Genetic Association of HLA Gene Variants with MRI Brain Structure in Alzheimer's Disease.

Abstract: There is accumulating evidence that the human leukocyte antigen (HLA) gene variants are associated with Alzheimer's disease (AD). However, how they affect AD occurrence is still unknown. In this study, we firstly investigated the association of gene variants in HLA gene variants and brain structures on MRI in a large sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to explore the effects of HLA on AD pathogenesis. We selected hippocampus, hippocampus CA1 subregion, parahippocampus, posterior cingulate, precuneus, middle temporal, entorhinal cortex, and amygdala as regions of interest (ROIs). According to the previous association studies of HLA variants and AD, 12 SNPs in HLA were identified in the dataset following quality control measures. In total group analysis, our results showed that TNF-α SNPs at rs2534672 and rs2395488 were significantly positively associated with the volume of the left middle temporal lobe (rs2534672: P = 0.00035, Pc = 0.004; rs2395488: P = 0.0038, Pc = 0.023) at baseline. In the longitudinal study, HFE rs1800562 was remarkably correlated with the lower atrophy rate of right middle temporal lobe (P = 0.0003, Pc = 0.003) and RAGE rs2070600 was associated with the atrophy rate of right hippocampus substructure-CA1 over 2 years (P = 0.003, Pc = 0.035). Furthermore, we detected the above four associations in mild cognitive impairment (MCI) subgroup analysis, as well as the association of rs2534672 with the baseline volume of the left middle temporal lobe in normal cognition (NC) subgroup analysis. Our study provided preliminary evidences that HLA gene variants might participate in the structural alteration of AD associated brain regions, hence modulating the susceptibility of AD.

Wang|Zi-Xuan|ZX| Wan|Yu|Y| Tan|Lin|L| Liu|Jinyuan|J| Wang|Hui-Fu|HF| Sun|Fu-Rong|FR| Tan|Meng-Shan|MS| Tan|Chen-Chen|CC| Jiang|Teng|T| Tan|Lan|L| Yu|Jin-Tai|JT| |||

Genetics
HLA
Brain structure
Neuroimaging
Alzheimer’s disease


Using a staircase procedure for the objective measurement of auditory stream integration and segregation thresholds.

Abstract: Auditory scene analysis describes the ability to segregate relevant sounds out from the environment and to integrate them into a single sound stream using the characteristics of the sounds to determine whether or not they are related. This study aims to contrast task performances in objective threshold measurements of segregation and integration using identical stimuli, manipulating two variables known to influence streaming, inter-stimulus-interval (ISI) and frequency difference (Δf). For each measurement, one parameter (either ISI or Δf) was held constant while the other was altered in a staircase procedure. By using this paradigm, it is possible to test within-subject across multiple conditions, covering a wide Δf and ISI range in one testing session. The objective tasks were based on across-stream temporal judgments (facilitated by integration) and within-stream deviance detection (facilitated by segregation). Results show the objective integration task is well suited for combination with the staircase procedure, as it yields consistent threshold measurements for separate variations of ISI and Δf, as well as being significantly related to the subjective thresholds. The objective segregation task appears less suited to the staircase procedure. With the integration-based staircase paradigm, a comprehensive assessment of streaming thresholds can be obtained in a relatively short space of time. This permits efficient threshold measurements particularly in groups for which there is little prior knowledge on the relevant parameter space for streaming perception.

Spielmann|Mona|M|
Schröger|Erich|E|
Kotz|Sonja A|SA|
Pechmann|Thomas|T|
Bendixen|Alexandra|A|

auditory streams
streaming
auditory scene analysis
threshold measurement
adaptive method
perceptual grouping
psychophysics


Assessment of left sided filling dynamics in diastolic dysfunction using cardiac computed tomography.

Abstract:
BACKGROUND
Left ventricular (LV) diastolic dysfunction (DD) often accompanies coronary artery disease but is difficult to assess since it involves a complex interaction between LV filling and left atrial (LA) emptying.

OBJECTIVE
To characterize simultaneous changes in LA and LV volumes using cardiac computed tomography (CT) in a group of patients with various grades of DD based on echocardiography.

METHODS
We identified 35 patients with DD by echocardiography, who had also undergone cardiac CT, and 35 age-matched normal controls. LV and LA volumes were measured every 10% of the RR interval, using semi-automatic software. From these, - systolic, early-diastolic and late-diastolic volume changes were calculated, and additional parameters of diastolic filling derived. Conduit volume was defined as the difference between the LV and LA early-diastolic volume change.

RESULTS
Patients with DD had significantly larger LV mass, and LA volumes, reduced early emptying volumes and increased conduit volume as percent of early LV filling (All p<0.001). LA function, manifesting as total emptying fraction (LATEF), decreased proportionately with worsening grades of DD (p<0.001). LA contractile function was maintained until advanced grade-3 DD. By receiver operating characteristic analysis, LATEF had an AUC of 0.88 to separate between normals and DD. At a threshold of <42.5%, LATEF has 97% sensitivity and 69% specificity to detect DD.

CONCLUSIONS
DD is characterized by reduced LA function and an alteration in the relative contributions of the atrial emptying and conduit volume components of early LV filling. In patients undergoing cardiac CT, it is possible to identify the presence and severity of DD.

Schweitzer|Ariel|A|
Agmon|Yoram|Y|
Aronson|Doron|D|
Abadi|Sobhi|S|
Mutlak|Diab|D|
Carasso|Shemy|S|
Walker|Jonathan R|JR|
Lessick|Jonathan|J|

Conduit volume
Atrial function
Atrial volume
Coronary CT angiography
Heart failure
Left ventricular mass


Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis.

Abstract: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.

Biomarkers
Mesothelioma
Angiogenesis
BDNF
Pleural effusions


Emerging Insights into the Roles of the Paf1 Complex in Gene Regulation.

Abstract: The conserved, multifunctional Polymerase-Associated Factor 1 complex (Paf1C) regulates all stages of the RNA polymerase (Pol) II transcription cycle. In this review, we examine a diverse set of recent studies from various organisms that build on foundational studies in budding yeast. These studies identify new roles for Paf1C in the control of gene expression and the regulation of chromatin structure. In exploring these advances, we find that various functions of Paf1C, such as the regulation of promoter-proximal pausing and development in higher eukaryotes, are complex and context dependent. As more becomes known about the role of Paf1C in human disease, interest in the molecular mechanisms underpinning Paf1C function will continue to increase.

Van Oss|S Branden|SB|
Cucinotta|Christine E|CE|
Arndt|Karen M|KM|

D005786:Gene Expression Regulation
D006801:Humans
D009687:Nuclear Proteins
D014157:Transcription Factors

Paf1 complex
RNA polymerase II
histone modifications
transcription elongation


Spatial distribution and risk areas of foot and mouth disease in mainland China.

Abstract: Foot-and-mouth disease (FMD) is a severe infectious disease in animal, which affects regional economies and food security of many countries. A total of 109 FMD outbreaks in China (from 2010 to 2019) were assessed. To investigate whether the FMD outbreaks were significantly aggregated in China, spatio-temporal cluster analysis was performed. A MaxEnt model was established to identify high risk areas for FMD in China and to identify relevant risk factors. As a result, both the FMD serotype A and O had one cluster each. Roads density, isothermality, UV-B seasonality and railways density were identified as important factors that affect the occurrence of FMD serotype A. The minimum temperature of the coldest month contributed most to FMD serotype O outbreak, followed by railways density and markets distribution. This study may provide useful information for decision makers for the tailoring of a risk-based surveillance of FMD in China.

Risk areas
Foot-and-mouth disease
Spatio-temporal cluster
MaxEnt


How to calculate sample size in animal studies?

Abstract: Calculation of sample size is one of the important component of design of any research including animal studies. If a researcher select less number of animals it may lead to missing of any significant difference even if it exist in population and if more number of animals selected then it may lead to unnecessary wastage of resources and may lead to ethical issues. In this article, on the basis of review of literature done by us we suggested few methods of sample size calculations for animal studies.

sample size
animal studies
Alpha error
power


Hypoxia-inducible factor 2α is a novel inhibitor of chondrocyte maturation.

Abstract: Hypoxic environment is essential for chondrocyte maturation and longitudinal bone growth. Although hypoxia-inducible factor 1 alpha (Hif-1α) has been known as a key player for chondrocyte survival and function, the function of Hif-2α in cartilage is mechanistically and clinically relevant but remains unknown. Here we demonstrated that Hif-2α was a novel inhibitor of chondrocyte maturation through downregulation of Runx2 stability. Mechanistically, Hif-2α binding to Runx2 inhibited chondrocyte maturation by Runx2 degradation through disrupting Runx2/Cbfβ complex formation. The Hif-2α-mediated-Runx2 degradation could be rescued by Cbfβ transfection due to the increase of Runx2/Cbfβ complex formation. Consistently, mesenchymal cells derived from Hif-2α heterozygous mice were more rapidly differentiated into hypertrophic chondrocytes than those of wild-type mice in a micromass culture system. Collectively, these findings demonstrate that Hif-2α is a novel inhibitor for chondrocyte maturation by disrupting Runx2/Cbfβ complex formation and consequential regulatory activity.

Che|Xiangguo|X|
Park|Na-Rae|NR|
Jin|Xian|X|
Jung|Youn-Kwan|YK|
Han|Min-Su|MS|
Park|Clara Yongjoo|CY|
Chun|Jang-Soo|JS|
Kim|Seong-Gon|SG|
Jin|Jingchun|J|
Kim|Hyun-Ju|HJ|0000-0002-5836-5841
Lian|Jane B|JB|
Stein|Janet L|JL|
Stein|Gary S|GS|
Choi|Je-Yong|JY|0000-0002-5057-8842

D051792:Basic Helix-Loop-Helix Transcription Factors

D050659:Core Binding Factor Alpha 1 Subunit

D050658:Core Binding Factor beta Subunit


The Utility of a 3D Endoscope and Robot-Assisted System for MIDCAB.

Abstract:
BACKGROUND
Minimally invasive direct coronary artery bypass (MIDCAB) has been revived with new techniques and hybrid procedures for MIDCAB and percutaneous coronary intervention (PCI). We reviewed the midterm results of MIDCAB with a three-dimensional (3D) endoscope in our institution.

METHODS
Of the 359 patients who underwent off-pump coronary artery bypass grafting (CABG) from December 2013 to March 2017, 54 had MIDCAB with the left internal thoracic artery (LITA) to left anterior descending (LAD) artery through a small left thoracotomy with a 3D endoscope. The same intercostal space was used for the main surgical incision and the insertion site of the 3D endoscope. In all, 22 patients had hybrid coronary revascularization (HCR), combined PCI and MIDCAB.

RESULTS
There was no operative death. One patient had cerebral infarction without disability. No cases showed significant increases in CKMB. In all, 34 patients commenced ambulation on postoperative day 1. The postoperative hospital stay was 9.1 ± 5.0 days. In total, 37 patients had coronary computed tomography (CT), and their patency of LITA was 100%. In HCR, there was no mortality and major adverse cardiovascular event (MACE). Target lesion revascularization among 12 months was 1.6%.

CONCLUSION
The midterm results of MIDCAB with 3D endoscope-assisted LITA harvesting were satisfactory. MIDCAB, including HCR, is a good alternative for selected high-risk patients.

Endo|Yuki|Y| Nakamura|Yoshitsugu|Y| Kuroda|Miho|M| Ito|Yujiro|Y| Hori|Takaki|T|

D047549:Coronary Artery Bypass, Off-Pump

minimally invasive direct coronary artery bypass


Immunomodulation of Host Chitinase 3-Like 1 During a Mammary Pathogenic Escherichia coli Infection.

Abstract: Chitin is a N-acetyl-d-glucosamine biopolymer that can be recognized by chitin-binding proteins. Although mammals lack chitin synthase, they induce proteins responsible for detecting chitin in response to bacterial infections. Our aim was to investigate whether chitinase 3-like 1 (CHI3L1) has a potential role in the innate immunity of the Escherichia coli (E. coli) infected mammary gland. CHI3L1 protein was found to be secreted in whey of naturally coliform-affected quarters compared to whey samples isolated from healthy udders. In addition, gene expression of CHI3L1 was confirmed in udder tissue of cows experimentally infected with a mammary pathogenic E. coli (MPEC) strain. Despite the known anatomical differences, the bovine udders' innate immune response was mimicked by applying an experimental mouse model using MPEC or non-MPEC isolates. The effect of CHI3L1 expression in the murine mammary gland in response to coliform bacteria was investigated through the use of CHI3L1-/- mice as well as through treatment with either a pan-caspase inhibitor or chitin particles in wild-type mice. The local induction of CHI3L1 postinfection with different E. coli strains was demonstrated to be independent of both bacterial growth and mammary interleukin (IL)-8 levels. Indeed, CHI3L1 emerged as a regulator impacting on the transcytosis of Ly6G-positive cells from the interstitial space into the alveolar lumen of the mammary tissue. Furthermore, CHI3L1 was found to be upstream regulated by caspase activity and had a major downstream effect on the local pro-inflammatory cytokine profile, including IL-1beta, IL-6, and RANTES/CCL5. In conclusion, CHI3L1 was demonstrated to play a key role in the cytokine and caspase signaling during E. coli triggered inflammation of the mammary gland.

Breyne|Koen|K|
Steenbrugge|Jonas|J|
Demeyere|Kristel|K|
Lee|Chun Geun|CG|
Elias|Jack A|JA|
Petzl|Wolfram|W|
Smith|David G E|DGE|
Germon|Pierre|P|
Meyer|Evelyne|E|

immunomodulation
chitinase 3-like 1
Escherichia coli
bovine mastitis
mouse mammary gland infection model


Obstetric and perinatal outcomes in women ≥40years of age: Associations with fetal growth disorders.

Abstract:
BACKGROUND
Evidence indicates that advanced maternal age is associated with adverse obstetric and perinatal outcomes. The purpose of this study was to evaluate pregnancy outcomes in women of advanced maternal age (≥40years).

METHODS
Using a prospective study design, data were collected by the Department of Obstetrics at the San Joan de Deu Hospital of Barcelona during the 1 June 2009 to 31 May 2012 period. The results were compared across three maternal age groups (≥40 [n=654], 35-39 [n=2781], and <35 [n=7893] years).

RESULTS
Of the 11328 births recorded during the study period, pregnancy-related complications were more common in women ≥40years of age. The most common disorder was diabetes (8.5% in the ≥40, 5.3% in the 35-39, and 3.0% in the <35years age groups). The women ≥40years of age also had significantly more premature births (p=0.001) and cesarean sections (17% in the ≥40, 12.5% in the 35-39, and 7.9% in the <35-year age groups; p=0.001). Intrauterine growth retardation was significantly more frequent in women aged ≥40years (17.4% in the ≥40, 15% in the 35-39, and 14.0% in the <35-year age groups; p=0.03). Fetal macrosomia was significantly more common in women ≥40years (15.4% in the ≥40, 12.6% in the 35-39, and 12% in the <35-year age groups; p=0.03).

CONCLUSION
Maternal age ≥40years was associated with poorer obstetric and perinatal outcomes and increased the risks of cesarean section, intrauterine growth retardation, and fetal macrosomia.

Zapata-Masias|Yesenia|Y|
Marqueta|Belén|B|
Gómez Roig|M D|MD|
Gonzalez-Bosquet|Eduardo|E|

D000328:Adult
D001724:Birth Weight
D002585:Cesarean Section
D005260:Female
D005317:Fetal Growth Retardation
D005320:Fetal Macrosomia
D006801:Humans
D008423:Maternal Age
D011247:Pregnancy
D011248:Pregnancy Complications
D011256:Pregnancy Outcome
D011254:Pregnancy in Diabetics
D047928:Premature Birth
D011446:Prospective Studies

Advanced maternal age
Cesarean section
Age over 40years
IUGR and macrosomia
Late motherhood
Maternal and perinatal morbidity


Role of ERLINs in the Control of Cell Fate through Lipid Rafts.

Abstract: ER lipid raft-associated protein 1 (ERLIN1) and 2 (ERLIN2) are 40 kDa transmembrane glycoproteins belonging to the family of prohibitins, containing a PHB domain. They are generally localized in the endoplasmic reticulum (ER), where ERLIN1 forms a heteroligomeric complex with its closely related ERLIN2. Well-defined functions of ERLINS are promotion of ER-associated protein degradation, mediation of inositol 1,4,5-trisphosphate (IP3) receptors, processing and regulation of lipid metabolism. Until now, ERLINs have been exclusively considered protein markers of ER lipid raft-like microdomains. However, under pathophysiological conditions, they have been described within mitochondria-associated endoplasmic reticulum membranes (MAMs), tethering sites between ER and mitochondria, characterized by the presence of specialized raft-like subdomains enriched in cholesterol and gangliosides, which play a key role in the membrane scrambling and function. In this context, it is emerging that ER lipid raft-like microdomains proteins, i.e., ERLINs, may drive mitochondria-ER crosstalk under both physiological and pathological conditions by association with MAMs, regulating the two main processes underlined, survival and death. In this review, we describe the role of ERLINs in determining cell fate by controlling the "interchange" between apoptosis and autophagy pathways, considering that their alteration has a significant impact on the pathogenesis of several human diseases.

Manganelli|Valeria|V| Longo|Agostina|A| Mattei|Vincenzo|V|0000-0003-4677-088X Recalchi|Serena|S| Riitano|Gloria|G| Caissutti|Daniela|D| Capozzi|Antonella|A| Sorice|Maurizio|M| Misasi|Roberta|R| Garofalo|Tina|T|0000-0003-0645-2510

ERLINs
lipid rafts
MAMs
apoptosis
autophagy


Optimizing the sulfation-modification system for scale preparation of chondroitin sulfate A.

Abstract: Chondroitin sulfate (CS) extracted from animal tissues has been widely used as nutraceutical and pharmaceutical products for osteoarthritis treatment. Here we developed an efficient sulfation-modification system for large scale preparation of CSA in vitro. First, the expression level of C4ST was improved by 30 times with fusion of the chaperone SUMO. Then, glycerol as a protein stabilizer was found to improve rat AST IV stability during the regeneration of cofactor PAPS. Then peptide linkers or protein scaffolds were employed to assemble AST IV and C4ST into artificial complexes to bring the enzymes and PAPS spatially closer and enhance the catalytic efficiency of chondroitin sulfation. Eventually, the system was scaled up to 1 L system and 15 g chondroitin was converted to CSA in 24 h, with a 98 % conversion. The present study made a step further towards the industrial production of CSA with different sulfation degrees.

Jin|Xuerong|X| Li|Qing|Q| Wang|Yang|Y| Zhang|Weijiao|W| Xu|Ruirui|R| Li|Jianghua|J| Du|Guocheng|G| Kang|Zhen|Z|

Sulfation-modification system
Chondroitin sulfate
Protein scaffolds
Aryl sulfotransferase IV
Enzymatic transformation
Sulfotransferase


Hepatitis B virus sub-genotype A1 infection is characterized by high replication levels and rapid emergence of drug resistance in HIV-positive adults receiving first-line antiretroviral therapy in Malawi.

Abstract:
BACKGROUND
It has been proposed that hepatitis B virus (HBV) sub-genotype A1 infections have mild outcomes and a low risk of drug-resistance among patients infected with human immunodeficiency virus (HIV) receiving lamivudine-containing antiretroviral therapy (ART) without tenofovir in Africa.

METHODS
The virologic expression of HBV sub-genotype A1 coinfection was studied over 12 months in HIV-positive adults starting stavudine/lamivudine/nevirapine in Malawi, using Sanger, deep, clonal, and single full-genome sequencing for the sensitive characterization of HBV resistance-associated mutations (RAMs).

RESULTS
Among 1117 subjects, 133 (12%) tested HBsAg-positive. After starting ART, retention rates were 96/133 (72%) at 6 months and 54/133 (41%) at 12 months. Based upon the last available follow-up, 92/96 (96%) subjects achieved HIV-1 RNA <40 copies/mL, 48/96 (50%) showed HBV DNA <14 IU/mL, and 24/96 (25%) acquired HBV RAMs. At 6 months, M204I was detected in 8/46 (17%) and 16/17 (94%) subjects using Sanger and deep sequencing, respectively. At 12 months, all viremic patients had multiple resistance and compensatory mutations coexisting on the same HBV genomes. Comparing HBeA-positive (67/133, 50%) with HBeAg-negative subjects, 64/67 (96%) vs 35/66 (55%) showed baseline HBV DNA >2000 IU/mL (P = .0006), 39/47 (17%) vs 9/49 (82%) had persistent HBV DNA detection during follow-up (P < .0001), and 23/47 (49%) vs 2/49 (4%) acquired HBV RAMs (P < .0001). Baseline HBV DNA levels were median 8.1 vs 5.3 log10 IU/mL in subjects with vs those without treatment-emergent RAMs (P < .0001).

CONCLUSIONS
HBV sub-genotype A1 infections showed a severe virologic expression in HIV-positive Malawians. The findings strengthen the urgency of interventions to improve ascertainment and management of chronic hepatitis B in the region.

González Del Castillo|Antonio Adrián|AA|

sub-genotype A1
resistance
Africa
lamivudine
viral load


COVID-19 in patients with juvenile idiopathic arthritis: frequency and severity.

Abstract: The aim of the study was to determine the frequency and the course of COVID-19 infection in children with juvenile idiopathic arthritis (JIA). The study involved 51 patients with JIA aged 2 to 18 years. Evidence of COVID-19 was found in 10 (19.6%) patients with JIA. COVID-19 infection occurred more often in patients with systemic arthritis (OR = 6.1667, 95% CI: 1.2053-31.5511, p = 0.0289). The course of COVID-19 infection in patients with JIA was generally similar to the course in the pediatric population, despite immunosuppressive therapy. In 3 out of 10 patients the infection caused an exacerbation of JIA, which required therapy escalation.

juvenile idiopathic arthritis
COVID-19 infection
immunosuppressive therapy


Plasmon-Enhanced, Self-Traced Nanomotors on the Surface of Silicon.

Abstract: Light-driven nanomotors have attracted much attention due to their potential applications. The movement of conventional nanomotors typically occurs in the solution phase, which limits their application fields. Utilizing visible light to drive nanomotors at the solid-liquid interface represents a grand challenge due to the large friction force between the nanomotor and the solid surface. Based on the attractive plasmon resonance of Au nanocrystals, for the first time, plasmon-enhanced Au nanocrystal-based nanomotors moving at the silicon-aqueous solution interface have been developed. Such nanomotors move with a clear trace engraved on the Si surface, representing an excellent and exceptional self-traced nanomotor system. In addition, the nanomotor trace on the Si surface also provides a unique and promising approach to the fabrication of nanoscale Si patterns, which is central to many applications, including microelectronics, sensing, information storage, and optoelectronics.

nanomotors
plasmon resonance
gold nanocrystals
hot charge carriers
plasmon-enhanced reactions


Characteristics of patients undergoing supraglottoplasty for laryngomalacia.

Abstract:
OBJECTIVE
To examine the characteristics of patients undergoing supraglottoplasty for the treatment of laryngomalacia and to better understand the features of laryngomalacia that may predispose patients to the need for supraglottoplasty.

METHODS
Review of patients who underwent supraglottoplasty for laryngomalacia at our academic tertiary care children's hospital between 2005 and 2012 examining demographic information, medical comorbidities, symptoms, indications for surgery, operative findings and procedure, site of laryngeal obstruction, operative techniques, and surgical success rates.

RESULTS
Seventeen patients with laryngomalacia underwent nineteen procedures. The most common indications for supraglottoplasty were persistent stridor beyond 18 months of age (64.7%), difficulty feeding (47%), and failure to thrive (29.4%). The most common comorbidities were gastroesophageal reflux (88.2%) and cardiopulmonary disease (35.3%). Operative findings included shortened aryepiglottic folds in sixteen patients (94.1%), retropositioned epiglottis in sixteen (94.1%), and prolapsed arytenoid mucosa in five (29.4%). Fifteen patients (88.2%) underwent division of the aryepiglottic folds and four underwent ablation of arytenoid mucosa (23.5%). Of the seventeen patients who had followed up at the time of study conclusion, sixteen (94.1%) had symptom improvement and twelve (70.6%) had complete resolution of their symptoms.

CONCLUSIONS
Supraglottoplasty is an effective treatment for laryngomalacia. Outcomes in our patients are similar to those reported in prior literature. The findings of shortened aryepiglottic folds and a retropositioned epiglottis appear to be disproportionately represented in our cohort of patients undergoing supraglottoplasty.

Garritano|Frank G|FG|
Carr|Michele M|MM|

Supraglottoplasty
Laryngomalacia
Stridor
Obstructive sleep apnea
Pediatric otolaryngology


The Role of Circulating Tumor DNA in Lung Cancer: Mutational Analysis, Diagnosis, and Surveillance Now and into the Future.

Abstract: Isolation and analysis of circulating tumor DNA (ctDNA) have emerged as an effective and promising tool for genomic profiling in non-small cell lung cancer. Analysis of ctDNA can be particularly useful in situations where tissue biopsy is not safely obtainable due to poor physical condition or inaccessible tumor biopsy location. In addition to identifying oncogenic driver mutations which can be treated with targetable therapy in the treatment naïve advanced non-small cell lung cancer (NSCLC) setting, ctDNA is being utilized in novel ways including monitoring during an advanced NSCLC patient's treatment course (real-time monitoring), determining mechanisms of resistance and, lastly, as a tool to identify minimal residual disease in early-stage NSCLC. Recent research demonstrates that ctDNA testing can provide a useful adjunct to tissue genotyping in NSCLC. Utilization of ctDNA into routine clinical practice for NSCLC should be strongly considered.

Circulating tumor DNA
Lung cancer
Liquid biopsy
Next-generation sequencing
Polymerase chain reaction


Differential CircRNA Expression Signatures May Serve as Potential Novel Biomarkers in Prostate Cancer.

Abstract: Circular RNAs (circRNAs), a recently discovered non-coding RNA, have a number of functions including the regulation of miRNA expression. They have been detected in a number of malignancies including prostate cancer (PCa). The differential expression pattern of circRNAs associated with PCa and androgen receptor (AR) status was investigated in this study. circRNA profiling was performed using a high throughout microarray assay on a panel of prostate cell lines, which consisted of normal, benign, and malignant cells (n = 9). circRNAs were more commonly significantly up-regulated (p < 0.05) than downregulated in malignant cell lines (n = 3,409) vs. benign cell lines (n = 2,949). In a grouped analysis based on AR status, there were 2,127 down-regulated circRNAs in androgen independent cell lines compared to 2,236 in androgen dependent cell lines, thus identifying a potential circRNA signature reflective of androgen dependency. Through a bioinformatics approach, the parental genes associated with the top 10 differentially expressed circRNAs were identified such as hsa_circ_0064644, whose predicted parental gene target is RBMS3, and hsa_circ_0060539, whose predicted gene target is SDC4. Furthermore, we identified three circRNAs associated with the parental gene Caprin1 (hsa_circ_0021652, hsa_circ_0000288, and hsa_circ_0021647). Other studies have shown the importance of Caprin1 in PCa cell survival and drug resistance. Given the modified circRNA expression signatures identified here, these hypothesis generating results suggest that circRNAs may serve as potential putative diagnostic and predictive markers in PCa. However, further validation studies are required to assess the true potential of these markers in the clinical setting.

Greene|John|J|
Baird|Anne-Marie|AM|
Lim|Marvin|M|
Flynn|Joshua|J|
McNevin|Ciara|C|
Brady|Lauren|L|
Sheils|Orla|O|
Gray|Steven G|SG|
McDermott|Raymond|R|
Finn|Stephen P|SP|

circRNA
biomarkers
prostate cancer
non-coding RNA
androgen signaling


Normalized handgrip strength and future risk of hypertension: findings from a prospective cohort study.

Abstract: Previous reports of an association between handgrip strength (HGS) and the risk of hypertension have utilized cross-sectional designs. We aimed to assess the prospective association between HGS and hypertension risk in a general population. Handgrip strength was assessed at baseline in 463 Finnish men and women aged 61-73 years. Handgrip strength was normalized (HGS/body weight2/3). After 16 years median follow-up, 110 hypertension cases occurred. Comparing the extreme tertiles of normalized HGS, the multivariable adjusted hazard ratio (95% CI) for hypertension was 0.63 (0.38-1.04). Previous evidence of associations may have been driven by study design limitations such as lack of temporality.

Kunutsor|Setor K|SK|0000-0002-2625-0273
Mäkikallio|Timo H|TH|
Voutilainen|Ari|A|0000-0002-0664-2675
Hupin|David|D|
Laukkanen|Jari A|JA|

Handgrip strength
hypertension
cohort study
risk factor


Returns to Operating Room After Colon and Rectal Surgery in a Tertiary Care Academic Medical Center: a Valid Measure of Surgical Quality?

Abstract:
INTRODUCTION
Returns to the operating room (ROR) have been suggested as a marker of surgical quality. Increasingly, quality and value metrics are utilized for reimbursement as well as public reporting to inform health care consumers. We sought to understand the etiology of ROR and assess the validity of simple ROR as a quality metric.

METHODS
This was a single referral center retrospective review of all colon and rectal operations between January 1, 2014 and December 31, 2014. Surgical Systems Nurse + was constructed and validated at our institution for classifying ROR as either an unplanned return to the OR, planned return due to complications, planned staged return, or an unrelated return. The primary outcome was the classification of ROR and total number of ROR within 30 days.

RESULTS
Of the 2389 colorectal patients who underwent surgery between January 1, 2014 and December 31, 2014; 214 returned to the operating room within 30 days (9.0%). Among the 214 patients, there were a total of 232 ROR with an average of 1.1 ROR per patient (range 1-4); 90 (38.8%) were unplanned ROR, 49 (21.1%) were planned returns due to complications, 92 (39.7%) were planned staged returns, and 1 (0.4%) were unrelated ROR. The most common reason for an unplanned ROR was an anastomotic leak (n = 21; 9.1%). Overall, unplanned reoperations were rare events (n = 90/2389; 3.8%), largely comprised of patients experiencing an anastomotic abscess or leak (n=21/2389; 0.9%).

CONCLUSIONS
In a high volume and complexity academic colon and rectal surgery practice, RORs within 30 days occurred after 10.4% of cases. Unplanned ROR were relatively rare and most commonly associated with an anastomotic leak. Since the majority of ROR were planned-staged returns, overall rate of ROR should be questioned as a metric of surgical quality. Perhaps, the anastomotic leak rate may be a better metric to monitor for quality improvement efforts.

Lightner|Amy L|AL|
Glasgow|Amy E|AE|
Habermann|Elizabeth B|EB|
Cima|Robert R|RR|

D013505:Digestive System Surgical Procedures

Return to operating room
Colon and rectal surgery
Surgical quality


IMPACT OF THE RIVNE NPP ACTIVITY ON NATURAL AND SOCIAL ENVIRONMENT OF THE CONTROL AREA.

Abstract:
OBJECTIVE
To assess an impact of the Rivne Nuclear Power Plant (RNPP) activity on the control area (CA) environ- ment according to environmental and radiation monitoring data over time of 2011-2017 as a component of the radiation safety system.

MATERIALS AND METHODS
Review of geographical and natural features of the territory of the «Rivne NPP» manufac- turing facility was carried out to assess its CA environment. Assessment of environmental and radiation situation of the CA was carried out according to the data of RNPP monitoring systems and a number of state institutions of Rivne oblast over time of 2011-2017. Opinion of the CA population about the RNPP environmental impact was studied. The sampled population of respondents was calculated based on the total population living in CA. The sampling error no more that 7.0%. Data from sociological survey of population were calculated using the statistical programs.

RESULTS
The radiation impact of RNPP on environment is related to emissions and discharges of radioactive sub- stances generated in the production cycle. Over time the total index of radionuclide discharge to the Styr River since 2011 is of a marked downward trend from 2.11 % to 0.18 %. The maximum concentrations of 60Co and 137Cs radionuclides at the three sampling points along the Styr River over time of 2011-2016 were about one thousandth of a percent, and of 131I - one hundredth of a permissible value according to the Radiation Safety Standards of Ukraine (RSSU). Emissions of inert radioactive gases and long-lived nuclides into the atmosphere were less than 0.2 % and iodine emissions were 0.01 % to the emission limit. Average radionuclide concentrations in the natural air of the RNPP CA settlements did not exceed the admissible concentration limit (ACL). Concentrations of chem- ical pollutants in discharges of the RNPP to the Styr River over time of 2012-2017 did not exceed the ACL. Integral wastewaters of municipal enterprises of the CA and RNPP result in an increased index of biochemical oxygen uti- lization and ammonium salt content in the Styr River, exceeding the ACL in fishery reservoir water. No exceedance of ACL of repugnant substances in the open air of settlements was observed regarding the pollutants under study. According to population survey the radiation contamination of territories as a result of the ChNPP accident and RNPP activities, which cause anxiety, are the key factors determining an environmental situation at the place of residence. The correlation coefficients between anxiety index and public estimates of environmental situation are established.

CONCLUSIONS
Content of radionuclides in emissions and discharges generated in the RNPP production cycle under everyday conditions does not exceed the allowed RSSU-97 values. The combined discharges of collective enterpri- ses and RNPP are the main sources of chemical pollution of surface waters in CA. There is a higher correlation coef- ficient between the anxiety and somatization rates and environmental sphere parameter in rural population com- pared to urban one. The combined effect of environmental, radiation and psychological factors on the RNPP CA population makes the health studies necessary in the latter.

Prylypko|V A|VA|
Morozova|M M|MM|
Bondarenko|I V|IV|
Petrychenko|O O|OO|
Romanenko|O M|OM|
Tuz|K K|KK|
Ozerova|Yu Yu|YY|

D000396:Air Pollutants, Radioactive
D002588:Cesium Radioisotopes
D003037:Cobalt Radioisotopes
D006801:Humans
D007457:Iodine Radioisotopes
D055848:Nuclear Power Plants
D000069079:Radiation Exposure
D011834:Radiation Monitoring
D045483:Rivers
D014455:Ukraine
D014875:Water Pollutants, Radioactive

environment
RNPP control area
environmental monitoring
public opinion


Modeling the odor-landscape resulting from the pumping behavior of bivalve clams in the presence of predators.

Abstract: Motivated by experimental findings, a computational fluid dynamics (CFD) model was used to investigate whether the clam Mercenaria mercenaria may alter its cue downstream variability by an exhalant random pumping behavior. This behavior was hypothesized to occur in the presence of predator chemical signals in order to prevent successful tracking by the predator. Simulated downstream flow and mixing conditions derived from the random nature of the clam exhalant jet in a crossflow were analyzed by computing an intermittency factor, determining the field of finite-time Lyapunov exponents (FTLEs) and identifying the resulting Lagrangian coherent structures (LCSs). Numerical simulations illustrate that the effectiveness of a fluctuating exhalant jet to prevent downstream tracking by a crab, depends on the ratio of the exhalant jet to the crossflow. Specifically, the clam could effectively enhance the downstream dispersion to prevent tracking, but only in the range of parameters where LCSs are generated (jet-to-crossflow ratio ≥ 1). Then, the probability of detection is reduced with respect to the case of a less fluctuating exhalant jet.

Computational fluid dynamics
Lagrangian coherent structures
Blue crab
Finite time Lyapunov exponents
Hard clam
Odor landscape


Presumed herpes simplex virus endotheliitis following ultra-thin Descemet's stripping automated endothelial keratoplasty.

Abstract: A 78.year.old male underwent ultra.thin DSAEK for PBK (OS) and achieved BCVA 6/12 at 9 months. The patient developed allograft rejection 10 months postoperatively and was treated with IV methyl prednisolone, systemic, and topical steroids. The patient then improved and achieved 6/18 BCVA at 8 weeks. Topical prednisolone 1% twice daily was continued. Six weeks later, the patient developed fever and diminished vision and had high IOP, corneal edema, and keratic precipitates on endothelium. Considering it to as second episode of graft rejection, IV methyl prednisolone and topical steroids were given. Seeing no response, presumed HSV endotheliitis was considered as diagnosis and treated with steroids, oral acyclovir. The patient improved and achieved BCVA 6/24 with no subsequent recurrence during 11 months follow.up.

D057111:Descemet Stripping Endothelial Keratoplasty


Docosahexaenoic acid inhibits mechanical allodynia and thermal hyperalgesia in diabetic rats by decreasing the excitability of DRG neurons.

Abstract: Diabetes mellitus is a common metabolic disease in human beings with characteristic symptoms of hyperglycemia, chronic inflammation and insulin resistance. One of the most common complications of early-onset diabetes mellitus is peripheral diabetic neuropathy, which is manifested either by loss of nociception or by allodynia and hyperalgesia. Dietary fatty acids, especially polyunsaturated fatty acids, have been shown the potential of anti-inflammation and modulating neuron excitability. The present study investigated the effects of docosahexaenoic acid (DHA) on the excitability of dorsal root ganglion (DRG) neurons in streptozotocin (STZ)-induced diabetes rats. The effects of DHA on the allodynia and hyperalgesia of diabetic rats were also evaluated. Dietary DHA supplementation effectively attenuated both allodynia and hyperalgesia induced by STZ injection. DHA supplementation decreased the excitability of DRG neurons by decreasing the sodium currents and increasing potassium currents, which may contribute to the effect of alleviating allodynia and hyperalgesia in diabetic rats. The results suggested that DHA might be useful as an adjuvant therapy for the prevention and treatment of painful diabetic neuropathy.

Heng|Li-Jun|LJ| Qi|Rui|R| Yang|Rui-Hua|RH| Xu|Guo-Zheng|GZ|

Docosahexaenoic acid
Neuron excitability
Dorsal root ganglion
Painful diabetic neuropathy
Potassium channel
Sodium channel


Missing something? A scoping review of venous thromboembolic events and their associations with bariatric surgery. Refining the evidence base.

Abstract:
Background
Venous thromboembolic events (VTE) post-bariatric surgery (BS) lead to morbidity and mortality.

Methods
This scoping review assessed whether reported VTE post-BS could be under/over-estimated; suggested a possible number of VTE post-BS; appraised whether VTE are likely to decrease/increase; examined BS as risk/protective factor for VTE; and mapped the gaps, proposing potential solutions.

Results
VTE appears under-estimated due to: identification/coding of BS and VTE; reporting of exposure (BS); and reporting of outcomes (VTE). The review proposes a hypothetical calculation of VTE post-BS. VTE are unlikely to decrease soon. BS represents risk and protection for VTE. Better appreciation of VTE-BS relationships requires longer-term strategies.

Conclusion
VTE are underestimated. Actions are required for understanding the VTE-BS relationships to in order to crease VTE by better-informed prevention strategy/ies.

Venous thromboembolism
Bariatric surgery
Policy
Porto/ mesenteric venous thrombosis
Post-operative
Pulmonary embolism
Upper extremity


Talent Selection Based on Sport-Specific Tasks Is Affected by the Relative Age Effects among Adolescent Handball Players.

Abstract:
Talent selection is often affected by the relative age effects (RAEs), resulting in the overrepresentation of relatively older (vs. relatively younger) players among those selected. The use of sport-specific tasks is suggested to reduce RAEs during talent selection.

PURPOSE
To test the hypothesis that talent selection including only sport-specific tasks is not affected by the RAEs and to analyse the body size and biological maturity of the top selection level according to relative age.

METHODS
Participants were U14 female (n = 5428) and U15 (n = 4408) male handball players participating in four programs consisting of four selection levels (local, county, regional, and national) grouped in bi-annual age. Handball-specific generic skills, position-specific technical drills and in-game performance were the selection criteria evaluated by experts and coaches. Body dimensions were measured and bone age, as an indicator of maturity, was estimated. The relative age quartile distributions within the bi-annual cohorts were examined using Chi-square and Odds Ratios.

RESULTS
In terms of all the registered players no RAEs were evident. However, the RAEs of moderate effect size were evident at the county level; χ2 = 53.2 (girls) and 66.4 (boys), OR = 2.5 and 3.3, respectively. The RAEs of a large effect size were found at the regional level; χ2 = 139.5 (girls) and 144.9 (boys), OR = 8.2 and 5.2, respectively. At national level, RAEs were still present, but with no further increase in the effect size. At the highest selection level, there were no differences in the anthropometric measures between the relatively older and younger players.

CONCLUSION
The findings provide support to the hypothesis that the selection process exacerbates RAEs even when using only sport-specific selection criteria. The performance metrics in technical skills, but also coaching assessments are likely involved. In addition, an advanced maturity and/or an above-average body size increases the selection odds for relatively younger players.

Tróznai|Zsófia|Z|0000-0002-4020-6447 Utczás|Katinka|K| Pápai|Júlia|J| Négele|Zalán|Z| Juhász|István|I| Szabó|Tamás|T| Petridis|Leonidas|L|

adolescence
maturity
birth asymmetry
youth sport


Evaluation of decision-to-delivery interval in emergency cesarean section: A 1-year prospective audit in a tertiary care hospital.

Abstract:
BACKGROUND AND AIMS
The American College of Obstetricians and Gynecologists (ACOG) committee on professional standards and the National Institute of Clinical Excellence (NICE) guidelines suggest that decision-to-delivery interval (DDI) and emergency cesarean section (CS) should not be more than 30 min, and a delay of more than75 min in the presence of maternal or fetal compromise can lead to poor outcome. This prospective 1-year study was conducted on emergency CS in a tertiary care hospital to evaluate the DDI, factors affecting it and to analyze their effects on maternal and neonatal outcome.

MATERIAL AND METHODS
A structured proforma was used to analyze the data from all women undergoing emergency CS, during a 1-year period, included in Category 1 and 2 of NICE guidelines for CS.

RESULTS
A total of 453 emergency CSs were evaluated, with a mean DDI of 36.3 ± 17.2 min for Category 1 CS and 38.1 ± 17.7 min for Category 2 CS (P > 0.05). Only 42.4% emergency CSs confirmed to the 30 min DDI while 57.6% had a DDI of more than 30 min. Reasons of delay were identified as a delay in shifting the patient to operation theater (22.1%), anesthesia factors (18.1%), and lack of resources or manpower (16.1%). Maternal complications occurred in 15 (3.3%) patients with 3 (0.7%) nonsurvivors having a DDI of 91.0 ± 97.0 min as compared to survivors with a DDI of 36.8 ± 15.7 min, P = 0.001. There was no significant association between DDI and occurrence of neonatal complications.

CONCLUSION
Failure to meet the current recommendations was associated with adverse maternal outcomes, but not with adverse neonatal outcome.

Gupta|Sunanda|S| Naithani|Udita|U| Madhanmohan|C|C| Singh|Ajay|A| Reddy|Pradeep|P| Gupta|Apoorva|A|

Decision-to-delivery interval
Decision-to-delivery interval
emergency cesarean section
neonatal outcome
maternal outcome
decision-to-delivery interval


Support and monitoring of families after child abuse detection based on parental characteristics at the Emergency Department.

Abstract:
BACKGROUND
The 'Hague Protocol' enables professionals at the adult Emergency Department (ED) to detect child abuse based on three parental characteristics: (i) suicide attempt or self-harm, (ii) domestic violence or (iii) substance abuse, and to refer them to the Reporting Centre for Child Abuse and Neglect (RCCAN). This study investigates what had happened to the families three months after this referral.

METHOD
ED referrals based on parental characteristics (N = 100) in which child abuse was confirmed after investigation by the RCCAN were analysed. Information was collected regarding type of child abuse, reason for reporting, duration of problems prior to the ED referral, previous involvement of support services or other agencies, re-occurrence of the problems and outcome of the RCCAN monitoring according to professionals and the families.

RESULTS
Of the 100 referred cases, 68 families were already known to the RCCAN, the police or family support services, prior to the ED referral. Of the 99 cases where information was available, existing support was continued or intensified in 31, a Child Protection Services (CPS) report had to be made in 24, new support was organized for 27 cases and in 17 cases support was not necessary, because the domestic problems were already resolved. Even though the RCCAN is mandated to monitor all referred families after three months, 31 cases which were referred internally were not followed up.

CONCLUSION
Before referral by the ED two thirds of these families were already known to organizations. Monitoring may help provide a better, more sustained service and prevent and resolve domestic problems. A national database could help to link data and to streamline care for victims and families. We recommend a Randomized Controlled Trial to test the effectiveness of this Protocol in combination with the outcomes of the provided family support.

Diderich|H M|HM|
Pannebakker|F D|FD|
Dechesne|M|M|
Buitendijk|S E|SE|
Oudesluys-Murphy|A M|AM|

D000328:Adult
D002648:Child
D002649:Child Abuse
D002669:Child Welfare
D016241:Child of Impaired Parents
D002985:Clinical Protocols
D017579:Domestic Violence
D004636:Emergency Service, Hospital
D005191:Family Characteristics
D005192:Family Health
D006801:Humans
D008403:Mass Screening
D009426:Netherlands
D010290:Parents
D012017:Referral and Consultation
D012307:Risk Factors
D012947:Social Work
D019966:Substance-Related Disorders
D013406:Suicide, Attempted

monitoring
child abuse
parental characteristics
emergency department
family support


Variability of anti-human transglutaminase testing in celiac disease across Mediterranean countries.

Abstract:
AIM
To verify the precision and accuracy of transglutaminase antibodies (TGA) assays across Mediterranean countries.

METHODS
This study involved 8 referral centres for celiac disease (CD) in 7 Mediterranean countries. A central laboratory prepared 8 kits of 7 blinded and randomized serum samples, with a titrated amount of Human TGA IgA. Each sample was analysed three times on three different days, with each centre running a total of 21 tests. The results were included in a blindly coded report form, which was sent to the coordinator centre. The coordinator estimated the mean coefficient of Variation (CoVar = σ/μ), the mean accuracy (Accur = Vobserved - Vreal) and the mean percent variation (Var% = [(Vobserved - Vreal)/Vreal] × 100).

RESULTS
The analysis showed that 79.17% of the mean variation fell between -25% and +25% of the expected value, with the accuracy and precision progressively increasing with higher titres of TGA. From values 1.25 times greater than the normal cut-off, the measurements were highly reliable.

CONCLUSION
TGA estimation is a crucial step for the diagnosis of CD; given its accuracy and precision, clinicians could be confident in establishing a diagnosis.

Smarrazzo|Andrea|A|
Magazzù|Giuseppe|G|
Ben-Hariz|Mongi|M|
Legarda Tamara|Maria|M|
Velmishi|Virtut|V|
Roma|Elefhteria|E|
Kansu|Aydan|A|
Mičetić-Turk|Dušanka|D|
Bravi|Enzo|E|
Stellato|Pio|P|
Arcidiaco|Carmela|C|
Greco|Luigi|L|

Transglutaminase
Precision
Accuracy
Coeliac disease
Gluten
Non-invasive testing


Early emotional and behavioral difficulties and adult educational attainment: an 18-year follow-up of the TEMPO study.

Abstract: Children who experience behavioral difficulties often have short and long-term school problems. However, the relationship between emotional difficulties and later academic achievement has not been thoroughly examined. Using data from the French TEMPO study (n = 666, follow-up 1991, 1999, 2009, mean age = 10.5, sd = 4.9 at baseline), we studied associations between internalizing and externalizing symptoms in: (a) childhood and (b) adolescence and educational attainment by young adulthood (< vs. ≥ high school degree), accounting for participants' age, sex, juvenile academic difficulties, and family income. High levels of childhood (but not adolescent) internalizing and externalizing symptoms were associated with low educational attainment; however, in multivariate models only the association with childhood internalizing symptoms remained statistically significant (OR = 1.75, 95 % CI 1.00-3.02). Supporting children with internalizing problems early on could help improve their long-term educational attainment.

Zbar|Ariella|A|
Surkan|Pamela J|PJ|
Fombonne|Eric|E|
Melchior|Maria|M|

Educational attainment
Emotional difficulties
Cohort study
Epidemiology


Detecting Proton Transfer in CO2 Species Chemisorbed on Amine-Modified Mesoporous Silicas by Using 13 C NMR Chemical Shift Anisotropy and Smart Control of Amine Surface Density.

Abstract: The wealth of site-selective structural information on CO2 speciation, obtained by spectroscopic techniques, is often hampered by the lack of easy-to-control synthetic routes. Herein, an alternative experimental protocol that relies on the high sensitivity of 13 C chemical shift anisotropy (CSA) tensors to proton transfer, is presented to unambiguously distinguish between ionic/charged and neutral CO2 species, formed upon adsorption of 13 CO2 in amine-modified porous materials. Control of the surface amine spacing was achieved through the use of amine protecting groups during functionalisation prior to CO2 adsorption. This approach enabled the formation of either "isolated" or "paired" carbamate/carbamic acid species, providing a first experimental NMR proof towards the identification of both aggregation states. Computer modelling of surface CO2 -amine adducts assisted the solid-state NMR assignments and validated various hydrogen-bond arrangements occurring upon formation of isolated/aggregated carbamic acid and alkylammonium carbamate ion species. This work extends the understanding of chemisorbed CO2 structures formed at pore surfaces and reveals structural insight about the protonation source responsible for the proton-transfer mechanism in such aggregates.

NMR spectroscopy
carbon dioxide fixation
density functional calculations
organic-inorganic hybrid composites
solid-state structures


Burdock (Arctium lappa L.) root attenuates preneoplastic lesion development in a diet and thioacetamide-induced model of steatohepatitis-associated hepatocarcinogenesis.

Abstract: Nonalcoholic steatohepatitis (NASH) is considered growing risk factor for hepatocellular carcinoma development in high-income countries. Diet- and chemically induced rodent models have been applied for the translational study of NASH-associated hepatocarcinogenesis due to their morphological and molecular similarities to the corresponding human disease. Arctium lappa L. (burdock) root tea has been extensively consumed in Traditional Chinese Medicine due to its potential therapeutic properties. Indeed, the bioactive compounds of A. lappa root, as the polyphenols, have already showed antioxidant and anti-inflammatory properties in different in vivo and in vitro bioassays. In this study, we investigated whether burdock root ethanolic extract (BRE) administration attenuates NASH-associated hepatocarcinogenesis. Eight-week-old male Wistar rats received choline-deficient high-fat diet for 8 weeks and multiple thioacetamide doses for 4 weeks in order to induce NASH and preneoplastic glutathione-S-transferase pi (GST-P)+ preneoplastic foci. Subsequently, rats were treated with BRE (100 or 200 mg/kg body weight) or vehicle by oral gavage for 2 weeks. BRE displayed high levels of chlorogenic and caffeic acids and BRE administration reduced total fatty acid and lipid hydroperoxide levels, while increasing the activities of antioxidant superoxide dismutase and catalase enzymes in the liver. Furthermore, burdock intervention diminished the size of GST-P+ remodeling preneoplastic lesions (PNLs) and displayed a trend on reducing hepatocyte proliferation (Ki-67) inside them. These findings suggest that short-term exposure to BRE alleviated remodeling PNL development in NASH-associated hepatocarcinogenesis.

D065626:Non-alcoholic Fatty Liver Disease

burdock (Arctium lappa L.)
nonalcoholic steatohepatitis
GST-P+ preneoplastic lesions
chlorogenic acid
rat hepatocarcinogenesis


The Smart Use of Smartphones in Pediatrics.

Abstract: The problematic overuse of electronic devices, in particular smartphones, is negatively affecting the lives of American youth. Cell phone technology has advanced its capabilities with smartphones to now easily provide children and teens with endless access to the internet, social media, and other online activities. Research is showing that addictive, smart phone activities of youth in their formative years is directly impacting their wellbeing. The excessive time youth spend on their smartphones results in less human interaction, sleep, exercise, and productivity, as well as, increased risk of exposure to inappropriate or violent online media, anxiety, and depression. The purpose of this column is to explore the potential behavioral and developmental problems in youth related to the problematic overuse of the smartphone; inform the importance of monitoring and controlling indiscriminate youth use of technology, and the approaches pediatric nurses can employ to guide youth and their families to prevent negative outcomes for this evolving public health problem.


Kadsura heteroclita stem suppresses the onset and progression of adjuvant-induced arthritis in rats.

Abstract:
BACKGROUND
Rheumatoid arthritis (RA) is a chronic autoimmune diseased state, characterized by hyperplasia of the synovial membrane, degradation of cartilage, and bone erosion of diarthrodial joints. Kadsura heteroclita (Roxb) Craib (Schizandraceae), a traditional Tujia ethnomedicine called Xue Tong in China, has been long used for the prevention and treatment of rheumatic and arthritic diseases, especially in the southern China. This study aimed to evaluate anti-arthritic effects of the ethanol extract of Kadsura heteroclita stems (KHS) on complete Freund's adjuvant (CFA)-induced arthritis (AIA) in rats, as well as to explore the underlying mechanisms of anti-arthritis.

METHODS
AIA was established in male Sprague-Dawley (SD) rats as described previously, and animals were daily treated by gavage with KHS ethanol extract (200, 400, or 800 mg/kg) or vehicle (0.3% CMCNa) throughout the 30-day experiment. The incidence and severity of arthritis were evaluated using clinical parameters. At the end of experiments, tissue swelling and bone destruction of the hind paws were assessed by computed tomography (CT) and histopathological analyses. Serum levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-17A and IL-17F were measured by ELISA, and protein expression of matrix metalloproteinases-1 (MMP-1), MMP-3 and tissue inhibitor of MMP-1 (TIMP-1) were detected by Western blot.

RESULTS
Treatment with KHS dose-dependently inhibited paw swelling and reduced arthritis scores of AIA rats. CT images displayed that KHS remarkably protected AIA rats from tissue swelling and bone erosion of joints. Histopathological analyses revealed that KHS markedly reduced inflammatory cell infiltration, synovial proliferation, and the formation of pannus in the ankle joints of AIA rats. KHS was found to significantly suppress the production of TNF-α, IL-1 β, IL-6, IL-17A and IL-17F, inhibited the protein expression of MMP-1 and MMP-3, and elevated the protein expressions of TIMP-1.

CONCLUSION
KHS demonstrates potential anti-arthritic effects via inhibiting pivotal mediators of inflammation and cartilage destruction. This study strongly supports identification and isolation of active fractions of KHS which would be a potential candidate for further investigation as a new anti-arthritic botanical drug.

Yu|Huanghe|H| Zeng|Rong|R| Lin|Ye|Y| Li|Xin|X| Tasneem|Shumaila|S| Yang|Zhen|Z| Qiu|Yi-Xing|YX| Li|Bin|B| Wang|Yu-Hong|YH| Cai|Xiong|X| Wang|Wei|W|

D019715:Tissue Inhibitor of Metalloproteinase-1

Kadsura heteroclita stem
Adjuvant-induced arthritis
Rheumatoid arthritis
Tujia ethnomedicine
Cytokines
MMPS


Role of indigenous bacteria in dark fermentation of organic substrates.

Abstract: Hydrogen production by dark fermentation of complex organic substrates, such as biowaste, can naturally take place with indigenous bacteria or by adding an external microbial inoculum issued from various natural environments. This study aims to determine whether indigenous bacteria associated with thermal pretreatment could impact dark fermentation performances. Biochemical hydrogen potential tests were carried out on seven organic substrates. Results showed a strong influence of the indigenous bacteria which are as effective as thermally pretreated exogenous bacteria to produce H2 and metabolites. High abundance in Clostridiales and/or Enterobacteriales was associated with high H2 yield. This study shows that no inoculum nor pretreatment are required to achieve satisfactory dark fermentation performances from organic waste.

Dauptain|K|K| Trably|E|E| Santa-Catalina|G|G| Bernet|N|N| Carrere|H|H|

Indigenous bacteria
Dark fermentation
Inoculum
Thermal pretreatment
Biohydrogen


A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis.

Abstract:
OBJECTIVES
We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability.

PATIENTS AND METHODS
We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients.

RESULTS
We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild.

CONCLUSIONS
The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin.

Yasuda|Mitsuru|M| Ito|Shin|S| Kido|Akira|A| Hamano|Kiminari|K| Uchijima|Yutaka|Y| Uwatoko|Noriyasu|N| Kusuyama|Hiroyuki|H| Watanabe|Akiko|A| Miyamura|Ryuzou|R| Miyata|Kazutoyo|K| Deguchi|Takashi|T|

azithromycin-SR
Neisseria gonorrhoeae
male urethritis


Hormonal and ultrasonographic characterization of the seasonal reproductive cycle of male and female Crotalus durissus terrificus.

Abstract: Research concerning to characterize seasonal reproductive cycle in males and females of Crotalus durissus terrificus by ultrasound and hormonal measurement. Reproductive aspects (follicular and testicular cycles, and pregnancy) from 28 adult snakes (14 males and 14 females) during different months of the years were studied. Snakes housed individually in cages in an environment with controlled luminosity and humidity, and fed monthly. Females were examined by ultrasound during quiescence and active follicular phase, and pregnancy for follicular and embryo/fetal development. Males were evaluated to testicular echotexture and measurements during reproductive and non-reproductive season. The blood samples were collected from males and females for serum testosterone and progesterone determination, respectively. In 77% males the testes were identified by ultrasound and found increased size during summer, decreased serum testosterone in winter, and positive correlation between serum testosterone and testes size. There was no change in testicular echotexture in according to season. Testosterone concentration was decreased during winter and it was positively correlated with testes size. In 71% females, were observed follicular development (vitellogenesis) and gestation since winter to spring by ultrasonography. Parturition occurred mainly in summer. Pregnancy length was 123.0 ± 11.4 days, with mean 6.9 ± 1.5 newborns/female, and there was gradual increase of serum progesterone during this period. There was no variation in progesterone concentration in non-gravid females. Males and females Tropical Rattlesnake show seasonal variation of reproductive cycle and was clear a biennial cycle in female. The ultrasonography can be considered an essential tool to accomplish the follicular development, pregnancy and testicular alterations in Tropical Rattlesnake.

Matayoshi|Priscilla M|PM|
Souza|Priscilla M|PM|
Gasparotto|Vinícius P O|VPO|
Araujo|Michelle S|MS|
Simões|Carla R B|CRB|
Souza|Fabiana F|FF|
Oba|Eunice|E|
Machado|Vânia M V|VMV|
Júnior|Rui S F|RSF|
Prestes|Nereu C|NC|

testosterone progesterone gestation rattlesnake follicle


Encoding of near-range spatial information by descending interneurons in the stick insect antennal mechanosensory pathway.

Abstract: Much like mammals use their whiskers, insects use their antennae for tactile near-range orientation during locomotion. Stick insects rapidly transfer spatial information about antennal touch location to the front legs, allowing for aimed reach-to-grasp movements. This adaptive behavior requires a spatial coordinate transformation from "antennal contact space" to "leg posture space." Therefore, a neural pathway must convey proprioceptive and tactile information about antennal posture and contact site to thoracic motor networks. Here we analyze proprioceptive encoding properties of descending interneurons (DINs) that convey information about antennal posture and movement to the thoracic ganglia. On the basis of response properties of 110 DINs to imposed movement of the distal antennal joint, we distinguish five functional DIN groups according to their sensitivity to three parameters: movement direction, movement velocity, and antennal joint angle. These groups are simple position-sensitive DINs, which signal the antennal joint angle; dynamic position-sensitive DINs, which signal the joint angle with strong dependence on movement; unspecific movement-sensitive DINs, which signal movement but not the velocity, position, or direction of movement; and ON- and OFF-type velocity-sensitive DINs. The activity of the latter two groups is increased/attenuated during antennal movement, with the spike rate increasing/decreasing linearly with antennal joint angle velocity. Some movement-sensitive DINs convey spikes to the thorax within 11 ms, suggesting a rapid, direct pathway from antennal mechanosensory to thoracic motor networks. We discuss how the population of DINs could provide the neural basis for the intersegmental spatial coordinate transfer between a touch sensor of the head and thoracic motor networks.

interneurons
antenna
coordination
proprioception
ensemble coding
tactile sensing


Ancient fishes and the functional evolution of the corticosteroid stress response in vertebrates.

Abstract: The neuroendocrine mechanism underlying stress responses in vertebrates is hypothesized to be highly conserved and evolutionarily ancient. Indeed, elements of this mechanism, from the brain to steroidogenic tissue, are present in all vertebrate groups; yet, evidence of the function and even identity of some elements of the hypothalamus-pituitary-adrenal/interrenal (HPA/I) axis is equivocal among the most basal vertebrates. The purpose of this review is to discuss the functional evolution of the HPA/I axis in vertebrates with a focus on our understanding of this neuroendocrine mechanism in the most ancient vertebrates: the agnathan (i.e., hagfish and lamprey) and chondrichthyan fishes (i.e., sharks, rays, and chimeras). A review of the current literature presents evidence of a conserved HPA/I axis in jawed vertebrates (i.e., gnathostomes); yet, available data in jawless (i.e., agnathan) and chondrichthyan fishes are limited. Neuroendocrine regulation of corticosteroidogenesis in agnathans and chondrichthyans appears to function through similar pathways as in bony fishes and tetrapods; however, key elements have yet to be identified and the involvement of melanotropins and gonadotropin-releasing hormone in the stress axis in these ancient fishes warrants further investigation. Further, the identities of physiological glucocorticoids are uncertain in hagfishes, chondrichthyans, and even coelacanths. Resolving these and other knowledge gaps in the stress response of ancient fishes will be significant for advancing knowledge of the evolutionary origins of the vertebrate stress response.

Bouyoucos|Ian A|IA|
Schoen|Alexandra N|AN|
Wahl|Ryan C|RC|
Anderson|W Gary|WG|


Streptococcus mutans isolated from children with severe-early childhood caries form higher levels of persisters.

Abstract:
OBJECTIVES
Dental caries is the most common chronic infectious disease in children. Streptococcus mutans, the main cariogenic bacterial species, produces persisters, nongrowing dormant variants of regular cells associated with chronicity of diseases. We hypothesized that the recurrent nature of caries, particularly within populations with high-caries risk, is due partly to specific phenotypic features of S. mutans such as its ability to form persisters. We aimed to investigate the genotypic and phenotypic differences between the S. mutans from children with severe early-childhood caries (S-ECC) and those without caries.

METHODS
S. mutans from plaque samples of caries-free (CF) and S-ECC children were tested for their ability to adapt to a lethal pH in an acid tolerance response assay. The persister levels of S. mutans isolates was quantified in both groups.

RESULTS
S. mutanswas identified in all 23 S-ECC but only 6 of the 21 CF subjects. In most subjects, only one dominant S. mutans genotype was detected. No statistically significant differences in the mean survival percentage of S. mutans were observed between the two groups at a lethal pH of 3.5. However, the dominant genotype within a particular S-ECC subject exhibited a higher percentage of cell survival compared to those in the CF group. In S-ECC patients, S. mutans isolates displayed a ∼15-fold higher persistence phenotype than S. mutans isolates from CF patients.

CONCLUSIONS
The ability of S. mutans to produce high levels of persisters may contribute to part of an individual's ability to control caries disease activity and recurrent lesions.

Bottner|Aaron|A|
He|Richard Y|RY|
Sarbu|Andrea|A|
Nainar|S M Hashim|SMH|
Dufour|Delphine|D|
Gong|Siew-Ging|SG|
Lévesque|Céline M|CM|

Streptococcus mutans
Persisters
Dental caries
Acid tolerance response


Polymorphisms in Stress-Related Genes Are Associated with Reduced Cocaine Abuse and Longer Retention in Methadone Maintenance Treatment for Opioid Use Disorder.

Abstract:
BACKGROUND
As CRH-binding protein (CRHBP) SNP rs1500 was associated with reduced cocaine abuse after 1 year in methadone maintenance treatment (MMT) for heroin addiction, we evaluated the association of additional 28 selected SNPs, in 17 stress-related genes, with MMT outcome.

METHODS
The distribution of genotypes of each SNP by cocaine abuse after 1 year in MMT was assessed under the dominant and recessive models using χ2. Cumulative retention (up to 26.5 years) was studied using Kaplan-Meier analyses. Logistic regression and Cox model were used for multivariate analyses.

RESULTS
Of a nonselective sample of 404 patients, 25 patients with <50% Europeans/Middle Eastern ancestry were excluded. Of the remaining 379 patients, 330 (87.1%) stayed at least 1 year in treatment. Four SNPs were associated with cocaine abuse after 1 year in MMT. A lower proportion of cocaine abusers was found in the groups of subjects with the following genotypes: arginine vasopressin (AVP) SNP rs2282018 CC, CRHBP rs7728378 TT, galanin rs3136541 TT/TC, and neuropeptide Y receptor Y1 (NPY1R) rs4518200 AA. The following independent variables were associated with lack of cocaine in urine after 1 year (multivariate analyses): CRHBP rs7728378 TT, NPY1R rs4518200 AA, no cocaine in urine on admission, as well as opiate and benzodiazepine use after 1 year in MMT. Cumulative retention (n = 379) was longer in carriers of AVP rs2282018 CC (13.7 years, 95% CI 11.1-16.2) versus TT/TC genotypes (10.5, 95% CI 9.4-11.5) (p = 0.0230) Conclusions: The study suggests that a reduction in cocaine abuse and longer retention among MMT patients is mediated in part by variants in stress-related genes and is a step toward precision medicine.

Peles|Einat|E|
Levran|Orna|O|
Randesi|Matthew|M|
Ott|Jurg|J|
Kreek|Mary Jeanne|MJ|
Adelson|Miriam|M|

D000701:Analgesics, Opioid
D019970:Cocaine-Related Disorders
D006801:Humans
D008691:Methadone
D058850:Opiate Substitution Treatment
D009293:Opioid-Related Disorders
D011110:Polymorphism, Genetic

Stress-related genes
Cocaine
Retention
Methadone maintenance treatment
CRH-binding protein


Capsicum chinense MYB Transcription Factor Genes: Identification, Expression Analysis, and Their Conservation and Diversification With Other Solanaceae Genomes.

Abstract: Myeloblastosis (MYB) genes are important transcriptional regulators of plant growth, development, and secondary metabolic biosynthesis pathways, such as capsaicinoid biosynthesis in Capsicum. Although MYB genes have been identified in Capsicum annuum, no comprehensive study has been conducted on other Capsicum species. We identified a total of 251 and 240 MYB encoding genes in Capsicum chinense MYBs (CcMYBs) and Capsicum baccatum MYBs (CbMYBs). The observation of twenty tandem and 41 segmental duplication events indicated expansion of the MYB gene family in the C. chinense genome. Five CcMYB genes, i.e., CcMYB101, CcMYB46, CcMYB6, CcPHR8, and CcRVE5, and two CaMYBs, i.e., CaMYB3 and CaHHO1, were found within the previously reported capsaicinoid biosynthesis quantitative trait loci. Based on phylogenetic analysis with tomato MYB proteins, the Capsicum MYBs were classified into 24 subgroups supported by conserved amino acid motifs and gene structures. Also, a total of 241 CcMYBs were homologous with 225 C. annuum, 213 C. baccatum, 125 potato, 79 tomato, and 23 Arabidopsis MYBs. Synteny analysis showed that all 251 CcMYBs were collinear with C. annuum, C. baccatum, tomato, potato, and Arabidopsis MYBs spanning over 717 conserved syntenic segments. Using transcriptome data from three fruit developmental stages, a total of 54 CcMYBs and 81 CaMYBs showed significant differential expression patterns. Furthermore, the expression of 24 CcMYBs from the transcriptome data was validated by quantitative real-time (qRT) PCR analysis. Eight out of the 24 CcMYBs validated by the qRT-PCR were highly expressed in fiery hot C. chinense than in the lowly pungent C. annuum. Furthermore, the co-expression analysis revealed several MYB genes clustered with genes from the capsaicinoid, anthocyanin, phenylpropanoid, carotenoid, and flavonoids biosynthesis pathways, and related to determining fruit shape and size. The homology modeling of 126 R2R3 CcMYBs showed high similarity with that of the Arabidopsis R2R3 MYB domain template, suggesting their potential functional similarity at the proteome level. Furthermore, we have identified simple sequence repeat (SSR) motifs in the CcMYB genes, which could be used in Capsicum breeding programs. The functional roles of the identified CcMYBs could be studied further so that they can be manipulated for Capsicum trait improvement.

Islam|Khushbu|K| Rawoof|Abdul|A| Ahmad|Ilyas|I| Dubey|Meenakshi|M| Momo|John|J| Ramchiary|Nirala|N|

Capsicum chinense
MYB
transcription factors
Solanaceae
baccatum
fruit development


Physical and chemical kernel traits affect starch digestibility and glycemic index of cooked maize flours.

Abstract: Maize starch is an important carbohydrate source in human diet, and its digestion contributes to the postprandial blood glucose level. This article describes in vitro starch digestibility and its relation to endosperm hardness and composition in cooked maize flours. Starch digestion and estimated glycemic index (GI) were significantly (p < 0.05) lower in hard endosperm genotypes (65.1 and 77.3, respectively) than in soft ones (70.7 and 80.7, respectively), and they were negatively correlated (p < 0.05) with specific zein concentrations (total zeins, Z1, Z2, and C1, E, and F zeins). Cooking with sodium sulfite significantly (p < 0.001) increased starch hydrolysis in all genotypes (∼13%), evidencing the impact of disulfide bonds on this attribute. Explored amylose:starch ratios did not impact starch digestibility. Regardless of hardness, fine grinding significantly (p < 0.001) increased total starch digestibility in >30%. Our results focus on specific kernel physicochemical traits for developing maize food products with lower starch digestibility and GI.

Caballero-Rothar|Nancy N|NN|
Borrás|Lucas|L|
Gerde|José A|JA|

Starch digestibility
Maize
Endosperm hardness
Zein


"Candidatus Thermonerobacter thiotrophicus," A Non-phototrophic Member of the Bacteroidetes/Chlorobi With Dissimilatory Sulfur Metabolism in Hot Spring Mat Communities.

Abstract: In this study we present evidence for a novel, thermophilic bacterium with dissimilatory sulfur metabolism, tentatively named "Candidatus Thermonerobacter thiotrophicus," which is affiliated with the Bacteroides/Ignavibacteria/Chlorobi and which we predict to be a sulfate reducer. Dissimilatory sulfate reduction (DSR) is an important and ancient metabolic process for energy conservation with global importance for geochemical sulfur and carbon cycling. Characterized sulfate-reducing microorganisms (SRM) are found in a limited number of bacterial and archaeal phyla. However, based on highly diverse environmental dsrAB sequences, a variety of uncultivated and unidentified SRM must exist. The recent development of high-throughput sequencing methods allows the phylogenetic identification of some of these uncultured SRM. In this study, we identified a novel putative SRM inhabiting hot spring microbial mats that is a member of the OPB56 clade ("Ca. Kapabacteria") within the Bacteroidetes/Chlorobi superphylum. Partial genomes for this new organism were retrieved from metagenomes from three different hot springs in Yellowstone National Park, United States, and Japan. Supporting the prediction of a sulfate-reducing metabolism for this organism during period of anoxia, diel metatranscriptomic analyses indicate highest relative transcript levels in situ for all DSR-related genes at night. The presence of terminal oxidases, which are transcribed during the day, further suggests that these organisms might also perform aerobic respiration. The relative phylogenetic proximity to the sulfur-oxidizing, chlorophototrophic Chlorobi further raises new questions about the evolution of dissimilatory sulfur metabolism.

Thiel|Vera|V|
Garcia Costas|Amaya M|AM|
Fortney|Nathaniel W|NW|
Martinez|Joval N|JN|
Tank|Marcus|M|
Roden|Eric E|EE|
Boyd|Eric S|ES|
Ward|David M|DM|
Hanada|Satoshi|S|
Bryant|Donald A|DA|

Bacteroidetes/Chlorobi
hot spring
dsrAB
microbial mat
metagenome
metatranscriptome
sulfate reducing bacteria


Clinical Marginal and Internal Adaptation of Maxillary Anterior Single All-Ceramic Crowns and 2-year Randomized Controlled Clinical Trial.

Abstract:
PURPOSE
The aims of this randomized-controlled clinical trial were to compare marginal and internal adaptation of all-ceramic crowns fabricated with CAD/CAM and heat-pressed (HP) techniques before luting and to evaluate the clinical outcomes at baseline and at 6, 12, and 24 months after luting.

MATERIALS AND METHODS
Fifteen CAD/CAM (CC) and 15 HP all-ceramic crowns were placed in 15 patients. A silicone replica was obtained to measure marginal and internal adaptation of each all-ceramic crown before luting, and they were sectioned buccolingually and mesiodistally. Marginal and internal adaptations were measured using computerized light microscope at 40× magnification. Clinical evaluations took place at baseline (2 days after luting) and at 6, 12, and 24 months after luting. Replica scores were analyzed with Mann-Whitney U and Student's t-test (α = 0.05). Survival rate of crowns was determined using Kaplan-Meier statistical analysis.

RESULTS
The median marginal gap for the CC group was 132.2 μm and was 130.2 μm for the HP group. The mean internal adaptation for the CC group was 220.3 ± 51.3 μm and 210.5 ± 31 μm for the HP group. There were no statistically significant differences with respect to marginal opening (Mann-Whitney U test; p = 0.95) and internal adaptation (Student's t-test; p = 0.535) between the 2 groups. Based on modified Ryge criteria, 100% of the crowns were rated satisfactory during the 2-year period.

CONCLUSION
In this in vivo study, CAD/CAM and HP all-ceramic crowns exhibited similar marginal and internal adaptations. A 100% success rate was recorded for the 15 CAD/CAM and for the 15 HP all-ceramic crowns during the 2-year period.

D017076:Computer-Aided Design
D003442:Crowns
D018772:Dental Marginal Adaptation
D003776:Dental Porcelain
D017267:Dental Prosthesis Design
D006801:Humans

internal adaptation
All-ceramic
CAD/CAM
heat-pressed
marginal adaptation


New-graduate physiotherapists' readiness for practice and experiences of managing chronic pain; a qualitative study.

Abstract: Background: Chronic pain management is a challenging area of practice for new graduate physiotherapists entering the workforce. Understanding the readiness and experience of new graduates entering this area of practice is important for informing requirements for preparation for practice.Objective: The aim of this study was to understand the readiness of new graduate physiotherapists in the area of chronic pain management and their experiences in entering clinical practice.Methods: A qualitative study with an inductive thematic approach was used. Semi-structured interviews of 15 new-graduate physiotherapists working in the area of chronic pain were undertaken.Results: Four themes emerged from the semi-structured interviews: 1) the reality of the complex nature of chronic pain; 2) negotiating management with the patient; 3) the role of direct experience; and 4) importance of workplace systems and further training.Discussion and Conclusion: New-graduate physiotherapists reflect strongly on challenges associated with the complexity of chronic pain and subsequent management. Readiness to manage chronic pain is strongly linked to direct experience and workplace support to foster confidence and perceived competency in this area.

D001291:Attitude of Health Personnel
D059350:Chronic Pain
D006801:Humans
D059408:Pain Management
D059825:Physical Therapists
D036301:Qualitative Research
D017132:Workplace

new-graduate
readiness
chronic pain
Physiotherapy
student


Bacterial community succession and degradation patterns of hydrocarbons in seawater at low temperature.

Abstract: The risk of oil spills in cold marine environments is expected to increase in response to trans-Arctic shipping and as Arctic oil reserves get exploited. Marine hydrocarbon-degrading microbes can reduce the impact of spilled hydrocarbons, but their degradation capabilities at low temperature are yet to be uncovered. We combined DNA amplicon sequencing and chemometrics to investigate the effect of decreasing temperature (0-15 °C) on the succession and function of hydrocarbon-degrading bacteria in seawater. The bacterial community and degradation patterns were investigated at time points when a similar amount of hydrocarbons was mineralised at the different temperatures. This allowed decomposing the effect of temperature into a main component related to the reduced microbial activity at low temperature and a secondary effect. The reduced microbial activity at low temperature delayed the microbial community succession and degradation rates. The secondary effect of temperature was most pronounced at 0 °C, where (1) degradation of the least water-soluble n-alkanes (>C12) was suppressed in contrast to a relative stronger degradation of the most water-soluble n-alkanes (<C12) and polycyclic aromatic hydrocarbons; and (2) bacterial taxa which we identified as psychrosensitive were inhibited, whereas taxa identified as psychrophilic flourished.

Vergeynst|Leendert|L|
Kjeldsen|Kasper U|KU|
Lassen|Pia|P|
Rysgaard|Søren|S|

Hydrocarbon
Seawater
Temperature
Microbial community
Biodegradation


Introduction of Medical Humanities in MBBS 1st Year.

Abstract:
Context
Most vital areas of patient management such as empathy, professionalism, and ethics are lacking in fresh undergraduates. These areas are considered to be part of hidden curriculum, and as these are not formally taught, we lack competent medical graduates. Introduction of medical humanities (MH) early in the medical curriculum can help to inculcate required soft skills.

Aims
This study aims to develop, administer, and evaluate MH module in 1st year MBBS students.

Settings and Design
Module of MH was introduced among 150 1st year MBBS medical students.

Subjects and Methods
After taking permission from ethical committee of the institute, a core committee for development of MH module was formed. A standardized validated module for MH comprising of three sessions was formed and was introduced in 1st year MBBS 150 students. Evaluation was done in the form of student and faculty feedback questionnaire, consisting of open- and closed-ended questions.

Statistical Analysis Used
Analysis was done using descriptive statistics using mean and standard deviation.

Results
According to participants' feedback and perception, mean overall rating of MH module was 4.69, indicating that it was received well by the students. Out of 3 sessions conducted, students gave maximum grades to session 2: cinemeducation. Results of faculty feedback questionnaire indicated that MH is needed and should be introduced in every batch of 1st year MBBS and should be continued longitudinally.

Conclusions
Awareness, knowledge, and attitude of students improved as a result of MH module. Our results indicate that such modules should be implemented in undergraduate medical curriculum.

Saiyad|Shaista M|SM|
Paralikar|Swapnil J|SJ|
Verma|Anita P|AP|


Association between LAPTM4B gene polymorphism and susceptibility to and prognosis of diffuse large B-cell lymphoma.

Abstract: Lysosomal protein transmembrane 4β (LAPTM4B) is an oncogene that is overexpressed in a number of various types of human cancer. There are two known alleles of LAPTM4B: LAPTM4B*1 and LAPTM4B*2. The present study assessed the association between LAPTM4B polymorphisms and the susceptibility to diffuse large B-cell lymphoma (DLBCL) and its prognosis. LAPTM4B genotypes were determined using polymerase chain reaction analysis in 164 DLBCL and 350 healthy control cases. The association between LAPTM4B polymorphisms and the risk of DLBCL was analyzed using unconditional logistic regression. Differences in patient survival were calculated using Kaplan-Meier analysis. The present study indicated no significant differences (P>0.05) in the frequency of LAPTM4B*2 alleles between DLBCL cases (26.5%) and controls (24.1%). The risk of DLBCL was slightly increased in cases with the LAPTM4B*1/2 genotype [odds ratio (OR)=1.160; 95% confidence interval (CI)=0.781-1.724] or the LAPTM4B*2/2 genotype (OR=1.446; 95% CI=0.648-3.227) compared with those with the LAPTM4B*1/1 genotype. There was no significant association between the presence of the LAPTM4B*2 allele and overall survival (OS) and disease-free survival (DFS) in patients with DLBCL (P=0.399 and 0.520, respectively). However, there was a tendency for patients with LAPTM4B*2 and International Prognostic Index (IPI) score 3-5 to have longer OS and DFS (P=0.126 and 0.109, respectively). These findings suggest that genetic polymorphisms of LAPTM4B is not a risk factor for the development of DLBCL, but the LAPTM4B*2 allele may a better prognostic indicator in patients with IPI score 3-5 in DLBCL.

Ding|Huirong|H| Cheng|Xiaojing|X| Ding|Ning|N| Tian|Zhihua|Z| Zhu|Jun|J| Zhou|Chunlian|C| Shen|Jing|J| Song|Yuqin|Y|

polymorphism
susceptibility
prognosis
diffuse large B-cell lymphoma
lysosomal protein transmembrane 4β


Linked semiconstrained and unlinked total elbow replacement in juvenile idiopathic arthritis: a case comparison series with mean 11.7-year follow-up.

Abstract:
BACKGROUND
Few series report the results of total elbow replacement (TER) in patients with juvenile idiopathic arthritis (JIA). Most report the use of a linked implant. There are theoretical benefits to using an unlinked prosthesis, and thus we report our experience of the clinical benefit and survivorship of both this implant and a linked semiconstrained prosthesis.

METHODS
There were 21 elbows replaced in 14 JIA patients (12 women and 2 men; 14 unlinked, 7 linked). Mean age at surgery was 39.5 years (range, 26-52 years). Mean clinical follow-up was 11.7 years (range, 5.4-17.6 years).

RESULTS
Reoperation, including implant revision, was required in 9 elbows (42.9%). Using revision as an end point, survivorship was 95% (95% confidence interval [CI], 74%-99%) at 5 years and 68% (95% CI, 45%-86%) at 10 years. The 10-year survival was 70% (95% CI, 40%-89%) for the unlinked group and 69% (95% CI, 28%-94%) for the linked group. The need for bilateral TER was found to be a risk factor for revision within 10 years of primary surgery (6/11 vs. 0/7 elbows; P = .037). The rate of aseptic loosening seen on radiographs was high in the unlinked group (12/14, 85.7%), but many of these patients continue to function well without need for revision.

CONCLUSION
Both the unlinked Kudo 5 and linked Coonrad-Morrey prostheses for TER can provide benefits in the long-term for most patients with JIA. The need for bilateral TER in this group is associated with higher rate of revision at 10 years.

Ibrahim|Edward F|EF|
Rashid|Abbas|A|
Thomas|Michael|M|

linked
semiconstrained
unlinked
Total elbow replacement
elbow arthroplasty
juvenile arthritis


Antiviral activity of gemcitabine against human rhinovirus in vitro and in vivo.

Abstract: Rhinovirus, a major causative agent of the common cold, is associated with exacerbation of asthma and chronic obstructive pulmonary disease. Currently, there is no antiviral treatment or vaccine for human rhinovirus (HRV). Gemcitabine (2',2'-difluorodeoxycytidine, dFdC) is a deoxycytidine analog with antiviral activity against rhinovirus, as well as enterovirus 71, in vitro. However, the antiviral effects of gemcitabine in vivo have not been investigated. In the current study, we assessed whether gemcitabine mediated antiviral effects in the murine HRV infection model. Intranasal administration of gemcitabine significantly lowered pulmonary viral load and inflammation by decreasing proinflammatory cytokines, including TNF-α and IL-1β, and reduction in the number of lung-infiltrating lymphocytes. Interestingly, we found that the addition of UTP and CTP significantly attenuated the antiviral activity of gemcitabine. Thus the limitation of UTP and CTP by the addition of gemcitabine may inhibit the viral RNA synthesis. These results suggest that gemcitabine, an antineoplastic drug, can be repositioned as an antiviral drug to inhibit HRV infection.

Song|Jae-Hyoung|JH| Kim|Seong-Ryeol|SR| Heo|Eun-Young|EY| Lee|Jae-Young|JY| Kim|Dong-Eun|DE| Cho|Sungchan|S| Chang|Sun-Young|SY| Yoon|Byung-Il|BI| Seong|Jeongmin|J| Ko|Hyun-Jeong|HJ|

Gemcitabine
Rhinovirus
Inflammation
Proinflammatory cytokines
Antiviral drug


Thermochemical Measurements of Cation Exchange in CdSe Nanocrystals Using Isothermal Titration Calorimetry.

Abstract: Among the various reported post synthetic modifications of colloidal nanocrystals, cation exchange (CE) is one of the most promising and versatile approaches for the synthesis of nanostructures that cannot be directly synthesized from their constitutive precursors. Numerous studies have reported on the qualitative analysis of these reactions, but rigorous quantitative study of the thermodynamics of CE in colloidal nanoparticles is still lacking. We demonstrate using isothermal titration calorimetry (ITC), the thermodynamics of the CE between cadmium selenide (CdSe) nanocrystals and silver in solution can be quantified. We survey the influence of CdSe nanocrystal diameter, capping ligands and temperature on the thermodynamics of the exchange reaction. Results obtained from ITC provide a detailed description of overall thermodynamic parameters-equilibrium constant ( K eq), enthalpy (Δ H), entropy (Δ S) and stoichiometry ( n)-of the exchange reaction. We compared the free energy change of reaction (Δ G) between CdSe and Ag+ obtained directly from ITC for both CdSe bulk and nanoparticles with values calculated from previously reported methods. While the calculated value is closer to the experimentally obtained Δ G rxn for bulk particles, nanocrystals show an additional Gibbs free energy stabilization of ∼-14 kJ/mol Se. We discuss a thermochemical cycle elucidating the steps involved in the overall cation exchange process. This work demonstrates the application of ITC to probe the thermochemistry of nanoscale transformations under relevant solution conditions.

Jharimune|Suprita|S|
Sathe|Ajay A|AA|
Rioux|Robert M|RM|0000-0002-6019-0032

cation exchange
CdSe nanocrystals
isothermal titration calorimetry
thermodynamics
capping ligands
nanocrystal size


Platelet distribution width as the prognostic marker in coronary bifurcation treatment.

Abstract:
BACKGROUND
Mean platelet volume (MPV) was proved to be a reliable prognostic factor in cardiac patients. However, platelet distribution width (PDW) was disclosed to be more specific marker of platelet reactivity. The aim of study was to evaluate whether baseline PDW value can predict the outcome in patients undergoing percutaneous coronary interventions (PCI) with drug-eluting stent implantation within coronary bifurcation lesions.

MATERIALS AND METHODS
It was a two-centre observational study, which included patients who underwent PCI within bifurcation lesions between January 2014 and December 2014. Thrombocytopenia below 100 000/μL and STEMI were the exclusion criteria. Analysed data came entirely from in-hospital records and information obtained from the 12-month telephone follow-up.

RESULTS
We included 269 patients. Mean PDW value was 13·4 ± 2·5 fL, whereas median was 13 (Q1 < 11·6 fL, Q2 11·6-13 fL, Q3 13-14·8 fL and Q4 > 14·8 fL). We found strong correlation between PDW and MPV (r = 0·96, P < 0·001), but no correlation was revealed between red blood cell distribution width (RDW) and PDW (r = 0·003, P = 0·95) as well as RDW and MPV (r = 0·0018, P = 0·98). Receiver operating characteristics (ROC) curve showed that PDW for cutoff 15·8% can predict MACE rate with sensitivity of 79% and specificity of 47% (area under curve - AUC 0·654; P = 0·01). A ROC curve for PDW categorized by 1-year TLR rate was described by optimal cutoff 16·3%, with sensitivity 69% and specificity 54% (AUC 0·697; P = 0·0015).

CONCLUSIONS
PDW is an affordable and reliable predictor of 1-year MACE and TLR rate after PCI within coronary bifurcation lesions.

D000072658:Non-ST Elevated Myocardial Infarction

platelets
mean platelet volume
red blood cell distribution width


Efficacy and Safety of Fixed-dose Combination Therapy With Telmisartan and Rosuvastatin in Korean Patients With Hypertension and Dyslipidemia: TELSTA-YU (TELmisartan-rosuvaSTAtin from YUhan), a Multicenter, Randomized, 4-arm, Double-blind, Placebo-controlled, Phase III Study.

Abstract:
PURPOSE
Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations.

METHODS
This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared.

FINDINGS
A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, -16.1 [1.6] mm Hg vs -1.7 [2.2] mm Hg [P < 0.001] for MSSBP; -8.8 [1.0] mm Hg vs -1.6 [1.4] mm Hg [P < 0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (-49.3% [2.2%] vs 1.5% [3.0%]; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups.

IMPLICATIONS
Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432.

Oh|Gyu Chul|GC|
Han|Jung-Kyu|JK|
Han|Ki Hoon|KH|
Hyon|Min-Su|MS|
Doh|Joon Hyung|JH|
Kim|Moo Hyun|MH|
Jeong|Jin-Ok|JO|
Bae|Jang-Ho|JH|
Kim|Sang Hyun|SH|
Yoo|Byung-Su|BS|
Baek|Sang Hong|SH|
Rhee|Moo-Yong|MY|
Ihm|Sang-Hyun|SH|
Sung|Jung Hoon|JH|
Choi|Young Jin|YJ|
Kim|Soo-Joong|SJ|
Hong|Kyung-Soon|KS|
Lee|Byoung Kwon|BK|
Cho|JangHyun|J|
Shin|Eun Seok|ES|
Rhew|Jay Young|JY|
Kim|Hyunsu|H|
Kim|Hyo-Soo|HS|

fixed-dose combination
telmisartan
hypertension
dyslipidemia
rosuvastatin calcium