bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV-1 Gag, Envelope, and Extracellular Determinants Cooperate To Regulate the Stability and Turnover of Virological Synapses
Authors: Gardiner Jaye C. , Mauer Eric J. , Sherer Nathan M.
Published: May 2016

Retroviruses spread more efficiently when infected and uninfected cells form tight, physical interfaces known as virological synapses (VSs). VS formation is initiated by adhesive interactions between viral Envelope (Env) glycoproteins on the infected cell and CD4 receptor molecules on the uninfected cell. How high-avidity Env-CD4 linkages are resolved over time is unknown. We describe here a tractable two-color, long-term (>24 h) live cell imaging strategy to study VS turnover in the context of a large cell population, quantitatively. We show that Env's conserved cytoplasmic tail (CT) can potently signal the recruitment of Gag capsid proteins to the VS, a process also dependent on residues within Gag's N-terminal matrix (MA) domain. Additionally, we demonstrate that Env's CT and Gag's MA domain both regulate the duration of interactions between viral donor and target cells, as well as the stability of this interaction over time (i.e., its capacity to resolve or form a syncytium). Finally, we report the unexpected finding that modulating extracellular fluid viscosity markedly impacts target T cell trafficking and thus affects the duration, stability, and turnover of virus-induced cell-cell contacts. Combined, these results suggest a stepwise model for viral cell-to-cell transmission wherein (i) Env-receptor interactions anchor target cells to infected cells, (ii) Env signals Gag's recruitment to the cell-cell contact dependent on an intact Env CT and Gag MA, and (iii) Env CT and Gag MA, in conjunction with extracellular forces, combine to regulate VS stability and infectious outcomes.

IMPORTANCE
HIV-1 spreads efficiently at physical, cell-cell interfaces known as virological synapses (VSs). The VS provides for spatiotemporal coupling of virus assembly and entry into new host cells and may transmit signals relevant to pathogenesis. Disrupting this mode of transmission may be critical to the goal of abolishing viral persistence in infected individuals. We describe here a long-term live cell imaging strategy for studying virus-induced effects on cell behavior in the context of a large cell population. We demonstrate cooperative roles for viral Gag capsid proteins and Envelope glycoproteins in regulating VS formation and turnover. We also show that modulating fluid viscosity markedly affects T cell trafficking and VS stability. Thus, extracellular factors also play an important role in modulating the nature of infectious cell-cell interactions. In sum, our study provides new tools and insights relevant to exposing vulnerabilities in how HIV-1 and other viruses spread infection among cells, tissues, and people.
Identification and Characterization of a Ribose 2′-
O
-Methyltransferase Encoded by the Ronivirus Branch of Nidovirales
Authors: Zeng Cong , Wu Andong , Wang Yi , Xu Shan , Tang Yingke , Jin Xu , Wang Shilei , Qin Lei , Sun Ying , Fan Chengpeng , Snijder Eric J. , Neuman Benjamin W. , Chen Yu , Ahola Tero , Guo Deyin
Published: May 2016

The order
Nidovirales
currently comprises four virus families:
Arteriviridae
,
Coronaviridae
(divided into the subfamilies
Coronavirinae
and
Torovirinae
),
Roniviridae
, and the recently recognized
Mesoniviridae
. RNA cap formation and methylation have been best studied for coronaviruses, with emphasis on the identification and characterization of two virus-encoded methyltransferases (MTases) involved in RNA capping, a guanine-N7-MTase and a ribose-2′-
O
-MTase. Although bioinformatics analyses suggest that these MTases may also be encoded by other nidoviruses with large genomes, such as toroviruses and roniviruses, no experimental evidence has been reported thus far. In this study, we show that a ronivirus, gill-associated virus (GAV), encodes the 2′-
O
-MTase activity, although we could not detect 2′-
O
-MTase activity for the homologous protein of a torovirus, equine torovirus, which is more closely related to coronaviruses. Like the coronavirus 2′-
O
-MTase, the roniviral 2′-
O
-MTase harbors a catalytic K-D-K-E tetrad that is conserved among 2′-
O
-MTases and can target only the N7-methylated cap structure of adenylate-primed RNA substrates. However, in contrast with the coronavirus protein, roniviral 2′-
O
-MTase does not require a protein cofactor for stimulation of its activity and differs in its preference for several biochemical parameters, such as reaction temperature and pH. Furthermore, the ronivirus 2′-
O
-MTase can be targeted by MTase inhibitors. These results extend our current understanding of nidovirus RNA cap formation and methylation beyond the coronavirus family.

IMPORTANCE
Methylation of the 5′-cap structure of viral RNAs plays important roles in genome replication and evasion of innate recognition of viral RNAs by cellular sensors. It is known that coronavirus nsp14 acts as an N7-(guanine)-methyltransferase (MTase) and nsp16 as a 2′-
O
-MTase, which are involved in the modification of RNA cap structure. However, these enzymatic activities have not been shown for any other nidoviruses beyond coronaviruses in the order
Nidovirales
. In this study, we identified a 2′-
O
-methyltransferase encoded by ronivirus that shows common and unique features in comparison with that of coronaviruses. Ronivirus 2′-
O
-MTase does not need a protein cofactor for MTase activity, whereas coronavirus nsp16 needs the stimulating factor nsp10 for its full activity. The conserved K-D-K-E catalytic tetrad is identified in ronivirus 2′-
O
-MTase. These results extend our understanding of nidovirus RNA capping and methylation beyond coronaviruses and also strengthen the evolutionary and functional links between roniviruses and coronaviruses.
Genome Structural Diversity among 31 Bordetella pertussis Isolates from Two Recent U.S. Whooping Cough Statewide Epidemics
Authors: Bowden Katherine E. , Weigand Michael R. , Peng Yanhui , Cassiday Pamela K. , Sammons Scott , Knipe Kristen , Rowe Lori A. , Loparev Vladimir , Sheth Mili , Weening Keeley , Tondella M. Lucia , Williams Margaret M.
Published: May 2016

Pertussis, or whooping cough, is the most poorly controlled vaccine-preventable bacterial disease in the United States, which has experienced a resurgence for more than a decade. Once viewed as a monomorphic pathogen,
B. pertussis
strains circulating during epidemics exhibit diversity visible on a genome structural level, previously undetectable by traditional sequence analysis using short-read technologies. For the first time, we combine short- and long-read sequencing platforms with restriction optical mapping for single-contig,
de novo
assembly of 31 isolates to investigate two geographically and temporally independent U.S. pertussis epidemics. These complete genomes reshape our understanding of
B. pertussis
evolution and strengthen molecular epidemiology toward one day understanding the resurgence of pertussis.
Identification and Characterization of Putative Translocated Effector Proteins of the Edwardsiella ictaluri Type III Secretion System
Authors: Dubytska Lidiya P. , Rogge Matthew L. , Thune Ronald L.
Published: May 2016

The bacterial pathogen
Edwardsiella ictaluri
causes enteric septicemia of catfish (ESC), an economically significant disease of farm-raised channel catfish. Commercial catfish production accounts for the majority of the total fin fish aquaculture in the United States, with almost 300,000 tons produced annually, and ESC is the leading cause of disease loss in the industry. We have demonstrated the survival and replication of
E. ictaluri
within channel catfish cells and identified a secretion system that is essential for
E. ictaluri
intracellular replication and virulence. We have also identified nine proteins encoded in the
E. ictaluri
genome that we believe are actively transferred from the bacterium to the cytoplasm of the host cell and act to manipulate host cell physiology to the advantage of the bacterium. The data presented here confirm that the proteins are actually transferred during an infection, which will lead to further work on approaches to preventing or controlling ESC.
Impact of integrated health system changes, accelerated due to an earthquake, on emergency department attendances and acute admissions: a Bayesian change-point analysis
Authors: Schluter Philip J , Hamilton Greg J , Deely Joanne M , Ardagh Michael W
Published: May 2016

Objective

To chart emergency department (ED) attendance and acute admission following a devastating earthquake in 2011 which lead to Canterbury's rapidly accelerated integrated health system transformations.

Design

Interrupted time series analysis, modelling using Bayesian change-point methods, of ED attendance and acute admission rates over the 2008–2014 period.

Setting

ED department within the Canterbury District Health Board; with comparison to two other district health boards unaffected by the earthquake within New Zealand.

Participants

Canterbury's health system services ∼500 000 people, with around 85 000 ED attendances and 37 000 acute admissions per annum.

Main outcome measures

De-seasoned standardised population ED attendance and acute admission rates overall, and stratified by age and sex, compared before and after the earthquake.

Results

Analyses revealed five global patterns: (1) postearthquake, there was a sudden and persisting decrease in the proportion of the population attending the ED; (2) the growth rate of ED attendances per head of population did not change between the pre-earthquake and postearthquake periods; (3) postearthquake, there was a sudden and persisting decrease in the proportion of the population admitted to hospital; (4) the growth rate of hospital admissions per head of the population declined between pre-earthquake and postearthquake periods and (5) the most dramatic reduction in hospital admissions growth after the earthquake occurred among those aged 65+ years. Extrapolating from the projected and fitted deseasoned rates for December 2014, ∼676 (16.8%) of 4035 projected hospital admissions were avoided.

Conclusions

While both necessarily and opportunistically accelerated, Canterbury's integrated health systems transformations have resulted in a dramatic and sustained reduction in ED attendances and acute hospital admissions. This natural intervention experiment, triggered by an earthquake, demonstrated that integrated health systems with high quality out-of-hospital care models are likely to successfully curb growth in acute hospital demand, nationally and internationally.
Laboratory assessment of vitamin B12status
Authors: Harrington Dominic J
Published: May 2016

The detection and correction of vitamin B12(B12) deficiency prevents megaloblastic anaemia and potentially irreversible neuropathy and neuropsychiatric changes. B12status is commonly estimated using the abundance of the vitamin in serum, with ∼148 pmol/L (200 ng/L) typically set as the threshold for diagnosing deficiency. Serum B12assays measure the sum of haptocorrin-bound and transcobalamin-bound (known as holotranscobalamin) B12. It is only holotranscobalamin that is taken up by cells to meet metabolic demand. Although receiver operator characteristic curves show holotranscobalamin measurement to be a moderately more reliable marker of B12status than serum B12, both assays have an indeterminate range. Biochemical evidence of metabolic abnormalities consistent with B12insufficiency is frequently detected despite an apparently sufficient abundance of the vitamin. Laboratory B12status markers that reflect cellular utilisation rather than abundance are available. Two forms of B12act as coenzymes for two different reactions. Methionine synthase requires methylcobalamin for the remethylation of methionine from homocysteine. A homocysteine concentration >20 µmol/L may suggest B12deficiency in folate-replete patients. In the second B12-dependent reaction, methylmalonyl-CoA mutase uses adenosylcobalamin to convert methylmalonyl-CoA to succinyl-CoA. In B12deficiency excess methylmalonyl-CoA is hydrolysed to methylmalonic acid. A serum concentration >280 nmol/L may suggest suboptimal status in young patients with normal renal function. No single laboratory marker is suitable for the assessment of B12status in all patients. Sequential assay selection algorithms or the combination of multiple markers into a single diagnostic indicator are both approaches that can be used to mitigate inherent limitations of each marker when used independently.
Value of SATB2 immunostaining in the distinction between small intestinal and colorectal adenocarcinomas
Authors: Kim Christopher J , Baruch-Oren Tamar , Lin Fan , Fan Xuemo (Sean) , Yang Ximing J , Wang Hanlin L
Published: May 2016

Aims

Special AT-rich sequence-binding protein 2 (SATB2) is a novel immunomarker that is expressed in glandular cells of the lower gastrointestinal tract with retained expression in the majority of primary and metastatic colorectal adenocarcinomas (CRCs). Because of its tissue specificity, SATB2 has been shown to be a clinically useful marker to distinguish CRC from non-CRC. In this study, we investigated whether or not SATB2 can help differentiate CRC from small intestinal adenocarcinoma (SIA), a practical diagnostic challenge due to their morphological and immunophenotypic similarities.

Methods

Fifty surgically resected primary SIAs and 50 CRCs were immunohistochemically examined for the expression of SATB2. Positive staining was graded as 1+ (5–25% of the tumour cells stained), 2+ (26–50%), 3+ (51–75%) or 4+ (>75%), as well as weak, intermediate or strong for staining intensity.

Results

Positive SATB2 immunoreactivity was observed in 23 (46%) SIAs in contrast to 48 (96%) CRCs (p<0.0001). Among these, only 4 (8%) SIAs showed strong and diffuse (4+) SATB2 staining compared with 38 (76%) of CRCs (p<0.0001).

Conclusions

SATB2 is not entirely CRC-specific and is expressed in a subset of SIAs. Unlike CRC, however, SIA infrequently shows a strong and diffuse staining pattern, which still makes SATB2 a useful immunomarker to distinguish SIA from CRC.
Reproductive strategy of a migratory fish stock: implications of spatial variations in natural mortality
Authors: Langangen Øystein , Ottersen Geir , Ciannelli Lorenzo , Vikebø Frode B. , Stige Leif Christian
Published: May 2016

We investigate how the reproductive strategy in a migratory marine fish may be influenced by spatial variations in mortality in early life stages. In particular, we examine how spawning time and location affect offspring survival and growth. A drift model for early life stages (eggs to age 1) of the Barents Sea cod (Gadus morhua) is combined with empirical estimates of spatial variation in mortality at two different life stages. We examine seasonal and interannual differences in survival and growth in offspring originating from two spawning grounds, with the central site requiring higher migration distance, and hence cost, than the northern site. When accounting for spatially explicit mortality fields, central and northern spawned offspring have about equal survival, as do early and late spawned offspring. Furthermore, central spawned offspring grow faster and are likely to reach a larger size compared with northern spawned offspring. Our results indicate that the fitness benefit of southward migration in the Barents Sea cod is not mainly due to higher early survival of offspring, but rather due to effects of offspring acquiring a larger size.
Long-term monitoring reveals the success of salmonid habitat restoration
Authors: Louhi Pauliina , Vehanen Teppo , Huusko Ari , Mäki-Petäys Aki , Muotka Timo
Published: May 2016

The growing concern on declining salmonid populations has resulted in numerous restoration projects with variable responses worldwide. In this spatially replicated multiyear study, we assessed the long-term (12 years postrestoration) effects of in-stream habitat restoration (i.e., addition of boulders or large woody debris (LWD) together with boulders) on densities of three age-classes of juvenile brown trout (Salmo trutta) in six forest streams in northern Finland. LWD combined with boulders was more beneficial, particularly for the larger trout (age-2 and older), than were boulder structures alone, indicating that the more diverse habitat created by LWD may have provided a safeguard against drought for the larger fish. Density of age-0+ trout showed a significant long-term increase in boulder-restored sections, providing evidence that log structures may need to be complemented by stony enhancement structures to guarantee the availability of suitable stream habitat for all trout age-classes. As trout densities are known to exhibit inherently wide interannual variability that tracks climatically induced hydrological variation, long-term postrestoration monitoring that encompasses extreme hydrological events is critical for evaluating the success of restoration projects.
Nucleotide diversity, natural variation, and evolution ofFlexible culm-1andStrong culm-2lodging resistance genes in rice
Authors: Rashid Muhammad Abdul Rehman , Zhao Yan , Zhang Hongliang , Li Jinjie , Li Zichao
Published: May 2016

Lodging resistance is one of the vital traits in yield improvement and sustainability. Culm wall thickness, diameter, and strength are different traits that can govern the lodging resistance in rice. The genes SCM2 and FC1 have been isolated for culm thickness, strength, and flexibility, but their functional nucleotide variations were still unknown. We used a 13× deep sequence of 795 diverse genotypes to present the functional variation and SNP diversity in SCM2 and FC1. The major functional variant for the SCM2 gene was at position 27480181 and for the FC1 gene at position 31072992. Haplotype analysis of both genes provided their various allelic differences among haplotypes. SCM2 alleles further presented the evolution of Oryza sativa L. subsp. indica and subsp. japonica genomes from common parent in different geographical zones, while the haplotypes of FC1 suggested their evolution from different strains of the common parent Oryza rufipogon. SCM2 showed purifying selection and functional associations with rare alleles, while FC1 displayed balanced selection favored by multiple heterozygous alleles. Genotypes with an allelic combination of SCM2-3 and FC1-2 in japonica background exhibited striking resistance against lodging, which can be used in further breeding programs.
From the Flamm–Einstein–Rosen bridge to the modern renaissance of traversable wormholes
Authors: Lobo Francisco S. N.
Published: May 2016

We consider the possibility of multiply-connected spacetimes, ranging from the Flamm–Einstein–Rosen bridge, geons, and the modern renaissance of traversable wormholes. A fundamental property in wormhole physics is the flaring-out condition of the throat, which through the Einstein field equation entails the violation of the null energy condition (NEC). In the context of modified theories of gravity, it has also been shown that the normal matter can be imposed to satisfy the energy conditions, and it is the higher order curvature terms, interpreted as a gravitational fluid, that sustain these nonstandard wormhole geometries, fundamentally different from their counterparts in general relativity (GR). We explore interesting features of these geometries, in particular, the physical properties and characteristics of these ‘exotic spacetimes’.
Experimental and DFT computational studies of L-alanine cadmium chloride crystals
Authors: Ignatius I. Cicili , Dheivamalar S. , Kirubavathi K. , Selvaraju K.
Published: May 2016

In this work, we report the combined experimental and theoretical study on molecular structure and vibrational spectra of nonlinear optical crystal L-alanine cadmium chloride (LACC). The single X-ray diffraction studies have revealed that the compound crystallizes in monoclinic system C2 space group with cell parameters [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text]. FTIR and Raman spectra of the nonlinear optical materials LACC have been recorded and analyzed. The optimized geometric bond length and bond angles are obtained with the help of density functional theory (DFT) (B3LYP) calculation. The optimized geometric bond lengths and bond angles obtained by using DFT show good agreement with the experimental data. Using the natural bond orbital analysis the electronic effect and hydrogen bonding were confirmed. The HOMO–LUMO energy gap and the first order hyperpolarizability were calculated and it supports the nonlinear optical activity of LACC crystal.
Chronic anemic hypoxemia increases plasma glucagon and hepatic PCK1 mRNA in late-gestation fetal sheep
Authors: Culpepper Christine , Wesolowski Stephanie R. , Benjamin Joshua , Bruce Jennifer L. , Brown Laura D. , Jonker Sonnet S. , Wilkening Randall B. , Hay William W. , Rozance Paul J.
Published: May 2016

Hepatic glucose production (HGP) normally begins just prior to birth. Prolonged fetal hypoglycemia, intrauterine growth restriction, and acute hypoxemia produce an early activation of fetal HGP. To test the hypothesis that prolonged hypoxemia increases factors which regulate HGP, studies were performed in fetuses that were bled to anemic conditions (anemic: n = 11) for 8.9 ± 0.4 days and compared with control fetuses ( n = 7). Fetal arterial hematocrit and oxygen content were 32% and 50% lower, respectively, in anemic vs. controls ( P < 0.005). Arterial plasma glucose was 15% higher in the anemic group ( P < 0.05). Hepatic mRNA expression of phosphonenolpyruvate carboxykinase ( PCK1) was twofold higher in the anemic group ( P < 0.05). Arterial plasma glucagon concentrations were 70% higher in anemic fetuses compared with controls ( P < 0.05), and they were positively associated with hepatic PCK1 mRNA expression ( P < 0.05). Arterial plasma cortisol concentrations increased 90% in the anemic fetuses ( P < 0.05), but fetal cortisol concentrations were not correlated with hepatic PCK1 mRNA expression. Hepatic glycogen content was 30% lower in anemic vs. control fetuses ( P < 0.05) and was inversely correlated with fetal arterial plasma glucagon concentrations. In isolated primary fetal sheep hepatocytes, incubation in low oxygen (3%) increased PCK1 mRNA threefold compared with incubation in normal oxygen (21%). Together, these results demonstrate that glucagon and PCK1 may potentiate fetal HGP during chronic fetal anemic hypoxemia.
Recording extracellular neural activity in the behaving monkey using a semichronic and high-density electrode system
Authors: Mendoza Germán , Peyrache Adrien , Gámez Jorge , Prado Luis , Buzsáki György , Merchant Hugo
Published: May 2016

We describe a technique to semichronically record the cortical extracellular neural activity in the behaving monkey employing commercial high-density electrodes. After the design and construction of low cost microdrives that allow varying the depth of the recording locations after the implantation surgery, we recorded the extracellular unit activity from pools of neurons at different depths in the presupplementary motor cortex (pre-SMA) of a rhesus monkey trained in a tapping task. The collected data were processed to classify cells as putative pyramidal cells or interneurons on the basis of their waveform features. We also demonstrate that short time cross-correlogram occasionally yields unit pairs with high short latency (<5 ms), narrow bin (<3 ms) peaks, indicative of monosynaptic spike transmission from pre- to postsynaptic neurons. These methods have been verified extensively in rodents. Finally, we observed that the pattern of population activity was repetitive over distinct trials of the tapping task. These results show that the semichronic technique is a viable option for the large-scale parallel recording of local circuit activity at different depths in the cortex of the macaque monkey and other large species.
Role of expected reward in frontal eye field during natural scene search
Authors: Glaser Joshua I. , Wood Daniel K. , Lawlor Patrick N. , Ramkumar Pavan , Kording Konrad P. , Segraves Mark A.
Published: May 2016

When a saccade is expected to result in a reward, both neural activity in oculomotor areas and the saccade itself (e.g., its vigor and latency) are altered (compared with when no reward is expected). As such, it is unclear whether the correlations of neural activity with reward indicate a representation of reward beyond a movement representation; the modulated neural activity may simply represent the differences in motor output due to expected reward. Here, to distinguish between these possibilities, we trained monkeys to perform a natural scene search task while we recorded from the frontal eye field (FEF). Indeed, when reward was expected (i.e., saccades to the target), FEF neurons showed enhanced responses. Moreover, when monkeys accidentally made eye movements to the target, firing rates were lower than when they purposively moved to the target. Thus, neurons were modulated by expected reward rather than simply the presence of the target. We then fit a model that simultaneously included components related to expected reward and saccade parameters. While expected reward led to shorter latency and higher velocity saccades, these behavioral changes could not fully explain the increased FEF firing rates. Thus, FEF neurons appear to encode motivational factors such as reward expectation, above and beyond the kinematic and behavioral consequences of imminent reward.
Dysregulation of Vascular Endothelial Progenitor Cells Lung-Homing in Subjects with COPD
Authors: Salter Brittany M. , Manzoor Fizza , Beaudin Suzanne , Kjarsgaard Melanie , Nair Parameswaran , Gauvreau Gail M. , Sehmi Roma
Published: May 2016

Chronic obstructive pulmonary disease (COPD) is characterized by fixed airflow limitation and progressive decline of lung function and punctuated by occasional exacerbations. The disease pathogenesis may involve activation of the bone marrow stimulating mobilization and lung-homing of progenitor cells. We investigated the hypothesis that lower circulating numbers of vascular endothelial progenitor cells (VEPCs) are a consequence of increased lung-sequestration in COPD. Nonatopic, current or ex-smokers with diagnosed COPD and nonatopic, nonsmoking normal controls were enrolled. Blood and induced sputum extracted primitive hemopoietic progenitors (HPCs) and VEPC were enumerated by flow cytometry. Migration and adhesive responses to fibronectin were assessed. In sputum, VEPC numbers were significantly greater in COPD compared to normal controls. In blood, VEPCs were significantly lower in COPD versus normal controls. There were no differences in HPC levels between the two groups in either compartment. Functionally, there was a greater migrational responsiveness of progenitors from COPD subjects to stromal cell-derived factor-1alpha (SDF-1α) compared to normal controls. This was associated with greater numbers of CXCR4+progenitors in sputum from COPD. Increased migrational responsiveness of progenitor cells may promote lung-homing of VEPC in COPD which may disrupt maintenance and repair of the airways and contribute to COPD disease pathogenesis.
Effect of Colonoscopy Volume on Quality Indicators
Authors: Pace David , Borgaonkar Mark , Lougheed Muna , Marcoux Curtis , Evans Brad , Hickey Nikita , O’Leary Meghan , Boone Darrell , McGrath Jerry
Published: May 2016

Background. The purpose of this study is to determine if colonoscopy quality is associated with the annual case volume of endoscopists.Methods. A retrospective cohort study was performed on 3235 patients who underwent colonoscopy in the city of St. John’s, NL, between January and June 2012. Data collected included completion of colonoscopy (CCR) and adenoma detection rates (ADR). Endoscopists were divided into quintiles based on annual case volume. To account for potential confounding variables, univariate analyses followed by multivariable logistic regression were used to identify variables independently associated with CCR and ADR.Results. A total of 13 surgeons and 8 gastroenterologists were studied. There was a significant difference in CCR (p< 0.001) and ADR (p< 0.001) based on annual volume. Following multivariable regression, predictors of successful colonoscopy completion included annual colonoscopy volume, lower age, male sex, an indication of screening or surveillance, and a low ASA score. Predictors of adenoma detection included older age, male sex, an indication of screening or surveillance, and gastroenterology specialty.Conclusion. Higher annual case volume is associated with better quality of colonoscopy in terms of completion. However, gastroenterology specialty appears to be a better predictor of ADR than annual case volume.
Human Papilloma Virus Persistence after Cone Excision in Women with Cervical High Grade Squamous Intraepithelial Lesion: A Prospective Study
Authors: Pirtea Laurențiu , Grigoraş Dorin , Matusz Petru , Pirtea Marilena , Moleriu Lavinia , Tudor Anca , Ilina Răzvan , Secoşan Cristina , Horhat Florin , Mazilu Octavian
Published: May 2016

Background. Persistent human papillomavirus (HPV) infection is a necessary event in cervical cancer tumorigenesis. Our objectives were to estimate the rate of HPV infection persistence after large loop excision of the transformation zone (LEEP) in patients with high grade squamous intraepithelial lesions (HSIL) and to investigate if HPV persistence is type related.Methods. We conducted a prospective study on 89 patients with HSIL treated with LEEP. DNA HPV was performed before surgery and at 6, 12, and 18 months after LEEP.Results. Four patients were excluded from the study. The HPV persistence in the remaining 85 patients was 32.95% (6 months), 14.12% (12 months), and 10.59% (18 months). Type 16 had the highest persistence rate, 23.5% (6 months), 11.8% (12 months), and 8.2% (18 months). Coinfection was found to be 54.12% before LEEP and 18.8% (6 months), 4.7% (12 months), and 3.5% (18 months) after LEEP. The rate of coinfections including type 16 was 46.83% of all coinfections. Coinfection including type 16 was not correlated with higher persistence rate compared to infection with type 16 only.Conclusions. HPV infection is not completely eradicated by LEEP in patients with HSIL lesion on PAP smear. HPV persistence after LEEP is influenced by HPV type. HPV type 16 has the highest persistence rate.
Comparing the Knotless Tension Band and the Traditional Stainless Steel Wire Tension Band Fixation for Medial Malleolus Fractures: A Retrospective Clinical Study
Authors: Downey Michael W. , Duncan Kyle , Kosmopoulos Victor , Motley Travis A. , Carpenter Brian B. , Ogunyankin Fadeke , Garrett Alan
Published: May 2016

The traditional stainless steel wire tension band (WTB) has been popularized for small avulsion fractures at the medial malleolus. Despite the tension band principle creating a stable construct, complications continue to arise utilizing the traditional stainless steel WTB with patients experiencing hardware irritation at the tension band site and subsequent hardware removal. Coupled with hardware irritation is fatigue failure with the wire. The goal of this investigation was to retrospectively compare this traditional wire technique to an innovative knotless tension band (KTB) technique in order to decrease costly complications. A total of 107 patients were reviewed with a minimum follow-up of 1 year. Outcome measures include descriptive data, fracture classification, results through economic costs, and fixation results (including hardware status, healing status, pain status, and time to healing). The KTB group had a 13% lower true cost as compared to the WTB group while the fixation results were equivocal for the measured outcomes. Our results demonstrate that the innovative KTB is comparable to the traditional WTB while offering a lower true cost, an irritation free reduction all without the frustration of returning to the operating room for additional hardware removal, which averages approximately to $8,288.
Influence of the Copper-Containing SBA-15 Silica Fillers on the Mechanical Properties of High Density Polyethylene
Authors: Gnatowski Adam , Jelonkiewicz Jerzy , Laskowski Łukasz , Laskowska Magdalena
Published: May 2016

The paper concerns the mechanical properties of the high density polyethylene (HDPE) with the copper-containing SBA-15 silica filler. The considered filler is the SBA-15 mesoporous silica containing copper ions bounded inside channels via propyl-phosphonate anchoring groups. With its help, we can impart the biocidal properties to this plastic. Research covered mechanical properties, thermal analysis, colour, shine, and nanomolecular structure. Dynamical properties of the samples like modulusE′changes and mechanical core loss angle tangenttgδversus temperature and vibration frequency were tested using DMTA method. Level of crystallinity was tested using DSC method while their structure was observed with going through light by optical microscope. Hardness and toughness of obtained samples were also defined. Colour and shine changes of the samples were observed for PE-HD with filler contents 0.5% and 1%. Modulus value changes versus temperature and frequency were notified for the samples with modifier. There were no differences in modulus changes versus temperature for samples with and without filler and frequencies 1 and 10 Hz. It was detected that melting enthalpy of the samples with the modifier decreases. Moreover, some influence of the samples with filler on colour and shine was observed.
Heuristic Data Placement for Data-Intensive Applications in Heterogeneous Cloud
Authors: Zhao Qing , Xiong Congcong , Wang Peng
Published: May 2016

Data placement is an important issue which aims at reducing the cost of internode data transfers in cloud especially for data-intensive applications, in order to improve the performance of the entire cloud system. This paper proposes an improved data placement algorithm for heterogeneous cloud environments. In the initialization phase, a data clustering algorithm based on data dependency clustering and recursive partitioning has been presented, and both the factor of data size and fixed position are incorporated. And then a heuristic tree-to-tree data placement strategy is advanced in order to make frequent data movements occur on high-bandwidth channels. Simulation results show that, compared with two classical strategies, this strategy can effectively reduce the amount of data transmission and its time consumption during execution.
A Hybrid IP/GA Approach to the Parallel Production Lines Scheduling Problem
Authors: Ren Huizhi , Sun Shenshen
Published: May 2016

A special parallel production lines scheduling problem is studied in this paper. Considering the time window and technical constraints, a mixed integer linear programming (MILP) model is formulated for the problem. A few valid inequalities are deduced and a hybrid mixed integer linear programming/constraint programming (MILP/CP) decomposition strategy is introduced. Based on them, a hybrid integer programming/genetic algorithm (IP/GA) approach is proposed to solve the problem. At last, the numerical experiments demonstrate that the proposed solution approach is effective and efficient.
Is the ASA Score in Geriatric Hip Fractures a Predictive Factor for Complications and Readmission?
Authors: Kastanis G. , Topalidou A. , Alpantaki K. , Rosiadis M. , Balalis K.
Published: May 2016

Hip fractures are the second cause of hospitalization in geriatric patients. The American Society of Anesthesiologists (ASA) classification scheme is a scoring system for the evaluation of the patients’ health and comorbidities before an operative procedure. The purpose of this study was to determine whether the ASA score is a predictive factor for perioperative and postoperative complications and a cause of readmission of geriatric patients with hip fractures. The study included 198 elderly patients. The mean values of hospitalization were6.4±2.1days for the patients with ASA II,10.4±3.4days for the patients with ASA III, and13.5±4.4days for the patients with ASA IV. The patients with ASA II exhibited minor complications, while patients with ASA III presented cutaneous ulcer and respiratory dysfunction. Five patients with ASA IV had pulmonary embolism, two patients had myocardial infarction, and three patients died. The ASA score seems to have direct correlation with multiple factors, such as the hospitalization days, the severity of the complications, and the total hospitalization costs. The treatment of geriatrics hip fractures in patients with a high ASA score requires a multidisciplinary approach and a special assessment in order to decrease postoperative morbidity and mortality and offer optimal functionality.
HCV‐Induced Oxidative Stress: Battlefield‐Winning Strategy
Authors: Rebbani Khadija , Tsukiyama-Kohara Kyoko
Published: May 2016

About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β‐hydroxysterol Δ24‐reductase (DHCR24) is one of the newly discovered host markers of oxidative stress. This protein, as HCV‐induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV‐induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis.
The Relevance of the Use of Radiographic Planning in Order to Avoid Complications in Mandibular Implantology: A Retrospective Study
Authors: Sammartino Gilberto , Prados-Frutos Juan Carlos , Riccitiello Francesco , Felice Pietro , Cerone Vincenzo , Gasparro Roberta , Wang Hom-Lay
Published: May 2016

The aim of this retrospective radiological study was to evaluate the variability of the mandibular anatomy in the presence and absence of teeth and to consider how it could influence implant planning. 187 mandibular CT DentaScans were selected from our department archive according to the inclusion criteria. The axial height, vertical height, angulation of the bone crest, and the bone available for ideal implant placement were measured. The analysis of the data shows that the mandible contour presents a constant degree of angulation. The variation of angulation in the absence of teeth was statistically significant only in the region between the canine and the first premolar and in that between the second premolar and the first molar. The difference between the crest height and the available distance to place the implant was greater in the region of the second molar while in the other regions the implant planning was made complex by postextraction resorption. Alveolar bone resorption after tooth loss can be considered as a risk factor for lingual cortical perforation during the insertion of an implant. To avoid potential intra/postoperative complications, 3D radiographic examination is recommended in order to study the mandibular anatomy and identify the risk areas.
Probing Neural Transplant Networks In Vivo with Optogenetics and Optogenetic fMRI
Authors: Weitz Andrew J. , Lee Jin Hyung
Published: May 2016

Understanding how stem cell‐derived neurons functionally integrate into the brain upon transplantation has been a long sought‐after goal of regenerative medicine. However, methodological limitations have stood as a barrier, preventing key insight into this fundamental problem. A recently developed technology, termed optogenetic functional magnetic resonance imaging (ofMRI), offers a possible solution. By combining targeted activation of transplanted neurons with large‐scale, noninvasive measurements of brain activity, ofMRI can directly visualize the effect of engrafted neurons firing on downstream regions. Importantly, this tool can be used to identify not only whether transplanted neurons have functionally integrated into the brain, but also which regions they influence and how. Furthermore, the precise control afforded over activation enables the input‐output properties of engrafted neurons to be systematically studied. This review summarizes the efforts in stem cell biology and neuroimaging that made this development possible and outlines its potential applications for improving and optimizing stem cell‐based therapies in the future.
A Comparison between Three-Dimensional Visualization Guided Hepatectomy and Ultrasonography Guided Radiofrequency Ablation in the Treatment of Small Hepatocellular Carcinoma within the Milan Criteria
Authors: Guan Tian-pei , Fang Chi-hua , Yang Jian , Xiang Nan , Chen Qing-shan , Zhong Shi-zhen
Published: May 2016

Background. Treatment selection for small hepatocellular carcinoma (sHCC) is controversial. We aimed to compare the outcomes of medical imaging three-dimensional visualization system (MI-3DVS) guided surgical resection (SR) and ultrasonography guided radiofrequency ablation (RFA) for sHCC.Methods. In total, 194 patients who underwent SR or RFA in our hospital between January 2006 and May 2010 were retrospectively enrolled. Overall survival (OS), recurrence-free survival (RFS), and postoperative complications were compared. Cox regression was used to estimate the benefits of MI-3DVS-guided SR on OS and RFS.Results. Ninety-two patients underwent SR and 102 underwent RFA. The SR group experienced more complications (41.3% versus 19.6%) and longer hospital stay (18.04±7.11versus13.06±5.59) (bothp<0.05). The 1-, 2-, 3-, 4-, and 5-year OS was 96.7%, 95.7%, 93.5%, 83.5%, and 61.1% in the SR group and 95.0%, 88.1%, 72.7%, 56.9%, and 39.5% in the RFA group. Corresponding RFS was 95.7%, 94.6%, 84.7%, 59.8%, and 40.2% in SR group and 91.2%, 80.3%, 60.5%, 32.3%, and 22.3% in RFA group. The 5-year OS and RFS were higher in SR group (bothp<0.001). Interestingly, there was no significance in OS and RFS among subgroups aged >60 years. Independent predictors of OS and RFS, respectively, were intervention (HR, 2.769 and 1.933), tumor number (HR, 5.128 and 3.903), and serum alpha-fetoprotein (AFP) (HR, 1.871 and 1.474) (allp<0.05).Conclusions. MI-3DVS based hepatectomy should be considered primary treatment while RFA can be treated as alternative therapy for older patients. Intervention, tumor number, and AFP are independent predictors for both survival and recurrence.
Ratio of Circulating IFNγ+“Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project
Authors: Kotake Shigeru , Nanke Yuki , Yago Toru , Kawamoto Manabu , Kobashigawa Tsuyoshi , Yamanaka Hisashi
Published: May 2016

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ+Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ+Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies.
Oral Health Status and Treatment Needs among Pregnant Women of Raichur District, India: A Population Based Cross-Sectional Study
Authors: Gupta Ritu , Acharya Arun Kumar
Published: May 2016

Background and Objectives. Pregnancy can be a risk factor for dental diseases as oral tissues are liable to changes due to hormonal variations. The aim of the study was to assess the oral health status and treatment needs among pregnant women of Raichur district, Karnataka, India.Methods. Cross-sectional data was collected from 300 primigravidae from all the 5 taluks of Raichur district visiting the respective community health centre at taluk headquarters. A specially designed questionnaire was used to assess the demographic variables and oral hygiene practices. A clinical examination was done according to WHO (World Health Organization) criteria 1997 and recorded using WHO Oral Health Assessment Form.Results. The mean age of the pregnant women in the study was 21.8 (2.12) years. The prevalence of caries and periodontal diseases was 62.7% and 95%, respectively. The mean DT, MT, FT, and DMFT were 2.06 (2.5), 0.03 (0.17), 0.04 (0.27), and 2.13 (2.54), respectively. The mean OHI-S was 2.87 (1.27). Chi-square test showed that CPI scores increased with the trimester of pregnancy.Conclusion. The present study demonstrates poor oral hygiene and high prevalence of periodontal diseases, as well as a large proportion of unmet dental treatment needs among pregnant women of Raichur district, India.
Molecular Pathways: Targeting DNA Repair Pathway Defects Enriched in Metastasis
Authors: Corcoran Niall M. , Clarkson Michael J. , Stuchbery Ryan , Hovens Christopher M.
Published: May 2016

The maintenance of a pristine genome, free from errors, is necessary to prevent cellular transformation and degeneration. When errors in DNA are detected, DNA damage repair (DDR) genes and their regulators are activated to effect repair. When these DDR pathways are themselves mutated or aberrantly downregulated, cancer and neurodegenerative disorders can ensue. Multiple lines of evidence now indicate, however, that defects in key regulators of DNA repair pathways are highly enriched in human metastasis specimens and hence may be a key step in the acquisition of metastasis and the ability of localized disease to disseminate. Some of the key regulators of checkpoints in the DNA damage response are the TP53 protein and the PARP enzyme family. Targeting of these pathways, especially through PARP inhibition, is now being exploited therapeutically to effect significant clinical responses in subsets of individuals, particularly in patients with ovarian cancer or prostate cancer, including cancers with a marked metastatic burden. Targeting DNA repair–deficient tumors with drugs that take advantage of the fundamental differences between normal repair–proficient cells and repair-deficient tumors offers new avenues for treating advanced disease in the future. Clin Cancer Res; 22(13); 3132–7. ©2016 AACR.