bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inducible satellite cell depletion attenuates skeletal muscle regrowth following a scald‐burn injury
Authors: Finnerty Celeste C. , McKenna Colleen F. , Cambias Lauren A. , Brightwell Camille R. , Prasai Anesh , Wang Ye , El Ayadi Amina , Herndon David N. , Suman Oscar E. , Fry Christopher S. 
Published: August 2017

Key points
Severe burns result in significant skeletal muscle cachexia that impedes recovery.
Activity of satellite cells, skeletal muscle stem cells, is altered following a burn injury and likely hinders regrowth of muscle.
Severe burn injury induces satellite cell proliferation and fusion into myofibres with greater activity in muscles proximal to the injury site.
Conditional depletion of satellite cells attenuates recovery of myofibre area and volume following a scald burn injury in mice.
Skeletal muscle regrowth following a burn injury requires satellite cell activity, underscoring the therapeutic potential of satellite cells in the prevention of prolonged frailty in burn survivors.
AbstractSevere burns result in profound skeletal muscle atrophy; persistent muscle atrophy and weakness are major complications that hamper recovery from burn injury. Many factors contribute to the erosion of muscle mass following burn trauma, and we have previously shown concurrent activation and apoptosis of muscle satellite cells following a burn injury in paediatric patients. To determine the necessity of satellite cells during muscle recovery following a burn injury, we utilized a genetically modified mouse model (Pax7CreER‐DTA) that allows for the conditional depletion of satellite cells in skeletal muscle. Additionally, mice were provided 5‐ethynyl‐2′‐deoxyuridine to determine satellite cell proliferation, activation and fusion. Juvenile satellite cell‐wild‐type (SC‐WT) and satellite cell‐depleted (SC‐Dep) mice (8 weeks of age) were randomized to sham or burn injury consisting of a dorsal scald burn injury covering 30% of total body surface area. Both hindlimb and dorsal muscles were studied at 7, 14 and 21 days post‐burn. SC‐Dep mice had >93% depletion of satellite cells compared to SC‐WT (P < 0.05). Burn injury induced robust atrophy in muscles located both proximal and distal to the injury site (∼30% decrease in fibre cross‐sectional area, P < 0.05). Additionally, burn injury induced skeletal muscle regeneration, satellite cell proliferation and fusion. Depletion of satellite cells impaired post‐burn recovery of both muscle fibre cross‐sectional area and volume (P < 0.05). These findings support an integral role for satellite cells in the aetiology of lean tissue recovery following a severe burn injury.
Molecular composition and heterogeneity of the LRRC8‐containing swelling‐activated osmolyte channels in primary rat astrocytes
Authors: Schober Alexandra L. , Wilson Corinne S. , Mongin Alexander A. 
Published: August 2017

Key pointsThe volume‐regulated anion channel (VRAC) is a swelling‐activated chloride channel that is permeable to inorganic anions and a variety of small organic molecules.VRAC is formed via heteromerization of LRRC8 proteins, among which LRRC8A is essential, while LRRC8B/C/D/E serve as exchangeable complementary partners.We used an RNAi approach and radiotracer assays to explore which LRRC8 isoforms contribute to swelling‐activated release of diverse organic osmolytes in rat astrocytes.Efflux of uncharged osmolytes (myo‐inositol and taurine) was suppressed by deletion of LRRC8A or LRRC8D, but not by deletion of LRRC8C+LRRC8E.Conversely, release of charged osmolytes (d‐aspartate) was strongly reduced by deletion of LRRC8A or LRRC8C+LRRC8E, but largely unaffected by downregulation of LRRC8D.Our findings point to the existence of multiple heteromeric VRACs in the same cell type: LRRC8A/D‐containing heteromers appear to dominate release of uncharged osmolytes, while LRRC8A/C/E, with the additional contribution of LRRC8D, creates a conduit for movement of charged molecules.AbstractThe volume‐regulated anion channel (VRAC) is the ubiquitously expressed vertebrate Cl−/anion channel that is composed of proteins belonging to the LRRC8 family and activated by cell swelling. In the brain, VRAC contributes to physiological and pathological release of a variety of small organic molecules, including the amino acid neurotransmitters glutamate, aspartate and taurine. In the present work, we explored the role of all five LRRC8 family members in the release of organic osmolytes from primary rat astrocytes. Expression of LRRC8 proteins was modified using an RNAi approach, and amino acid fluxes via VRAC were quantified by radiotracer assays in cells challenged with hypoosmotic medium (30% reduction in osmolarity). Consistent with our prior work, knockdown of LRRC8A potently and equally suppressed the release of radiolabelledd‐[14C]aspartate and [3H]taurine. Among other LRRC8 subunits, downregulation of LRRC8D strongly inhibited release of the uncharged osmolytes [3H]taurine andmyo‐[3H]inositol, without major impact on the simultaneously measured efflux of the chargedd‐[14C]aspartate. In contrast, the release ofd‐[14C]aspartate was preferentially sensitive to deletion of LRRC8C+LRRC8E, but unaffected by downregulation of LRRC8D. Finally, siRNA knockdown of LRRC8C+LRRC8D strongly inhibited the release of all osmolytes. Overall, our findings suggest the existence of at least two distinct heteromeric VRACs in astroglial cells. The LRRC8A/D‐containing permeability pathway appears to dominate the release of uncharged osmolytes, while an alternative channel (or channels) is composed of LRRC8A/C/D/E and responsible for the loss of charged molecules.
Prevalence of Slow-Growth Vancomycin Nonsusceptibility in Methicillin-Resistant Staphylococcus aureus
Authors: Katayama Yuki , Azechi Takuya , Miyazaki Motoyasu , Takata Tohru , Sekine Miwa , Matsui Hidehito , Hanaki Hideaki , Yahara Koji , Sasano Hiroshi , Asakura Kota , Takaku Tomoiku , Ochiai Tomonori , Komatsu Norio , Chambers Henry F. 
Published: August 2017

ABSTRACT

We previously reported a novel phenotype of vancomycin-intermediate
Staphylococcus aureus
(VISA), i.e., “slow VISA,” whose colonies appear only after 72 h of incubation. Slow-VISA strains can be difficult to detect because prolonged incubation is required and the phenotype is unstable. To develop a method for detection of slow-VISA isolates, we studied 23 slow-VISA isolates derived from the heterogeneous VISA (hVISA) clinical strain Mu3. We identified single nucleotide polymorphisms (SNPs) in genes involved in various pathways which have been implicated in the stringent response, such as purine/pyrimidine synthesis, cell metabolism, and cell wall peptidoglycan synthesis. We found that mupirocin, which also induces the stringent response, caused stable expression of vancomycin resistance. On the basis of these results, we developed a method for detection of slow-VISA strains by use of 0.032 μg/ml mupirocin (Yuki Katayama, 7 March 2017, patent application PCT/JP2017/008975). Using this method, we detected 53 (15.6%) slow-VISA isolates among clinical methicillin-resistant
S. aureus
(MRSA) isolates. In contrast, the VISA phenotype was detected in fewer than 1% of isolates. Deep-sequencing analysis showed that slow-VISA clones are present in small numbers among hVISA isolates and proliferate in the presence of vancomycin. This slow-VISA subpopulation may account in part for the recurrence and persistence of MRSA infection.
Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice
Authors: Reis Levi Eduardo Soares , Fortes de Brito Rory Cristiane , Cardoso Jamille Mirelle de Oliveira , Mathias Fernando Augusto Siqueira , Aguiar Soares Rodrigo Dian Oliveira , Carneiro Claudia Martins , de Abreu Vieira Paula Melo , Ramos Guilherme Santos , Frézard Frédéric Jean Georges , Roatt Bruno Mendes , Reis Alexandre Barbosa 
Published: August 2017

ABSTRACT

Pentavalent antimonial has been the first choice treatment for visceral leishmaniasis; however, it has several side effects that leads to low adherence to treatment. Liposome-encapsulated meglumine antimoniate (MA) arises as an important strategy for chemotherapy enhancement. We evaluated the immunopathological changes using the mixture of conventional and pegylated liposomes with MA. The mice were infected with
Leishmania infantum
and a single-dose treatment regimen. Comparison was made with groups treated with saline, empty liposomes, free MA, and a liposomal formulation of MA (Lipo MA). Histopathological analyses demonstrated that animals treated with Lipo MA showed a significant decrease in the inflammatory process and the absence of granulomas. The
in vitro
stimulation of splenocytes showed a significant increase of gamma interferon (IFN-γ) produced by CD8
+
T cells and a decrease in interleukin-10 (IL-10) produced by CD4
+
and CD8
+
T cells in the Lipo MA. Furthermore, the Lipo MA group showed an increase in the IFN-γ/IL-10 ratio in both CD4
+
and CD8
+
T cell subsets. According to the parasite load evaluation using quantitative PCR, the Lipo MA group showed no
L. infantum
DNA in the spleen (0.0%) and 41.4% in the liver. In addition, we detected a low positive correlation between parasitism and histopathology findings (inflammatory process and granuloma formation). Thus, our results confirmed that Lipo MA is a promising antileishmanial formulation able to reduce the inflammatory response and induce a type 1 immune response, accompanied by a significant reduction of the parasite burden into hepatic and splenic compartments in treated animals.
Antifungal Activity of SCY-078 and Standard Antifungal Agents against 178 Clinical Isolates of Resistant and Susceptible Candida Species
Authors: Schell Wiley A. , Jones A. M. , Borroto-Esoda Katyna , Alexander Barbara D. 
Published: August 2017

ABSTRACT

SCY-078
in vitro
activity was determined for 178 isolates of resistant or susceptible
Candida albicans
,
Candida dubliniensis
,
Candida glabrata
,
Candida krusei
,
Candida lusitaniae
, and
Candida parapsilosis
, including 44
Candida
isolates with known genotypic (
FKS1
or
FKS2
mutations), phenotypic, or clinical resistance to echinocandins. Results were compared to those for anidulafungin, caspofungin, micafungin, fluconazole, and voriconazole. SCY-078 was shown to have excellent activity against both wild-type isolates and echinocandin- and azole-resistant isolates of
Candida
species.
Antibacterial Resistance in Ureaplasma Species and Mycoplasma hominis Isolates from Urine Cultures in College-Aged Females
Authors: Valentine-King Marissa A. , Brown Mary B. 
Published: August 2017

ABSTRACT

Urinary tract infections (UTIs) affect nearly 20% of women age 15 to 29 and account for an estimated $3.5 billion in costs. Antibiotic resistance prolongs UTI treatment, and resistance profiles vary regionally. This regional variation is an important consideration in guiding empirical treatment selection. Regional studies in the United States have identified tetracycline resistance in over one-third of
Ureaplasma
species isolates, but no studies have evaluated antibiotic resistance levels in college-aged women with a first-time UTI. We tested a panel of antibiotics and determined the MICs of
Ureaplasma
species (60
U. parvum
and 13
U. urealyticum
) and 10
Mycoplasma hominis
isolates obtained from urine from college-aged women with a first-time UTI. Low antibiotic resistance was found in this population of women with a first-time UTI. All
M. hominis
and
U. urealyticum
isolates were sensitive. However, two
U. parvum
isolates were resistant, with one to levofloxacin (MIC, 4 μg/ml) and one to tetracycline (MIC, 8 μg/ml). For the
Ureaplasma
spp., the MIC
90
s were highest against gentamicin (21 μg/ml) and lowest against doxycycline (0.25 μg/ml). In a comparison of MIC levels between
Ureaplasma
spp.,
U. urealyticum
had significantly higher MICs against each antibiotic except doxycycline. For the resistant isolates, the genetic mechanisms of resistance were determined. PCR amplification identified
tetM
to be present in the tetracycline-resistant isolate and an S83W mutation within the
parC
gene of the quinolone-resistant isolate. To our knowledge, this study is the first to provide molecular and phenotypic evidence of the S83W
parC
mutation conferring levofloxacin resistance in
U. parvum
isolated from a patient in the United States.
A content analysis of the representation of statins in the British newsprint media
Authors: Chisnell Julia , Marshall Tom , Hyde Chris , Zhelev Zhivko , Fleming Lora E 
Published: August 2017

ObjectiveThis study reviewed the news media coverage of statins, seeking to identify specific trends or differences in viewpoint between media outlets and examine common themes.DesignThe study is a content analysis of the frequency and content of the reporting of statins in a selection of the British newsprint media. It involved an assessment of the number, timing and thematic content of articles followed by a discourse analysis examining the underlying narratives. The sample was the output of four UK newspapers, covering a broad-spectrum readership, over a six month timeframe 1 October 2013 to 31 March 2014.ResultsA total of 67 articles included reference to statins. The majority (39, 58%) were reporting or responding to publication of a clinical study. The ratio of negative to positive coverage was greater than 2:1 overall. In the more politically right-leaning newspapers, 67% of coverage was predominantly negative (30/45 articles); 32% in the more left-leaning papers (7/22 articles). Common themes were the perceived ‘medicalisation’ of the population; the balance between lifestyle modification and medical treatments in the primary prevention of heart disease; side effects and effectiveness of statins; pharmaceutical sponsorship and implications for the reliability of evidence; trust between the public and government, institutions, research organisations and the medical profession.ConclusionsNewsprint media coverage of statins was substantially influenced by the publication of national guidance and by coverage in the medical journals of clinical studies and comment. Statins received a predominantly negative portrayal, notably in the more right-leaning press. There were shared themes: concern about the balance between medication and lifestyle change in the primary prevention of heart disease; the adverse effects of treatment; and a questioning of the reliability of evidence from research institutions, scientists and clinicians in the light of their potential allegiances and funding.
Multiple treatment comparison of seven new drugs for patients with advanced malignant melanoma: a systematic review and health economic decision model in a Norwegian setting
Authors: Pike Eva , Hamidi Vida , Saeterdal Ingvil , Odgaard-Jensen Jan , Klemp Marianne 
Published: August 2017

ObjectiveTo assess the relative effectiveness and cost-effectiveness of seven new drugs (cobimetinib, dabrafenib, ipilimumab, nivolumab, pembrolizumab, trametinib and vemurafenib) used for treatment of patients with advanced malignant melanoma in the Norwegian setting.DesignA multiple technology assessment.PatientsPatients with advanced malignant melanoma aged 18 or older.Data sourcesA systematic search for randomised controlled trials in relevant bibliographic databases.MethodsWe performed network meta-analyses using both direct and indirect evidence with dacarbazine as a common comparator. We ranked the different treatments in terms of their likelihood of leading to the best results for each endpoint. The cost-utility analysis was based on a probabilistic discrete-time Markov cohort model. The model calculated the costs and quality-adjusted life years (QALYs) with different treatment strategies from a healthcare perspective. Sensitivity analysis was performed by means of Monte Carlo simulation.ResultsMonotherapies with a programmed cell death 1 (PD-1) immune-checkpoint-inhibitor had a higher probability of good performance for overall survival than monotherapies with ipilimumab or BRAF/MEK inhibitors. The combination treatments had all similar levels of effectiveness to the PD-1 immune-checkpoint-inhibitors.PD-1 immune-checkpoint-inhibitors are more effective and more costly compared with ipilimumab in monotherapy. Nivolumab in combination with ipilimumab had higher costs and the same level of effectiveness as the PD-1 immune-checkpoint-inhibitors in monotherapy.BRAF/MEK inhibitor combinations (dabrafenib and trametinib or vemurafenib and cobimetinib) had both similar effectiveness and cost-effectiveness; however, the combination therapies are more likely to give higher quality adjusted life year gains than BRAF or MEK inhibitor monotherapies, but to a higher cost.ConclusionsNone of the drugs investigated can be considered cost-effective at what has normally been considered a reasonable willingness-to-pay (WTP) in Norway. Price reductions (from the official list prices) in the region of 63%–84% would be necessary for these drugs to be cost-effective at a WTP of €55 850 per QALY.
National audit of pressure ulcers and incontinence-associated dermatitis in hospitals across Wales: a cross-sectional study
Authors: Clark Michael , Semple Martin J , Ivins Nicola , Mahoney Kirsten , Harding Keith 
Published: August 2017

ObjectiveThe Chief Nurse National Health Service Wales initiated a national survey of acute and community hospital patients in Wales to identify the prevalence of pressure ulcers and incontinence-associated dermatitis.MethodsTeams of two nurses working independently assessed the skin of each inpatient who consented to having their skin observed.ResultsOver 28 September 2015 to 2nd October 2015, 8365 patients were assessed across 66 hospitals with 748 (8.9%) found to have pressure ulcers. Not all patients had their skin inspected with all mental health patients exempt from this part of the audit along with others who did not consent or were too ill. Of the patients with pressure ulcers, 593 (79.3%) had their skin inspected with 158 new pressure ulcers encountered that were not known to ward staff, while 152 pressure ulcers were incorrectly categorised by the ward teams. Incontinence-associated dermatitis was encountered in 360 patients (4.3%), while medical device-related pressure ulcers were rare (n=33). The support surfaces used while patients were in bed were also recorded to provide a baseline against which future changes in equipment procurement could be assessed. The presence of other wounds was also recorded with 2537 (30.3%) of all hospital patients having one or more skin wounds.ConclusionsThis survey has demonstrated that although complex, it is feasible to undertake national surveys of pressure ulcers, incontinence-associated dermatitis and other wounds providing comprehensive and accurate data to help plan improvements in wound care across Wales.
Extracellular cardiac matrix biomarkers in patients with reduced ejection fraction heart failure as predictors of response to cardiac resynchronisation therapy: a systematic review
Authors: McAloon Christopher J , Ali Danish , Hamborg Thomas , Banerjee Prithwish , O'Hare Paul , Randeva Harpal , Osman Faizel 
Published: August 2017

ObjectiveCardiac resynchronisation therapy (CRT) is an effective therapy for selected patients with heart failure (HF); however, a significant non-response rate exists. We examined current evidence on extracellular cardiac matrix (ECM) biomarkers in predicting response following CRT.MethodsComplete literature review of PubMed, Ovid SP MEDLINE, Cochrane Library and TRIP, reference lists, international cardiology conferences and ongoing studies between December 1999 and December 2015 conducted according to prospectively registered study selection and analysis criteria (PROSPERO:CRD42016025864) was performed. All observational and randomised control trials (RCT) were included if they tested prespecified ECM biomarkers’ ability to predict CRT response. Risk of bias assessment and data extraction determined pooling of included studies was not feasible due to heterogeneity of the selected studies.ResultsA total of 217 studies were screened; six (five prospective cohort and one RCT substudy) were included in analysis with 415 participants in total. Study sizes varied (n=55–260), cohort characteristics contrasted (male: 67.8%–83.6%, ischaemic aetiology: 40.2%–70.3%) and CRT response definitions differed (three clinical/functional, three echocardiographic). Consistent observation in all ECM biomarker behaviour before and after CRT implantation was not observed between studies. Lower type I and type III collagen synthesis biomarkers (N-terminal propeptides of type I and III procollagens) expression demonstrated replicated ability to predict reverse left ventricular remodelling.ConclusionCollagen synthesis biomarkers offer the most potential as ECM biomarkers for predicting CRT response. Heterogeneity between these studies was large and limited the ability to pool and compare results numerically. Use of different response definitions was one of the biggest challenges.
The viability of phantom dark energy: A review
Authors: Ludwick Kevin J. 
Published: August 2017

In this brief review, we examine the theoretical consistency and viability of phantom dark energy. Almost all data sets from cosmological probes are compatible with the dark energy of the phantom variety (i.e. equation-of-state parameter [Formula: see text]) and may even favor evolving dark energy, and since we expect every physical entity to have some kind of field description, we set out to examine the case for phantom dark energy as a field theory. We discuss the many attempts at frameworks that may mitigate and eliminate theoretical pathologies associated with phantom dark energy. We also examine frameworks that provide an apparent measurement [Formula: see text] while avoiding the need for a phantom field theory.
Light charged Higgs boson scenario in 3-Higgs doublet models
Authors: Akeroyd A. G. , Moretti Stefano , Yagyu Kei , Yildirim Emine 
Published: August 2017

The constraints from the measurements of the [Formula: see text] decay rate on the parameter space of 3-Higgs Doublet Models (3HDMs), where all the doublets have nonzero vacuum expectation values, are studied at the next-to-leading order in QCD. In order to naturally avoid the presence of flavour changing neutral currents at the tree level, we impose two softly-broken discrete [Formula: see text] symmetries. This gives rise to five independent types of 3HDMs that differ in their Yukawa couplings. We show that in all these 3HDMs (including the case of type-II-like Yukawa interactions) both masses of the two charged Higgs bosons [Formula: see text] and [Formula: see text] can be smaller than the top mass [Formula: see text] while complying with the constraints from [Formula: see text]. As an interesting phenomenological consequence, the branching ratios of the charged Higgs bosons decay into the [Formula: see text] final states can be as large as [Formula: see text] when their masses are taken to be below [Formula: see text] in two of the five 3HDMs (named as Type-Y and Type-Z). This light charged Higgs boson scenario provides a hallmark 3HDM signature that cannot be realised in [Formula: see text] symmetric 2-Higgs doublet models. We find that in the Type-Y and Type-Z 3HDMs the scenario with [Formula: see text], [Formula: see text] is ruled out by the direct searches at the LHC, but in the Type-Y 3HDM [Formula: see text] and [Formula: see text] is allowed by [Formula: see text] and direct searches at LEP2, Tevatron and LHC due to the reduced sensitivity of these searches to the degenerate case [Formula: see text]. The cases where only one or both charged Higgs bosons are above the top quark mass are also naturally allowed in the both Type-Y and Type-Z 3HDMs.