bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular Localization of HIV-1
gag-pol
mRNAs Regulates Sites of Virion Assembly
Authors: Becker Jordan T. , Sherer Nathan M.
Published: January 2017

Full-length unspliced human immunodeficiency virus type 1 (HIV-1) RNAs serve dual roles in the cytoplasm as mRNAs encoding the Gag and Gag-Pol capsid proteins as well as genomic RNAs (gRNAs) packaged by Gag into virions undergoing assembly at the plasma membrane (PM). Because Gag is sufficient to drive the assembly of virus-like particles even in the absence of gRNA binding, whether viral RNA trafficking plays an active role in the native assembly pathway is unknown. In this study, we tested the effects of modulating the cytoplasmic abundance or distribution of full-length viral RNAs on Gag trafficking and assembly in the context of single cells. Increasing full-length viral RNA abundance or distribution had little-to-no net effect on Gag assembly competency when provided in
trans
. In contrast, artificially tethering full-length viral RNAs or surrogate
gag-pol
mRNAs competent for Gag synthesis to non-PM membranes or the actin cytoskeleton severely reduced net virus particle production. These effects were explained, in large part, by RNA-directed changes to Gag's distribution in the cytoplasm, yielding aberrant subcellular sites of virion assembly. Interestingly, RNA-dependent disruption of Gag trafficking required either of two
cis
-acting RNA regulatory elements: the 5′ packaging signal (Psi) bound by Gag during genome encapsidation or, unexpectedly, the Rev response element (RRE), which regulates the nuclear export of gRNAs and other intron-retaining viral RNAs. Taken together, these data support a model for native infection wherein structural features of the
gag-pol
mRNA actively compartmentalize Gag to preferred sites within the cytoplasm and/or PM.

IMPORTANCE
The spatial distribution of viral mRNAs within the cytoplasm can be a crucial determinant of efficient translation and successful virion production. Here we provide direct evidence that mRNA subcellular trafficking plays an important role in regulating the assembly of human immunodeficiency virus type 1 (HIV-1) virus particles at the plasma membrane (PM). Artificially tethering viral mRNAs encoding Gag capsid proteins (
gag-pol
mRNAs) to distinct non-PM subcellular locales, such as cytoplasmic vesicles or the actin cytoskeleton, markedly alters Gag subcellular distribution, relocates sites of assembly, and reduces net virus particle production. These observations support a model for native HIV-1 assembly wherein HIV-1
gag-pol
mRNA localization helps to confine interactions between Gag, viral RNAs, and host determinants in order to ensure virion production at the right place and right time. Direct perturbation of HIV-1 mRNA subcellular localization may represent a novel antiviral strategy.
Gut Microbiome of the Canadian Arctic Inuit
Authors: Girard Catherine , Tromas Nicolas , Amyot Marc , Shapiro B. Jesse
Published: January 2017

Non-Western populations have been shown to have distinct gut microbial communities shaped by traditional diets. The hitherto-uncharacterized microbiome of the Inuit may help us to better understand health risks specific to this population such as diabetes and obesity, which increase in prevalence as many Inuit transition to a Western diet. Here we show that even Inuit consuming a mostly traditional diet have a broadly Western-like microbiome. This suggests that similarities between the Inuit diet and the Western diet (low fiber, high fat) may lead to a convergence of community structures and diversity. However, certain species and strains of microbes have significantly different levels of abundance and diversity in the Inuit, possibly driven by differences in diet. Furthermore, the Inuit diet provides an exception to the correlation between traditional diets and high microbial diversity, potentially due to their transitioning diet. Knowledge of the Inuit microbiome may provide future resources for interventions and conservation of Inuit heritage.
Long-term effect of intensive lifestyle intervention on cardiovascular risk factors in patients with diabetes in real-world clinical practice: a 5-year longitudinal study
Authors: Hamdy Osama , Mottalib Adham , Morsi Amr , El-Sayed Nuha , Goebel-Fabbri Ann , Arathuzik Gillian , Shahar Jacqueline , Kirpitch Amanda , Zrebiec John
Published: January 2017

Objective

We evaluated long-term impact of sustained weight loss versus weight regain on cardiovascular risk factors in real-world clinical practice.

Methods

We evaluated 129 obese patients with diabetes enrolled in Weight Achievement and Intensive Treatment (Why WAIT) program, a 12-week clinical model of intensive lifestyle intervention. After 1 year, we divided participants into group A, who maintained <7% weight loss (47.3%) and group B (52.7%), who maintained ≥7% weight loss. We continued to follow them for a total of 5 years.

Results

The total cohort lost 23.8 lbs (−9.7%) at 12 weeks and maintained −16.2 lbs (−6.4%) at 5 years (p<0.001). Group A maintained −8.4 lbs (−3.5%) and group B maintained −23.1 lbs (−9.0%) at 5 years. In group A, A1C decreased from 7.5±1.3% to 6.7±0.9% at 12 weeks but increased to 7.7±1.4% at 1 year and 8.0±1.9% at 5 years. In group B, A1C decreased from 7.4±1.2% to 6.4±0.9% at 12 weeks and rose to 6.8±1.2% at 1 year and 7.3±1.5% at 5 years. Despite weight regain, group A maintained improvement in low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol with worsening of serum triglycerides and no change in blood pressure (BP). Group B maintained improvement in lipid profile for 5 years and had significantly lower BP for 18 months.

Conclusions

Weight reduction in patients with diabetes can be maintained for 5 years and is predicted by patients’ ability to maintain ≥7% weight loss at 1 year. A1C and triglycerides deteriorate with weight regain, while other lipid improvements are maintained. Sustained weight loss is associated with significantly lower A1C for 5 years and lowers BP for 18 months.

Trial registration number

NCT01937845.
Associations between altered movement patterns during single-leg squat and muscle activity at weight-transfer initiation in individuals with anterior cruciate ligament injury
Authors: Trulsson Anna , Miller Michael , Gummesson Christina , Garwicz Martin
Published: January 2017

Background

Little is known about factors contributing to the altered movement patterns observed in many individuals with anterior cruciate ligament (ACL) injury. We addressed whether altered muscular activity is such a factor.

Methods

16 participants with unilateral, non-reconstructed ACL rupture were scored for altered movement patterns according to Test for Substitution Patterns (TSP), which includes the single-leg squat (SLS). Surface electromyography (SEMG), was recorded in the lower extremities at initiation of weight-transfer from double-leg to single-leg stance (eyes closed), simulating the initiation of an SLS. Normalised SEMG amplitudes 200–300 ms after weight-transfer initiation were compared between injured and non-injured sides, and correlated to the TSP scores for the SLS. Peak absolute SEMG amplitudes during 5 TSP test movements were also compared between sides.

Results

At weight-transfer initiation, muscle activity was lower in the tibialis anterior, gastrocnemius and peroneus longus muscles on the injured side. Low muscle activity correlated moderately to worse TSP scores for the SLS for the gluteus medius (rs=−0.56, p=0.03), and gastrocnemius muscles (rs=−0.56, p=0.02). Median peak absolute amplitude during TSP movements was lower in the quadriceps, gastrocnemius and peroneus longus muscles on the injured side.

Conclusions

The altered patterns of muscle activity at weight-transfer initiation, correlations between lower activity at movement initiation and altered movement patterns during SLS and the altered peak amplitudes during TSP movements together indicate alterations in sensorimotor control that may contribute to the observed altered movement patterns. Future studies will determine if exercises targeting muscle activity initiation should complement customary ACL injury rehabilitation.
Acute-on-chronic liver failure: an update
Authors: Hernaez Ruben , Solà Elsa , Moreau Richard , Ginès Pere
Published: January 2017

Acute-on-chronic liver failure (ACLF) is a syndrome characterised by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic viral hepatitis are the most common underlying liver diseases. Up to 40%–50% of the cases of ACLF have no identifiable trigger; in the remaining patients, sepsis, active alcoholism and relapse of chronic viral hepatitis are the most common reported precipitating factors. An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF. Using a liver-adapted sequential organ assessment failure score, it is possible to triage and prognosticate the outcome of patients with ACLF. The course of ACLF is dynamic and changes over the course of hospital admission. Most of the patients will have a clear prognosis between day 3 and 7 of hospital admission and clinical decisions such as evaluation for liver transplant or discussion over goals of care could be tailored using clinical scores. Bioartificial liver support systems, granulocyte-colony stimulating factors or stem-cell transplant are in the horizon of medical care of this patient population; however, data are too premature to implement them as standard of care.
Multireader assessment as an alternative to reference assessment to improve the detection of radiographic progression in a large longitudinal cohort of rheumatoid arthritis (ESPOIR)
Authors: Gandjbakhch Frederique , Granger Benjamin , Freund Romain , Foltz Violaine , Jousse-Joulin Sandrine , Devauchelle Valerie , Afshar Mona , Albert Jean David , Bailly Florian , Constant Elodie , Biale Lisa , Milin Morgane , Couderc Marion , Denarie Delphine , Fradin Anne , Martaille Virginie , Pierreisnard Audrey , Poursac Nicolas , Saraux Alain , Fautrel Bruno
Published: January 2017

Introduction

Structural damage progression is a major outcome in rheumatoid arthritis (RA). Its evaluation and follow-up in trials should involve radiographic scoring by 1 or 2 readers (reference assessment), which is challenging in large longitudinal cohorts with multiple assessments.

Objectives

To compare the reproducibility of multireader and reference assessment to improve the feasibility of detecting radiographic progression in a large cohort of patients with early arthritis (ESPOIR).

Methods

We used 3 sessions to train 12 rheumatologists in radiographic scoring by the van der Heijde-modified Sharp score (SHS). Multireader scoring was based on 10 trained-reader assessments, each reader scoring a random sample of 1/5 of all available radiographs (for double scoring for each X-ray set) for patients included in the ESPOIR cohort with complete radiographic data at M0 and M60. Reference scoring was performed by 2 experienced readers. Scoring was performed blindly to clinical data, with radiographs in chronological order. We compared multireader and reference assessments by intraclass correlation coefficients (ICCs) for SHS and significant radiographic progression (SRP).

Results

The intrareader and inter-reader reproducibility for trained assessors increased during the training sessions (ICC 0.79 to 0.94 and 0.76 to 0.92), respectively. For the 524 patients included, agreement between multireader and reference assessment of SHS progression between M0 and M60 and SRP assessment were almost perfect, ICC (0.88 (95% CI 0.82 to 0.93)) and (0.99 (95% CI 0.99 to 0.99)), respectively.

Conclusions

Multireader assessment of radiographic structural damage progression is comparable to reference assessment and could be used to improve the feasibility of radiographic scoring in large longitudinal cohort with numerous X-ray evaluations.
Chinese Atherosclerosis Risk Evaluation (CARE II) study: a novel cross-sectional, multicentre study of the prevalence of high-risk atherosclerotic carotid plaque in Chinese patients with ischaemic cerebrovascular events—design and rationale
Authors: Zhao Xihai , Li Rui , Hippe Daniel S , Hatsukami Thomas S , Yuan Chun ,   CARE-II Investigators
Published: January 2017

Background

Carotid atherosclerotic plaque is identified as one of the main sources of ischaemic stroke. However, the prevalence of carotid high-risk atherosclerotic plaque in Chinese patients with ischaemic cerebrovascular events has been inconsistently reported and needs to be investigated in a large population.

Objectives

The primary objective of CARE II study was to determine the prevalence and characteristics of high-risk features of atherosclerotic plaques in the carotid arteries in Chinese patients with recent ischaemic stroke or transient ischaemia attack (TIA). The relationship between carotid plaque features and cerebral infarcts, the differences of carotid plaque patterns among different regions of China and the gender specific characteristics of carotid plaque will be also determined.

Study design

The CARE II study will enrol 1000 patients with recent ischaemic stroke or TIA and carotid plaque from 13 hospitals and medical centres across China. In this cross-sectional, non-randomised, observational, multicentre study, all patients will undergo carotid artery MRI of bilateral carotid arteries and routine brain MRI with standardised protocols. The MRI will be interpreted at core reading centres to evaluate the characteristics of morphology and compositions of carotid plaque.

Conclusions

This is a cross-sectional, multicentre study to investigate the prevalence and characteristics of high-risk atherosclerotic carotid plaque in Chinese patients with stroke and TIA by using high-resolution MRI of vessel wall. This trial is sufficiently powered to demonstrate the prevalence of carotid high-risk plaque and to explore regional differences in Chinese patients who suffered stroke.

Trial registration number

NCT02017756.
Ciprofloxacin-resistant Neisseria meningitidis in Canada: likely imported strains
Authors: Tsang Raymond S.W. , Law Dennis K.S. , Deng Saul , Hoang Linda
Published: January 2017

The prevalence of ciprofloxacin-resistant Neisseria meningitidis in Canada was studied by testing 346 isolates received at the National Microbiology Laboratory during the calendar years 2013 to 2015. Of the 277 individual invasive and 69 noninvasive isolates tested, only 2 serogroup C (MenC) isolates were found to be resistant to ciprofloxacin. Both MenC were typed as sequence type (ST)-4821, a unique clone found mainly in China, thus suggesting both isolates might be from travel-related or imported cases. This prompted us to also examine 6 serogroup A (MenA) isolates in our collection, since MenA is not currently endemic in Canada. Three MenA from 2006 were resistant to ciprofloxacin and they were typed as ST-4789. A ciprofloxacin-resistant MenA strain of ST-4789 was responsible for a meningococcal disease outbreak in Delhi, India, in 2005 to 2006. The 2 MenC and 3 MenA ciprofloxacin-resistant N. meningitidis were from patients residing in British Columbia.
Schwarzschild solution from Weyl transverse gravity
Authors: Oda Ichiro
Published: January 2017

We study classical solutions in the Weyl-transverse (WTDiff) gravity. The WTDiff gravity is invariant under both the local Weyl (conformal) transformation and the volume preserving diffeomorphisms (Diff) (transverse diffeomorphisms (TDiff)) and is known to be equivalent to general relativity at least at the classical level. In particular, we find that in a general spacetime dimension, the Schwarzschild metric is a classical solution in the WTDiff gravity when it is expressed in the Cartesian coordinate system.
Fermionic condensate and the Casimir effect in cosmic string spacetime
Authors: Grigoryan A. Kh. , Mkrtchyan A. R. , Saharian A. A.
Published: January 2017

We investigate combined effects of nontrivial topology, induced by a cosmic string, and boundaries on the fermionic condensate and the vacuum expectation value (VEV) of the energy–momentum tensor for a massive fermionic field. As geometry of boundaries we consider two plates perpendicular to the string axis on which the field is constrained by the MIT bag boundary condition. By using the Abel–Plana type summation formula, the VEVs in the region between the plates are decomposed into the boundary-free and boundary-induced contributions for general case of the planar angle deficit. The boundary-induced parts in both the fermionic condensate and the energy–momentum tensor vanish on the cosmic string. Fermionic condensate is positive near the string and negative at large distances, whereas the vacuum energy density is negative everywhere. The radial stress is equal to the energy density. For a massless field, the boundary-induced contribution in the VEV of the energy–momentum tensor is different from zero in the region between the plates only and it does not depend on the coordinate along the string axis. In the region between the plates and at large distances from the string, the decay of the topological part is exponential for both massive and massless fields. This behavior is in contrast to that for the VEV of the energy–momentum tensor in the boundary-free geometry with the power law decay for a massless field. The vacuum pressure on the plates is inhomogeneous and vanishes at the location of the string. The corresponding Casimir forces are attractive.
Recent Developments in the Fluid Dynamics of Tropical Cyclones
Authors: Montgomery Michael T. , Smith Roger K.
Published: January 2017

This article reviews progress in understanding the fluid dynamics and moist thermodynamics of tropical cyclone vortices. The focus is on the dynamics and moist thermodynamics of vortex intensification and structure. We discuss previous ideas on many facets of the subject and articulate also some open questions. The advances reviewed herein provide new insight and tools for interpreting complex vortex-convective phenomenology in simulated and observed tropical cyclones.
Lipopolysaccharide inhibits colonic biotin uptake via interference with membrane expression of its transporter: a role for a casein kinase 2-mediated pathway
Authors: Lakhan Ram , Said Hamid M.
Published: January 2017

Biotin (vitamin B7), an essential micronutrient for normal cellular functions, is obtained from both dietary sources as well as gut microbiota. Absorption of biotin in both the small and large intestine is via a carrier-mediated process that involves the sodium-dependent multivitamin transporter (SMVT). Although different physiological and molecular aspects of intestinal biotin uptake have been delineated, nothing is known about the effect of LPS on the process. We addressed this issue using in vitro (human colonic epithelial NCM460 cells) and in vivo (mice) models of LPS exposure. Treating NCM460 cells with LPS was found to lead to a significant inhibition in carrier-mediated biotin uptake. Similarly, administration of LPS to mice led to a significant inhibition in biotin uptake by native colonic tissue. Although no changes in total cellular SMVT protein and mRNA levels were observed, LPS caused a decrease in the fraction of SMVT expressed at the cell surface. A role for casein kinase 2 (CK2) (whose activity was also inhibited by LPS) in mediating the endotoxin effects on biotin uptake and on membrane expression of SMVT was suggested by findings that specific inhibitors of CK2, as well as mutating the putative CK2 phosphorylation site (Thr78Ala) in the SMVT protein, led to inhibition in biotin uptake and membrane expression of SMVT. This study shows for the first time that LPS inhibits colonic biotin uptake via decreasing membrane expression of its transporter and that these effects likely involve a CK2-mediated pathway.
Renal denervation in male rats with heart failure improves ventricular sympathetic nerve innervation and function
Authors: Pinkham Maximilian I. , Loftus Michael T. , Amirapu Satya , Guild Sarah-Jane , Quill Gina , Woodward William R. , Habecker Beth A. , Barrett Carolyn J.
Published: January 2017

Heart failure is characterized by the loss of sympathetic innervation to the ventricles, contributing to impaired cardiac function and arrhythmogenesis. We hypothesized that renal denervation (RDx) would reverse this loss. Male Wistar rats underwent myocardial infarction (MI) or sham surgery and progressed into heart failure for 4 wk before receiving bilateral RDx or sham RDx. After additional 3 wk, left ventricular (LV) function was assessed, and ventricular sympathetic nerve fiber density was determined via histology. Post-MI heart failure rats displayed significant reductions in ventricular sympathetic innervation and tissue norepinephrine content (nerve fiber density in the LV of MI+sham RDx hearts was 0.31 ± 0.05% vs. 1.00 ± 0.10% in sham MI+sham RDx group, P < 0.05), and RDx significantly increased ventricular sympathetic innervation (0.76 ± 0.14%, P < 0.05) and tissue norepinephrine content. MI was associated with an increase in fibrosis of the noninfarcted ventricular myocardium, which was attenuated by RDx. RDx improved LV ejection fraction and end-systolic and -diastolic areas when compared with pre-RDx levels. This is the first study to show an interaction between renal nerve activity and cardiac sympathetic nerve innervation in heart failure. Our findings show denervating the renal nerves improves cardiac sympathetic innervation and function in the post-MI failing heart.
Myoglobin facilitates angiotensin II-induced constriction of renal afferent arterioles
Authors: Liu Z. Z. , Mathia S. , Pahlitzsch T. , Wennysia I. C. , Persson P. B. , Lai E. Y. , Högner A. , Xu M. Z. , Schubert R. , Rosenberger C. , Patzak A.
Published: January 2017

Vasoconstriction plays an important role in the development of acute kidney injury in rhabdomyolysis. We hypothesized that myoglobin enhances the angiotensin II (ANG II) response in afferent arterioles by increasing superoxide and reducing nitric oxide (NO) bioavailability. Afferent arterioles of C57Bl6 mice were isolated perfused, and vasoreactivity was analyzed using video microscopy. NO bioavailability, superoxide concentration in the vessel wall, and changes in cytosolic calcium were measured using fluorescence techniques. Myoglobin treatment (10−5M) did not change the basal arteriolar diameter during a 20-min period compared with control conditions. NG-nitro-l-arginine methyl ester (l-NAME, 10−4M) and l-NAME + myoglobin reduced diameters to 94.7 and 97.9% of the initial diameter, respectively. Myoglobin or l-NAME enhanced the ANG II-induced constriction of arterioles compared with control (36.6 and 34.2%, respectively, vs. 65.9%). Norepinephrine responses were not influenced by myoglobin. Combined application of myoglobin and l-NAME further facilitated the ANG II response (7.0%). Myoglobin or l-NAME decreased the NO-related fluorescence in arterioles similarly. Myoglobin enhanced the superoxide-related fluorescence, and tempol prevented this enhancement. Tempol also partly prevented the myoglobin effect on the ANG II response. Myoglobin increased the fura 2 fluorescence ratio (cytosolic calcium) during ANG II application (10−12to 10−6M). The results suggest that the enhanced afferent arteriolar reactivity to ANG II is mainly due to a myoglobin-induced increase in superoxide and associated reduction in the NO bioavailability. Signaling pathways for the augmented ANG II response include enhanced cytosolic calcium transients. In conclusion, myoglobin may contribute to the afferent arteriolar vasoconstriction in this rhabdomyolysis model.
DNA methylation assessment from human slow- and fast-twitch skeletal muscle fibers
Authors: Begue Gwénaëlle , Raue Ulrika , Jemiolo Bozena , Trappe Scott
Published: January 2017

A new application of the reduced representation bisulfite sequencing method was developed using low-DNA input to investigate the epigenetic profile of human slow- and fast-twitch skeletal muscle fibers. Successful library construction was completed with as little as 15 ng of DNA, and high-quality sequencing data were obtained with 32 ng of DNA. Analysis identified 143,160 differentially methylated CpG sites across 14,046 genes. In both fiber types, selected genes predominantly expressed in slow or fast fibers were hypomethylated, which was supported by the RNA-sequencing analysis. These are the first fiber type-specific methylation data from human skeletal muscle and provide a unique platform for future research.

NEW & NOTEWORTHY This study validates a low-DNA input reduced representation bisulfite sequencing method for human muscle biopsy samples to investigate the methylation patterns at a fiber type-specific level. These are the first fiber type-specific methylation data reported from human skeletal muscle and thus provide initial insight into basal state differences in myosin heavy chain I and IIa muscle fibers among young, healthy men.
Blood flow regulation and oxygen uptake during high-intensity forearm exercise
Authors: Nyberg S. K. , Berg O. K. , Helgerud J. , Wang E.
Published: January 2017

The vascular strain is very high during heavy handgrip exercise, but the intensity and kinetics to reach peak blood flow, and peak oxygen uptake, are uncertain. We included 9 young (25 ± 2 yr) healthy males to evaluate blood flow and oxygen uptake responses during continuous dynamic handgrip exercise with increasing intensity. Blood flow was measured using Doppler-ultrasound, and venous blood was drawn from a deep forearm vein to determine arteriovenous oxygen difference (a-vO2diff) during 6-min bouts of 60, 80, and 100% of maximal work rate (WRmax), respectively. Blood flow and oxygen uptake increased ( P < 0.05) from 60%WRmax [557 ± 177(SD) ml/min; 56.0 ± 21.6 ml/min] to 80%WRmax (679 ± 190 ml/min; 70.6 ± 24.8 ml/min), but no change was seen from 80%WRmax to 100%WRmax. Blood velocity (49.5 ± 11.5 to 58.1 ± 11.6 cm/s) and brachial diameter (0.49 ± 0.05 to 0.50 ± 0.06 cm) showed concomitant increases ( P < 0.05) with blood flow from 60% to 80%WRmax, whereas no differences were observed in a-vO2diff. Shear rate also increased ( P < 0.05) from 60% (822 ± 196 s−1) to 80% (951 ± 234 s−1) of WRmax. The mean response time (MRT) was slower ( P < 0.05) for blood flow (60%WRmax 50 ± 22 s; 80%WRmax 51 ± 20 s; 100%WRmax 51 ± 23 s) than a-vO2diff (60%WRmax 29 ± 9 s; 80%WRmax 29 ± 5 s; 100%WRmax 20 ± 5 s), but not different from oxygen uptake (60%WRmax 44 ± 25 s; 80%WRmax 43 ± 14 s; 100%WRmax 41 ± 32 s). No differences were observed in MRT for blood flow or oxygen uptake with increased exercise intensity. In conclusion, when approaching maximal intensity, oxygen uptake appeared to reach a critical level at ~80% of WRmax and be regulated by blood flow. This implies that high, but not maximal, exercise intensity may be an optimal stimulus for shear stress-induced small muscle mass training adaptations.

NEW & NOTEWORTHY This study evaluated blood flow regulation and oxygen uptake during small muscle mass forearm exercise with high to maximal intensity. Despite utilizing only a fraction of cardiac output, blood flow reached a plateau at 80% of maximal work rate and regulated peak oxygen uptake. Furthermore, the results revealed that muscle contractions dictated bulk oxygen delivery and yielded three times higher peak blood flow in the relaxation phase compared with mean values.
Orientation selectivity in the visual cortex of the nine-banded armadillo
Authors: Scholl Benjamin , Rylee Johnathan , Luci Jeffrey J. , Priebe Nicholas J. , Padberg Jeffrey
Published: January 2017

Orientation selectivity in primary visual cortex (V1) has been proposed to reflect a canonical computation performed by the neocortical circuitry. Although orientation selectivity has been reported in all mammals examined to date, the degree of selectivity and the functional organization of selectivity vary across mammalian clades. The differences in degree of orientation selectivity are large, from reports in marsupials that only a small subset of neurons are selective to studies in carnivores, in which it is rare to find a neuron lacking selectivity. Furthermore, the functional organization in cortex varies in that the primate and carnivore V1 is characterized by an organization in which nearby neurons share orientation preference while other mammals such as rodents and lagomorphs either lack or have only extremely weak clustering. To gain insight into the evolutionary emergence of orientation selectivity, we examined the nine-banded armadillo, a species within the early placental clade Xenarthra. Here we use a combination of neuroimaging, histological, and electrophysiological methods to identify the retinofugal pathways, locate V1, and for the first time examine the functional properties of V1 neurons in the armadillo ( Dasypus novemcinctus) V1. Individual neurons were strongly sensitive to the orientation and often the direction of drifting gratings. We uncovered a wide range of orientation preferences but found a bias for horizontal gratings. The presence of strong orientation selectivity in armadillos suggests that the circuitry responsible for this computation is common to all placental mammals.

NEW & NOTEWORTHY The current study shows that armadillo primary visual cortex (V1) neurons share the signature properties of V1 neurons of primates, carnivorans, and rodents. Furthermore, these neurons exhibit a degree of selectivity for stimulus orientation and motion direction similar to that found in primate V1. Our findings in armadillo visual cortex suggest that the functional properties of V1 neurons emerged early in the mammalian lineage, near the time of the divergence of marsupials.
Subglottic Metastatic Rectal Adenocarcinoma: A Specialist Multidisciplinary Airway Team Approach for Optimized Voice and Airway Outcome
Authors: Heyes Richard , Balakumar Ramkishan , Ramdoo Krishan , Tatla Taran
Published: January 2017

A 56-year-old female with a background of metastatic rectal adenocarcinoma presented with a subglottic mass causing biphasic stridor. Transoral laser microsurgery and the use of fibrin glue prevented the need for tracheostomy. Six months postoperatively there was no evidence of recurrence. Laryngeal metastasis of colorectal adenocarcinoma, although remarkably rare, is perhaps more prevalent than commonly perceived and the presence of laryngeal symptoms in a patient with colorectal adenocarcinoma should raise concern. This case is presented to aid physicians should they encounter a similar presentation of metastasis to the subglottis.
Detection of Methicillin ResistantStaphylococcus aureusand Determination of Minimum Inhibitory Concentration of Vancomycin forStaphylococcus aureusIsolated from Pus/Wound Swab Samples of the Patients Attending a Tertiary Care Hospital in Kathmandu, Nepal
Authors: Adhikari Raghabendra , Pant Narayan Dutt , Neupane Sanjeev , Neupane Mukesh , Bhattarai Roshan , Bhatta Sabita , Chaudhary Raina , Lekhak Binod
Published: January 2017

The present study was conducted to evaluate the performance of cefoxitin disc diffusion method and oxacillin broth microdilution method for detection of methicillin resistantS. aureus(MRSA), taking presence of mecA gene as reference. In addition, inducible clindamycin resistance and beta-lactamase production were studied and minimum inhibitory concentration (MIC) of vancomycin forS. aureusisolates was determined. A total of 711 nonrepeated pus/wound swab samples from different anatomic locations were included in the study. TheStaphylococcus aureuswas identified on the basis of colony morphology, Gram’s stain, and biochemical tests. A total of 110 (15.47%)S. aureusisolates were recovered, of which 39 (35.50%) isolates were identified as MRSA by cefoxitin disc diffusion method. By oxacillin broth microdilution method, 31.82% of theStaphylococcus aureusisolates were found to be MRSA. However, mecA gene was present in only 29.1% of the isolates. Further, beta-lactamase production was observed in 71.82% of the isolates, while inducible clindamycin resistance was found in 10% ofS. aureusisolates. The MIC value of vancomycin forS. aureusranged from 0.016 μg/mL to 1 μg/mL. On the basis of the absolute sensitivity (100%), both phenotypic methods could be employed for routine diagnosis of MRSA in clinical microbiology laboratory; however cefoxitin disc diffusion could be preferred over MIC method considering time and labour factor.
UTE-T2⁎Analysis of Diseased and Healthy Achilles Tendons and Correlation with Clinical Score: An In Vivo Preliminary Study
Authors: Qiao Yang , Tao Hong-Yue , Ma Kui , Wu Zi-Ying , Qu Jian-Xun , Chen Shuang
Published: January 2017

Objective. To compareT2⁎value of healthy and diseased Achilles tendons (AT) with a recently introduced three-dimensional ultrashort echo time (3D-UTE) sequence and analyze the correlation betweenT2⁎value and clinical scores.Methods. Ten patients with symptomatic Achilles tendon and ten healthy volunteers were investigated with 3D-UTE sequence on a 3T magnetic resonance (MR) scanner.T2⁎values of four regions in Achilles tendons were calculated. The clinical outcomes of patients were evaluated according to the American Orthopaedic Foot and Ankle Society (AOFAS) score and Achilles Tendon Rupture Score (ATRS). An independent samplet-test was used to compare the differences ofT2⁎value and clinical scores between two groups. The Pearson correlation coefficient between clinical scores andT2⁎values was assessed.Results. TheT2⁎values of Achilles tendon were statistically significantly different between patients and volunteers. The Pearson correlation coefficients betweenT2⁎and AOFAS or ATRS scores of patients werer=-0.733andr=-0.634, respectively.Conclusion. The variability ofT2⁎in healthy and pathologic AT can be quantified by UTE-T2⁎.T2⁎may be a promising marker to detect and diagnose AT tendinopathy. UTE-T2⁎could give a precise guidance to clinical outcome.
HbA1c-Based Score Model for Predicting Death Risk in Patients with Hepatocellular Carcinoma and Type 2 Diabetes Mellitus
Authors: He Lingling , Zhang Shuan , Liu Xiaoli , Jiang Yuyong , Wang Xianbo , Yang Zhiyun
Published: January 2017

Aim. To establish a new score model to predict risk of death in patients with hepatocellular carcinoma and type 2 diabetes mellitus.Methods. This was a retrospective study of 147 patients with hepatocellular carcinoma and type 2 diabetes mellitus who came to Beijing Ditan Hospital between October 2008 and June 2013. Univariate and multivariate logistic regression analysis was performed to obtain the independent factors associated with death risk. A new score model was devised according to these factors.Results. A prediction score model composed of HbA1c, NLR, age, and CTP class was devised, which ranged from 0 to 7. AUROC of the score was 0.853 (P<0.001, 95% CI: 0.791–0.915). Scores 0–2, 3-4, and 5–7 identified patients as low-, medium-, and high-risk categories. The cumulative survival rate was 93.6%, 83.0%, and 74.5% in the low-risk group in 1, 2, and 3 years, while it was 64.0%, 46.0%, and 26.0% in the medium-risk group, whereas it was 24.0%, 12.0%, and 6.0% in the high-risk group, respectively. The cumulative survival rate was significantly higher in the low-risk group than that in the medium-risk group and high-risk group (P<0.001).Conclusion. The HbA1c-based score model can be used to predict death risk in patients with hepatocellular carcinoma and type 2 diabetes mellitus.
TargetingO-Acetyl-GD2 Ganglioside for Cancer Immunotherapy
Authors: Fleurence Julien , Fougeray Sophie , Bahri Meriem , Cochonneau Denis , Clémenceau Béatrice , Paris François , Heczey Andras , Birklé Stéphane
Published: January 2017

Target selection is a key feature in cancer immunotherapy, a promising field in cancer research. In this respect, gangliosides, a broad family of structurally related glycolipids, were suggested as potential targets for cancer immunotherapy based on their higher abundance in tumors when compared with the matched normal tissues. GD2 is the first ganglioside proven to be an effective target antigen for cancer immunotherapy with the regulatory approval of dinutuximab, a chimeric anti-GD2 therapeutic antibody. Although the therapeutic efficacy of anti-GD2 monoclonal antibodies is well documented, neuropathic pain may limit its application.O-Acetyl-GD2, theO-acetylated-derivative of GD2, has recently received attention as novel antigen to target GD2-positive cancers. The present paper examines the role ofO-acetyl-GD2 in tumor biology as well as the available preclinical data of anti-O-acetyl-GD2 monoclonal antibodies. A discussion on the relevance ofO-acetyl-GD2 in chimeric antigen receptor T cell therapy development is also included.
Role of Alexithymia, Anxiety, and Depression in Predicting Self-Efficacy in Academic Students
Authors: Faramarzi Mahbobeh , Khafri Soraya
Published: January 2017

Objective. Little research is available on the predictive factors of self-efficacy in college students. The aim of the present study is to examine the role of alexithymia, anxiety, and depression in predicting self-efficacy in academic students. Design. In a cross-sectional study, a total of 133 students at Babol University of Medical Sciences (Medicine, Dentistry, and Paramedicine) participated in the study between 2014 and 2015. All participants completed the Toronto Alexithymia Scale (TAS-20), College Academic Self-Efficacy Scale (CASES), and 14 items on anxiety and depression derived from the 28 items of the General Health Questionnaire (28-GHQ). Results. Pearson correlation coefficients revealed negative significant relationships between alexithymia and the three subscales with student self-efficacy. There was no significant correlation between anxiety/depression symptoms and student self-efficacy. A backward multiple regression analysis revealed that alexithymia was a negative significant predictor of self-efficacy in academic students (B=-0.512, P<0.001). The prevalence of alexithymia was 21.8% in students. Multiple backward logistic analysis regression revealed that number of passed semesters, gender, mother’s education, father’s education, and doctoral level did not accurately predict alexithymia in college students. Conclusion. As alexithymia is prevalent in college students and affects self-efficacy and academic functioning, we suggest it should be routinely evaluated by mental physicians at universities.
Combined Effect of Synthetic and Natural Polymers in Preparation of Cetirizine Hydrochloride Oral Disintegrating Tablets: Optimization by Central Composite Design
Authors: Patro Chandra Sekhar , Sahu Prafulla Kumar
Published: January 2017

Our aim was to employ experimental design to formulate and optimize cetirizine hydrochloride oral disintegrating tablets (ODTs) by direct compression technique, using the mutual effect of synthetic croscarmellose sodium (CCS) and natural Hibiscus rosa-sinensis mucilage (HRM) as disintegrants in the formulation. Central composite design (CCD) was applied to optimize the influence of three levels each of CCS (X1) and HRM (X2) concentrations (independent variables) for investigated responses: disintegration time (DT) (Y1), % friability (F) (Y2), and % cumulative drug release (DR) (Y3) (dependent variables). This face-centered second-order model’s reliability was verified by the probability and adequate precision values from the analysis of variance, while the significant factor effects influencing the studied responses were identified using multiple linear regression analysis. Perturbation and response surface plots were interpreted to evaluate the responses’ sensitivity towards the variables. During optimization, the concentrations of the processed factors were evaluated, and the resulting values were in good agreement with predicted estimates endorsing the validity. Spectral study by Fourier Transform Infrared Spectroscopy (FTIR) and thermograms from Differential Scanning Calorimetry (DSC) demonstrated the drug-excipients compatibility of the optimized formulation. The optimized formulation has concentrations of 9.05 mg and 16.04 mg of CCS and HRM each, respectively, and the model predicted DT of 13.271 sec, F of 0.498, and DR of 99.768%.
The Outcomes of Minimally Invasive versus Open Posterior Approach Spinal Fusion in Treatment of Lumbar Spondylolisthesis: The Current Evidence from Prospective Comparative Studies
Authors: Wu Ai-Min , Chen Chun-Hui , Shen Zhi-Hao , Feng Zhen-Hua , Weng Wan-Qing , Li Shu-Min , Chi Yong-Long , Yin Li-Hui , Ni Wen-Fei
Published: January 2017

Purpose. To investigate the evidence of minimally invasive (MI) versus open (OP) posterior lumbar fusion in treatment of lumbar spondylolisthesis from current prospective literatures.Methods. The electronic literature database of Pubmed, Embase, and Cochrane library was searched at April 2016. The data of operative time, estimated blood loss and length of hospital stay, visual analog scale (VAS) of both lower back pain and leg pain, Oswestry disability index (ODI), SF-36 PCS (physical component scores) and SF-36 MCS (mental component scores), complications, fusion rate, and secondary surgery were extracted and analyzed by STATA 12.0 software.Results. Five nonrandom prospective comparative studies were included in this meta-analysis. The meta-analysis showed that the MI group had a significantly longer operative time than OP group, less blood loss, and shorter hospital stay. No significant difference was found in back pain, leg pain, ODI, SF-36 PCS, SF-36 MCS, complications, fusion rate, and secondary surgery between MI and OP groups.Conclusion. The prospective evidence suggested that MI posterior fusion for spondylolisthesis had less EBL and hospital stay than OP fusion; however it took more operative time. Both MI and OP fusion had similar results in pain and functional outcomes, complication, fusion rate, and secondary surgery.
Railway Container Station Reselection Approach and Application: Based on Entropy‐Cloud Model
Authors: Huang Wencheng , Shuai Bin , Wang Lei , Antwi Eric
Published: January 2017

Reasonable railway container freight stations layout means higher transportation efficiency and less transportation cost. To obtain more objective and accurate reselection results, a new entropy‐cloud approach is formulated to solve the problem. The approach comprises three phases: Entropy Method is used to obtain the weight of each subcriterion during Phase  1, then cloud model is designed to form the evaluation cloud for each subcriterion during Phase  2, and finally during Phase  3 we use the weight during Phase  1 to multiply the initial evaluation cloud during Phase  2. MATLAB is applied to determine the evaluation figures and help us to make the final alternative decision. To test our approach, the railway container stations in Wuhan Railway Bureau were selected for our case study. The final evaluation result indicates only Xiangyang Station should be renovated and developed as a Special Transaction Station, five other stations should be kept and developed as Ordinary Stations, and the remaining 16 stations should be closed. Furthermore, the results show that, before the site reselection process, the average distance between two railway container stations was only 74.7 km but has improved to 182.6 km after using the approach formulated in this paper.
Valgus Slipped Capital Femoral Epiphysis in Patient with Hypopituitarism
Authors: Kotoura Yoshihiro , Fujiwara Yasuhiro , Hayashida Tatsuro , Murakami Koji , Makio Satoshi , Shimizu Yuichi , Oka Yoshinobu , Kim Wook-Choel , Ogura Taku , Kubo Toshikazu
Published: January 2017

Slipped capital femoral epiphysis (SCFE) is a common disease of adolescent and the epiphysis is positioned more posteromedially in relation to the femoral neck shaft with varus SCFE; however, posterolateral displacement of the capital epiphysis, valgus SCFE, occurs less frequently. We report a case of valgus SCFE in a 17-year-old boy with hypopituitarism. After falling down, he experienced difficulty in walking. The radiographs were inconclusive; however three-dimensional computed tomography images showed lateral displacement of the epiphysis on the right femoral head. Valgus SCFE was diagnosed. The patient underwent in situ pinning of both sides. In situ pinning on the left side was performed as a prophylactic pinning because of endocrine abnormalities. At the 1-year follow-up, he could walk without any difficulty and there were no signs of pain. The epiphysis is commonly positioned more posteromedially in relation to the femoral neck shaft with most SCFE, but, in this case, the epiphysis slipped laterally. Differential diagnosis included femoral neck fracture (Delbet-Colonna type 1); however, this was less likely due to the absence of other clinical signs. Therefore, we diagnosed the patient as SCFE. When children complain of leg pain and limp, valgus SCFE that may not be visualized on anteroposterior radiographs needs to be considered.
Physicochemical Process, Crustacean, andMicrocystisBiomass Changes In Situ Enclosure after Introduction of Silver Carp at Meiliang Bay, Lake Taihu
Authors: Yin Chengjie , Guo Longgen , Yi Chunlong , Luo Congqiang , Ni Leyi
Published: January 2017

In order to control cyanobacteria blooms with silver carp in Lake Taihu, an in situ experiment was carried out by stocking silver carp at a biomass of 35, 70, and 150 g m-3and no carp control in waterproof enclosures. Physicochemical water parameters and biomass of plankton were measured in enclosures to evaluate the suitable stocking density of silver carp for relieving internal nutrients and constraining cyanobacteria growth in Lake Taihu. It is found that the 35 g m-3silver carp group and 70 g m-3silver carp group presented lower total phosphorus, lower chlorophyll-a, and higher water transparency. Increased nitrogen to phosphorus ratio, which indicated the result of algae decline in fish presence enclosures, was attributed to decline of phosphorus. Phosphorus decline also exerted limitation on reestablish of cyanobacteria bloom. Crustacean zooplankton biomass andMicrocystisbiomass decreased significantly in fish presence enclosures. Silver carp could be more effective to regulate algae bloom in enclosures with dense cyanobacteria. Therefore, nonclassic manipulation is supposed to be appropriate method to get rid of cyanobacteria blooms in Lake Taihu by stocking 35 to 70 g m-3silver carp in application.
Phase I Study of ONT-380, a HER2 Inhibitor, in Patients with HER2+-Advanced Solid Tumors, with an Expansion Cohort in HER2+ Metastatic Breast Cancer (MBC)
Authors: Moulder Stacy L. , Borges Virginia F. , Baetz Tara , Mcspadden Tessa , Fernetich Gina , Murthy Rashmi K. , Chavira Renae , Guthrie Kari , Barrett Emma , Chia Stephen K.
Published: January 2017

Purpose: ONT-380 (ARRY-380) is a potent and selective oral HER2 inhibitor. This Phase I study determined the MTD, pharmacokinetics (PK) and antitumor activity of ONT-380 in HER2-positive advanced solid tumors, with an expansion cohort of patients with HER2+ MBC.

Experimental Design: ONT-380 was administered twice daily (BID) in continuous 28-day cycles. After a modified 3+3 dose-escalation design determined the MTD, the expansion cohort was enrolled. PK properties of ONT-380 and a metabolite were determined. Response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST).

Results: Fifty patients received ONT-380 (escalation = 33; expansion = 17); 43 patients had HER2+ MBC. Median prior anticancer regimens = 5. Dose-limiting toxicities of increased transaminases occurred at 800 mg BID, thus 600 mg BID was the MTD. Common AEs were usually Grade 1/2 in severity and included nausea (56%), diarrhea (52%), fatigue (50%), vomiting (40%) constipation, pain in extremity and cough (20% each). 5 patients (19%) treated at MTD had grade 3 AEs (increased transaminases, rash, night sweats, anemia, and hypokalemia). The half-life of ONT-380 was 5.38 hours and increases in exposure were approximately dose proportional. In evaluable HER2+ MBC (n = 22) treated at doses ≥ MTD, the response rate was 14% [all partial response (PR)] and the clinical benefit rate (PR + stable disease ≥ 24 weeks) was 27%.

Conclusions: ONT-380 had a lower incidence and severity of diarrhea and rash than that typically associated with current dual HER2/EGFR inhibitors and showed notable antitumor activity in heavily pretreated HER2+ MBC patients, supporting its continued development. Clin Cancer Res; 23(14); 3529–36. ©2017 AACR.