bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol 25-Hydroxylase Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication through Enzyme Activity-Dependent and -Independent Mechanisms
Authors: Ke Wenting , Fang Liurong , Jing Huiyuan , Tao Ran , Wang Ting , Li Yang , Long Siwen , Wang Dang , Xiao Shaobo 
Published: July 2017

ABSTRACTCholesterol 25-hydroxylase (CH25H) has recently been identified as a host restriction factor that exerts antiviral effects by catalyzing the production of 25-hydroxycholesterol (25HC). CH25H can be rapidly induced upon infection with some viruses. Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, has ranked among the most important swine pathogens since it was discovered in the late 1980s. In this study, we found that PRRSV infection significantly downregulated the expression of CH25H in cells by a so-far unknown mechanism, suggesting that CH25H exerts antiviral activity against PRRSV. Indeed, overexpression of CH25H inhibited PRRSV replication, whereas knockdown of CH25H by short interfering RNA (siRNA) promoted PRRSV infection. The anti-PRRSV effect of 25HC operates via inhibition of viral penetration. Interestingly, a CH25H mutant (CH25H-M) lacking hydroxylase activity still inhibited PRRSV infection. Screening using a yeast two-hybrid system followed by coimmunoprecipitation and immunofluorescence colocalization analyses confirmed that both CH25H and CH25H-M interact with the nonstructural protein 1 alpha (nsp1α) of PRRSV. Unexpectedly, the expression of nsp1α decreased following coexpression with CH25H or CH25H-M. Detailed analyses demonstrated that CH25H/CH25H-M could degrade nsp1α through the ubiquitin-proteasome pathway and that site K169 in the nsp1α protein is the key site of ubiquitination. Taken together, our findings demonstrate that CH25H restricts PRRSV replication by targeting viral penetration as well as degrading nsp1α, revealing a novel antiviral mechanism used by CH25H.IMPORTANCEPRRSV has been a continuous threat to the global swine industry, and current vaccines are insufficient to provide sustainable control. CH25H has been found to exert a broad antiviral effect; thus, it is an attractive target for the development of anti-PRRSV drugs. Here, we demonstrate that CH25H is an interferon-stimulated gene that is highly expressed in porcine alveolar macrophages. CH25H exerts its anti-PRRSV effect not only via the production of 25HC to inhibit viral penetration but also by degrading viral protein through the ubiquitin-proteasome pathway, suggesting that CH25H is a candidate for the development of antiviral therapeutics. However, PRRSV infection appears to actively decrease CH25H expression to promote viral replication, highlighting the complex game between PRRSV and its host.
Magnetic resonance spectroscopy in preterm infants: association with neurodevelopmental outcomes
Authors: Hyodo Reina , Sato Yoshiaki , Ito Miharu , Sugiyama Yuichiro , Ogawa Chikako , Kawai Hisashi , Nakane Toshiki , Saito Akiko , Hirakawa Akihiro , Kidokoro Hiroyuki , Natsume Jun , Hayakawa Masahiro 
Published: July 2017

ObjectiveTo compare magnetic resonance spectroscopy (MRS) metabolite ratios in preterm infants at term-equivalent age with those in term infants and to evaluate the association between MRS metabolites and neurodevelopmental outcomes at 18 months corrected age in preterm infants.DesignWe studied infants born at a gestational age <37 weeks and weighing <1500 g during 2009–2013 using MRS at term-equivalent age. Infants with major brain abnormalities were excluded. The ratios of N-acetylaspartate (NAA) to creatine (Cre), NAA to choline-containing compounds (Cho) and Cho to Cre in the frontal white matter and thalamus were measured using multivoxel point-resolved proton spectroscopy sequence. Neurodevelopmental outcomes were assessed at 18 months corrected age.ResultsThirty-three preterm infants and 16 term infants were enrolled in this study. Preterm infants with normal development at 18 months showed significantly lower NAA/Cho ratios in the frontal white matter than term infants. There were no differences in the Cre/Cho ratios between preterm and term infants. At 18 months corrected age, 9 preterm infants with a mild developmental delay showed significantly lower NAA/Cho ratios in the thalamus than 24 preterm infants with normal development.ConclusionsPreterm infants at term-equivalent age showed reduced MRS metabolites (NAA/Cho) compared with term infants. Decreased NAA/Cho ratios in the thalamus were associated with neurodevelopmental delay at 18 months corrected age in preterm infants.
Cost of injury care in India: cross-sectional analysis of National Sample Survey 2014
Authors: Tripathy JP , Jagnoor J , Prasad BM , Ivers R 
Published: July 2017

BackgroundInjuries account for nearly 10% of total deaths in India and this burden is likely to rise. We aimed to estimate the out-of-pocket (OOP) expenditure and catastrophic expenditure due to hospitalisation or outpatient care as a result of any injury and factors associated with incurring catastrophic expenditure.MethodsSecondary analysis of nationally representative data for India collected by National Sample Survey Organization in 2014, reporting on health service utilisation and healthcare-related OOP expenditure by income quintiles and by type of health facility (public or private).ResultsThe median expenditure per episode of hospitalisation due to any injury was US$156, and it was three times higher among the richest quintile compared with the poorest quintile (p<0.001). There was a significantly higher prevalence (p<0.001) of catastrophic expenditure among the poorest quintile (32%) compared with the richest (21%). Mean private sector OOP hospitalisation expenditure was five times higher than in the public sector (p<0.001). Medicines accounted for 37% and 58% of public sector hospitalisation and outpatient care, respectively. Patients treated in a private facility, hospitalised for over 7 days, in the poorest wealth quintiles and of general caste had higher odds of incurring catastrophic expenditure.ConclusionPeople who sustain an injury have a high risk of catastrophic household expenditure, particularly for those in lowest income quartiles. There is a clear need for publicly funded risk protection mechanisms targeting the poor. Promotion of generic medicines and subsidisation for the poorest wealth quintile may also reduce OOP expenditure in public sector facilities.
Improving the healthcare response to domestic violence and abuse in sexual health clinics: feasibility study of a training, support and referral intervention
Authors: Sohal Alex Hardip , Pathak Neha , Blake Sarah , Apea Vanessa , Berry Judith , Bailey Jayne , Griffiths Chris , Feder Gene 
Published: July 2017

ObjectivesSexual health and gynaecological problems are the most consistent and largest physical health differences between abused and non-abused female populations. Sexual health services are well placed to identify and support patients experiencing domestic violence and abuse (DVA). Most sexual health professionals have had minimal DVA training despite English National Institute for Health and Care Excellence recommendations. We sought to determine the feasibility of an evidence-based complex DVA training intervention in female sexual health walk-in services (IRIS ADViSE: Identification and Referral to Improve Safety whilst Assessing Domestic Violence in Sexual Health Environments).MethodsAn adaptive mixed method pilot study in the female walk-in service of two sexual health clinics. Following implementation and evaluation at site 1, the intervention was refined before implementation at site 2. The intervention comprised electronic prompts, multidisciplinary training sessions, clinic materials and simple referral pathways to IRIS ADViSE advocate-educators (AEs). The pilot lasted 7 weeks at site 1 and 12 weeks at site 2. Feasibility outcomes were to assign a supportive DVA clinical lead, an IRIS ADViSE AE employed by a local DVA service provider, adapt electronic records, develop local referral pathways, assess whether enquiry, identification and referral rates were measurable.ResultsBoth sites achieved all feasibility outcomes: appointing a supportive DVA clinical lead and IRIS ADViSE AE, establishing links with a local DVA provider, adapting electronic records, developing local referral pathways and rates of enquiry, identification and referral were found to be measurable. Site 1: 10% enquiry rate (n=267), 4% identification rate (n=16) and eight AE referrals. Site 2: 61% enquiry rate (n=1090), a 7% identification rate (n=79) and eight AE referrals.ConclusionsIRIS ADViSE can be successfully developed and implemented in sexual health clinics. It fulfils the unmet need for DVA training. Longer-term evaluation is recommended.
Body fat of rats of different age groups and nutritional states: assessment by micro-CT and skinfold thickness
Authors: Tekus Eva , Miko Alexandra , Furedi Nora , Rostas Ildiko , Tenk Judit , Kiss Tamas , Szitter Istvan , Balasko Marta , Helyes Zsuzsanna , Wilhelm Marta , Petervari Erika 
Published: July 2017

Obesity presents a growing public health problem. Therefore the analysis of body composition is important in clinical practice as well as in animal research models of obesity; hence precise methods for the assessment of body fat would be essential. We aimed to evaluate in vivo abdominal microcomputed tomography scan restricted to the L1–L3 region [micro-CT(L1–L3)], a skinfold thickness-based method (STM), and postmortem body composition analysis (PMA) with regard to whole body micro-CT scan in rats. Male Wistar rats of different age groups (from 3 to 24 mo) and nutritional states (normally fed, high-fat diet-induced obese, and calorie-restricted) were used. The fat percentage was determined with micro-CT(L1–L3) and whole body scan in anesthetized rats. Their skinfold thickness was measured in five locations with a Lange caliper. Wet weights of epididymal and retroperitoneal fat pads were determined via PMA. With regard to fat mass, the strongest correlation was observed between abdominal and whole body micro-CT. The other methods showed weaker associations with whole body micro-CT and with each other. Micro-CT(L1–L3) and PMA showed similar age-associated increase in fat mass between 3 and 18 mo. Micro-CT(L1–L3), STM, and PMA were efficient to detect differences in fat mass values in groups of different nutritional states. Micro-CT(L1–L3) appears to be a useful method for body fat assessment in rats with reduced scanning time. In rats, STM may also be a useful, low priced, noninvasive, and simple in vivo technique to assess obesity. NEW & NOTEWORTHY Body fat of rats assessed by in vivo abdominal microcomputed tomography of the L1–L3 region strongly correlates with values determined by whole body scan. Therefore, it is a useful method for fat assessment with reduced scanning time. Skinfold thickness measurement is an in vivo technique to assess progression of obesity in rats.
Relationship between exercise volume and muscle protein synthesis in a rat model of resistance exercise
Authors: Ogasawara Riki , Arihara Yuki , Takegaki Junya , Nakazato Koichi , Ishii Naokata 
Published: July 2017

Resistance exercise (RE) volume is recognized as an important factor that stimulates muscle protein synthesis (MPS) and is considered, at least in part, to be involved in the mammalian target of rapamycin complex 1 (mTORC1)-associated signaling. However, the effects of relatively high-volume RE on mTORC1 and MPS remain unclear. In the present study, we used an animal model of RE to investigate the relationship between RE volume and MPS. Male Sprague-Dawley rats were subjected to RE, and muscle samples were obtained 6 h after performing 1, 3, 5, 10, or 20 sets of RE. Although 1 set of RE did not increase MPS [measured by the surface sensing of translation (SUnSET) method], multiple sets (3, 5, 10, and 20 sets) significantly increased MPS. However, the increase in MPS reached a plateau after 3 or 5 sets of RE, and no further increase in MPS was observed with additional RE sets. In contrast to the MPS response, we observed that p70S6K phosphorylation at Thr389, a marker of mTORC1 activity, and Ser240/244 phosphorylation of rpS6, a downstream target of p70S6K, gradually increased with higher RE volume. The above results suggest that the relationship between RE volume and MPS was not linear. Thus the increase in MPS with increasing RE volume saturates before p70S6K phosphorylation, suggesting a threshold effect for the relationship between p70S6K activation and MPS. NEW & NOTEWORTHY The aim of this study was to investigate the relationship between resistance exercise (RE) volume and muscle protein synthesis. We found that the relationship between RE volume and p70S6K phosphorylation was almost linear, but the increase in muscle protein synthesis began to plateau after approximately five sets of RE.
PD-L1 Expression and Immune Escape in Melanoma Resistance to MAPK Inhibitors
Authors: Kakavand Hojabr , Rawson Robert V. , Pupo Gulietta M. , Yang Jean Y. H. , Menzies Alexander M. , Carlino Matteo S. , Kefford Richard F. , Howle Julie R. , Saw Robyn P.M. , Thompson John F. , Wilmott James S. , Long Georgina V. , Scolyer Richard A. , Rizos Helen 
Published: July 2017

Abstract
Purpose: To examine the relationship between immune activity, PD-L1 expression, and tumor cell signaling, in metastatic melanomas prior to and during treatment with targeted MAPK inhibitors.
Experimental Design: Thirty-eight tumors from 17 patients treated with BRAF inhibitor (n = 12) or combination BRAF/MEK inhibitors (n = 5) with known PD-L1 expression were analyzed. RNA expression arrays were performed on all pretreatment (PRE, n = 17), early during treatment (EDT, n = 8), and progression (PROG, n = 13) biopsies. HLA-A/HLA-DPB1 expression was assessed by IHC.
Results: Gene set enrichment analysis (GSEA) of PRE, EDT, and PROG melanomas revealed that transcriptome signatures indicative of immune cell activation were strongly positively correlated with PD-L1 staining. In contrast, MAPK signaling and canonical Wnt/-β-catenin activity was negatively associated with PD-L1 melanoma expression. The expression of PD-L1 and immune activation signatures did not simply reflect the degree or type of immune cell infiltration, and was not sufficient for tumor response to MAPK inhibition.
Conclusions: PD-L1 expression correlates with immune cells and immune activity signatures in melanoma, but is not sufficient for tumor response to MAPK inhibition, as many PRE and PROG melanomas displayed both PD-L1 positivity and immune activation signatures. This confirms that immune escape is common in MAPK inhibitor–treated tumors. This has important implications for the selection of second-line immunotherapy because analysis of mechanisms of immune escape will likely be required to identify patients likely to respond to such therapies. Clin Cancer Res; 23(20); 6054–61. ©2017 AACR.
The Fluid Mechanics of Transcatheter Heart Valve Leaflet Thrombosis in the Neosinus
Authors: Midha Prem A. , Raghav Vrishank , Sharma Rahul , Condado Jose F. , Okafor Ikechukwu U. , Rami Tanya , Kumar Gautam , Thourani Vinod H. , Jilaihawi Hasan , Babaliaros Vasilis , Makkar Raj R. , Yoganathan Ajit P. 
Published: July 2017

Background:
Transcatheter heart valve (THV) thrombosis has been increasingly reported. In these studies, thrombus quantification has been based on a 2-dimensional assessment of a 3-dimensional phenomenon.

Methods:
Postprocedural, 4-dimensional, volume-rendered CT data of patients with CoreValve, Evolut R, and SAPIEN 3 transcatheter aortic valve replacement enrolled in the RESOLVE study (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Dysfunction With Multimodality Imaging and Its Treatment with Anticoagulation) were included in this analysis. Patients on anticoagulation were excluded. SAPIEN 3 and CoreValve/Evolut R patients with and without hypoattenuated leaflet thickening were included to study differences between groups. Patients were classified as having THV thrombosis if there was any evidence of hypoattenuated leaflet thickening. Anatomic and THV deployment geometries were analyzed, and thrombus volumes were computed through manual 3-dimensional reconstruction. We aimed to identify and evaluate risk factors that contribute to THV thrombosis through the combination of retrospective clinical data analysis and in vitro imaging in the space between the native and THV leaflets (neosinus).

Results:

SAPIEN 3 valves with leaflet thrombosis were on average 10% further expanded (by diameter) than those without (95.5±5.2% versus 85.4±3.9%;
P
<0.001). However, this relationship was not evident with the CoreValve/Evolut R. In CoreValve/Evolut Rs with thrombosis, the thrombus volume increased linearly with implant depth (
R
2
=0.7,
P
<0.001). This finding was not seen in the SAPIEN 3. The in vitro analysis showed that a supraannular THV deployment resulted in a nearly 7-fold decrease in stagnation zone size (velocities <0.1 m/s) when compared with an intraannular deployment. In addition, the in vitro model indicated that the size of the stagnation zone increased as cardiac output decreased.

Conclusions:
Although transcatheter aortic valve replacement thrombosis is a multifactorial process involving foreign materials, patient-specific blood chemistry, and complex flow patterns, our study indicates that deployed THV geometry may have implications on the occurrence of thrombosis. In addition, a supraannular neosinus may reduce thrombosis risk because of reduced flow stasis. Although additional prospective studies are needed to further develop strategies for minimizing thrombus burden, these results may help identify patients at higher thrombosis risk and aid in the development of next-generation devices with reduced thrombosis risk.
Dynamic Relation of Changes in Weight and Indices of Fat Distribution With Cardiac Structure and Function: The Dallas Heart Study
Authors: Wilner Bryan , Garg Sonia , Ayers Colby R. , Maroules Christopher D. , McColl Roderick , Matulevicius Susan A. , de Lemos James A. , Drazner Mark H. , Peshock Ronald , Neeland Ian J. 
Published: July 2017

Background
Obesity may increase heart failure risk through cardiac remodeling. Cross‐sectional associations between adiposity and cardiac structure and function have been elucidated, but the impact of longitudinal changes in adiposity on cardiac remodeling is less well understood.

Methods and Results

Participants in the Dallas Heart Study without cardiovascular disease or left ventricular dysfunction underwent assessment of body weight, anthropometrics, and cardiac magnetic resonance imaging at baseline and 7 years later. Associations between changes in indices of generalized and central adiposity with changes in left ventricular mass, volume, mass/volume ratio (concentricity), wall thickness, and ejection fraction were assessed using multivariable linear regression. The study cohort (n=1262) mean age was 44 years with 57% women, 44% black, and 36% obese participants. At follow‐up, 41% had ≥5% weight gain, and 15% had ≥5% weight loss. Greater weight gain was associated with younger age, lower risk factor burden, and lower body mass index at baseline. In multivariable models adjusting for age, sex, race, comorbid conditions at baseline and follow‐up, baseline adiposity, and cardiac measurement, increasing weight was associated with increases in left ventricular mass (β=0.10,
P
<0.0001), wall thickness (β=0.10,
P
<0.0001), and concentricity (β=0.06,
P
=0.002), with modest effects on end‐diastolic volume (β=0.04,
P
=0.044) and ejection fraction (β=0.05,
P
=0.046). Similar results were seen with other adiposity indices.

Conclusions
Concentric left ventricular remodeling is the predominant phenotype linked to increasing adiposity in middle age. Our findings support the importance of weight management to prevent secular changes in adiposity, concentric remodeling, and eventual heart failure over time.
Grip Type Alters Maximal Pinch Forces in Syringe Use
Authors: MacDonald Victoria , Wilson Katherine , Sonne Michael W. L. , Keir Peter J. 
Published: July 2017

Objective: The purpose of this study was to determine maximum forces during syringe use for different grips found in the field. Background: Prolonged syringe use in chemotherapy drug delivery is associated with pain and injury in nurses and technicians. Method: Twenty healthy female hospital workers generated isometric maximum voluntary force using a 30 cc syringe with four pinch grips (chuck, chuck variation, thenar, two-handed). Both dominant and nondominant hands were used with the syringe plunger fixed in wide (8.3 cm) and narrow (2.5 cm) grip spans. Participants were encouraged to position the apparatus in the most comfortable position and exert a maximal effort for 5 seconds. Results: Significant interaction effects were found: Grip Span × Pinch Type, Hand × Pinch Type, and Grip Span × Hand × Pinch Type ( p < .05). The results demonstrated that the thenar (103.6 ± 22.9 N) and two-handed (104.7 ± 17.1 N) pinches produced the highest forces. Conclusion: Thenar and two-handed pinch grips may be the preferred pinch type to lower the relative efforts required to use a syringe and may be one strategy to assist with reduction of musculoskeletal disorder risk associated with syringe use. Application: Determining maximal syringe press forces allows workers and ergonomists to develop better strategies for managing the cumulative loads during drug delivery and mixing.
Visual Fatigue and Cathode Ray Tube Display Terminals
Authors: Mourant Ronald R. , Lakshmanan Raman , Chantadisai Roongrojn 
Published: July 2017

Study I investigated the effects of display type, amount of information presented, and display contrast on the visual mechanism during a visual search task. In the first phase, two subjects performed the visual task for four 3-h sessions. In the second phase, subjects were tested for two 6-h sessions. CRT usage for 3 h produced measurable visual fatigue in the eye movement and/or accommodation mechanism, as measured by increased durations to move from a near point and focus on a far point (and vice versa). Such visual fatigue was not present in the hard-copy visual search task. In a second study, subjects performed the visual task for two 4-h sessions. Two h of CRT usage produced measurable fatigue in the eye accommodation mechanism as well as an increased blink rate. Such visual fatigue was also present in the hard-copy task but to a lesser extent. In both studies, I-h breaks produced a marked reduction in visual fatigue indices.
Characteristics of Reading Rate and Manual Scanning Patterns of Blind Optacon Readers
Authors: Hislop David W. , Zuber B. L. , Trimble John L. 
Published: July 2017

Tactual reading is slow compared with sighted reading, and the rate-limiting constraints imposed on tactile readers are only vaguely understood. Like the eye movements of sighted reading, the text-scanning hand movements of tactual reading provide a means to investigate the operative system. We examined the reading hand movements of 10 blind readers using the Optacon, the electronic reading aid used most commonly by blind readers. Subjects read texts of graded difficulty, and their reading hand movements were recorded. Rate and scanning measures were used to characterize reading performance. The group mean reading rate was found to be 28.2 words/min. Reading rate measured in letter spaces per minute was independent of text difficulty.