bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling Drug Penetration of Echinocandin Antifungals at the Site of Infection in an Intra-abdominal Abscess Model
Authors: Zhao Yanan , Prideaux Brendan , Nagasaki Yoji , Lee Min Hee , Chen Pei-Yu , Blanc Landry , Ho Hsinpin , Clancy Cornelius J. , Nguyen Minh Hong , Dartois Véronique , Perlin David S. 
Published: July 2017

ABSTRACT
Intra-abdominal candidiasis (IAC) is a prominent invasive fungal infection associated with high mortality. Prompt antifungal therapy and source control are crucial for successful treatment. Echinocandin antifungal drugs are first-line agents; however, their clinical effectiveness is highly variable, with known potential for breakthrough resistance, and little is known about drug exposure at the site of infection. Using matrix-assisted desorption ionization mass spectrometry imaging technology, we investigated the spatial and quantitative distribution in tissue lesions for two echinocandin drugs, micafungin and CD101, in a clinically relevant IAC mouse model. Drug accumulation within lesions was observed with both drugs at their humanized therapeutic doses. CD101, but not micafungin, accumulated in lesions at levels above the mutant prevention concentration of the infecting strain. These findings indicate that current echinocandin drugs are limited by penetration at the site of infection and have implications for clinical outcomes and emergence of resistance in patients with IAC.
Epigenetic Mechanisms Regulate Innate Immunity against Uropathogenic and Commensal-Like Escherichia coli in the Surrogate Insect Model Galleria mellonella
Authors: Heitmueller Miriam , Billion André , Dobrindt Ulrich , Vilcinskas Andreas , Mukherjee Krishnendu 
Published: July 2017

ABSTRACT

Innate-immunity-related genes in humans are activated during urinary tract infections (UTIs) caused by pathogenic strains of
Escherichia coli
but are suppressed by commensals. Epigenetic mechanisms play a pivotal role in the regulation of gene expression in response to environmental stimuli. To determine whether epigenetic mechanisms can explain the different behaviors of pathogenic and commensal bacteria, we infected larvae of the greater wax moth,
Galleria mellonella
, a widely used model insect host, with a uropathogenic
E. coli
(UPEC) strain that causes symptomatic UTIs in humans or a commensal-like strain that causes asymptomatic bacteriuria (ABU). Infection with the UPEC strain (CFT073) was more lethal to larvae than infection with the attenuated ABU strain (83972) due to the recognition of each strain by different Toll-like receptors, ultimately leading to differential DNA/RNA methylation and histone acetylation. We used next-generation sequencing and reverse transcription (RT)-PCR to correlate epigenetic changes with the induction of innate-immunity-related genes. Transcriptomic analysis of
G. mellonella
larvae infected with
E. coli
strains CFT073 and 83972 revealed strain-specific variations in the class and expression levels of genes encoding antimicrobial peptides, cytokines, and enzymes controlling DNA methylation and histone acetylation. Our results provide evidence for the differential epigenetic regulation of transcriptional reprogramming by UPEC and ABU strains of
E. coli
in
G. mellonella
larvae, which may be relevant to understanding the different behaviors of these bacterial strains in the human urinary tract.
Mouse Bone Marrow Sca-1
+
CD44
+
Mesenchymal Stem Cells Kill Avirulent Mycobacteria but Not Mycobacterium tuberculosis through Modulation of Cathelicidin Expression via the p38 Mitogen-Activated Protein Kinase-Dependent Pathway
Authors: Naik Sumanta Kumar , Padhi Avinash , Ganguli Geetanjali , Sengupta Srabasti , Pati Sanghamitra , Das Dasarathi , Sonawane Avinash 
Published: July 2017

ABSTRACT

Mycobacterium tuberculosis
primarily infects lung macrophages. However, a recent study showed that
M. tuberculosis
also infects and persists in a dormant form inside bone marrow mesenchymal stem cells (BM-MSCs) even after successful antibiotic therapy. However, the mechanism(s) by which
M. tuberculosis
survives in BM-MSCs is still not known. Like macrophages, BM-MSCs do not contain a well-defined endocytic pathway, which is known to play a central role in the clearance of internalized mycobacteria. Here, we studied the fate of virulent and avirulent mycobacteria in Sca-1
+
CD44
+
BM-MSCs. We found that BM-MSCs were able to kill avirulent
Mycobacterium smegmatis
and
Mycobacterium bovis
BCG but not the pathogenic species
M. tuberculosis
. Further mechanistic studies revealed that pathogenic
M. tuberculosis
dampens the antibacterial response of BM-MSCs by downregulating the expression of the cationic antimicrobial peptide cathelicidin. In contrast, avirulent mycobacteria were effectively killed by inducing the Toll-like receptor 2/4 (TLR2/4) pathway-dependent expression of cathelicidin, while small interfering RNA (siRNA)-mediated cathelicidin silencing increased the survival of
M. bovis
BCG in BM-MSCs. We also showed that
M. bovis
BCG infection caused increased expression levels of MyD88, phospho-interleukin-1 receptor-associated kinase 4 (pIRAK-4), and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Further downstream investigations demonstrated that IRAK-4–p38 activation increased the nuclear translocation of NF-κB, which subsequently induced the expression of cathelicidin and the cytokine interleukin-1β (IL-1β), resulting in the decreased survival of
M. bovis
BCG. On the other hand, inhibition of TLR2/4, pIRAK-4, p38, and NF-κB nuclear translocation decreased cathelicidin and IL-1β expression levels and therefore increased the survival of avirulent mycobacteria. This is the first report that demonstrates that virulent mycobacteria manipulate the TLR2/4–MyD88–IRAK-4–p38–NF-κB–Camp–IL-1β pathway to survive inside bone marrow stem cells.
Robot-assisted surgery in a broader healthcare perspective: a difference-in-difference-based cost analysis of a national prostatectomy cohort
Authors: Hyldgård Vibe Bolvig , Laursen Karin Rosenkilde , Poulsen Johan , Søgaard Rikke 
Published: July 2017

ObjectiveTo estimate costs attributable to robot-assisted laparoscopic prostatectomy (RALP) as compared with open prostatectomy (OP) and laparoscopic prostatectomies (LP) in a National Health Service perspective.Patients and methodsRegister-based cohort study of 4309 consecutive patients who underwent prostatectomy from 2006 to 2013 (2241 RALP, 1818 OP and 250 LP). Patients were followed from 12 months before to 12 months after prostatectomy with respect to service use in primary care (general practitioners, therapists, specialists etc) and hospitals (inpatient and outpatient activity related to prostatectomy and comorbidity). Tariffs of the activity-based remuneration system for primary care and the Diagnosis-Related Grouping case-mix system for hospital-based care were used to value service use. Costs attributable to RALP were estimated using a difference-in-difference analytical approach and adjusted for patient-level and hospital-level risk selection using multilevel regression.ResultsNo significant effect of RALP on resource-use was observed except for a marginally lower use of primary care and fewer bed days as compared with OP (not LP). The overall cost consequence of RALP was estimated at an additional €2459 (95% CI 1377 to 3540, p=0.003) as compared with OP and an additional €3860 (95% CI 559 to 7160, p=0.031) as compared with LP, mainly due to higher cost intensity during the index admissions.ConclusionsIn this study from the Danish context, the use of RALP generates a factor 1.3 additional cost when compared with OP and a factor 1.6 additional cost when compared with LP, on average, based on 12 months follow-up. The policy interpretation is that the use of robots for prostatectomy should be driven by clinical superiority and that formal effectiveness analysis is required to determine whether the current and eventual new purchasing of robot capacity is best used for prostatectomy.
The Burdens and Uncertainties of Doing What One Should Do
Authors: Vogel Victor G. 
Published: July 2017

AbstractDespite FDA approval of drugs to reduce the risk of breast cancer in women at increased risk, uptake of these drugs has been poor despite the publication of numerous studies that demonstrate both their effectives and safety. National organizations have made recommendations for their use, but both physicians and their patients do not fully understand either breast cancer risk factors or risk assessment or the indications for using risk-reducing agents. Histologically predisposing conditions, such as ductal or lobular atypia and lobular carcinoma in situ, impart particularly high risks of developing subsequent invasive breast cancer. Resources should be committed to both provider and patient education to reduce the risk of breast cancer in women who are at increased risk. Cancer Prev Res; 10(8); 431–3. ©2017 AACR.
ὁµότονος: When did Words Have the Same Accent?
Authors: Roussou Stephanie 
Published: July 2017

AbstractLSJ (s.v. ὁµότονος, ΙΙ) offers the definition ‘having the same accent’ for ὁµότονος as a grammatical term. This definition does not make clear whether ‘having the same accent’ involves having the same type of accent (acute or circumflex), having the accent in the same position, or both. This article examines the use and interpretation of the term ὁµότονος in grammatical and lexicographical works and scholia. The patterns of use that emerge reflect an implicit awareness of important structural features of the Greek accent system.
Conspiracy as Plot Type in Herodian’s Roman History
Authors: Scott Andrew G. 
Published: July 2017

AbstractDespite positioning himself as a contemporary eyewitness and heir to Thucydides, Herodian has generally been judged to be a poor historian prone to the use of compression, formulaic scenes, and even free invention. This paper examines Herodian’s application of a specific plot type to conspiracies against the emperor by praetorian prefects. The use of this plot type reveals something of Herodian’s understanding of history and historical methodology, while also serving an important narrative function in his text.
Evaluation of Noise Exposure Secondary to Wind Noise in Cyclists
Authors: Seidman Michael D. , Wertz Anna G. , Smith Matthew M. , Jacob Steve , Ahsan Syed F. 
Published: July 2017

ObjectiveDetermine if the noise levels of wind exposure experienced by cyclists reach levels that could contribute to noise‐induced hearing loss.Study DesignIndustrial lab research.SettingIndustrial wind tunnel.Subjects and MethodsA commercial‐grade electric wind tunnel was used to simulate different speeds encountered by a cyclist. A single cyclist was used during the simulation for audiometric measurements. Microphones attached near the ears of the cyclist were used to measure the sound (dB sound pressure level) experienced by the cyclist. Loudness levels were measured with the head positioned at 15‐degree increments from 0 degrees to 180 degrees relative to the oncoming wind at different speeds (10‐60 mph).ResultsWind noise ranged from 84.9 dB at 10 mph and increased proportionally with speed to a maximum of 120.3 dB at 60 mph. The maximum of 120.3 dB was measured at the downwind ear when the ear was 90 degrees away from the wind.ConclusionsWind noise experienced by a cyclist is proportional to the speed and the directionality of the wind current. Turbulent air flow patterns are observed that contribute to increased sound exposure in the downwind ear. Consideration of ear deflection equipment without compromising sound awareness for cyclists during prolonged rides is advised to avoid potential noise trauma. Future research is warranted and can include long‐term studies including dosimetry measures of the sound and yearly pre‐ and postexposure audiograms of cyclists to detect if any hearing loss occurs with long‐term cycling.
Neck and Upper Limb Dysfunction in Patients following Neck Dissection: Looking beyond the Shoulder
Authors: Gane Elise M. , O’Leary Shaun P. , Hatton Anna L. , Panizza Benedict J. , McPhail Steven M. 
Published: July 2017

ObjectiveTo measure patient‐perceived upper limb and neck function following neck dissection and to investigate potential associations between clinical factors, symptoms, and function.Study DesignCross‐sectional.SettingTwo tertiary hospitals in Brisbane, Australia.Subjects and MethodsInclusion criteria: patients treated with neck dissection (2009‐2014). Exclusion criteria: aged <18 years, accessory nerve or sternocleidomastoid sacrifice, previous neck dissection, preexisting shoulder/neck injury, and inability to provide informed consent (cognition, insufficient English). Primary outcomes were self‐reported function of the upper limb (Quick Disabilities of the Arm, Shoulder, and Hand) and neck (Neck Disability Index). Secondary outcomes included demographics, oncological management, self‐efficacy, and pain. Generalized linear models were prepared to examine relationships between explanatory variables and self‐reported function.ResultsEighty‐nine participants (male n = 63, 71%; median age, 62 years; median 3 years since surgery) reported mild upper limb and neck dysfunction (median [quartile 1, quartile 3] scores of 11 [3, 32] and 12 [4, 28], respectively). Significant associations were found between worse upper limb function and longer time since surgery (coefficient, 1.76; 95% confidence interval [CI], 0.01‐3.51), having disease within the thyroid (17.40; 2.37‐32.44), postoperative radiation therapy (vs surgery only) (13.90; 6.67‐21.14), and shoulder pain (0.65; 0.44‐0.85). Worse neck function was associated with metastatic cervical lymph nodes (coefficient, 6.61; 95% CI, 1.14‐12.08), shoulder pain (0.19; 0.04‐0.34), neck pain (0.34; 0.21‐0.47), and symptoms of neuropathic pain (0.61; 0.25‐0.98).ConclusionPatients can experience upper limb and neck dysfunction following nerve‐preserving neck dissection. The upper quadrant as a whole should be considered when assessing rehabilitation priorities after neck dissection.
Performance and Return to Sport After Achilles Tendon Repair in National Football League Players
Authors: Jack Robert A. , Sochacki Kyle R. , Gardner Stephanie S. , McCulloch Patrick C. , Lintner David M. , Cosculluela Pedro E. , Varner Kevin E. , Harris Joshua D. 
Published: July 2017

Background: Achilles tendon injuries are common in sports, including football. The purpose of this study was to determine (1) return-to-sport rate in National Football League (NFL) players following Achilles tendon repair, (2) postoperative career length and games per season, (3) pre- and postoperative performance, and (4) postoperative performance compared with control players matched by position, age, years of experience, and performance. Methods: Publicly available records were used to identify NFL players who underwent Achilles tendon repair and matched controls were identified. Ninety-five players (98 surgeries) were analyzed (mean age 28.2 ± 2.8 years; mean 5.5 ± 2 .8 years in NFL at time of surgery). Demographic and performance data were collected. Comparisons between case and control groups and preoperative and postoperative time points were made using paired-samples Student t tests. Results: Seventy-one (72.4%) players were able to return to sport in the NFL at a mean of 339.8 ± 84.8 days following surgery. Thirty-one (32%) Achilles tendon repairs were performed during training camp or preseason. Controls (3.6 ± 2.1 years) had a significantly longer NFL career ( P < .05) than players who underwent Achilles tendon repair (2.7 ± 2.1 years). There was no significant difference in games per season in subsequent seasons following surgery compared with controls. Postoperative performance scores were significantly worse ( P < .05) for running backs (RBs) (n = 4) and linebackers (LBs) (n = 12) compared to preoperative scores. LBs had significantly worse postoperative performance scores when compared to matched controls ( P < .05). Conclusion: Following Achilles tendon repair, less than 75% of players returned to the NFL. Postoperative career length was 1 season shorter than matched controls. No difference was observed in the number of games per season played compared to matched controls. Postoperative performance scores were significantly worse for RBs and LBs compared to preoperative and LBs had significantly worse postoperative performance when compared to matched controls. Level of Evidence: Level III, retrospective comparative series.
Fampridine response in MS patients with gait impairment in a real-world setting: Need for new response criteria?
Authors: Rodriguez-Leal Francisco Alejandro , Haase Rocco , Thomas Katja , Eisele Judith Christina , Proschmann Undine , Schultheiss Thorsten , Kern Raimar , Ziemssen Tjalf 
Published: July 2017

Objective: The primary objective of this real-world study was to describe the response to fampridine and changes of gait parameters in multiple sclerosis (MS) patients’ walking disability (Expanded Disability Status Scale (EDSS): 4–7) after treatment with fampridine for 2 weeks as recommended by the European Medicines Agency (EMA) and compare it with the overall physician’s judgement. Methods: A total of 211 adult MS patients were analyzed using a multimodal gait assessment including the timed 25-foot walk test (T25FW), 2-minute walking test (2-MWT), 12-item Multiple Sclerosis Walking Scale (MSWS-12), the GAITRite electronic walkway system, and the patients’ clinical global impression (CGI). Multimodal gait assessment was compared with the clinician’s impression of overall improvement after 2 weeks. Results: In total, 189 subjects were included, of which 133 (70.37%) were responders to fampridine (RF), according to physician’s judgement. Looking at independent multimodal gait assessment, RFs showed improvement of 12.60% in the T25FW, 19.25% in the 2-MWT, 21.12% in the MSWS-12, and 6.54% in their Functional Ambulation Profile (FAP) score. The combination of the T25FW and the MSWS-12 would offer the best sensitivity and specificity for determining response to fampridine according to both neurologists’ and patients’ classification. Conclusion: This study provides new information on the use of fampridine in a real-world setting with a large patient sample on the potential benefit of using more definitive responder criteria to fampridine for the clinical setting.
The role of person in subject auxiliary inversion in English wh-questions: Evidence from Korean-English bilingual children
Authors: Park-Johnson Sunny K 
Published: July 2017

Aims: The present study investigates whether Korean-English (K-E) bilingual children develop subject auxiliary inversion (SAI) in English wh-questions differently from monolingual English (M-E) speaking children. Specifically, an experimental study was designed to determine whether there is an effect of subject person in their acquisition of SAI in English wh-questions, a factor that had been suggested but not tested as a contributing factor in SAI in a previous study. Design: Twenty-six K-E bilingual and 20 M-E preschool-aged children were recruited for an elicitation study testing the effect of person on the use of SAI in wh-questions in English. The experiment consisted of having children interact with puppets in a guessing game that elicited first, second, and third person object- what questions in English. Data and analysis: Data from the experiment were analyzed through a binomial logistic regression, which accounts for the binary nature of the data (auxiliary inversion: present or absent) and identified which variables contribute significantly to the presence and absence of SAI. Findings/conclusions: Results indicated a significant difference between K-E and M-E groups and a significant main effect for person on SAI for the K-E group. The paper proposes that the [prs] feature is part of the bundle of features that drives the movement of the features in T to C. Originality: The paper contributes evidence for a link between the person feature and SAI, a link that has not been seen before for wh-question research. Significance/implications: The new evidence of a possible link between subject person and auxiliary inversion may open a window to new avenues for wh-question acquisition research.
Slow ventricular tachycardia presenting with acute liver failure
Authors: Wannhoff Andreas , Nusshag Christian , Stremmel Wolfgang , Merle Uta 
Published: July 2017

Objectives: Cardiac hepatopathy is an important differential diagnosis of acute liver failure. Slow ventricular tachycardia (slow VT) is a ventricular tachycardia (VT), in which heart rate is below the typical frequency of VT. We here report a case of acute liver failure in a patient with slow VT. Methods: The 64-year old male patient with history of cardiac pacemaker implantation for complete atrioventricular block was referred to our intensive care unit because of acute liver failure. Results: Workup identified cardiac failure as cause of hepatopathy; however, reason for cardiac failure remained unknown even after left heart catheterization with coronary angiography. Finally, the analysis of cardiac pacemaker recordings led to the diagnosis of slow VT. This could not be terminated with either electric cardioversion or pharmacological treatment, and the patient died of cardiac failure. Conclusion: Diagnosis of VT can be challenging if occurring at unexpected slow heart rates. Analysis of pacemaker recordings could help to make the diagnosis of slow VT.
Endoscopic submucosal dissection of gastric superficial neoplastic lesions: a single Western center experience
Authors: Petruzziello Lucio , Campanale Mariachiara , Spada Cristiano , Ricci Riccardo , Hassan Cesare , Gullo Gaia , Costamagna Guido 
Published: July 2017

BackgroundEndoscopic submucosal dissection (ESD) allows “en bloc” resection of superficial gastric lesions.ObjectiveThe aim of this study is to report “en bloc" resection rate, procedure results, post resection features, analysis of complications, and relapses at mid–long term follow‐up on an Italian center case series of patients with superficial gastric neoplastic lesions treated with ESD.MethodsThis is a retrospective evaluation of a prospectively collected series of patients diagnosed with gastric superficial lesions who underwent ESD between November 2007 and May 2015. The analysis included demographic, clinical, endoscopic, and histological data. In detail, the following features were analyzed: (1) “en bloc” resection rate; (2) R0, R1, and RX rate; (3) complication rate; and (4) neoplastic recurrence during follow‐up. A comparison was performed between lesions treated according to standard and to extended criteria.ResultsIn the analysis, therefore, 70 superficial lesions and 70 endoscopic procedures were considered.Overall, 53 (76%) procedures were performed according to the extended‐ESD criteria. The remaining 17 (24%) cases were performed according to standard criteria. In 68/70 (97%) procedures “en bloc” resection was successful. Forty‐four (65.6%) patients had a R0 resection, while 15 (22%) patients had a R1 and the remaining 8 (12.4%) patients were RX. Two patients (2.8%) experienced a major complication. Overall, 7 patients (10.4%) required surgery: in two cases because of local recurrence, in one case for an intraprocedural complication not amenable to endoscopic treatment, in three patients with R1 vertical margins, and in the last patient because of an aggressive pathology (i.e. signet ring cell adenocarcinoma). The mean follow‐up of patients with neoplastic lesions was 36.6 ± 13.1 months.ConclusionESD for early gastric cancer is a safe and effective technique when performed by experienced Endoscopists also in Western setting. When comparing the outcomes of the ESD in patients with standard and extended indication there is no significant difference in terms of complete resection, complications and local recurrence rates. Larger Western studies are needed to clearly define the role and the outcomes of ESD in regions at low incidence for gastric neoplasia.