bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term Follow-up of a Randomized Controlled Trial Comparing Scarf to Chevron Osteotomy in Hallux Valgus Correction
Authors: Jeuken Ralph M. , Schotanus Martijn G. M. , Kort Nanne P. , Deenik Axel , Jong Bob , Hendrickx Roel P. M. 
Published: March 2016

Background: Hallux valgus is one of the most common foot deformities. This long-term follow-up study compared the results of 2 widely used operative treatments for hallux valgus: the scarf and chevron osteotomy. Methods: Conventional weight bearing anteroposterior (AP) radiographs of the foot were made for evaluating the intermetatarsal angle and hallux valgus angle. For clinical evaluation, the American Orthopaedic Foot & Ankle Society (AOFAS) rating system for the hallux metatarsophalangeal-interphalangeal scale was used together with physical examination of the foot. These data were compared with the results from the original study. The Short Form 36 questionnaire, the Manchester-Oxford Foot Questionnaire (MOXFQ), and a general questionnaire including a visual analog scale (VAS) pain score were used for subjective evaluation. The primary outcome measures were the radiologic recurrence of hallux valgus and reoperation rate of the same toe. Secondary outcome measures were the results from the radiographs and subjective and clinical evaluation. The response rate was 76% at the follow-up of 14 years; in the chevron group, 37 feet were included compared with 36 feet in the scarf group. Results: Twenty-eight feet in the chevron group and 27 in the scarf group developed recurrence of hallux valgus ( P = .483). One patient in the scarf group had a reoperation of the same toe compared with none in the chevron group ( P = .314). Current VAS pain scores and results from the SF-36, MOXFQ, and AOFAS did not significantly differ between groups. Conclusion: Both techniques showed similar results after 2 years of follow-up. At 14 years of follow-up, neither technique was superior in preventing recurrence. Level of Evidence: Level II, randomized controlled trial.
Safe handling of oral antineoplastic medications: Focus on targeted therapeutics in the home setting
Authors: Cass Yaakov , Connor Thomas H , Tabachnik Alexander 
Published: March 2016

Introduction With the growing number of oral targeted therapies being approved for use in cancer therapy, the potential for long-term administration of these drugs to cancer patients is expanding. The use of these drugs in the home setting has the potential to expose family members and caregivers to them either through direct contact with the drugs or indirectly by exposure to the parent compounds and/or their active metabolites in contaminated patients’ waste. Methods A systematic literature review was performed and the known adverse health effect of 32 oral targeted therapeutics is summarized. In particular, the carcinogenicity, genotoxicity, and embryo-fetal toxicity, along with the route of excretion were evaluated. Results Carcinogenicity testing has not been performed on most of the oral targeted therapeutics and the genotoxicity data are mixed. However, the majority of these drugs exhibit adverse reproductive effects, some of which are severe. Currently, available data does not permit the possibility of a health hazard from inappropriate handling of drugs and contaminated patients waste to be ignored, especially in a long-term home setting. Further research is needed to understand these issues. Conclusions With the expanding use of targeted therapies in the home setting, family members and caregivers, especially those of reproductive risk age, are, potentially at risk. Overall basic education and related precautions should be taken to protect family members and caregivers from indirect or direct exposure from these drugs. Further investigations and discussion on this subject are warranted.
Does the ‘diffusion of innovations’ model enrich understanding of research use? Case studies of the implementation of thrombolysis services for stroke
Authors: Boaz Annette , Baeza Juan , Fraser Alec 
Published: March 2016

Objective To test whether the model of ‘diffusion of innovations’ enriches understanding of the implementation of evidence-based thrombolysis services for stroke patients. Methods Four case studies of the implementation of evidence on thrombolysis in stroke services in England and Sweden. Semistructured interviews with 95 staff including doctors, nurses and managers working in stroke units, emergency medicine, radiology, the ambulance service, community rehabilitation services and commissioners. Results The implementation of thrombolysis in acute stroke management benefited from a critical mass of the factors featured in the model including: the support of national and local opinion leaders; a strong evidence base and financial incentives. However, while the model provided a starting point as an organizational framework for mapping the critical factors influencing implementation, to understand properly the process of implementation and the importance of the different factors identified, more detailed analyses of context and, in particular, of the human and social dimensions of change was needed. Conclusions While recognising the usefulness of the model of diffusion of innovations in mapping the processes by which diffusion occurs, the use of methods that lend themselves to in-depth analysis, such as ethnography and the application of relevant bodies of social theory, are needed.
The potential role of atrial natriuretic peptide in the effects of Angiotensin-(1–7) in a chronic atrial tachycardia canine model
Authors: Zhao Jun , Liu Tiecheng , Liu Enzhao , Li Guangping , Qi Lingshan , Li Jian 
Published: March 2016

Objective: The objective of this article is to investigate the possible role of atrial natriuretic peptide (ANP) in Angiotensin-(1–7) (Ang-(1–7)) signaling pathway on atrial electrical and structural remodeling in a chronic rapid atrial pacing canine model. Methods: Twenty-four dogs were randomly assigned to four groups: a sham group, paced control group, a paced + Ang-(1–7) group and a paced + Ang-(1–7) + A-71915 group. Atrial rapid pacing (ARP) at 600 bpm was maintained for 14 days except in the animals from the sham group. During the pacing, Ang-(1–7) (6 μg•kg-1•h-1) or Ang-(1–7) (6 μg•kg-1•h-1) + A-71915 (ANP receptor antagonist, 0.30 μg•kg-1•h-1) were given intravenously, respectively. After pacing, it was measured that electrophysiological parameters including atrial effective refractory periods (ERPs), inducibility and duration of atrial fibrillation (AF), ICaL and INa changed, where ICaL refers to voltage-dependent L-type Ca2+ current and INa refers to cardiac sodium current. Then, the fibrosis and the expression of Cav1.2, INav1.5α subunit, TGF-β1 and ANP in atria were assessed. Results: After ARP, compared with the sham group, the atrial ERPs at six sites in each dog were shortened with the increasing in inducibility and duration of AF in the paced control group. The density of ICaL, INa and the expression of Cav1.2, INav1.5α subunit mRNA were decreased. Atrial tissue from the paced dogs showed significant interstitial fibrosis. The expression of TGF-β1 and ANP in mRNA and protein levels were increased. Compared with the paced control group, the shortening of atrial ERPs, and the increasing of inducibility and duration of AF induced by ARP were alleviated by Ang-(1–7) treatment ( p < 0.05). The density of ICaL and INa and the expression of Cav1.2 and INav1.5α subunit mRNA were slightly decreased. Atrial tissue showed less interstitial fibrosis after Ang-(1–7) treatment. The increasing of ANP expression was improved by Ang-(1–7), while the increasing of TGF-β1 expression was alleviated by Ang-(1–7) ( p < 0.05). A-71915 treatment blocked the beneficial effects of Ang-(1–7) on the aforementioned electrophysiological parameters and atrial fibrosis. And A-71915 treatment blocked Ang-(1–7), improving the expression of TGF-β1. Conclusion: Ang-(1–7) prevented atrial structural and electrical remodeling induced by ARP. Furthermore, Ang-(1–7) promoted ANP secretion, and ANP played a crucial role in the cardiac protection of the former.
Comparison of the relative importance of vascular and plasma drug concentrations to the hypotensive effect of telmisartan in rats
Authors: Takai Shinji , Sakonjo Hiroshi , Jin Denan 
Published: March 2016

Introduction: To clarify the importance of the vascular concentration of an angiotensin II receptor blocker (ARB) to its hypotensive effect, the relationships between the drug concentrations in plasma and vascular tissues and the hypotensive effect after administration of an ARB were compared. Materials and methods: In spontaneously hypertensive/NDmcr-cp rats (SHR/NDmcr-cp), systolic blood pressure (SBP) and angiotensin II-induced vascular contraction were measured 2 h and 24 h after administration of telmisartan (3 mg/kg). Plasma and vascular concentrations of telmisartan were also measured at 2 h and 24 h. Results: SBP was significantly lower 2 h after administration of telmisartan, and the significant hypotensive effect was continued until 24 h. A significant attenuation of angiotensin II-induced vascular contraction at 2 h was also continued until 24 h. No significant difference between 2 h and 24 h was observed both in SBP and angiotensin II-induced vascular contraction. Vascular concentration at 24 h was 90.0% when the concentration at 2 h was assumed to be 100%, and no significant difference was observed. However, the plasma concentration of telmisartan at 2 h was significantly decreased by 88.2% at 24 h. Conclusion: The vascular drug concentration, not the plasma drug concentration, may be related to the hypotensive effect after administration of telmisartan.
Deletion of fabN in Enterococcus faecalis results in unsaturated fatty acid auxotrophy and decreased release of inflammatory cytokines
Authors: Diederich Ann-Kristin , Duda Katarzyna A , Romero-Saavedra Felipe , Engel Regina , Holst Otto , Huebner Johannes 
Published: March 2016

The Gram-positive bacterium Enterococcus faecalis can cause life-threatening infections and is resistant to several commonly used antibiotics. The type II fatty acid pathway in bacteria is discussed as a potential target for antimicrobial therapy. However, it was shown that inhibition or deletion of its enzymes can be rescued in Gram-positive bacteria by supplementation with fatty acids. Here we show that by deletion of the fabN gene, which is essential for unsaturated fatty acid (UFA) synthesis in E. faecalis, growth is impaired but can be rescued by supplementation with oleic acid or human serum. Nonetheless, we demonstrate alterations of the UFA profile after supplementation with oleic acid in the Δ fabN mutant using a specific glycolipid. In addition, we demonstrate that cytokine release in vitro is almost abolished after stimulation of mouse macrophages by the mutant in comparison to the wild type. The results indicate that fabN is not a suitable target for antimicrobials as UFA auxotrophy can be overcome. However, deletion of fabN resulted in a decreased inflammatory response indicating that fabN and resulting UFA synthesis are relevant for virulence.
Collagenase Clostridium histolyticum in the management of Peyronie’s disease: a review of the evidence
Authors: Traore Elizabeth J. , Wang William , Yafi Faysal A. , Hellstrom Wayne J. G. 
Published: March 2016

Objectives: Peyronie’s disease (PD) is a connective tissue disorder resulting in the abnormal accumulation of scar or plaques in the tunica albuginea of the penis. The condition is characterized by two phases: an active, inflammatory phase, and a stable, chronic phase. Collagenase Clostridium histolyticum (CCH) was isolated in the mid-1900s and postulated as a potential pharmacologic strategy for breaking down the abnormal connective tissue plaques of PD. Prior to the introduction of CCH, a wide variety of treatment modalities for PD were used in clinical practice, including oral and topical medications, intralesional injections, electromotive drug administration, extracorporeal shockwave therapy, traction, and invasive surgery, all with variable results. This review aims to examine the known data surrounding the use of intralesional CCH injections in the treatment of PD. Methods: CCH is a recently US Food and Drug Administration approved pharmacologic treatment for PD. Clinical trials using intralesional CCH injection therapy for the treatment of PD were reviewed for clinical safety and efficacy of treatment. Results: Studies demonstrated that CCH treatment administered in multiple cycles led to significant benefit in both the psychological and physical aspects of PD. The strongest evidence for CCH’s effectiveness was revealed in large, multicenter randomized controlled trials (Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies I and II) in which intralesional CCH was combined with manual modeling of the penis. Although adverse events from treatment are relatively common, the majority are mild to moderate in degree, including penile pain, swelling, and bruising, which all resolve spontaneously. Conclusion: Overall, evidence indicates that CCH is a valuable, effective, and safe minimally invasive treatment option for men with PD.
Fibular Strut Graft for Revisional Tibiotalocalcaneal Arthrodesis
Authors: Monaco Spencer J. , Lowery Nick , Crim Brandon 
Published: March 2016

Tibiotalocalcaneal arthrodesis with an intramedullary nail is a procedure reserved for patients who have conditions affecting the ankle joint and subtalar joint. The most common complications include nonunion, malunion, delayed union, infection, periprosthetic fracture, hardware failure, lateral plantar nerve injury, and wound healing. Significant bone void may result if the hardware requires removal secondary to one of these complications. The purpose of this article is to report on 2 cases of infected intramedullary nails, which were revised with fibular inlay strut grafts. Both cases were augmented with either internal or external fixation. Levels of evidence: Therapeutic, Level IV: Case report
Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD
Authors: Rabinovich Roberto A. , Miller Bruce E. , Wrobel Karolina , Ranjit Kareshma , Williams Michelle C. , Drost Ellen , Edwards Lisa D. , Lomas David A. , Rennard Stephen I. , Agustí Alvar , Tal-Singer Ruth , Vestbo Jørgen , Wouters Emiel F.M. , John Michelle , van Beek Edwin J.R. , Murchison John T , Bolton Charlotte E , MacNee William , Huang Jeffrey T.J. 
Published: March 2016

Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality.pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic–femoral pulse wave velocity.pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=−0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05).In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.
Pseudomonasinfection and mucociliary and absorptive clearance in the cystic fibrosis lung
Authors: Locke Landon W. , Myerburg Michael M. , Weiner Daniel J. , Markovetz Matthew R. , Parker Robert S. , Muthukrishnan Ashok , Weber Lawrence , Czachowski Michael R. , Lacy Ryan T. , Pilewski Joseph M. , Corcoran Timothy E. 
Published: March 2016

Airway surface liquid hyperabsorption and mucus accumulation are key elements of cystic fibrosis lung disease that can be assessedin vivousing functional imaging methods. In this study we evaluated experimental factors affecting measurements of mucociliary clearance (MCC) and small-molecule absorption (ABS) and patient factors associated with abnormal absorption and mucus clearance.Our imaging technique utilises two radiopharmaceutical probes delivered by inhalation. Measurement repeatability was assessed in 10 adult cystic fibrosis subjects. Experimental factors were assessed in 29 adult and paediatric cystic fibrosis subjects (51 scans). Patient factors were assessed in a subgroup with optimal aerosol deposition (37 scans; 24 subjects). Paediatric subjects (n=9) underwent initial and 2-year follow-up scans. Control subjects from a previously reported study are included for comparison.High rates of central aerosol deposition influenced measurements of ABS and, to a lesser extent, MCC. Depressed MCC in cystic fibrosis was only detectable in subjects with previousPseudomonas aeruginosainfection. Cystic fibrosis subjects withoutP. aeruginosahad similar MCC to control subjects. Cystic fibrosis subjects had consistently higher ABS rates.We conclude that the primary experimental factor affecting MCC/ABS measurements is central deposition percentage. Depressed MCC in cystic fibrosis is associated withP. aeruginosainfection. ABS is consistently increased in cystic fibrosis.
Does the choice of nucleotide substitution models matter topologically?
Authors: Hoff Michael , Orf Stefan , Riehm Benedikt , Darriba Diego , Stamatakis Alexandros 
Published: March 2016

Abstract
Background
In the context of a master level programming practical at the computer science department of the Karlsruhe Institute of Technology, we developed and make available an open-source code for testing all 203 possible nucleotide substitution models in the Maximum Likelihood (ML) setting under the common Akaike, corrected Akaike, and Bayesian information criteria. We address the question if model selection matters topologically, that is, if conducting ML inferences under the optimal, instead of a standard General Time Reversible model, yields different tree topologies. We also assess, to which degree models selected and trees inferred under the three standard criteria (AIC, AICc, BIC) differ. Finally, we assess if the definition of the sample size (#sites versus #sites × #taxa) yields different models and, as a consequence, different tree topologies.

Results
We find that, all three factors (by order of impact: nucleotide model selection, information criterion used, sample size definition) can yield topologically substantially different final tree topologies (topological difference exceeding 10 %) for approximately 5 % of the tree inferences conducted on the 39 empirical datasets used in our study.

Conclusions
We find that, using the best-fit nucleotide substitution model may change the final ML tree topology compared to an inference under a default GTR model. The effect is less pronounced when comparing distinct information criteria. Nonetheless, in some cases we did obtain substantial topological differences.
Rinne test: Does the tuning fork position affect the sound amplitude at the ear?
Authors: Butskiy Oleksandr , Ng Denny , Hodgson Murray , Nunez Desmond A. 
Published: March 2016

Background Guidelines and text-book descriptions of the Rinne test advise orienting the tuning fork tines in parallel with the longitudinal axis of the external auditory canal (EAC), presumably to maximise the amplitude of the air conducted sound signal at the ear. Whether the orientation of the tuning fork tines affects the amplitude of the sound signal at the ear in clinical practice has not been previously reported. The present study had two goals: determine if (1) there is clinician variability in tuning fork placement when presenting the air-conduction stimulus during the Rinne test; (2) the orientation of the tuning fork tines, parallel versus perpendicular to the EAC, affects the sound amplitude at the ear. Methods To assess the variability in performing the Rinne test, the Canadian Society of Otolaryngology – Head and Neck Surgery members were surveyed. The amplitudes of the sound delivered to the tympanic membrane with the activated tuning fork tines held in parallel, and perpendicular to, the longitudinal axis of the EAC were measured using a Knowles Electronics Mannequin for Acoustic Research (KEMAR) with the microphone of a sound level meter inserted in the pinna insert. Results 47.4 and 44.8 % of 116 survey responders reported placing the fork parallel and perpendicular to the EAC respectively. The sound intensity (sound-pressure level) recorded at the tympanic membrane with the 512 Hz tuning fork tines in parallel with as opposed to perpendicular to the EAC was louder by 2.5 dB (95 % CI: 1.35, 3.65 dB; p < 0.0001) for the fundamental frequency (512 Hz), and by 4.94 dB (95 % CI: 3.10, 6.78 dB; p < 0.0001) and 3.70 dB (95 % CI: 1.62, 5.78 dB; p = .001) for the two harmonic (non-fundamental) frequencies (1 and 3.15 kHz), respectively. The 256 Hz tuning fork in parallel with the EAC as opposed to perpendicular to was louder by 0.83 dB (95 % CI: −0.26, 1.93 dB; p = 0.14) for the fundamental frequency (256 Hz), and by 4.28 dB (95 % CI: 2.65, 5.90 dB; p < 0.001) and 1.93 dB (95 % CI: 0.26, 3.61 dB; p = .02) for the two harmonic frequencies (500 and 4 kHz) respectively. Conclusions Clinicians vary in their orientation of the tuning fork tines in relation to the EAC when performing the Rinne test. Placement of the tuning fork tines in parallel as opposed to perpendicular to the EAC results in a higher sound amplitude at the level of the tympanic membrane.
Xanthogranuloma in the heavily irradiated low neck in a patient with head and neck cancer
Authors: Singer Lisa , Calkins Sarah M. , Horvai Andrew E. , Ryan William R. , Yom Sue S. 
Published: March 2016

Background Head and neck cancer is often managed with a combination of surgery, radiation therapy, and chemotherapy, and skin toxicity is not uncommon. Xanthogranuloma is a pathological finding resulting from an inflammatory reaction that has not been previously reported following head and neck radiation therapy. Case presentation A patient with squamous cell carcinoma of the oropharynx, treated with definitive chemoradiation and hyperthermia, presented at eight-month follow-up with an in-field cutaneous lesion in the low neck, initially concerning for recurrent tumor. Biopsy showed xanthogranuloma and the patient underwent complete resection with congruent surgical pathology. The patient remained free of malignancy but continued to experience wound healing difficulties at the resection site which resolved with specialized wound care and hyperbaric oxygen. Conclusions Skin toxicity is not uncommon in patients with head and neck cancer treated with radiation therapy. Awareness of unusual pathologic sequelae, such as xanthogranuloma, is needed to provide patient counseling while continuing appropriate surveillance for recurrent malignancy.