Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 297-301.
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Παρασκευή 20 Οκτωβρίου 2017
HIF-1α Promotes Breast Cancer Cell MCF-7 Proliferation and Invasion Through Regulating miR-210
PERK-Phosphorylated eIF2α Pathway Suppresses Tumor Metastasis Through Downregulating Expression of Programmed Death Ligand 1 and CXCL5 in Triple-Negative Breast Cancer
Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 282-287.
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An Overview of Unfolded Protein Response Signaling and Its Role in Cancer
Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 275-281.
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Imaging of Integrin αvβ3 Expression in Lung Cancers and Brain Tumors Using Single-Photon Emission Computed Tomography with a Novel Radiotracer 99mTc-IDA-D-[c(RGDfK)]2
Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 288-296.
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Low Concentration of 5-Fluorouracil Increases the Effectiveness of Tumor RNA to Activate Murine Dendritic Cells
Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 302-308.
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HIF-1α Promotes Breast Cancer Cell MCF-7 Proliferation and Invasion Through Regulating miR-210
Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 297-301.
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PERK-Phosphorylated eIF2α Pathway Suppresses Tumor Metastasis Through Downregulating Expression of Programmed Death Ligand 1 and CXCL5 in Triple-Negative Breast Cancer
Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 282-287.
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An Overview of Unfolded Protein Response Signaling and Its Role in Cancer
Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 275-281.
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Imaging of Integrin αvβ3 Expression in Lung Cancers and Brain Tumors Using Single-Photon Emission Computed Tomography with a Novel Radiotracer 99mTc-IDA-D-[c(RGDfK)]2
Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 288-296.
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Low Concentration of 5-Fluorouracil Increases the Effectiveness of Tumor RNA to Activate Murine Dendritic Cells
Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 302-308.
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Effect of Myostatin SNP on muscle fiber properties in male Thoroughbred horses during training period
Abstract
Variants of the Myostatin gene have been shown to have an influence on muscle hypertrophy phenotypes in a wide range of mammalian species. Recently, a Thoroughbred horse with a C-Allele at the g.66493737C/T single-nucleotide polymorphism (SNP) has been reported to be suited to short-distance racing. In this study, we examined the effect of the Myostatin SNP on muscle fiber properties in young Thoroughbred horses during a training period. To investigate the effect of the Myostatin SNP on muscle fiber before training, several mRNA expressions were relatively quantified in biopsy samples from the middle gluteal muscle of 27 untrained male Thoroughbred horses (1.5 years old) using real-time RT-PCR analysis. The remaining muscle samples were used for immunohistochemical analysis to determine the population and area of each fiber type. All measurements were revaluated in biopsy samples of the same horses after a 5-month period of conventional training. Although the expressions of Myostatin mRNA decreased in all SNP genotypes, a significant decrease was found in only the C/C genotype after training. While, expression of VEGFa, PGC1α, and SDHa mRNAs, which relate to the biogenesis of mitochondria and capillaries, was significantly higher (54–82%) in the T/T than the C/C genotypes after training. It is suggested that hypertrophy of muscle fiber is directly associated with a decrease in Myostatin mRNA expression in the C/C genotype, and that increased expressions of VEGFa, PGC1α, and SDHa in the T/T genotype might be indirectly caused by the Myostatin SNP.
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Rifampicin Resistance and Multidrug-Resistant Tuberculosis Detection Using Xpert MTB/RIF in Wuhan, China: A Retrospective Study
Microbial Drug Resistance , Vol. 0, No. 0.
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Lessons From Team Nursing
When I hear discussions of or read about team-based care, I often think back to when I was in my BSN program, and team nursing was the relatively new model of care being implemented in hospital settings. As an integrated system of care, team nursing replaced the older functional models of nursing care. It was designed to accommodate multiple categories of hospital personnel to provide comprehensive care to groups of patients. I can still remember my senior clinical rotation (as well as the accompanying trepidation that my fellow students and I experienced) when it was our opportunity to be the team leaders and to be responsible for making the patient assignments, overseeing the development of care plans, scheduling team conferences, revising plans, and putting together a report for the next shift.
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Taking Care While Being Part of Something Bigger Than Ourselves
Nurses are the best caretakers. We give so much to others and that seems to double around the holiday season. As we leap with both feet into the season, I want to remind you to take care of yourself. If you work in the clinical setting like me, you are hitting the start of flu season. Patient volumes are up and breaks are short to nonexistent. On top of that, you're trying to finagle family time while covering your shift, call, or clinic obligations. My teammates and I attempt to give each other at least one 3-to-5–day stint off for family time around the holidays.
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States' Progress Toward Nurse Practitioner Full Practice Authority: Contemporary Challenges and Strategies
In 2017, South Dakota became the 22nd state to grant nurse practitioners (NPs) full practice authority (FPA; American Association of Nurse Practitioners, 2017a). Legislation for NP FPA introduced during 2017 in Arkansas, Illinois, Massachusetts, North Carolina, Oklahoma, and Pennsylvania resulted in varied outcomes. FPA legislation in Massachusetts, North Carolina, and Pennsylvania is still in progress. The goal of attaining NP FPA across the nation is steady albeit slow. NP advocates leading state FPA legislative campaigns are working diligently to address continually evolving challenges and gain support for FPA legislation.
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Pediatric Hip Pain: A Case Study
Hip pain in children can present a diagnostic challenge for the pediatric primary care provider. This case study examines an otherwise healthy 3-year-old girl with unilateral hip pain and intermittent refusal to bear weight on the affected side. Through history and physical examination, the provider was able to appropriately diagnose transient synovitis. This case study will summarize the care for hip pain in a child, including potential causes, a focused history and physical examination, appropriate diagnostic testing, and recommendations for home care and follow-up.
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Heterogeneous Patterns of Genetic Diversity and Differentiation in European and Siberian Chiffchaff (Phylloscopus collybita abietinus / P. tristis)
Identification of candidate genes for trait variation in diverging lineages and characterization of mechanistic underpinnings of genome differentiation are key steps towards understanding the processes underlying the formation of new species. Hybrid zones provide a valuable resource for such investigations since they allow for studying how genomes evolve as species exchange genetic material and for associating particular genetic regions with phenotypic traits of interest. Here we use whole-genome resequencing of both allopatric and hybridising populations of the European (Phylloscopus collybita abietinus) and the Siberian chiffchaff (P. tristis) - two recently diverged species which differ in morphology, plumage, song, habitat and migration - to quantify the regional variation in genome-wide genetic diversity and differentiation and to identify candidate regions for trait variation. We find that the levels of diversity, differentiation and divergence are highly heterogeneous with significantly reduced global differentiation and more pronounced differentiation peaks in sympatry than in allopatry. This pattern is consistent with regional differences in effective population size and recurrent background selection or selective sweeps reducing the genetic diversity in specific regions prior to lineage divergence, but the data also suggest that post-divergence selection has resulted in increased differentiation and fixed differences in specific regions. We find that hybridization and backcrossing is common in sympatry and that phenotype is a poor predictor of the genomic composition of sympatric birds. The combination of a differentiation scan approach with identification of fixed differences pinpoint a handful of candidate regions that might be important for trait variation between the two species.
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Surveying the Literature: Synopsis of Recent Key Publications
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Effect of Stellate Ganglion Block on the Regional Hemodynamics of the Upper Extremity: A Randomized Controlled Trial
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Postoperative Outcomes in Obstructive Sleep Apnea Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis of Comparative Studies
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Physiology and Role of Intraocular Pressure in Contemporary Anesthesia
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Insight Into Our Technology: Anesthesia Information Management Systems
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Fatigue Risk Management: The Impact of Anesthesiology Residents’ Work Schedules on Job Performance and a Review of Potential Countermeasures
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Noninfectious Fever in the Near-Term Pregnant Rat Induces Fetal Brain Inflammation: A Model for the Consequences of Epidural-Associated Maternal Fever
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Multisensory modulation of experimentally evoked perceptual distortion of the face
Abstract
Background
Chronic orofacial pain patients often perceive the painful face area as 'swollen' without clinical signs, i.e., a perceptual distortion (PD). Local anesthetic (LA) injections in healthy participants are also associated with PD
Objective
The aim was to explore whether PD evoked by LA into the infraorbital region of could be modulated by adding mechanical stimulation (MS) to the affected area
Methods
MS was given with a brush and a 128 mN von Frey filament. First, sixty healthy participants were randomly divided into three groups: 1) LA control, 2) LA with MS, 3) Isotonic solution (ISO) with MS as an additional control condition. To further examine the role of a multisensory modulation an additional experiment was conducted. Twenty participants received LA with MS (filament) in addition to visual feedback of their distorted face. The results of the two experiments are presented together
Results
All three LA groups experienced PD, per contra PD was not reported in the ISO group. MS alone did not change the magnitude of PD: brush (p = 0.089), filament (p = 0.203). However, when the filament stimulation was combined with additional visual information of a distorted face there was observable decrease in PD (p = 0.002)
Conclusion
The findings indicate the importance of multisensory integration for PD, and represent a significant step forward in the understanding of the factors that may influence this common condition. Future studies are encouraged to investigate further the cortical processing for possible implications for PD in pain management.
This article is protected by copyright. All rights reserved.
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Oesophageal motor function in chronic intestinal idiopathic pseudo-obstruction: a study with high-resolution manometry
Chronic intestinal idiopathic pseudo-obstruction (idiopathic CIPO) is a rare heterogeneous condition for which the different phenotypes are difficult to be established. Oesophageal motility has shown to be impaired in patients with idiopathic CIPO at traditional manometry, whereas no studies have assessed it by high resolution manometry (HRM).
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Oesophageal motor function in chronic intestinal idiopathic pseudo-obstruction: a study with high-resolution manometry
Chronic intestinal idiopathic pseudo-obstruction (idiopathic CIPO) is a rare heterogeneous condition for which the different phenotypes are difficult to be established. Oesophageal motility has shown to be impaired in patients with idiopathic CIPO at traditional manometry, whereas no studies have assessed it by high resolution manometry (HRM).
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The spectrum of Charcot-Marie-Tooth disease due to myelin protein zero: An electrodiagnostic, nerve ultrasound and histological study
Charcot-Marie-Tooth disease (CMT) is the most frequent inherited neuromuscular disorder and encompasses heterogeneous motor-sensory length-dependent polyneuropathies. CMT manifests commonly in the first-second decade with moderate functional involvement and slow evolution. Variations in age of onset, from early infancy to late adulthood, and degree of severity, from an asymptomatic neuropathy to loss of the ambulatory autonomy, are not necessarily linked to specific genotypes. Clinical phenotypes, mode of inheritance and nerve conduction study (NCS) still address genetic tests in the Next-Generation Sequencing era (Rossor et al., 2016).
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Motor cortex excitability in seizure-free STX1B mutation carriers with a history of epilepsy and febrile seizures
Febrile seizures affect 2-4% of all children and have been related to strong genetic predisposition (Berg et al., 2013). Recently, mutations of the STX1B gene have been identified as a shared genetic mechanism implicated in the pathogenesis of febrile seizures with or without epilepsy (Schubert et al., 2014). STX1B encodes the presynaptic protein syntaxin-1B, a significant component of the soluble-N-ethylmaleimide sensitive factor attachment receptor (SNARE) complex, which tethers synaptic vesicles in the presynaptic membrane and mediates the vesicle exocytosis and release of neurotransmitters at the synapse (Kearney, 2015).
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Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study
Sleep is a natural occurring state of decreased arousal that is crucial for normal cardiovascular, immune and cognitive function (Rosenberg-Adamsen et al., 1996; Saper et al., 2010). However, the principal sedative drugs, most of which modulate the γ amino butyric acid A (GABAA) receptor, do not produce the neurophysiological oscillations of sleep (Akeju et al., 2017). Rather, they produce neurophysiological oscillations that reflect cortical circuit disruptions, which manifest as electroencephalogram frontal beta oscillations, frontal alpha oscillations, burst suppression and isoelectricity (Patat et al., 1994; Feinberg et al., 2000; van Lier et al., 2004; Purdon et al., 2013; Akeju et al., 2014a; Akeju et al., 2014b, Akeju et al., 2017).
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Cerebellar transcranial direct current stimulation improves adaptive postural control
Adaptive postural control is essential for almost all aspects of every day life. Impaired postural control results in substantial functional limitations in advanced age (Maki and McIlroy, 1996) and in pathological ageing conditions like stroke (Beyaert et al., 2015), Parkinson's disease (Schoneburg et al., 2013) or multiple sclerosis (Huisinga et al., 2012). Although rehabilitation and conditioning programs have shown promising results in recovery of postural control, those interventions are typically time and cost intensive and may only yield moderate effects (Howard-Wilsher et al., 2016; Smania et al., 2011; Yitayeh and Teshome, 2016).
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Early corticospinal tract damage in prodromal SCA2 revealed by EEG-EMG and EMG-EMG coherence
SCA2 is caused by a polyglutamine-coding CAG trinucleotide repeat expansion (>34) in the ataxin-2 gene (Pulst et al., 1996). The complex SCA2 phenotype results from multi-system degeneration, involving cerebellum, spinal cord, brainstem and thalamus (Rüb et al., 2013). The prodromal stage of SCA2 was defined here according to Maas et al. (2015) as individuals with already detectable central and/or peripheral nervous system changes but without or with only minimal signs of ataxia (Maas et al., 2015).
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Cervical vestibular evoked myogenic potential tuning properties of patients with recurrent peripheral vestibulopathy: Is it Meniere’s disease without hearing loss?
Clinicians often encounter patients who complain of episodic vertigo. Meniere's disease (MD) and vestibular migraine (VM) are representative diseases in this category. Recently, new diagnostic criteria for both of these diseases have been published (Lopez-Escamez et al., 2015; Lempert et al., 2012). MD patients exhibit auditory symptoms in association with episodic vertigo attacks, while VM patients also have migrainous symptoms in addition to these symptoms. However, many patients have episodic vertigo without auditory or migrainous symptoms.
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Natural and artificial radionuclides in a marine core. First results of 236U in North Atlantic Ocean sediments
Source:Journal of Environmental Radioactivity
Author(s): M. Villa-Alfageme, E. Chamizo, F.J. Santos-Arévalo, J.M. López-Gutierrez, I. Gómez-Martínez, S. Hurtado-Bermúdez
There are very few data available of 236U in marine sediment cores. In this study we present the results from the first oceanic depth profile of 236U in a sediment core sampled in the North Atlantic Ocean, at the PAP site (4500 m depth, Porcupine Abyssal Plain (PAP) site, 49°0′ N, 16°30′ W). Additionally, the sediment core was radiologically characterized through the measurement of anthropogenic 137Cs, 239Pu, 240Pu, 129I and 14C and natural 210Pb, 40K and 226Ra.The measured 236U concentrations decrease from about 90·106 at g−1 at the seafloor down to 0.5·106 at g−1 at 6 cm depth. They are several orders of magnitude lower than the reported values for soils from the Northern Hemisphere solely influenced by global fallout (i.e. from 2700·106 to 7500·106 at g−1). 236U/238U atom ratios measured are at least three orders of magnitude above the estimated level for the naturally occurring dissolved uranium. The obtained inventories are 1·1012 at m−2 for 236U, 80 Bq m−2 for 137Cs, 45 Bq m−2 for 239+240Pu and 2.6·1012 at m−2 for 129I. Atomic ratios for 236U/239Pu, 137Cs/236U and 129I/236U, obtained from the inventories are 0.036, 0.11 and 2.5 respectively. Concentration profiles show mobilization probably due to bioturbation from the abundant detritivore holothurian species living at the PAP site sea-floor. The range of 236U, 137Cs, 239+240Pu and 129I values, inventories and ratios of these anthropogenic radionuclides are more similar to the values due to fall-out than values from a contribution from the Nuclear Fuel Reprocessing Plants dispersed to the south-west of the North Atlantic Ocean. However, signs of an additional source are detected and might be associated to the nuclear wastes dumped on the Eastern North Atlantic Ocean.
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Paramedic - UCHealth
At UCHealth, we do things differently Paramedic Testing & Interview Session, by invitation only, will be held on Monday, December 11, 2017. Applicants extended a contingent offer will need to clear pre-employment requirements by January 10th and will be expected to start in New Employee ...
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EMT- Intermediate and Basic - Community Care Ambulance Network
Please Visit www.ccan.org/careers to apply The EMT-basic is primarily responsible for providing basic life support to patients and/or assisting the paramedic in the delivery of advanced life support. Locations: Cuyahoga, Portage, Summit, Geauga, Ashtabula Counties 15228 Madison Rd, Middlefield, Ohio 44062, United States 115 E 24th St, Ashtabula, Ohio 44004, United States 830 W Main St, Geneva, Ohio ...
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EMS agency proposes ambulance chase car
The chase car would be available during a mass casualty event anywhere in the county; it could be provided to make up a BLS crew if all other avenues were exhausted
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Paramedics - Community Care Ambulance Network
The EMT-P is primarily responsible for providing patient care and customer service that meets or exceeds the national Standard of Care for Advanced Life Support personnel and all CCAN standards. The paramedic is ultimately responsible for all actions of the entire crew. Locations: Cuyahoga, Portage, Summit, Geauga, Ashtabula Counties 15228 Madison Rd, Middlefield, Ohio 44062, United States 115 E 24th ...
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What EMS leaders, educators can learn from continuing education data
An analysis of 8.7 million CAPCE continuing education records show how and when paramedics and EMTs earn CE for state and National Registry recertification
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Correction to: Effectiveness of Exercise Interventions to Improve Postural Control in Older Adults: A Systematic Review and Meta-Analyses of Centre of Pressure Measurements
Page 103, Table 1: The cell entry in the 'Terms used' column which previously read: "Centre of pressure OR center of pressure OR COP OR postural sway OR postural stability OR postural control OR balance OR force plat*".
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EMS credits WhatsApp with aiding in faster heart attack response
The messaging app is used to send diagnostic electrocardiograms directly to hospital cath labs
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Dallas officials reassure city that 911 problems are fixed
After two families claimed deaths due to 911 issues, Assistant Dallas Police Department Chief David Pughes said he is confident it will not happen again
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Pediatric population-specific disaster management
As we face more and different disasters, communities must consider the special needs of the pediatric portion that makes up one quarter of the population
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Ohio seeks technology ideas to solve national opioid crisis
Officials launched an $8 million effort to attract ideas for using technology to solve the national opioid addiction crisis that has touched scores of families
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Cover Image, Volume 173A, Number 11, November 2017
The cover image, by Cristina M. Justice et al., is based on the Original Article A Variant Associated with Sagittal Nonsydromic Craniosynostosis Alters the Regulatory Function of a Non-Coding Element, DOI: 10.1002/ajmg.a.38392. Photo Credit: Blake Carrington (NIH/NHGRI).
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Association analysis of the SNP (rs345476947) in the FUT2 gene with the production and reproductive traits in pigs
Abstract
The FUT2 gene was considered as an important candidate for pathogenic infections, while the potential associations between this gene and the production and reproductive traits of pigs have not been explored. In this study, we detected the genetic variants of porcine FUT2 gene and analyzed the associations of the polymorphisms with FUT2 mRNA expression and production and reproductive traits (age at 100 kg, backfat thickness at 100 kg, eye muscle thickness, the number of newborn piglets, the number of weaned piglets, and birth weight) in 100 Large White sows. One single nucleotide polymorphism (SNP) (rs345476947, C→T) in the intron of FUT2 and three genotypes (TT, CT and CC) were determined. Association analysis revealed significant associations between this SNP with the number of newborn piglets and weaned piglets. Furthermore, individuals with the TT genotype had significantly higher numbers of newborn piglets and weaned piglets than those with the CC genotype (P < 0.05). Quantitative PCR analysis showed that FUT2 expression in individuals with CC genotype was significantly higher than those with TT and CT genotypes in the liver and lymph gland (P < 0.05) and higher than that of CT in the spleen, kidney, and duodenum (P < 0.05). These findings indicated that the TT genotype may be a favorable genotype for the reproductive traits of pigs. Our study revealed the genetic variants of the FUT2 gene and identified a promising candidate SNP (rs345476947) associated with the reproductive traits, which has the potential to be applied in selective breeding of pigs.
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Genes linked to species diversity in a sexually dimorphic communication signal in electric fish
Abstract
Sexually dimorphic behaviors are often regulated by androgens and estrogens. Steroid receptors and metabolism are control points for evolutionary changes in sexual dimorphism. Electric communication signals of South American knifefishes are a model for understanding the evolution and physiology of sexually dimorphic behavior. These signals are regulated by gonadal steroids and controlled by a simple neural circuit. Sexual dimorphism of the signals varies across species. We used transcriptomics to examine mechanisms for sex differences in electric organ discharges (EODs) of two closely related species, Apteronotus leptorhynchus and Apteronotus albifrons, with reversed sexual dimorphism in their EODs. The pacemaker nucleus (Pn), which controls EOD frequency (EODf), expressed transcripts for steroid receptors and metabolizing enzymes, including androgen receptors, estrogen receptors, aromatase, and 5α-reductase. The Pn expressed mRNA for ion channels likely to regulate the high-frequency activity of Pn neurons and for neuromodulator and neurotransmitter receptors that may regulate EOD modulations used in aggression and courtship. Expression of several ion channel genes, including those for Kir3.1 inward-rectifying potassium channels and sodium channel β1 subunits, was sex-biased or correlated with EODf in ways consistent with EODf sex differences. Our findings provide a basis for future studies to characterize neurogenomic mechanisms by which sex differences evolve.
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Perceived stress is associated with smaller hippocampal volume in adolescence
Abstract
Perceived stress has been associated with decreased hippocampal, amygdala, and prefrontal cortex volume, as well as decreased memory and executive functioning performance in adulthood. Parents' perceived stress has been linked to decreased hippocampal volume in young children. However, no studies have investigated the links between self-perceived stress and brain structure or function in adolescents. Additionally, findings from previous research with younger or older samples are inconsistent, likely in part due to inconsistencies in participants' age range. In this study, we investigated the associations among self-perceived stress, family socioeconomic factors (family income, parental education), subcortical (hippocampus, amygdala) volumes, prefrontal cortical thickness and surface area, and memory and executive functioning performance in adolescents. One hundred and forty-three participants (12–20 years old) were administered a cognitive battery, a questionnaire to assess perceived stress, and a structural MRI scan. Higher levels of perceived stress were associated with decreased adolescent hippocampal volume. This study provides empirical evidence of how experience may shape brain development in adolescence—a period of plasticity during which it may be possible to intervene and prevent negative developmental outcomes.
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Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection
Abstract
Background
Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1).
Methods
This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen; GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2); and GT3-infected patients. Patients in the renal impairment and GT3 cohorts were treatment-naive or interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-naïve patients in the renal impairment cohort received G/P for 8 weeks; all other patients were treated for 12 weeks. Primary outcome was SVR (HCV RNA < 15 IU/mL) 12 weeks post-treatment (SVR12).
Results
The study enrolled 33 GT1/2-infected patients who failed previous DAA treatment (four with cirrhosis); 12 GT1/2-infected patients with severe renal impairment (two with cirrhosis); and 12 GT3-infected patients (two with cirrhosis). SVR12 was achieved by 31/33 (93.9%), 12/12 (100%), and 10/12 (83.3%) patients, respectively. One serious adverse event (fluid overload, not related to G/P) occurred in a patient on chronic intermittent hemodialysis.
Conclusions
G/P achieved high SVR12 rates and was well tolerated in three difficult-to-treat patient subgroups with limited treatment options in Japan (DAA-experienced patients, patients with severe renal impairment, and GT3-infected patients). These results support the potential suitability of this regimen for these special populations in Japan.
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Hepatic Complications of Anorexia Nervosa
Abstract
Anorexia nervosa (AN) has the highest mortality rate of all psychiatric illnesses due to the widespread organ dysfunction caused by the underlying severe malnutrition. Starvation causes hepatocyte injury and death leading to a rise in aminotransferases. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases. Acute liver failure associated with coagulopathy and encephalopathy can rarely occur. Liver enzymes may also less commonly increase as part of the refeeding process due to hepatic steatosis and can be distinguished from starvation hepatitis by the finding of a fatty liver on ultrasonography. Individuals with AN and starvation-induced hepatitis are at increased risk of hypoglycemia due to depleted glycogen stores and impaired gluconeogenesis. Gastroenterology and hepatology consultations are often requested when patients with AN and signs of hepatitis are hospitalized. It should be noted that additional laboratory testing, imaging, or liver biopsy all have low diagnostic yield, are costly, and potentially invasive, therefore, not generally recommended for diagnostic purposes. While the hepatitis of AN can reach severe levels, a supervised increase in caloric intake and a return to a healthy body weight often quickly lead to normalization of elevated aminotransferases caused by starvation.
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MicroRNA-30a Inhibits Colorectal Cancer Metastasis Through Down-Regulation of Type I Insulin-Like Growth Factor Receptor
Abstract
Background
miR-30a expression is down-regulated and regulates tumor suppressors in various cancers.
Aim
We investigated the mechanisms underlying the biological role of miR-30a in CRC.
Methods
MicroRNA, mRNA, and protein expression were analyzed by quantitative real-time PCR and Western blot. The migration and invasion abilities of CRC were determined by wound healing assay, and trans-well migration and invasion. A luciferase reporter assay was used to confirm the targets of miR-30a.
Results
miR-30a expression was significantly down-regulated in CRC tissues and in CRC tissue with lymph node metastasis compared to CRC tissue without metastasis. Overexpression of miR-30a suppressed migration and invasion through insulin-like growth factor 1 receptor (IGF1R) in CRC cells. miR-30a suppresses IGF1R protein expression and inhibits β-catenin or p-AKT and increases E-cadherin expression. The IGF1R expression level is also up-regulated in CRC tumors and inversely correlated with miR-30a in CRC specimens.
Conclusions
miR-30a functions as a tumor-suppressive miRNA, which may provide a therapeutic strategy for metastasis of CRC.
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Chromoendoscopy, Narrow-Band Imaging or White Light Endoscopy for Neoplasia Detection in Inflammatory Bowel Diseases
Abstract
Background
Studies have confirmed an increased risk of colorectal cancer in patients with ulcerative colitis; hence, surveillance is recommended. Optional modalities include white light endoscopy (WLE) or dye-spray chromoendoscopy. However, narrow-band imaging (NBI) is still not considered comparable to chromoendoscopy.
Aim
The aim of this study was to compare the diagnostic yield (DY) of WLE, chromoendoscopy, NBI for detection of neoplasia in patients with inflammatory bowel disease (IBD) by performing a meta-analysis of the existing literature.
Methods
We searched databases for prospective studies. For each modality, we performed comparative per-lesion analysis (any neoplasia detection) and per-patient analysis (patient with neoplastic lesions). Meta-analysis was performed using fixed-effect model unless heterogeneity was high. Odds ratios (ORs) with 95% CIs were calculated and pooled.
Results
Five studies compared chromoendoscopy to WLE. Chromoendoscopy (n = 361) was superior to WLE (n = 358) with per-patient analysis OR 2.05 (95% CI 1.26, 3.35) and per-lesion analysis OR 2.79 (95% CI 2.08, 3.73). High-definition (HD) chromoendoscopy was superior to HD-WLE with per-lesion analysis OR 2.48 (95% CI 1.55, 3.97). In four studies comparing NBI to WLE (n = 305), no difference was found in per-patient analysis OR 0.97 (95% CI 0.62, 1.53) and per-lesion analysis OR 0.94 (95% CI 0.63, 1.4). In two studies comparing CE to NBI (n = 104), no difference was found in per-patient analysis OR 1.0 (95% CI 0.51, 1.95) and per-lesion analysis OR 1.29 (95% CI 0.69, 2.41).
Conclusion
Chromoendoscopy is superior to WLE for detection of dysplasia in IBD, even with HD endoscopy. No difference in DY could be demonstrated for NBI in comparison with other modalities.
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LncRNA-CCAT1 Promotes Migration, Invasion, and EMT in Intrahepatic Cholangiocarcinoma Through Suppressing miR-152
Abstract
Background
Increasing evidence has suggested that lncRNA CCAT1 is upregulated and functions as a potential tumor promoter in many cancers. However, the potential biological roles and regulatory mechanisms of CCAT1 in intrahepatic cholangiocarcinoma (ICC) remain unclear.
Methods
We used real-time PCR to measure CCAT1 expression in ICC tissues and the adjacent normal tissues. The statistical analyses were applied to evaluate the prognostic value and associations of CCAT1 expression with clinical parameters. The CCAT1 was silenced with siRNA in ICC cells. The migration and invasion of ICC cells were detected with Transwell assay. The expressions of epithelial–mesenchymal transition (EMT)-related proteins were evaluated to discover whether the process of EMT was involved.
Results
We found that CCAT1 expression was elevated in ICC tissues compared to the adjacent normal tissues. We also found that high CCAT1 expression is closely correlated with tumor progression in ICC patients. Furthermore, our results show that knockdown of CCAT1 significantly suppressed the migration and invasion of ICC cells. Additionally, CCAT1 silencing remarkably reverses the EMT phenotype of ICC cells. Moreover, bioinformatics analysis and luciferase reporter assay revealed that CCAT1 directly bound to the miR-152, which has been reported to serve as a tumor suppressor in variety cancers. Further investigation demonstrated that CCAT1 led to the metastasis and EMT activation of ICC cells through inhibiting miR-152.
Conclusions
Our results suggested that CCAT1 functions as an oncogenic lncRNA in ICC, which could serve as a potential diagnostic and therapeutic target for ICC patients.
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Rapid Fecal Calprotectin Test and Symptom Index in Monitoring the Disease Activity in Colonic Inflammatory Bowel Disease
Abstract
Background
Fecal calprotectin is a reliable surrogate marker for inflammatory activity in inflammatory bowel disease (IBD).
Aims
For the noninvasive monitoring of the activity of colonic inflammation, we validated a symptom index suitable for ulcerative colitis and colonic Crohn's disease. By combining the symptom index with a rapid semi-quantitative calprotectin test, we constructed a new activity index based on the highest AUCs, using histological remission as a reference. We also evaluated the correlation of the patient-reported influence of the IBD in the daily life, measured by a VAS, with the inflammation activity.
Methods
The disease activity of 72 patients with IBD of the colon was determined by endoscopic activity scores (SES-CD/UCEIS). The patients provided stool samples for determination of calprotectin and filled in a questionnaire about their symptoms during the last week.
Results
The results of the symptom index demonstrated a statistically significant correlation with the rapid calprotectin test, histological inflammation activity, and the VAS. No correlations were found between the VAS and calprotectin or the histological inflammation activity. The sensitivity of the combination index to detect active inflammation was slightly superior to fecal calprotectin alone.
Conclusion
The new symptom index and the combination index are simple, noninvasive means for distinguishing remission from active inflammation in colonic IBD. With the VAS, we can pick up patients who need psychosocial support because of the disease burden, even if their IBD is in remission.
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Longtime concerns of poor EMS working conditions to be improved at agency
By EMS1 Staff RICHLAND COUNTY, S.C. — Millions of dollars are being set aside to upgrade a county's embattled EMS services. WACH.com reported that Richland County Councilman Seth Rose started receiving complaints from EMS providers about poor working conditions a year ago. "People are leaving for higher paying jobs in other counties," Rose said. "We can't have that if we ...
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Utility of Genetics for Risk Stratification in Pediatric Hypertrophic Cardiomyopathy
Children with hypertrophic cardiomyopathy (HCM) experience sudden cardiac death (SCD) and other life-threatening events. We assessed if affected gene and variant burden predict outcomes. Patients <18 years old with primary HCM with a pathogenic variant or variant of uncertain significance in cardiomyopathy genes were included. Association of gene and variant number and type with freedom from major adverse cardiac events (MACE) i.e. ICD insertion, myectomy, aborted SCD, transplantation or death, was assessed by Cox regression. 98 of 155 gene-tested patients carried a non-benign variant. The primary affected gene was MYH7 in 35% (MYH7+) and MYBPC3 in 49% (MYBPC3+). MYH7+ patients had earlier disease onset and higher risk of MACE (hazard ratio 2.7, 95% CI 1.3 - 5.7). Risk of MACE was also higher in patients with multiple variants (n=16) (HR 2.5, CI: 1.1-5.9) compared to a propensity score-matched single variant subset, after adjustment for primary gene, and in patients with de novo (n=18) vs inherited variants (HR 5.7, CI: 2.6-12.7). Affected gene (e.g. MYH7), higher variant burden and de novo variant status are independently associated with earlier onset and higher frequency of adverse outcomes in pediatric HCM, highlighting the importance of genetic risk stratification in HCM.
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Longtime concerns of poor EMS working conditions to be improved
By EMS1 Staff RICHLAND COUNTY, S.C. — Millions of dollars are being set aside to upgrade a county's embattled EMS services. WACH.com reported that Richland County Councilman Seth Rose started receiving complaints from EMS providers about poor working conditions a year ago. "People are leaving for higher paying jobs in other counties," Rose said. "We can't have that if we ...
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UK research: 1 in 5 witnesses do not perform CPR on victims
Researchers found that cardiac arrest survival rates remain low in the U.K. due to the lack of knowledge and skills to perform CPR
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(Dis)advantaged childhoods and premature mortality: cumulative inequalities over the life-course Josephine Jackisch
The process of culture in implementation research: linking the clinic and the community in Stockholm Helle Mölsted Alvesson
‘Feeling threatened’ and self-reported health after terrorist attacks in Belgium. Are we prone to ‘terrorification’? Reginald Deschepper
Organisational actors who engage in Scottish e-cigarette policy debates: A mixed methods approach Shona Hilton
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‘Models’ of Children’s Primary Care Michael Rigby
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Stockholm county councils health advisers in collaboration with the center of civic orientation Haibe Hussein
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Workloads as mediator for the association between job requirement level and health of older workers Karolin Hiesinger
“One Good Year Added” for every citizen within a community Joachim Fischer
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“Overweight” adults think they are “underweight”: a household survey in rural Zambia Yukiko Tateyama
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“Public Health Genomics in Cancer “in Cancer Control - Joint Action Policy Papers Marc Van Den Bulcke
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School tobacco policies, complex contagion and smoking inequalities among adolescents: a longitudinal study in seven European cities Pierre-Olivier Robert
1.B. Round Table: Upholding public health research, policy and practice in a future European Union
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Defective ciliogenesis in INPP5E-related Joubert syndrome
Joubert syndrome is a neurodevelopmental disorder, characterized by malformation of the mid and hindbrain leading to the pathognomonic molar tooth appearance of the brainstem and cerebellum on axial MRI. Core clinical manifestations include hypotonia, tachypnea/apnea, ataxia, ocular motor apraxia, and developmental delay of varying degrees. In addition, a subset of patients has retinal dystrophy, chorioretinal colobomas, hepatorenal fibrocystic disease, and polydactyly. Joubert syndrome exhibits genetic heterogeneity, with mutations identified in more than 30 genes, including INPP5E, a gene encoding inositol polyphosphate 5-phosphatase E, which is important in the development and stability of the primary cilium. Here, we report the detailed clinical phenotypes of two sisters with a novel homozygous variant in INPP5E (NM_019892.4: c.1565G>C, NP_063945.2: p.Gly552Ala), expanding the phenotype associated with Joubert syndrome type 1. Expression studies using patient-derived fibroblasts showed changes in mRNA and protein levels. Analysis of fibroblasts from patients revealed that a significant number of cells had shorter or no cilia, indicating defects in ciliogenesis, and cilia maintenance.
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Fitness-related differences in the rate of whole-body evaporative heat loss in exercising men are heat-load dependent
Abstract
The effect of aerobic fitness (defined as rate of peak oxygen consumption) on heat loss during exercise is thought to be related to the level of heat stress. However, it remains unclear at what combined exercise and environmental (net) heat load threshold these fitness-related differences occur. To identify this, we assessed whole-body heat exchange (dry and evaporative) by direct calorimetry in young (22 ± 3 years) men matched for physical characteristics with low (Low-fit) (39.8 ± 2.5 mLO2·kg−1·min−1), moderate (Mod-fit) (50.9 ± 1.2 mLO2·kg−1·min−1), and high (High-fit) (62.0 ± 4.4 mLO2·kg−1·min−1) aerobic fitness (each n = 8), during three 30-min bouts of cycling in dry heat (40°C, 12% relative humidity) at increasing rates of metabolic heat production of 300 (Ex1), 400 (Ex2), 500 W (Ex3), each followed by a 15-min recovery period. Each group was exposed to a similar net heat load (metabolic plus ∼100 W dry heat gain; P = 0.83) during each exercise bout (∼400 (Ex1), ∼500 (Ex2) and ∼600 W (Ex3); P < 0.01). However, while evaporative heat loss was similar between groups during Ex1 (P = 0.33), evaporative heat loss was greater in the High-fit [Ex2: 466 ± 21 W; Ex3: 557 ± 26 W] compared to the Low-fit [Ex2: 439 ± 22 W; Ex3: 511 ± 20 W] during Ex2 and Ex3 (P ≤ 0.03). Conversely, evaporative heat loss for the Mod-Fit did not differ from either the High-fit or Low-fit during all exercise bouts (P ≥ 0.09). We demonstrate that aerobic fitness modulates heat loss in a heat-load dependent manner, such that young highly-fit men display greater heat-loss capacity only at heat loads ∼≥500 W compared to their lesser trained counterparts.
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Advance in physiologically based pharmacokinetic modelling: from the organ level to sub-organ level based on experimental data
Abstract
Understanding the pharmacokinetics and target organ dosimetry properties of small molecular drugs and large molecular biologics is essential in the design of proper therapeutic regimens for disease treatments.
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Omecamtiv Mercabil and Blebbistatin modulate cardiac contractility by perturbing the regulatory state of the myosin filament
Abstract
Contraction of heart muscle is triggered by a transient rise in intracellular free calcium concentration linked to a change in the structure of the actin-containing thin filaments that allows the head or motor domains of myosin from the thick filaments to bind to them and induce filament sliding. It is becoming increasingly clear that cardiac contractility is also regulated through structural changes in the thick filaments, although the molecular mechanisms underlying thick filament regulation are still relatively poorly understood. Here we investigated those mechanisms using small molecules- Omecamtiv Mecarbil (OM) and Blebbistatin (BS) - that bind specifically to myosin and respectively activate or inhibit contractility in demembranated cardiac muscle cells. We measured isometric force and ATP utilization at different calcium and small-molecule concentrations in parallel with in situ structural changes determined using fluorescent probes on the myosin regulatory light chain in the thick filaments and on troponin C in the thin filaments. The results show that BS inhibits contractility and actin-myosin ATPase by stabilizing the OFF state of the thick filament in which myosin head domains are more parallel to the filament axis. In contrast, OM stabilizes the ON state of the thick filament, but inhibits contractility at high intracellular calcium concentration by disrupting the actin-myosin ATPase pathway. The effects of BS and OM on the calcium sensitivity of isometric force and filament structural changes suggest that the co-operativity of calcium activation in physiological conditions is due to positive coupling between the regulatory states of the thin and thick filaments.
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