use of corticosteroids suggest that a public education program would be most helpful regarding that group of recommendations.
Management of Depression and Related Neuropsychiatric Symptoms Associated with HIV/AIDS and Antiretroviral Therapy
Authors: Halman Mark
Published: May 2016

Persons with HIV/AIDS may experience a wide range of neuropsychiatric symptoms, including depressed mood, anxiety,
irritability, suicidal ideation, agitation and insomnia. These symptoms may be related to psychosocial stressors,
biological diathesis to psychiatric syndromes, HIV‐related medical illness and/or the medications used in the treatment
of HIV/AIDS. Depressed mood is the most common neuropsychiatric complaint in persons with HIV/AIDS seeking
psychiatric evaluation. Prevalence rates of major depression in persons with HIV/AIDS have been reported to
range between 22% and 45%. Despite the high prevalence, major depression remains underdiagnosed in patients with
HIV/AIDS. Depression has a significant impact on quality of life, has a negative impact on antiretroviral adherence
and is a significant risk factor for suicide.
With the advent of highly active antiretroviral therapy, HIV/AIDS has evolved into a chronic, manageable illness.
The management of mental health concerns and neuropsychiatric symptoms has, therefore, become an integral part
of comprehensive HIV/AIDS care. Clinical experience to date suggests that psychiatric syndromes in persons with
HIV/AIDS and treatment‐emergent neuropsychiatric side effects related to antiretroviral medications can be successfully
managed using standard psychiatric interventions. The present article focuses on the treatment and management
of major depression, including the choice of antidepressants and potential drug interaction considerations.
Management of related symptoms of agitation and sleep disturbances are also reviewed.
Development and Evaluation of an Online Fall-Risk Questionnaire for Nonfrail Community-Dwelling Elderly Persons: A Pilot Study
Authors: Obrist Seraina , Rogan Slavko , Hilfiker Roger
Published: May 2016

Introduction. Falls are frequent in older adults and may have serious consequences but awareness of fall-risk is often low. A questionnaire might raise awareness of fall-risk; therefore we set out to construct and test such a questionnaire.Methods. Fall-risk factors and their odds ratios were extracted from meta-analyses and a questionnaire was devised to cover these risk factors. A formula to estimate the probability of future falls was set up using the extracted odds ratios. The understandability of the questionnaire and discrimination and calibration of the prediction formula were tested in a cohort study with a six-month follow-up. Community-dwelling persons over 60 years were recruited by an e-mail snowball-sampling method.Results and Discussion. We included 134 persons. Response rates for the monthly fall-related follow-up varied between the months and ranged from low 38% to high 90%. The proportion of present risk factors was low. Twenty-five participants reported falls. Discrimination was moderate (AUC: 0.67, 95% CI 0.54 to 0.81). The understandability, with the exception of five questions, was good. The wording of the questions needs to be improved and measures to increase the monthly response rates are needed before test-retest reliability and final predictive value can be assessed.
The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat
Authors: Milani D. , Knuckey N. W. , Anderton R. S. , Cross J. L. , Meloni B. P.
Published: May 2016

We examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cerebral artery occlusion (MCAO). The TAT-NR2B9c peptide, which is known to be neuroprotective in rodent and nonhuman primate stroke models, served as a positive control. At 24 hours after MCAO, there was reduced total infarct volume in R18 treated animals at all doses, but this reduction only reached statistical significance at doses of 100 and 1000 nmol/kg. The TAT-NR2B9c peptide reduced infarct volume at doses of 300 and 1000 nmol/kg, but not to a statistically significant extent, while the 100 nmol/kg dose was ineffective. The reduction in infarct volume with R18 and TAT-NR2B9c peptide treatments was mirrored by improvements in one or more functional outcomes (namely, neurological score, adhesive tape removal, and rota-rod), but not to a statistically significant extent. These findings further confirm the neuroprotective properties of polyarginine peptides and for R18 extend its therapeutic time window and dose range, as well as demonstrating its greater efficacy compared to TAT-NR2B9c in a severe stroke model. The superior neuroprotective efficacy of R18 over TAT-NR2B9c highlights the potential of this polyarginine peptide as a lead candidate for studies in human stroke.
Severe Left Ventricular Hypertrophy, Small Pericardial Effusion, and Diffuse Late Gadolinium Enhancement by Cardiac Magnetic Resonance Suspecting Cardiac Amyloidosis: Endomyocardial Biopsy Reveals an Unexpected Diagnosis
Authors: Hofmann Nina P. , Giusca Sorin , Klingel Karin , Nunninger Peter , Korosoglou Grigorios
Published: May 2016

Left ventricular (LV) hypertrophy can be related to a multitude of cardiac disorders, such as hypertrophic cardiomyopathy (HCM), cardiac amyloidosis, and hypertensive heart disease. Although the presence of LV hypertrophy is generally associated with poorer cardiac outcomes, the early differentiation between these pathologies is crucial due to the presence of specific treatment options. The diagnostic process with LV hypertrophy requires the integration of clinical evaluation, electrocardiography (ECG), echocardiography, biochemical markers, and if required CMR and endomyocardial biopsy in order to reach the correct diagnosis. Here, we present a case of a patient with severe LV hypertrophy (septal wall thickness of 23 mm, LV mass of 264 g, and LV mass index of 147 g/m2), severely impaired longitudinal function, and preserved radial contractility (ejection fraction = 55%), accompanied by small pericardial effusion and diffuse late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR). Due to the imaging findings, an infiltrative cardiomyopathy, such as cardiac amyloidosis, was suspected. However, amyloid accumulation was excluded by endomyocardial biopsy, which revealed the presence of diffuse myocardial fibrosis in an advanced hypertensive heart disease.
Extracellular Biofabrication, Characterization, and Antimicrobial Efficacy of Silver Nanoparticles Loaded on Cotton Fabrics Using Newly IsolatedStreptomycessp. SSHH-1E
Authors: El-Naggar Noura El-Ahmady , Mohamedin Attiya , Hamza Sarah Shawqi , Sherief Abdel-Dayem
Published: May 2016

Biological method for silver nanoparticles synthesis has been developed to obtain cost effective, clean, nontoxic, and ecofriendly size-controlled nanoparticles. The objective of this study is extracellular biosynthesis of antimicrobial AgNPs using cell-free supernatant of a localStreptomycessp. strain SSHH-1E. Different medium composition and fermentation conditions were screened for maximal AgNPs biosynthesis using Plackett-Burman experimental design and the variables with statistically significant effects were selected to study their combined effects and to find out the optimum values using a Box-Behnken design. The synthesized AgNPs were characterized using UV-visible spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and energy dispersive X-ray spectroscopy. Rapid biosynthesis of AgNPs was achieved by addition of 1 mM AgNO3solution to the cell-free supernatant. The produced particles showed a single surface plasmon resonance peak at 400 nm by UV-Vis spectroscopy which confirmed the presence of AgNPs.Streptomycessp. SSHH-1E was identified asStreptomyces narbonensisSSHH-1E. Transmission electron microscopy study indicated that the shape of AgNPs is spherical and the size is ranging from 20 to 40 nm. Fourier transform infrared spectroscopy analysis provides evidence for proteins as possible reducing and capping agents. Furthermore, the biosynthesized AgNPs significantly inhibited the growth of medically important pathogenic Gram-positive and Gram-negative bacteria and yeast. The maximum biosynthesis of AgNPs was achieved at initial pH of 8, peptone of 0.5 g, and inoculum age of 48 h. The statistical optimization resulted in a 4.5-fold increase in the production of AgNPs byStreptomyces narbonensisSSHH-1E.
Study on Synthesis and Antibacterial Properties of Ag NPs/GO Nanocomposites
Authors: Huang Lei , Yang Hongtao , Zhang Yanhua , Xiao Wei
Published: May 2016

Using graphene oxide as substrate and stabilizer for the silver nanoparticles, silver nanoparticles-graphene oxide (Ag NPs/GO) composites with different Ag loading were synthesized through a facile solution-phase method. During the synthesis process, AgNO3on GO matrix was directly reduced by NaBH4. The structure characterization was studied through X-ray diffraction (XRD), atomic force microscopy (AFM), high-resolution transmission electron microscope (HRTEM), ultraviolet-visible spectroscopy (UV-Vis), and selected area electron diffraction (SAED). The results show that Ag nanoparticles (Ag NPs) with the sizes ranging from 5 to 20 nm are highly dispersed on the surfaces of GO sheets. The shape and size of the Ag NPs are decided by the volume of initial AgNO3solution added in the GO. The antibacterial activities of Ag NPs/GO nanocomposites were investigated and the result shows that all the produced composites exhibit good antibacterial activities against Gram-negative (G−) bacterial strainEscherichia coli(E. coli) and Gram-positive (G+) strainStaphylococcus aureus(S. aureus). Moreover, the antibacterial activities of Ag NPs/GO nanocomposites gradually increased with the increasing of volume of initial AgNO3solution added in the GO and this improvement of the antibacterial activities results from the combined action of size effect and concentration effect of Ag NPs in Ag NPs/GO nanocomposites.
Impacted and Fractured Biliary Basket: A Second Basket Rescue Technique
Authors: Benatta Mohammed Amine , Desjeux Ariane , Barthet Marc , Grimaud Jean Charles , Gasmi Mohamed
Published: May 2016

A 59-year-old woman was treated with ERCP, ES, and biliary plastic stent, for large and multiple common bile duct stones. During a second ERCP basket extraction was impacted with a round entrapped stone. The basket handle was cut off; a metal sheath of extraendoscopic lithotriptor was advanced over the basket. The mechanical lithotripsy was complicated with basket traction wires fracturing, without breakage of the stone. A rescue standard basket was pushed until it caught the basket/stone complex. Using this method disengagement of the whole fractured basket/stone complex was achieved without need of surgery. It is the third case reported in the English literature.
Age-Dependent Switch of the Role of Serotonergic 5-HT1AReceptors in Gating Long-Term Potentiation in Rat Visual CortexIn Vivo
Authors: Gagolewicz Peter J. , Dringenberg Hans C.
Published: May 2016

The rodent primary visual cortex (V1) is densely innervated by serotonergic axons and previousin vitrowork has shown that serotonin (5-HT) can modulate plasticity (e.g., long-term potentiation (LTP)) at V1 synapses. However, little work has examined the effects of 5-HT on LTP underin vivoconditions. We examined the role of 5-HT on LTP in V1 elicited by theta burst stimulation (TBS) of the lateral geniculate nucleus in urethane-anesthetized (adult and juvenile) rats. Thalamic TBS consistently induced potentiation of field postsynaptic potentials (fPSPs) recorded in V1. While 5-HT application (0.1–10 mM) itself did not alter LTP levels, the broad-acting 5-HT receptor antagonists methiothepin (1 mM) resulted in a clear facilitation of LTP in adult animals, an effect that was mimicked by the selective 5-HT1Areceptor antagonist WAY 100635 (1 mM). Interestingly, in juvenile rats, WAY 100635 application inhibited LTP, indicative of an age-dependent switch in the role of 5-HT1Areceptors in gating V1 plasticity. Analyses of spontaneous electrocorticographic (ECoG) activity in V1 indicated that the antagonist-induced LTP enhancement was not related to systematic changes in oscillatory activity in V1. Together, these data suggest a facilitating role of 5-HT1Areceptor activation on LTP in the juvenile V1, which switches to a tonic, inhibitory influence in adulthood.
Anti‐Inflammatory Effects of Pomegranate Peel Extract in THP‐1 Cells Exposed to Particulate Matter PM10
Authors: Park Soojin , Seok Jin Kyung , Kwak Jun Yup , Suh Hwa-Jin , Kim Young Mi , Boo Yong Chool
Published: May 2016

Epidemiological and experimental evidence support health risks associated with the exposure to airborne particulate matter with a diameter of <10 μM (PM10). PM10 stimulates the production of reactive oxygen species (ROS) and inflammatory mediators. Thus, we assumed that natural antioxidants might provide health benefits attenuating hazardous effects of PM10. In the present study, we examined the effects of pomegranate peel extract (PPE) on THP‐1 monocytic cells exposed to PM10. PM10 induced cytotoxicity and the production of ROS. It also increased the expression and secretion of inflammatory cytokines, such as tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and monocyte chemoattractant protein‐1 (MCP‐1), and cell adhesion molecules, such as intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1). PPE at 10–100 μg mL−1 attenuated the production of ROS and the expression of TNF‐α, IL‐1β, MCP‐1, and ICAM‐1, but not VCAM‐1, in THP‐1 cells stimulated by PM10 (100 μg mL−1). PPE also attenuated the adhesion of PM10‐stimulated THP‐1 cells to EA.hy926 endothelial cells. PPE constituents, punicalagin and ellagic acid, attenuated PM10‐induced monocyte adhesion to endothelial cells, and punicalagin was less cytotoxic compared to ellagic acid. The present study suggests that PPE and punicalagin may be useful in alleviating inflammatory reactions due to particulate matter.
Differential Expression of Inflammation-Related Genes in Children with Down Syndrome
Authors: Silva Cláudia Regina Santos , Biselli-Périco Joice Matos , Zampieri Bruna Lancia , Silva Wilson Araujo , de Souza Jorge Estefano Santana , Bürger Matheus Carvalho , Goloni-Bertollo Eny Maria , Pavarino Érika Cristina
Published: May 2016

Objective. The aim of the study was to investigate the expression patterns of a specific set of genes involved in the inflammation process in children with Down Syndrome (DS) and children without the syndrome (control group) to identify differences that may be related to the immune abnormalities observed in DS individuals.Method. RNA samples were obtained from peripheral blood, and gene expression was quantified using the TaqMan® Array Plate Human Inflammation Kit, which facilitated the investigation into 92 inflammation-related genes and four reference genes using real-time polymerase chain reaction (qPCR).Results. Twenty genes showed differential expression in children with DS; 12 were overexpressed (PLA2G2D,CACNA1D,ALOX12,VCAM1,ICAM1,PLCD1,ADRB1,HTR3A,PDE4C,CASP1,PLA2G5,andPLCB4), and eight were underexpressed (LTA4H,BDKRB1,ADRB2,CD40LG,ITGAM,TNFRSF1B,ITGB1,andTBXAS1). After statistically correcting for the false discovery rate, only the genesBDKRB1andLTA4Hshowed differential expression, and both were underexpressed within the DS group.Conclusion. DS children showed differential expression of inflammation-related genes that were not located on chromosome 21 compared with children without DS. TheBDKRB1andLTA4Hgenes may differentiate the case and control groups based on the inflammatory response, which plays an important role in DS pathogenesis.
Barium Titanate Nanoparticles Formed by Chlorine-Free Ambient Condition Sol Process Using Tetrabutylammonium Hydroxide
Authors: Han Wooje , Yoo Byungwook , Park Hyung-Ho
Published: May 2016

Barium titanate (BaTiO3: BTO) nanoparticles (NPs) were synthesized by chlorine-free ambient condition sol (ACS) process using heat reflux at low temperature of 90°C. The size distribution and morphology of BTO NPs were investigated by varying the concentration of tetrabutylammonium hydroxide (TBAH). The crystalline size of BTO NPs was decreased with increasing the amount of TBAH capping agent (average size changes from 54.3 to 38.7 nm for 0 to 0.5 M TBAH in X-ray diffraction measurement). The particle size of BTO NPs was principally controlled by a synthetic control of butyl chain of TBAH and also a steric effect of excess amount of TBAH. The dielectric constant of BTO NPs was decreased from 152 to 144 at 1 MHz after an adoption of TBAH capping agent with almost uniform dielectric loss (<0.027). But the dielectric constant of BTO NPs synthesized with various molar ratio of TBAH (0.1, 0.3, and 0.5) did not show a distinguished decrease. At the particle size range in this experiment, the dielectric behavior of BTO NPs was found to be mainly dependent on the TBAH ligands at BTO NPs formed during capping process, not on the size of BTO NPs.
DPFFs:C2MOSDirect Path Flip-Flops for Process-Resilient Ultradynamic Voltage Scaling
Authors: Hwang Myeong-Eun , Kwon Sungoh
Published: May 2016

We propose two master-slave flip-flops (FFs) that utilize the clocked CMOS (C2MOS) technique with an internal direct connection along the main signal propagation path between the master and slave latches and adopt an adaptive body bias technique to improve circuit robustness.C2MOSstructure improves the setup margin and robustness while providing full compatibility with the standard cell characterization flow. Further, the direct path shortens the logic depth and thus speeds up signal propagation, which can be optimized for less power and smaller area. Measurements from test circuits fabricated in 130 nm technology show that the proposed FF operates down to 60 mV, consuming 24.7 pW while improving the propagation delay, dynamic power, and leakage by 22%, 9%, and 13%, respectively, compared with conventional FFs at the iso-output-load condition. The proposed FFs are integrated into an8×8FIR filter which successfully operates all the way down to 85 mV.
Green Synthesis of Silver Nanoparticles and Their Bactericidal and Antimycotic Activities against Oral Microbes
Authors: Rodríguez-Luis Osvelia E. , Hernandez-Delgadillo Rene , Sánchez-Nájera Rosa Isela , Martínez-Castañón Gabriel Alejandro , Niño-Martínez Nereyda , Sánchez Navarro María del Carmen , Ruiz Facundo , Cabral-Romero Claudio
Published: May 2016

Nanotechnology is a new discipline with huge applications including medicine and pharmacology industries. Although several methods and reducing agents have been employed to synthesize silver nanoparticles, reactive chemicals promote toxicity and nondesired effects on the human and biological systems. The objective of this work was to synthesize silver nanoparticles fromGlycyrrhiza glabraandAmphipterygium adstringensextracts and determine their bactericidal and antimycotic activities againstEnterococcus faecalisandCandida albicansgrowth, respectively. 1 and 10 mM silver nitrate were mixed with an extract ofGlycyrrhiza glabraandAmphipterygium adstringens.Green silver nanoparticles (AgNPs) were characterized by TEM, Vis-NIR, FTIR, fluorescence, DLS, TGA, and X-ray diffraction (XRD) analysis. Bactericidal and antimycotic activities of AgNPs were determined by Kirby and Bauer method and cell viability MTT assays. AgNPs showed a spherical shape and average size of 9 nm if prepared withGlycyrrhiza glabraextract and 3 nm if prepared withAmphipterygium adstringensextract. AgNPs inhibited the bacterial and fungal growth as was expected, without a significant cytotoxic effect on human epithelial cells. Altogether, these results strongly suggest that AgNPs could be an interesting option to control oral biofilms.
Cardiac Function and Diastolic Dysfunction in Behcet’s Disease: A Systematic Review and Meta-Analysis
Authors: Aslam Fawad , Bandeali Salman J. , Crowson Cynthia , Alam Mahboob
Published: May 2016

Background. Cardiovascular involvement in Behcet’s disease (BD) is reported and has variable manifestations. It is not clear if diastolic dysfunction (DD) is increased in BD. Our objective was to evaluate the existing literature to determine if cardiac dysfunction, particularly DD, was more prevalent in these patients.Methods. A systematic review and meta-analysis of the available studies analyzing the echocardiographic findings in BD was conducted using a random-effects model. Mean differences were used to calculate the effect sizes of the echocardiographic parameters of interest.Results. A total of 22 studies with 1624 subjects were included in the analysis. Patients with BD had statistically significantly larger mean left atrial dimension (0.08,p=0.0008), greater aortic diameter (0.16,p=0.02), significantly reduced ejection fraction (−1.08,p<0.0001), significantly prolonged mitral deceleration time (14.20,p<0.0001), lowerE/Aratio (−0.24,p=0.05), and increased isovolumetric relaxation time (7.29,p<0.00001).Conclusion.DD is increased in patients with BD by the presence of several echocardiographic parameters favoring DD as compared to controls. The meta-analysis also identified that LA dimension is increased in BD patients. EF has also been found to be lower in BD patients. Aortic diameter was also increased in BD patients as compared to controls.
Prognostic Value of Programmed Death Ligand 1 and Programmed Death 1 Expression in Thymic Carcinoma
Authors: Yokoyama Shintaro , Miyoshi Hiroaki , Nakashima Kazutaka , Shimono Joji , Hashiguchi Toshihiro , Mitsuoka Masahiro , Takamori Shinzo , Akagi Yoshito , Ohshima Koichi
Published: May 2016

Purpose: The immune checkpoint of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is believed to play an important role in evasion of host antitumor immune surveillance in various malignancies; however, little is known about its role in thymic carcinoma. This study investigated PD-1/PD-L1 expression and its association with clinicopathologic features, the expression of immune-related proteins in tumor-infiltrating lymphocytes (TIL), and patient prognosis.

Experimental Design: PD-L1 and PD-1 expression was evaluated by IHC in 25 thymic carcinoma tissue specimens. Copy number alterations of the PD-L1 gene in 11 cases were assessed in formalin-fixed, paraffin-embedded material using qRT-PCR.

Results: Compared with normal subjects, 3 thymic carcinoma patients showed an increase in PD-L1 copy number, whereas 8 did not. PD-L1 was significantly overexpressed in cases with copy number gain as compared with normal cases. High PD-L1 expression was associated with higher disease-free and overall survival rates as compared to cases with low expression. Prognostic analysis revealed low PD-L1 expression and high number of PD-1+ TILs as significant predictors of poor survival, together with Masaoka–Koga stage IVa/IVb disease and incomplete resection. In the quantitative analysis of TILs, PD-L1 expression correlated proportionally with the number of infiltrating CTLs.

Conclusions: Here, for the first time, we report that PD-L1 and PD-1 expression might be useful prognostic predictors in thymic carcinoma. Further studies are expected to substantiate the prognostic value of PD-L1 and PD-1 expression, and the potential efficacy of targeting the PD-1/PD-L1 pathway in thymic carcinoma via immunotherapy. Clin Cancer Res; 22(18); 4727–34. ©2016 AACR.
Orange/Red Fluorescence of Active Caries by Retrospective Quantitative Light-Induced Fluorescence Image Analysis
Authors: Felix Gomez Grace , Eckert George J. , Ferreira Zandona Andrea
Published: May 2016

This retrospective clinical study determined the association of caries activity and orange/red fluorescence on quantitative light-induced fluorescence (QLF) images of surfaces that progressed to cavitation, as determined by clinical visual examination. A random sample of QLF images from 565 children (5-13 years) previously enrolled in a longitudinal study was selected. Buccal, lingual and occlusal surface images obtained after professional brushing at baseline and every 4 months over a 4-year period were analyzed for red fluorescence. Surfaces that progressed (n = 224) to cavitation according to the International Caries Detection and Assessment System (ICDAS 0/1/2/3/4 to 5/6 or filling), and surfaces that did not progress (n = 486) were included. QA2 image analysis software outputs the percentage increase of the red/green components as ΔR and area of ΔR (areaΔR) at different thresholds. Mixed-model ANOVA was used to compare progressive and nonprogressive surfaces to account for correlations of red fluorescence (ΔR and areaΔR) between surfaces within a subject. The first analysis used the first observation for each surface or the first available visit if the surface was unerupted (baseline), while the second analysis used the last observation prior to cavitation for surfaces that progressed and the last observation for surfaces that did not progress (final). There was a significant (p < 0.05) association between red fluorescence and progression to cavitation at thresholds ΔR0, ΔR10, ΔR20, ΔR60, ΔR70, ΔR80, ΔR90 and ΔRmax at baseline and for ΔR0 and ΔR10 at the final observation. Quantification of orange/red fluorescence may help to identify lesions that progress to cavitation. Future studies identifying microbiological factors causing orange/ red fluorescence and its caries activity are indicated.
Feasibility and Safety of Transhiatal Approach and D2 Total Gastrectomy after Neoadjuvant Chemotherapy for Adenocarcinoma of the Esophago-Gastric Junction: A Subset Analysis of the COMPASS Trial
Authors: Yoshikawa Takaki , Aoyama Toru , Tanabe Kazuaki , Nishikawa Kazuhiro , Ito Yuichi , Hayashi Tsutomu , Cho Haruhiko , Miyashita Yumi , Tsuburaya Akira , Sakamoto Junichi
Published: May 2016

Background: It was unclear whether the transhiatal approach and D2 total gastrectomy after neoadjuvant chemotherapy (NAC) for adenocarcinoma of the esophago-gastric (AEG) junction are as feasible and safe as D2 gastrectomy following NAC. Patients and Methods: We clarified the short-term surgical results in AEG and non-AEG patients in a subset analysis of the COMPASS trial. Results: Eighty-three patients, 24 with AEG and 59 with non-AEG, were registered in the study. Among 24 patients with AEG, 5 were classified to have Siewert type I, 11 to have type II and 8 to have type III. The tumor progression, completion of NAC, and clinical and pathological responses were similar between the groups. Twenty-four AEG and 51 non-AEG patients proceeded to surgery. The extent of dissection (D1/D2) was 3/21 in the AEG and 3/48 in the non-AEG patients. The R0 resection rate was 69% in the non-AEG and 88% in the AEG patients. Neither grade 3b/4 morbidity nor surgical mortality was observed in either group. Conclusions: The transhiatal approach and D2 total gastrectomy after NAC seem to be as safe and feasible as D2 gastrectomy for non-AEG cancer.
Hepatitis E Virus: Time to Change the Textbooks
Authors: Dalton Harry R. , Webb Glynn W. , Norton Ben C. , Woolson Kathy L.
Published: May 2016

Until recently, hepatitis E virus (HEV) was thought not to occur in developed countries. It is now clear that locally acquired HEV is common in such settings. HEV infection acquired in these areas differs from that in developing countries in a number of important aspects: it is caused by genotype 3 (and 4 in China and Japan), it mainly affects middle-aged/elderly males and it is zoonotic with a porcine primary host. Pig herds worldwide are infected with HEV genotype 3 and HEV has been found in the human food chain in a number of developed countries. However, the route of transmission is not fully understood, since most cases are not obviously associated with pigs/pig products. HEV can be transmitted by blood transfusion and surprisingly high numbers of asymptomatic blood donors are viremic at the time of donation: Germany 1:1,200, Netherlands 1:2,671, England 1:2,848. Our understanding of the clinical phenotype of HEV infection in humans has undergone a sea-change in recent years. Previously, HEV was thought to cause only acute self-limiting hepatitis. However, HEV may cause persistent disease in the immunocompromised. Patients with chronic HEV infection have no symptoms, but some develop rapidly progressive liver cirrhosis. The full clinical spectrum of HEV is still emerging. HEV has important extra-hepatic manifestations, which deserve further investigation. For example, HEV can cause a wide range of neurological illness. In particular, very recent data suggest that Guillain-Barré syndrome and neuralgic amyotrophy are associated with locally acquired HEV in approximately 5 and 10% of the cases, respectively.
Challenges in Special Populations: HIV/HCV Coinfection, Liver Transplantation and Patients with End-Stage Renal Disease
Authors: Bonacci Martín , Lens Sabela , Mariño Zoe , Forns Xavier
Published: May 2016

Until recently, the combination of PEG-interferon and ribavirin (RBV) was the main treatment for all genotypes of chronic hepatitis C virus (HCV) infection. Sustained virological response (SVR) rates varied signiﬁcantly across patient subgroups and the concept of ‘special populations' emerged. Now, in the era of direct acting antivirals, with a better safety profile and higher efficacy rates, those patients with comorbidities or conditions that limited IFN-based antiviral treatment but with unmet medical needs have been considered for therapy again. With the currently approved all-oral antivirals, patients coinfected with human immunodeficiency virus and HCV have SVR rates similar to patients with HCV monoinfection. However, drug-drug interactions (DDIs) with antiretroviral drugs are still challenging. In the setting of liver transplantation, with an accelerated course of hepatitis C, previous IFN-RBV treatments were poorly tolerated and attained low SVR rates. Today, all-oral therapies have proven to be efficacious and safe in this population. Nevertheless, questions such as the optimal treatment duration or the need for RBV still remain opened. In this population as well, DDIs are an issue, as some regimens require adjustments and monitoring of immunosuppressive drugs during therapy. Finally, preliminary data show promising results in terms of efficacy and safety in patients with end-stage renal disease. However, there is clear need for more clinical studies since treatment options are still very limited.
Non-Alcoholic Steatohepatitis: From Pathophysiology to Novel Therapies
Authors: Jahn Daniel , Rau Monika , Wohlfahrt Julia , Hermanns Heike M. , Geier Andreas
Published: May 2016

Non-alcoholic fatty liver (NAFL) disease is defined by an accumulation of liver fat exceeding 5% of its weight in the absence of significant alcoholic intake. In 5-20%, there is a progression from NAFL to non-alcoholic steatohepatitis (NASH). Until now, it is not well understood why only some patients develop NASH, and currently, no drugs are licensed for this indication. Different T-cell populations such as T-regulatory, Th1 and Th17 cells play a central role in the immunopathogenesis of fatty liver disease and open the option of future interleukin (IL)-17-based therapeutics. The inflammatory process underlying NASH is furthermore characterized by elevated expression of pro-inflammatory cytokines such as TNFα and IL-1β. Anakinra, a recombinant version of IL-1Ra shows promising metabolic effects with improved hyperglycemia and beta-cell secretory function in a double-blind placebo controlled randomized trial in type 2 diabetic patients but such studies are still in their preliminary stages for NASH. Several studies point out that bile acid farnesoid X receptor (FXR)-mediated signals (such as the enterohepatic hormone fibroblast growth factor 15/19) are involved in the regulation of triglyceride and glucose metabolism. Recent clinical trials have revealed a beneficial impact of the FXR agonist obeticholic acid on body weight, insulin sensitivity and liver histology in patients with NASH. Further potential novel therapeutic targets in NASH are currently in phase II clinical development.
Guide and Position of the International Society of Nutrigenetics/Nutrigenomics on Personalised Nutrition: Part 1 - Fields of Precision Nutrition
Authors: Ferguson Lynnette R. , De Caterina Raffaele , Görman Ulf , Allayee Hooman , Kohlmeier Martin , Prasad Chandan , Choi Myung Sook , Curi Rui , de Luis Daniel Antonio , Gil Ángel , Kang Jing X. , Martin Ron L. , Milagro Fermin I. , Nicoletti Carolina Ferreira , Nonino Carla Barbosa , Ordovas Jose Maria , Parslow Virginia R. , Portillo María P. , Santos José Luis , Serhan Charles N. , Simopoulos Artemis P. , Velázquez-Arellano Antonio , Zulet Maria Angeles , Martinez J. Alfredo
Published: May 2016

Diversity in the genetic profile between individuals and specific ethnic groups affects nutrient requirements, metabolism and response to nutritional and dietary interventions. Indeed, individuals respond differently to lifestyle interventions (diet, physical activity, smoking, etc.). The sequencing of the human genome and subsequent increased knowledge regarding human genetic variation is contributing to the emergence of personalized nutrition. These advances in genetic science are raising numerous questions regarding the mode that precision nutrition can contribute solutions to emerging problems in public health, by reducing the risk and prevalence of nutrition-related diseases. Current views on personalized nutrition encompass omics technologies (nutrigenomics, transcriptomics, epigenomics, foodomics, metabolomics, metagenomics, etc.), functional food development and challenges related to legal and ethical aspects, application in clinical practice, and population scope, in terms of guidelines and epidemiological factors. In this context, precision nutrition can be considered as occurring at three levels: (1) conventional nutrition based on general guidelines for population groups by age, gender and social determinants; (2) individualized nutrition that adds phenotypic information about the person's current nutritional status (e.g. anthropometry, biochemical and metabolic analysis, physical activity, among others), and (3) genotype-directed nutrition based on rare or common gene variation. Research and appropriate translation into medical practice and dietary recommendations must be based on a solid foundation of knowledge derived from studies on nutrigenetics and nutrigenomics. A scientific society, such as the International Society of Nutrigenetics/Nutrigenomics (ISNN), internationally devoted to the study of nutrigenetics/nutrigenomics, can indeed serve the commendable roles of (1) promoting science and favoring scientific communication and (2) permanently working as a ‘clearing house' to prevent disqualifying logical jumps, correct or stop unwarranted claims, and prevent the creation of unwarranted expectations in patients and in the general public. In this statement, we are focusing on the scientific aspects of disciplines covering nutrigenetics and nutrigenomics issues. Genetic screening and the ethical, legal, social and economic aspects will be dealt with in subsequent statements of the Society.
Alpha-1 Antitrypsin Deficiency Today: New Insights in the Immunological Pathways
Authors: Baraldo Simonetta , Balestro Elisabetta , Bazzan Erica , Tiné Maria Enrica , Biondini Davide , Turato Graziella , Cosio Manuel G. , Saetta Marina
Published: May 2016

More than 50 years ago, the observation that absence of the α1 band from protein electrophoresis is associated with severe emphysema established the link between α1-antitrypsin deficiency (AATD) and lung damage. From this discovery, the classic paradigm of protease/antiprotease imbalance was derived, linking lung destruction in patients with AATD to the unopposed effect of proteases. By extension, this paradigm was also applied to patients with ‘common' chronic obstructive pulmonary disease, in whom large increases in smoke-induced proteases could overwhelm the antiprotease capability of AAT. However, it has become increasingly evident that AAT has important anti-inflammatory and immunoregulatory activities which, beside its antiprotease function, may be critically involved in lung destruction. From this perspective, we will consider recent evidence, based on epidemiological, clinical and immunopathological studies, suggesting that it is time to move on from the original protease/antiprotease paradigm toward a more complex view of the condition, which embraces its immunomodulating functions. Of importance, the potent immunoregulatory, tolerogenic role of AAT may support its therapeutic use in a number of diseases other than AATD, particularly in immune-related disorders.
Calcium and Magnesium Infusions for the Prevention of Oxaliplatin-Induced Peripheral Neurotoxicity: A Systematic Review
Authors: Jordan Berit , Jahn Franziska , Beckmann Juliane , Unverzagt Susanne , Müller-Tidow Carsten , Jordan Karin
Published: May 2016

Objectives: The objective of this systematic review was to summarize the evidence of calcium and magnesium (CaMg) infusions in the prevention of oxaliplatin-induced neuropathy on the basis of prospective randomized controlled trials (RCTs). Methods: A systematic search included MEDLINE and CENTRAL, plus major oncology conferences, and identified RCTs evaluating CaMg. Efficacy endpoints were chronic neurotoxicity measured with National Cancer Institute Common Terminology Criteria for Adverse Events grades and the oxaliplatin-specific scale (OSS). Data were synthesized using a random effects model. Results: A total of 5 trials with 694 evaluable patients were included in this analysis. The pooled result stated the outcome of the largest study included [Loprinzi et al.: J Clin Oncol 2014;32:997-1005], in which no differences were detected for the incidence of grade ≥2 neuropathy between those receiving CaMg infusions and controls [relative risk (RR) 0.81, 95% confidence interval (CI) 0.60-1.11]. Only 2 studies (n = 52) quoted an incidence of chronic neurotoxicity for all grades (with a pooled RR of 0.95 and 95% CI 0.69-1.32), with substantial statistical heterogeneity. Three studies reported an actual incidence of the OSS but, due to the detected substantial statistical heterogeneity, the studies were not pooled. Conclusion: The results of our systematic review demonstrated the nonbeneficial effect of CaMg infusions for the prevention of oxaliplatin-induced peripheral neuropathy.
A Case of a Newborn with Agenesis of the Corpus Callosum Complicated with Ocular Albinism
Authors: Miki Michiko , Miyamoto Makiko , Mitsutsuji Tatsuma , Watanabe Hiroko , Shimizu Kazuhiro , Matsuo Junko , Tonari Masahiro , Kida Teruyo , Sugasawa Jun , Ikeda Tsunehiko
Published: May 2016

Purpose: To report a case of ocular albinism found in a newborn infant in whom agenesis of the corpus callosum (ACC) was indicated in utero. Case Report: This study involved a female newborn who was delivered after a gestational period of 41 weeks. The patient was referred to the Obstetrics Department at Takatsuki Hospital, Takatsuki City, Japan, after the indication of ACC by magnetic resonance imaging (MRI) at a nearby clinic during the fetal period. At birth, the baby’s weight was 2,590 g, and ACC and ventricular enlargement were found by cranial sonography and cranial MRI. While initial ophthalmic findings noted partial loss of pigmentation of the iris and hypopigmentation of broad areas of the fundus in both eyes, nystagmus was not observed. The patient’s hair pigment was slightly diluted, and the color of her skin was slightly off-white. At 2 years after birth, obvious mental retardation was observed. With regard to other systemic findings, no apparent heart, kidney, or immune system abnormalities were found. Conclusion: Although the patient in question is presently growing without any major systemic problems, it will be necessary in the future to pay attention to any changes in systemic and ophthalmic findings.
М’ЯЗОВИЙ ДИСБАЛАНС У ДИТЯЧОМУ ВІЦІ
Authors: Andriyuk L. V.
Published: May 2016

РЕЗЮМЕ. Мануальна терапія є одним з адекватних немедикаментозних методів лікувально-реабілітаційної дії,
спрямованої на усунення характерних для сколіозу у дітей патобіомеханічних проявів, на розвиток компенсаторних
саногенетичних механізмів і корекцію рухового стереотипу при його неоптимальності і постуральному дисбалансі
м’язів. Цілеспрямоване і обгрунтоване застосування прийомів мануальної терапії і коригуючої гімнастики сприяє
ефективності лікування і підвищує рівень реабілітації при сколіозах у дітей.

КЛЮЧОВІ СЛОВА: сколіоз, порушення постави, діагностика, мануальна терапія.
Áreas sociais – uma avaliação e perspectivas
Authors: Corrêa Roberto Lobato
Published: May 2016

O espaço social pode ser analisado segundo várias abordagens distintas entre si no que diz respeito à matriz teórica adotada e aos indicadores dela derivados. Este texto considera o espaço social segundo as proposições da “análise de áreas sociais”. A adoção dessa abordagem deriva das possibilidades que oferece na identificação de áreas relativamente uniformes no espaço urbano, centradas em aspectos sociais interligados tanto no plano conceitual como operacional. A análise de áreas sociais permite, por outro lado, identificar diferentes tipos de cidades a partir de suas configurações espaciais.
A ilha de calor urbana e o uso e cobertura do solo no município de São Paulo-SP
Authors: Barros Hugo Rogério , Lombardo Magda Adelaide
Published: May 2016

O vigente trabalho visou avaliar e apresentar a relação espacial entre os distintos padrões de uso e cobertura do solo e suas respostas térmicas, a fim de compreender a conformação espacial do fenômeno da Ilha de Calor Urbana no território do municipio de São Paulo-SP. Para tal, foram utilizadas as análises descritiva, comparativa seguidas da integrada descritiva. As variáveis testadas na análise espacial foram o índice de área foliar, a temperatura da superfície, uso do solo além da classificação térmica da ilha de calor urbana. Foi verificado que os ambientes com ausência de vegetação, principalmente nos espaços ocupados por atividades industriais e de comércio e serviços apresentaram forte intensidade do fenômeno, com diferenças de temperaturas superiores a 8°C. Desta forma contatamos a importância do arboreto urbano e áreas verdes para a qualidade ambiental térmica dos espaços urbanos do município de São Paulo.
Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation
Authors: Sirish Padmini , Li Ning , Timofeyev Valeriy , Zhang Xiao-Dong , Wang Lianguo , Yang Jun , Lee Kin Sing Stephen , Bettaieb Ahmed , Ma Sin Mei , Lee Jeong Han , Su Demetria , Lau Victor C. , Myers Richard E. , Lieu Deborah K. , López Javier E. , Young J. Nilas , Yamoah Ebenezer N. , Haj Fawaz , Ripplinger Crystal M. , Hammock Bruce D. , Chiamvimonvat Nipavan
Published: May 2016

Background—

Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the soluble epoxide hydrolase enzyme can result in an increase in the levels of epoxyeicosatrienoic acids, leading to the attenuation of atrial structural and electric remodeling and the prevention of atrial fibrillation.

Methods and Results—

For the first time, we report findings that inhibition of soluble epoxide hydrolase reduces inflammation, oxidative stress, atrial structural, and electric remodeling. Treatment with soluble epoxide hydrolase inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor κ-light-chain-enhancer, mitogen-activated protein kinase, and transforming growth factor-β.

Conclusions—

This study provides insights into the underlying molecular mechanisms leading to atrial fibrillation by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in atrial fibrillation.